The Influence of Preoperative Interventions on Postoperative Surgical Wound Healing in Patients Without Risk Factors: A Systematic Review

The Influence of Preoperative Interventions on Postoperative Surgical Wound Healing in Patients... Abstract Background Poor wound healing and scar formation remain critical problems in daily surgical practice. Generally, most attention is paid to intra- and postoperative interventions to improve wound healing after surgery, while preoperative interventions remain unsatisfactorily explored. Objectives In this systematic review, the available literature on the beneficial effects of preoperative interventions on wound healing and scar formation have been summarized and compared. Methods A comprehensive and systematic search has been conducted in MEDLINE, Pubmed, Embase, Web of Science, and Cochrane, supplemented by reference and citation tracking. All preoperative interventions and all clinically relevant outcome parameters have been considered for inclusion, due to the expected limited availability of literature. Results A total of 13 studies were included, which were all randomized trials. No cohort studies or retrospective studies have been identified. All studies described different preoperative interventions and outcome parameters and could hence not be pooled and compared. Eight studies showed significantly better wound healing after a preoperative intervention. The individual studies have been summarized in this review. Conclusions This systemic review shows that preoperative interventions can be beneficial in improving wound healing and scar formation. In selected cases, wound healing was found to benefit from a higher preoperative body temperature, topical vitamin E application, and low patient stress levels. Level of Evidence: 2 Poor wound healing remains a critical problem in daily surgical practice, concerning either impaired healing or excessive scarring.1,2 The normal stages involved in wound healing seem to fail to progress. Processes during haemostasis, inflammation, epithelialization, connective tissue deposition, and contraction can either independently, or in combination, be responsible for impaired healing. Known risk factors for poor wound healing are smoking, corticosteroid use, advanced age, and diabetes.3-6 In patients with these risk factors, more complications occur and both the healing process and hospital stay take longer. Moreover, in patients without these risk factors, there is a typical risk of excessive scarring, infections, or dehiscence after surgical interventions. Surgical site infections (SSI) and excessive scar formation have major implications that affect patient morbidity and mortality rates as well as quality of life, and add to unnecessary hospital costs. Preventing poor wound healing is hence of great value to ensure good quality patient care and to control patient care costs.7 Here lies a challenge for the surgeon and the whole team involved in patient cure and care. There is much awareness of the positive effects of intra- and postoperative interventions on wound healing exists, such as antimicrobial agents, antiseptic dressings, and negative pressure wound therapy (NPWT). Nevertheless, impaired wound healing remains a common complication of surgery.8 Much less attention is generally paid to the influence of preoperative interventions in patients without risk factors on wound healing in order to prepare a patient for surgery and to minimize postoperative complications. This systematic review of the available literature has focused on the beneficial effects of any preoperative interventions on the wound healing and scar formation sequence after surgery. METHODS The search strategy has focused on patients who underwent elective operations during which a skin wound was made. The influence of additional preoperative interventions on wound healing was studied (ie, healing rate, dehiscence, infection rate, or scar tissue). Preoperative interventions have here been defined as all interventions the patient underwent before entering the operation room in addition to the usual care. Search Methods for Identification of Studies A comprehensive and systematic search has been conducted in MEDLINE, PubMed, Embase, Web of Science, and Cochrane up to May 2017. The search strategy is given in Appendices A1 to A5. During each search, Appendix A1 was combined with the search strategy of Appendices A2, A3, A4, or A5. No restriction was made in regard to patient age or publication date. Only articles written in English have been considered for inclusion. References from the included studies have been also screened in order to identify additional primary studies, which had not previously been identified. Two review authors (N.G. and M.Z.), working independently from one another, examined titles and abstracts from the electronic search. Full articles were obtained if necessary. The third and fourth review authors (J.H. and F.N.) have been consulted if consensus was not reached. Inclusion Criteria References have been selected if they met all of the following inclusion criteria: • The study design was either a randomized controlled trial, a nonrandomized study with a control group, or a case series. • A minimum of ten patients was included. • The included patients underwent elective operations during which a skin wound was made. • The study evaluated the results of any preoperative intervention which aimed at improving wound healing and the reduction of any wound healing complications (eg, dehiscence, infection rate, scar tissue). • The criteria for inclusion were explicit (eg, type of surgery, interventions). • The number of patients deceased or lost to follow up was reported. • Clear descriptions of intervention and follow up were given and results were provided for each distinct treatment in the study. • The outcome(s) included at least one clinically relevant/measurable outcome (eg, reduced infections/dehiscence rate or scar formation). Exclusion Criteria • The study described patients with active infections before surgical intervention. • The study included patients with known risk factors for poor wound healing. • The study described pressure ulcers, chronic skin wounds, and traumatic skin wounds. • Prophylactic antibiotics have already widely been examined, and therefore, were not a topic of this review. Assessment of Risk of Bias for the Included Studies Two review authors (N.G. and M.Z.) working independently from each other conducted the risk-of-bias assessment and data extraction. Risk-of-bias of the individual studies was assessed with methodology scores based on the type of study concerned: Cochrane form II for randomized controlled trial (RCTs) and Cochrane form III for cohort studies. The authors added a number of items. Items were scored positive if they fulfilled the criteria, negative when bias was likely, or marked as inconclusive if there was insufficient information. Differences in the scoring of the risk-of-bias assessment and data extraction were discussed during a consensus meeting. If an item was scored positive, one point was awarded. The number of positively scored items has been summed per study. Data Collection and Analysis The data have been extracted onto separate, predeveloped forms. From each study, basic information has been gathered concerning authors (affiliation, sponsoring), methods (study design, sample size), patients (selection criteria and diagnoses), treatments (preoperative interventions), and outcome variables with results. With sufficient clinically and statistically homogeneous and comparable reported outcomes, data were planned to be pooled. For continuous outcomes, a mean difference (MD) was planned to be calculated. For dichotomous outcomes, relative risks (RR) were planned to be calculated. For each outcome, a 95% confidence interval (95% CI) was planned to be computed. RESULTS The initial search yielded 3448 unique references. A total of only 13 studies were eventually identified, which were all randomized controlled trials (Figure 1). The main reasons for exclusion were that interventions were not carried out preoperatively (but intra- or postoperatively); patients with known risk factors were described; no clinically relevant/measurable outcome parameter was described; or there was no surgical wound involved. The main characteristics of the included studies are given in Table 1. The PRISMA Checklist is provided in Appendix B. Figure 1. View largeDownload slide Flowchart for study inclusion. Figure 1. View largeDownload slide Flowchart for study inclusion. Table 1. Characteristics of Included Studies Study Inclusion criteria Exclusion criteria Intervention group Control group Age Time of intervention Sample size (female) Systemic treatments Vaxman (1995)10 Tattoo removal Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR >165/90 mmHg, no respect of procedure, blood concentrations of transferrin <2 g/L, prealbumin <100mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12g/dL Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid (n = 18) Placebo (n = 22) 28.5 Once a day for 21 days, started 8 days prior to surgery 40 (13) Vaxman (1996)9 Tattoo (too big to be removed by single resection), 18-40 years Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR > 165/90 mmHg, blood concentrations of transferrin <2 g/L, prealbumin <100 mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12 g/dL Oral 0.9 g Pantothenic acid and 3 g Ascorbic acid (n = 10) 0.2 g Pantothenic acid and 1 g Ascorbic acid (n = 17) 28.5 Once a day, started 8 days prior to surgery and continued until 13 days after 27 (-) Levandovski (2008)11 Patients undergoing abdominal hysterectomy Contraindications to regional anesthesia, mental impairment, chronic pain, history of congestive heart failure, valvular heart disease, renal or hepatic disease, psychotropic drug, language/communication difficulties, BMI >35 kg/m2, history of psychiatric disorders Oral 10 mg diazepam (n = 61) Placebo (n = 62) Between 19–60 years 1 night before and one hour prior to surgery 123 (123) Künzli (2013)12 Age 25-90 years, all aseptic operations with median or transverse laparotomy Laparoscopic operations, apparent infection before operation, MRSA infection, body temperature >38°C for more than 5 days preoperatively, myocardial infarction within 6 weeks before operation, radio- and/or chemotherapy within 4 weeks before surgery, Albumin <3.3 g/dL, leucocytes < 2.0 G/L, inadvertent loss of weight >10% within 6 months before operation Exposure to the hydrosun radiator for 20 minutes and prophylactic antibiotics (n = 178) Receiving only visible light (sham lamp) for 20 minutes and prophylactic antibiotics (n = 182) Between 25-90 years Same day of surgery 360 (77) Melling (2001)13 >18 years, having an elective hernia repair, varicose vein surgery, or breast surgery that would result in scar >3 cm Pregnant, taking long-term oral steroids, received radiotherapy (at incision site) or chemotherapy during the last 4 weeks, or had an infection at the time of surgery Systemic warming group received standard care, plus warming the whole body using a forced-air, warming blanket. (n = 139) Local warming group received standard care, plus warming to just the planned wound area using a noncontact, radiant heat dressing. (n = 138) Received standard care only, not including any active temperature control. (n = 139) Average 50.03 (SD 14.36) At least 30 min before surgery 242 (174) Topical application Zampieri (2010)14 Need for elective inguinal surgery (no previous or abdominal surgery), no keloids due to previous trauma, no systemic diseases, no skin diseases nor infections, no previous use of topical steroids or drugs Atopic eczema and napkin dermatitis Topical vitamin E (n = 228) Petrolatum-based emollient (n = 200) Between 2 and 9 years Trice daily for 15 days prior to surgery and twice daily for 30 days after surgery 428 (109) Psychological interventions Robles (2007)15 Healthy volunteers, 18-44 years Pregnancy, medical conditions or medications with obvious immunological, dermatological or endocrinological consequences, smoking and excessive caffeine or alcohol use Trier social stress test plus support (n = 27) Trier social stress test (n = 31) No stress (n = 27) 22.6 (4.41) 1 hour prior to surgery 85 (44) Koschwanez (2013)16 >60 years, able to write in English Smoking, significant skin disease, allergic to lignocaine, or clinically depressed Writing about a traumatic experience (n = 26) Writing about time management without mentioning emotions, opinions, or beliefs. (n = 23) 78.8 (7.2) 20 minutes daily, started 2 weeks prior to surgery and stopped 1 day prior to surgery 49 (28) Weinman (2008)17 Healthy volunteers, 18-40 years >15 cigarettes per week, skin complaint (ie, eczema or psoriasis), glucocorticoid medication use during last month, chronic inflammatory disorders, allergic rhinitis, or allergic asthma, clinical depression, acute illness, family history of keloid scarring Writing about a traumatic experience (n = 18) Writing about time management (n = 18) 22.2 (4.08) 20 minutes for three days, 2 weeks prior to surgery 36 (0) Broadbent (2012)18 Undergoing elective laparoscopic cholecystectomy, >18 years, able to read and write English - Brief relaxation intervention (n = 37) No stress (read an article silently and alone, no following test) (n = 38) 51.3 (16.8) 3 days prior to surgery and 7 days after 45 (30) Ginandes(2003) 19 Healthy women with macromastia Systemic illness, medications ,and/or behaviours affecting wound healing (diabetes, immune compromise, prescribed steroids, cigarette smoking), psychological conditions, language barriers Hypnosis (n = 6) supportive attention (n = 6) No hypnosis or support (n = 6) 38.9 (8.7) 8 half-hour weekly for 2 weeks prior to surgery 18 (18) Rao (2008)20 Recently diagnosed breast cancer, mastectomy as primary treatment, 30-70 years, Zubrod’s performance status 0-2 (ambulatory >50% of time), high school education Concurrent medical condition likely to interfere with treatment, any major psychiatric, neurological illness or autoimmune disorders, secondary malignancy, presented with infections or history of recent infections in the past month Yoga program (n = 24) Supportive therapy and exercise rehabilitation (n = 28) 49.2 (9.6) 1 hour prior to surgery and daily 3 times a week postsurgery 52 (52) Pereira (2016)21 Undergoing general ambulatory surgery Major psychiatric or neurologic pathologies Empathic personal information about surgery (n = 52) Standardized information about hospitalization norms and description of the surgical procedures (n = 52) 44.2 (14.6) One month prior to surgery 104 (35) Study Inclusion criteria Exclusion criteria Intervention group Control group Age Time of intervention Sample size (female) Systemic treatments Vaxman (1995)10 Tattoo removal Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR >165/90 mmHg, no respect of procedure, blood concentrations of transferrin <2 g/L, prealbumin <100mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12g/dL Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid (n = 18) Placebo (n = 22) 28.5 Once a day for 21 days, started 8 days prior to surgery 40 (13) Vaxman (1996)9 Tattoo (too big to be removed by single resection), 18-40 years Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR > 165/90 mmHg, blood concentrations of transferrin <2 g/L, prealbumin <100 mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12 g/dL Oral 0.9 g Pantothenic acid and 3 g Ascorbic acid (n = 10) 0.2 g Pantothenic acid and 1 g Ascorbic acid (n = 17) 28.5 Once a day, started 8 days prior to surgery and continued until 13 days after 27 (-) Levandovski (2008)11 Patients undergoing abdominal hysterectomy Contraindications to regional anesthesia, mental impairment, chronic pain, history of congestive heart failure, valvular heart disease, renal or hepatic disease, psychotropic drug, language/communication difficulties, BMI >35 kg/m2, history of psychiatric disorders Oral 10 mg diazepam (n = 61) Placebo (n = 62) Between 19–60 years 1 night before and one hour prior to surgery 123 (123) Künzli (2013)12 Age 25-90 years, all aseptic operations with median or transverse laparotomy Laparoscopic operations, apparent infection before operation, MRSA infection, body temperature >38°C for more than 5 days preoperatively, myocardial infarction within 6 weeks before operation, radio- and/or chemotherapy within 4 weeks before surgery, Albumin <3.3 g/dL, leucocytes < 2.0 G/L, inadvertent loss of weight >10% within 6 months before operation Exposure to the hydrosun radiator for 20 minutes and prophylactic antibiotics (n = 178) Receiving only visible light (sham lamp) for 20 minutes and prophylactic antibiotics (n = 182) Between 25-90 years Same day of surgery 360 (77) Melling (2001)13 >18 years, having an elective hernia repair, varicose vein surgery, or breast surgery that would result in scar >3 cm Pregnant, taking long-term oral steroids, received radiotherapy (at incision site) or chemotherapy during the last 4 weeks, or had an infection at the time of surgery Systemic warming group received standard care, plus warming the whole body using a forced-air, warming blanket. (n = 139) Local warming group received standard care, plus warming to just the planned wound area using a noncontact, radiant heat dressing. (n = 138) Received standard care only, not including any active temperature control. (n = 139) Average 50.03 (SD 14.36) At least 30 min before surgery 242 (174) Topical application Zampieri (2010)14 Need for elective inguinal surgery (no previous or abdominal surgery), no keloids due to previous trauma, no systemic diseases, no skin diseases nor infections, no previous use of topical steroids or drugs Atopic eczema and napkin dermatitis Topical vitamin E (n = 228) Petrolatum-based emollient (n = 200) Between 2 and 9 years Trice daily for 15 days prior to surgery and twice daily for 30 days after surgery 428 (109) Psychological interventions Robles (2007)15 Healthy volunteers, 18-44 years Pregnancy, medical conditions or medications with obvious immunological, dermatological or endocrinological consequences, smoking and excessive caffeine or alcohol use Trier social stress test plus support (n = 27) Trier social stress test (n = 31) No stress (n = 27) 22.6 (4.41) 1 hour prior to surgery 85 (44) Koschwanez (2013)16 >60 years, able to write in English Smoking, significant skin disease, allergic to lignocaine, or clinically depressed Writing about a traumatic experience (n = 26) Writing about time management without mentioning emotions, opinions, or beliefs. (n = 23) 78.8 (7.2) 20 minutes daily, started 2 weeks prior to surgery and stopped 1 day prior to surgery 49 (28) Weinman (2008)17 Healthy volunteers, 18-40 years >15 cigarettes per week, skin complaint (ie, eczema or psoriasis), glucocorticoid medication use during last month, chronic inflammatory disorders, allergic rhinitis, or allergic asthma, clinical depression, acute illness, family history of keloid scarring Writing about a traumatic experience (n = 18) Writing about time management (n = 18) 22.2 (4.08) 20 minutes for three days, 2 weeks prior to surgery 36 (0) Broadbent (2012)18 Undergoing elective laparoscopic cholecystectomy, >18 years, able to read and write English - Brief relaxation intervention (n = 37) No stress (read an article silently and alone, no following test) (n = 38) 51.3 (16.8) 3 days prior to surgery and 7 days after 45 (30) Ginandes(2003) 19 Healthy women with macromastia Systemic illness, medications ,and/or behaviours affecting wound healing (diabetes, immune compromise, prescribed steroids, cigarette smoking), psychological conditions, language barriers Hypnosis (n = 6) supportive attention (n = 6) No hypnosis or support (n = 6) 38.9 (8.7) 8 half-hour weekly for 2 weeks prior to surgery 18 (18) Rao (2008)20 Recently diagnosed breast cancer, mastectomy as primary treatment, 30-70 years, Zubrod’s performance status 0-2 (ambulatory >50% of time), high school education Concurrent medical condition likely to interfere with treatment, any major psychiatric, neurological illness or autoimmune disorders, secondary malignancy, presented with infections or history of recent infections in the past month Yoga program (n = 24) Supportive therapy and exercise rehabilitation (n = 28) 49.2 (9.6) 1 hour prior to surgery and daily 3 times a week postsurgery 52 (52) Pereira (2016)21 Undergoing general ambulatory surgery Major psychiatric or neurologic pathologies Empathic personal information about surgery (n = 52) Standardized information about hospitalization norms and description of the surgical procedures (n = 52) 44.2 (14.6) One month prior to surgery 104 (35) BMI, body mass index. View Large Table 1. Characteristics of Included Studies Study Inclusion criteria Exclusion criteria Intervention group Control group Age Time of intervention Sample size (female) Systemic treatments Vaxman (1995)10 Tattoo removal Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR >165/90 mmHg, no respect of procedure, blood concentrations of transferrin <2 g/L, prealbumin <100mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12g/dL Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid (n = 18) Placebo (n = 22) 28.5 Once a day for 21 days, started 8 days prior to surgery 40 (13) Vaxman (1996)9 Tattoo (too big to be removed by single resection), 18-40 years Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR > 165/90 mmHg, blood concentrations of transferrin <2 g/L, prealbumin <100 mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12 g/dL Oral 0.9 g Pantothenic acid and 3 g Ascorbic acid (n = 10) 0.2 g Pantothenic acid and 1 g Ascorbic acid (n = 17) 28.5 Once a day, started 8 days prior to surgery and continued until 13 days after 27 (-) Levandovski (2008)11 Patients undergoing abdominal hysterectomy Contraindications to regional anesthesia, mental impairment, chronic pain, history of congestive heart failure, valvular heart disease, renal or hepatic disease, psychotropic drug, language/communication difficulties, BMI >35 kg/m2, history of psychiatric disorders Oral 10 mg diazepam (n = 61) Placebo (n = 62) Between 19–60 years 1 night before and one hour prior to surgery 123 (123) Künzli (2013)12 Age 25-90 years, all aseptic operations with median or transverse laparotomy Laparoscopic operations, apparent infection before operation, MRSA infection, body temperature >38°C for more than 5 days preoperatively, myocardial infarction within 6 weeks before operation, radio- and/or chemotherapy within 4 weeks before surgery, Albumin <3.3 g/dL, leucocytes < 2.0 G/L, inadvertent loss of weight >10% within 6 months before operation Exposure to the hydrosun radiator for 20 minutes and prophylactic antibiotics (n = 178) Receiving only visible light (sham lamp) for 20 minutes and prophylactic antibiotics (n = 182) Between 25-90 years Same day of surgery 360 (77) Melling (2001)13 >18 years, having an elective hernia repair, varicose vein surgery, or breast surgery that would result in scar >3 cm Pregnant, taking long-term oral steroids, received radiotherapy (at incision site) or chemotherapy during the last 4 weeks, or had an infection at the time of surgery Systemic warming group received standard care, plus warming the whole body using a forced-air, warming blanket. (n = 139) Local warming group received standard care, plus warming to just the planned wound area using a noncontact, radiant heat dressing. (n = 138) Received standard care only, not including any active temperature control. (n = 139) Average 50.03 (SD 14.36) At least 30 min before surgery 242 (174) Topical application Zampieri (2010)14 Need for elective inguinal surgery (no previous or abdominal surgery), no keloids due to previous trauma, no systemic diseases, no skin diseases nor infections, no previous use of topical steroids or drugs Atopic eczema and napkin dermatitis Topical vitamin E (n = 228) Petrolatum-based emollient (n = 200) Between 2 and 9 years Trice daily for 15 days prior to surgery and twice daily for 30 days after surgery 428 (109) Psychological interventions Robles (2007)15 Healthy volunteers, 18-44 years Pregnancy, medical conditions or medications with obvious immunological, dermatological or endocrinological consequences, smoking and excessive caffeine or alcohol use Trier social stress test plus support (n = 27) Trier social stress test (n = 31) No stress (n = 27) 22.6 (4.41) 1 hour prior to surgery 85 (44) Koschwanez (2013)16 >60 years, able to write in English Smoking, significant skin disease, allergic to lignocaine, or clinically depressed Writing about a traumatic experience (n = 26) Writing about time management without mentioning emotions, opinions, or beliefs. (n = 23) 78.8 (7.2) 20 minutes daily, started 2 weeks prior to surgery and stopped 1 day prior to surgery 49 (28) Weinman (2008)17 Healthy volunteers, 18-40 years >15 cigarettes per week, skin complaint (ie, eczema or psoriasis), glucocorticoid medication use during last month, chronic inflammatory disorders, allergic rhinitis, or allergic asthma, clinical depression, acute illness, family history of keloid scarring Writing about a traumatic experience (n = 18) Writing about time management (n = 18) 22.2 (4.08) 20 minutes for three days, 2 weeks prior to surgery 36 (0) Broadbent (2012)18 Undergoing elective laparoscopic cholecystectomy, >18 years, able to read and write English - Brief relaxation intervention (n = 37) No stress (read an article silently and alone, no following test) (n = 38) 51.3 (16.8) 3 days prior to surgery and 7 days after 45 (30) Ginandes(2003) 19 Healthy women with macromastia Systemic illness, medications ,and/or behaviours affecting wound healing (diabetes, immune compromise, prescribed steroids, cigarette smoking), psychological conditions, language barriers Hypnosis (n = 6) supportive attention (n = 6) No hypnosis or support (n = 6) 38.9 (8.7) 8 half-hour weekly for 2 weeks prior to surgery 18 (18) Rao (2008)20 Recently diagnosed breast cancer, mastectomy as primary treatment, 30-70 years, Zubrod’s performance status 0-2 (ambulatory >50% of time), high school education Concurrent medical condition likely to interfere with treatment, any major psychiatric, neurological illness or autoimmune disorders, secondary malignancy, presented with infections or history of recent infections in the past month Yoga program (n = 24) Supportive therapy and exercise rehabilitation (n = 28) 49.2 (9.6) 1 hour prior to surgery and daily 3 times a week postsurgery 52 (52) Pereira (2016)21 Undergoing general ambulatory surgery Major psychiatric or neurologic pathologies Empathic personal information about surgery (n = 52) Standardized information about hospitalization norms and description of the surgical procedures (n = 52) 44.2 (14.6) One month prior to surgery 104 (35) Study Inclusion criteria Exclusion criteria Intervention group Control group Age Time of intervention Sample size (female) Systemic treatments Vaxman (1995)10 Tattoo removal Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR >165/90 mmHg, no respect of procedure, blood concentrations of transferrin <2 g/L, prealbumin <100mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12g/dL Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid (n = 18) Placebo (n = 22) 28.5 Once a day for 21 days, started 8 days prior to surgery 40 (13) Vaxman (1996)9 Tattoo (too big to be removed by single resection), 18-40 years Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR > 165/90 mmHg, blood concentrations of transferrin <2 g/L, prealbumin <100 mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12 g/dL Oral 0.9 g Pantothenic acid and 3 g Ascorbic acid (n = 10) 0.2 g Pantothenic acid and 1 g Ascorbic acid (n = 17) 28.5 Once a day, started 8 days prior to surgery and continued until 13 days after 27 (-) Levandovski (2008)11 Patients undergoing abdominal hysterectomy Contraindications to regional anesthesia, mental impairment, chronic pain, history of congestive heart failure, valvular heart disease, renal or hepatic disease, psychotropic drug, language/communication difficulties, BMI >35 kg/m2, history of psychiatric disorders Oral 10 mg diazepam (n = 61) Placebo (n = 62) Between 19–60 years 1 night before and one hour prior to surgery 123 (123) Künzli (2013)12 Age 25-90 years, all aseptic operations with median or transverse laparotomy Laparoscopic operations, apparent infection before operation, MRSA infection, body temperature >38°C for more than 5 days preoperatively, myocardial infarction within 6 weeks before operation, radio- and/or chemotherapy within 4 weeks before surgery, Albumin <3.3 g/dL, leucocytes < 2.0 G/L, inadvertent loss of weight >10% within 6 months before operation Exposure to the hydrosun radiator for 20 minutes and prophylactic antibiotics (n = 178) Receiving only visible light (sham lamp) for 20 minutes and prophylactic antibiotics (n = 182) Between 25-90 years Same day of surgery 360 (77) Melling (2001)13 >18 years, having an elective hernia repair, varicose vein surgery, or breast surgery that would result in scar >3 cm Pregnant, taking long-term oral steroids, received radiotherapy (at incision site) or chemotherapy during the last 4 weeks, or had an infection at the time of surgery Systemic warming group received standard care, plus warming the whole body using a forced-air, warming blanket. (n = 139) Local warming group received standard care, plus warming to just the planned wound area using a noncontact, radiant heat dressing. (n = 138) Received standard care only, not including any active temperature control. (n = 139) Average 50.03 (SD 14.36) At least 30 min before surgery 242 (174) Topical application Zampieri (2010)14 Need for elective inguinal surgery (no previous or abdominal surgery), no keloids due to previous trauma, no systemic diseases, no skin diseases nor infections, no previous use of topical steroids or drugs Atopic eczema and napkin dermatitis Topical vitamin E (n = 228) Petrolatum-based emollient (n = 200) Between 2 and 9 years Trice daily for 15 days prior to surgery and twice daily for 30 days after surgery 428 (109) Psychological interventions Robles (2007)15 Healthy volunteers, 18-44 years Pregnancy, medical conditions or medications with obvious immunological, dermatological or endocrinological consequences, smoking and excessive caffeine or alcohol use Trier social stress test plus support (n = 27) Trier social stress test (n = 31) No stress (n = 27) 22.6 (4.41) 1 hour prior to surgery 85 (44) Koschwanez (2013)16 >60 years, able to write in English Smoking, significant skin disease, allergic to lignocaine, or clinically depressed Writing about a traumatic experience (n = 26) Writing about time management without mentioning emotions, opinions, or beliefs. (n = 23) 78.8 (7.2) 20 minutes daily, started 2 weeks prior to surgery and stopped 1 day prior to surgery 49 (28) Weinman (2008)17 Healthy volunteers, 18-40 years >15 cigarettes per week, skin complaint (ie, eczema or psoriasis), glucocorticoid medication use during last month, chronic inflammatory disorders, allergic rhinitis, or allergic asthma, clinical depression, acute illness, family history of keloid scarring Writing about a traumatic experience (n = 18) Writing about time management (n = 18) 22.2 (4.08) 20 minutes for three days, 2 weeks prior to surgery 36 (0) Broadbent (2012)18 Undergoing elective laparoscopic cholecystectomy, >18 years, able to read and write English - Brief relaxation intervention (n = 37) No stress (read an article silently and alone, no following test) (n = 38) 51.3 (16.8) 3 days prior to surgery and 7 days after 45 (30) Ginandes(2003) 19 Healthy women with macromastia Systemic illness, medications ,and/or behaviours affecting wound healing (diabetes, immune compromise, prescribed steroids, cigarette smoking), psychological conditions, language barriers Hypnosis (n = 6) supportive attention (n = 6) No hypnosis or support (n = 6) 38.9 (8.7) 8 half-hour weekly for 2 weeks prior to surgery 18 (18) Rao (2008)20 Recently diagnosed breast cancer, mastectomy as primary treatment, 30-70 years, Zubrod’s performance status 0-2 (ambulatory >50% of time), high school education Concurrent medical condition likely to interfere with treatment, any major psychiatric, neurological illness or autoimmune disorders, secondary malignancy, presented with infections or history of recent infections in the past month Yoga program (n = 24) Supportive therapy and exercise rehabilitation (n = 28) 49.2 (9.6) 1 hour prior to surgery and daily 3 times a week postsurgery 52 (52) Pereira (2016)21 Undergoing general ambulatory surgery Major psychiatric or neurologic pathologies Empathic personal information about surgery (n = 52) Standardized information about hospitalization norms and description of the surgical procedures (n = 52) 44.2 (14.6) One month prior to surgery 104 (35) BMI, body mass index. View Large Risk-of-Bias Assessments The results of the risk-of-bias assessments are shown in Table 2. The 13 RCTs were scored on a 10-point scale (0 being worst, 10 excellent quality). Table 2. Results of Risk-of-Bias Assessment of the RCTs Randomized controlled trials Vaxman (1995)10 Vaxman (1996)9 Levandovski (2008)11 Künzli (2013)12 Melling (2001)13 Zampieri (2010)14 Robles (2007)15 Koschwanez (2013)16 Weinman (2008)17 Broadbent (2012)18 Ginandes (2003)19 Rao (2008)20 Pereira (2014)21 Clear study objective + + + + + + + + + + + + + Criteria for inclusion explicit + + + + + + + + + + + + + Comparable groups apart from the intervention - - + + + + + + + + + + + Number of men and women + - + + + + + + + + + + + Outcome valid and clinically relevant + + + + + + + + + + + + + Randomized trial + + + + + + + + + + + + + Patient blinded for treatment + + + + - + - - + - - - - Clinician blinded for treatment + + + + + - - + - + + - - Assessors blinded for treatment - - + - + + + + - + + + - Complete follow up of each patient + + + - + + + + + + + + + Conclusion 8/10 7/10 10/10 8/10 9/10 9/10 8/10 9/10 8/10 9/10 9/10 8/10 7/10 Randomized controlled trials Vaxman (1995)10 Vaxman (1996)9 Levandovski (2008)11 Künzli (2013)12 Melling (2001)13 Zampieri (2010)14 Robles (2007)15 Koschwanez (2013)16 Weinman (2008)17 Broadbent (2012)18 Ginandes (2003)19 Rao (2008)20 Pereira (2014)21 Clear study objective + + + + + + + + + + + + + Criteria for inclusion explicit + + + + + + + + + + + + + Comparable groups apart from the intervention - - + + + + + + + + + + + Number of men and women + - + + + + + + + + + + + Outcome valid and clinically relevant + + + + + + + + + + + + + Randomized trial + + + + + + + + + + + + + Patient blinded for treatment + + + + - + - - + - - - - Clinician blinded for treatment + + + + + - - + - + + - - Assessors blinded for treatment - - + - + + + + - + + + - Complete follow up of each patient + + + - + + + + + + + + + Conclusion 8/10 7/10 10/10 8/10 9/10 9/10 8/10 9/10 8/10 9/10 9/10 8/10 7/10 RCT, randomized controlled trial. View Large Table 2. Results of Risk-of-Bias Assessment of the RCTs Randomized controlled trials Vaxman (1995)10 Vaxman (1996)9 Levandovski (2008)11 Künzli (2013)12 Melling (2001)13 Zampieri (2010)14 Robles (2007)15 Koschwanez (2013)16 Weinman (2008)17 Broadbent (2012)18 Ginandes (2003)19 Rao (2008)20 Pereira (2014)21 Clear study objective + + + + + + + + + + + + + Criteria for inclusion explicit + + + + + + + + + + + + + Comparable groups apart from the intervention - - + + + + + + + + + + + Number of men and women + - + + + + + + + + + + + Outcome valid and clinically relevant + + + + + + + + + + + + + Randomized trial + + + + + + + + + + + + + Patient blinded for treatment + + + + - + - - + - - - - Clinician blinded for treatment + + + + + - - + - + + - - Assessors blinded for treatment - - + - + + + + - + + + - Complete follow up of each patient + + + - + + + + + + + + + Conclusion 8/10 7/10 10/10 8/10 9/10 9/10 8/10 9/10 8/10 9/10 9/10 8/10 7/10 Randomized controlled trials Vaxman (1995)10 Vaxman (1996)9 Levandovski (2008)11 Künzli (2013)12 Melling (2001)13 Zampieri (2010)14 Robles (2007)15 Koschwanez (2013)16 Weinman (2008)17 Broadbent (2012)18 Ginandes (2003)19 Rao (2008)20 Pereira (2014)21 Clear study objective + + + + + + + + + + + + + Criteria for inclusion explicit + + + + + + + + + + + + + Comparable groups apart from the intervention - - + + + + + + + + + + + Number of men and women + - + + + + + + + + + + + Outcome valid and clinically relevant + + + + + + + + + + + + + Randomized trial + + + + + + + + + + + + + Patient blinded for treatment + + + + - + - - + - - - - Clinician blinded for treatment + + + + + - - + - + + - - Assessors blinded for treatment - - + - + + + + - + + + - Complete follow up of each patient + + + - + + + + + + + + + Conclusion 8/10 7/10 10/10 8/10 9/10 9/10 8/10 9/10 8/10 9/10 9/10 8/10 7/10 RCT, randomized controlled trial. View Large Study Comparison A wide variety of patients, interventions, and outcome parameters were used to assess wound healing. Because of this heterogeneity, no pooling, comparisons, or statistical analyses were possible between the included studies. The included articles individually, however, do allow for some interesting observations to be made. The main findings were grouped into three main categories: systemic treatments (n = 5), topical application (n = 1), and psychological interventions (n = 7). The main findings (Table 3) of the studies are summarized and reported below. Table 3. Outcome of Data Extraction Study Outcome Outcome measurement Follow up time Result control group Result intervention group P-value Systemic treatments Vaxman (1995)10 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Placebo 38 ± 2 29 ± 1 Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid 39 ± 1 29 ± 1 “ns” “ns” Fibroblast count Mean number of Fibroblasts per optical field in skin and scar 8 days 21 days 26 ± 2 83 ± 6 28 ± 2 91 ± 7 “ns” “ns” Vaxman (1996)9 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Oral 0.2 g/day Pantothenic acid and 1.0 g/day Ascorbic acid 39 ± 6 27 ± 6 Oral 0.9 g/day Pantothenic acid and 3 g/day Ascorbic acid 36 ± 4 25 ± 8 “ns” “ns” Fibroblast count n/field 8 days 21 days 28 ± 7 90 ± 31 19 ± 7 80 ± 30 “ns” “ns” Levandovski (2008)11 SSI = either of two distinct criteria for diagnosis: 1. pus could be expressed from the incision; 2. incisional or organ space; with a diagnostic period up to 30 days Yes or no (number of SSI) 30 days Placebo 16/26 Oral 10 mg diazepam 4/61 P = 0.00 State-trait anxiety inventory (STAI): The preoperative score were measured just before surgery; The postoperative anxiety was defined as the average of the score obtained at 6 and 24 hours following surgery Anxiety point scale 0 (no anxiety) - 45.5 (most anxiety) points Patients in the highest quartile were classified as High anxiety and patients in the lowest or equal to the quartile were classifies as Low anxiety 24 hours 41.91 ± 8.88 38.13 ± 6.94 P = 0.01 Künzli (2013)12 Postoperative wound infection (SSI) ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks 30 days (9/178) (22/182) FAS P = 0.018 ITT P = 0.248 Wound healing assessed by treating surgeon? 100 mm visual analog scale (VAS) 0 mm = extremely bad and 100 mm extremely good healing 30 days FAS 90 (80-100) ITT 86 (30-98) 88 (75-100) 80 (17-96) P = 0.147 P = 0.217 Postoperative pain VAS score (0, extremely bad; 100, extremely good). 30 days The median (interquartile range) FAS 3.5 (0–12) ITT 10 (0-35) 7 (0-20) 13 (0-57) P = 0.045 P = 0.092 Melling (2001)13 Wound infection Antibiotics ASEPSIS wound score: purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks 6 weeks Nonwarmed group 19 (14%) Local warming 5 (4%) Systemic warming 8 (6%) All warmed patients (Local+systemic) 13 (5%) P = 0.003 P = 0.026 P = 0.001 Systemic warming 8 (6%) Local warming 5 (4%) “ns” Nonwarmed group 22 (16%) All warmed patients (local+systemic) 18 (57%) P = 0.002 Topical application Zampieri (2010)14 Cosmetic results 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dyschromic signs), 2 = good (flared margins, no dyschromic signs), 3 = very good (excellent cosmetic results, no visible scars) 6 months Petrolatum-based emollient (two independent reviewers?) Poor 7%-5% Fairly good 15%-18% Good 0% Very good 78%-77% Topical vitamin E (two independent reviewers?) Poor 0% Fairly good 0% Good 4%-5% Very good 96%-95% P < 0.05 Psychological interventions Robles (2007)15 TEWL (transepidermal water loss) g/m2h 2 hour No stress 18.64 ± 9.71 Stress 21.81 ± 14.06 Stress + support 21.98 ± 6.83 “ns” Koschwanez (2013)16 Reepithelialisation % 7 days 11 days 14 days 17 days 21 days Write about time management 10% 42.1% 90% 95% 100% Write about traumatic experience 27% 76.2% 90% 100% 100% “ns” P = 0.028 “ns” “ns” “ns” Weinman (2008)17 Wound diameter mm 7 days 14 days 21 days Write about time management 4.15 ± 0.48 mm 3.67 ± 0.56 mm 3.27 ± 0.54 mm Write about traumatic experience 4.10 ± 0.62 mm 3.28 ± 0.44 mm 2.98 ± 0.39 mm “ns” P < 0.05 “ns” Broadbent (2012)18 Hydroxyproline level μg/cm of tubing 7 days Normal care 13.56 ± 6.04 Psychological relaxing intervention 22.35 ± 17.48 P = 0.02 Ginandes (2003)19 Doctor’s WAI rating Edema (1-3), erythema (1-3), exudates (1-3); 0 = no signs to 3 = marked signs Total score = 9 Week 1 Week 7 No hypnosis or support 3.07 2.72 Hypnosis 2.89 1.28 P < 0.01 Week 1 Week 7 Supportive attention 3.47 1.94 Hypnosis 2.89 1.28 P < 0.01 Rao (2008)20 Interval before suture removal Number of days 4 weeks Supportive therapy and exercise rehabilitation 13.7 ± 5.3 Yoga program 10.8 ± 3.3 P = 0.03 Drain retention Number of days Variable 6.79 ± 2.4 4.8 ± 1.5 P = 0.001 Pereira (2016)21 Push Ranging from 0-4; 0 = no exudate/scarring tissue 4 = abundant exudate, necrotic tissue 1 month Routinely standardised information 0.4 Empathic patient-centred interview 0.1 P < 0.005 Anxiety level Y (STAY-Y): 20 item self-report instrument which includes separate measures of state and trait anxiety, each subtest ranging from 20 to 80, higher scores indicating greater anxiety Before interview After interview After surgery 38.7 38.5 37.9 33.9 31.6 30.7 P = 0.001 Study Outcome Outcome measurement Follow up time Result control group Result intervention group P-value Systemic treatments Vaxman (1995)10 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Placebo 38 ± 2 29 ± 1 Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid 39 ± 1 29 ± 1 “ns” “ns” Fibroblast count Mean number of Fibroblasts per optical field in skin and scar 8 days 21 days 26 ± 2 83 ± 6 28 ± 2 91 ± 7 “ns” “ns” Vaxman (1996)9 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Oral 0.2 g/day Pantothenic acid and 1.0 g/day Ascorbic acid 39 ± 6 27 ± 6 Oral 0.9 g/day Pantothenic acid and 3 g/day Ascorbic acid 36 ± 4 25 ± 8 “ns” “ns” Fibroblast count n/field 8 days 21 days 28 ± 7 90 ± 31 19 ± 7 80 ± 30 “ns” “ns” Levandovski (2008)11 SSI = either of two distinct criteria for diagnosis: 1. pus could be expressed from the incision; 2. incisional or organ space; with a diagnostic period up to 30 days Yes or no (number of SSI) 30 days Placebo 16/26 Oral 10 mg diazepam 4/61 P = 0.00 State-trait anxiety inventory (STAI): The preoperative score were measured just before surgery; The postoperative anxiety was defined as the average of the score obtained at 6 and 24 hours following surgery Anxiety point scale 0 (no anxiety) - 45.5 (most anxiety) points Patients in the highest quartile were classified as High anxiety and patients in the lowest or equal to the quartile were classifies as Low anxiety 24 hours 41.91 ± 8.88 38.13 ± 6.94 P = 0.01 Künzli (2013)12 Postoperative wound infection (SSI) ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks 30 days (9/178) (22/182) FAS P = 0.018 ITT P = 0.248 Wound healing assessed by treating surgeon? 100 mm visual analog scale (VAS) 0 mm = extremely bad and 100 mm extremely good healing 30 days FAS 90 (80-100) ITT 86 (30-98) 88 (75-100) 80 (17-96) P = 0.147 P = 0.217 Postoperative pain VAS score (0, extremely bad; 100, extremely good). 30 days The median (interquartile range) FAS 3.5 (0–12) ITT 10 (0-35) 7 (0-20) 13 (0-57) P = 0.045 P = 0.092 Melling (2001)13 Wound infection Antibiotics ASEPSIS wound score: purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks 6 weeks Nonwarmed group 19 (14%) Local warming 5 (4%) Systemic warming 8 (6%) All warmed patients (Local+systemic) 13 (5%) P = 0.003 P = 0.026 P = 0.001 Systemic warming 8 (6%) Local warming 5 (4%) “ns” Nonwarmed group 22 (16%) All warmed patients (local+systemic) 18 (57%) P = 0.002 Topical application Zampieri (2010)14 Cosmetic results 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dyschromic signs), 2 = good (flared margins, no dyschromic signs), 3 = very good (excellent cosmetic results, no visible scars) 6 months Petrolatum-based emollient (two independent reviewers?) Poor 7%-5% Fairly good 15%-18% Good 0% Very good 78%-77% Topical vitamin E (two independent reviewers?) Poor 0% Fairly good 0% Good 4%-5% Very good 96%-95% P < 0.05 Psychological interventions Robles (2007)15 TEWL (transepidermal water loss) g/m2h 2 hour No stress 18.64 ± 9.71 Stress 21.81 ± 14.06 Stress + support 21.98 ± 6.83 “ns” Koschwanez (2013)16 Reepithelialisation % 7 days 11 days 14 days 17 days 21 days Write about time management 10% 42.1% 90% 95% 100% Write about traumatic experience 27% 76.2% 90% 100% 100% “ns” P = 0.028 “ns” “ns” “ns” Weinman (2008)17 Wound diameter mm 7 days 14 days 21 days Write about time management 4.15 ± 0.48 mm 3.67 ± 0.56 mm 3.27 ± 0.54 mm Write about traumatic experience 4.10 ± 0.62 mm 3.28 ± 0.44 mm 2.98 ± 0.39 mm “ns” P < 0.05 “ns” Broadbent (2012)18 Hydroxyproline level μg/cm of tubing 7 days Normal care 13.56 ± 6.04 Psychological relaxing intervention 22.35 ± 17.48 P = 0.02 Ginandes (2003)19 Doctor’s WAI rating Edema (1-3), erythema (1-3), exudates (1-3); 0 = no signs to 3 = marked signs Total score = 9 Week 1 Week 7 No hypnosis or support 3.07 2.72 Hypnosis 2.89 1.28 P < 0.01 Week 1 Week 7 Supportive attention 3.47 1.94 Hypnosis 2.89 1.28 P < 0.01 Rao (2008)20 Interval before suture removal Number of days 4 weeks Supportive therapy and exercise rehabilitation 13.7 ± 5.3 Yoga program 10.8 ± 3.3 P = 0.03 Drain retention Number of days Variable 6.79 ± 2.4 4.8 ± 1.5 P = 0.001 Pereira (2016)21 Push Ranging from 0-4; 0 = no exudate/scarring tissue 4 = abundant exudate, necrotic tissue 1 month Routinely standardised information 0.4 Empathic patient-centred interview 0.1 P < 0.005 Anxiety level Y (STAY-Y): 20 item self-report instrument which includes separate measures of state and trait anxiety, each subtest ranging from 20 to 80, higher scores indicating greater anxiety Before interview After interview After surgery 38.7 38.5 37.9 33.9 31.6 30.7 P = 0.001 FAS, full-analysis set; ITT, intention to treat; ns, not significant; SSI, surgical site infections; STAI, state-trait anxiety inventory; TEWL, transepidermal water loss; VAS, visual analog scale; WAI, wound assessment inventory. View Large Table 3. Outcome of Data Extraction Study Outcome Outcome measurement Follow up time Result control group Result intervention group P-value Systemic treatments Vaxman (1995)10 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Placebo 38 ± 2 29 ± 1 Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid 39 ± 1 29 ± 1 “ns” “ns” Fibroblast count Mean number of Fibroblasts per optical field in skin and scar 8 days 21 days 26 ± 2 83 ± 6 28 ± 2 91 ± 7 “ns” “ns” Vaxman (1996)9 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Oral 0.2 g/day Pantothenic acid and 1.0 g/day Ascorbic acid 39 ± 6 27 ± 6 Oral 0.9 g/day Pantothenic acid and 3 g/day Ascorbic acid 36 ± 4 25 ± 8 “ns” “ns” Fibroblast count n/field 8 days 21 days 28 ± 7 90 ± 31 19 ± 7 80 ± 30 “ns” “ns” Levandovski (2008)11 SSI = either of two distinct criteria for diagnosis: 1. pus could be expressed from the incision; 2. incisional or organ space; with a diagnostic period up to 30 days Yes or no (number of SSI) 30 days Placebo 16/26 Oral 10 mg diazepam 4/61 P = 0.00 State-trait anxiety inventory (STAI): The preoperative score were measured just before surgery; The postoperative anxiety was defined as the average of the score obtained at 6 and 24 hours following surgery Anxiety point scale 0 (no anxiety) - 45.5 (most anxiety) points Patients in the highest quartile were classified as High anxiety and patients in the lowest or equal to the quartile were classifies as Low anxiety 24 hours 41.91 ± 8.88 38.13 ± 6.94 P = 0.01 Künzli (2013)12 Postoperative wound infection (SSI) ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks 30 days (9/178) (22/182) FAS P = 0.018 ITT P = 0.248 Wound healing assessed by treating surgeon? 100 mm visual analog scale (VAS) 0 mm = extremely bad and 100 mm extremely good healing 30 days FAS 90 (80-100) ITT 86 (30-98) 88 (75-100) 80 (17-96) P = 0.147 P = 0.217 Postoperative pain VAS score (0, extremely bad; 100, extremely good). 30 days The median (interquartile range) FAS 3.5 (0–12) ITT 10 (0-35) 7 (0-20) 13 (0-57) P = 0.045 P = 0.092 Melling (2001)13 Wound infection Antibiotics ASEPSIS wound score: purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks 6 weeks Nonwarmed group 19 (14%) Local warming 5 (4%) Systemic warming 8 (6%) All warmed patients (Local+systemic) 13 (5%) P = 0.003 P = 0.026 P = 0.001 Systemic warming 8 (6%) Local warming 5 (4%) “ns” Nonwarmed group 22 (16%) All warmed patients (local+systemic) 18 (57%) P = 0.002 Topical application Zampieri (2010)14 Cosmetic results 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dyschromic signs), 2 = good (flared margins, no dyschromic signs), 3 = very good (excellent cosmetic results, no visible scars) 6 months Petrolatum-based emollient (two independent reviewers?) Poor 7%-5% Fairly good 15%-18% Good 0% Very good 78%-77% Topical vitamin E (two independent reviewers?) Poor 0% Fairly good 0% Good 4%-5% Very good 96%-95% P < 0.05 Psychological interventions Robles (2007)15 TEWL (transepidermal water loss) g/m2h 2 hour No stress 18.64 ± 9.71 Stress 21.81 ± 14.06 Stress + support 21.98 ± 6.83 “ns” Koschwanez (2013)16 Reepithelialisation % 7 days 11 days 14 days 17 days 21 days Write about time management 10% 42.1% 90% 95% 100% Write about traumatic experience 27% 76.2% 90% 100% 100% “ns” P = 0.028 “ns” “ns” “ns” Weinman (2008)17 Wound diameter mm 7 days 14 days 21 days Write about time management 4.15 ± 0.48 mm 3.67 ± 0.56 mm 3.27 ± 0.54 mm Write about traumatic experience 4.10 ± 0.62 mm 3.28 ± 0.44 mm 2.98 ± 0.39 mm “ns” P < 0.05 “ns” Broadbent (2012)18 Hydroxyproline level μg/cm of tubing 7 days Normal care 13.56 ± 6.04 Psychological relaxing intervention 22.35 ± 17.48 P = 0.02 Ginandes (2003)19 Doctor’s WAI rating Edema (1-3), erythema (1-3), exudates (1-3); 0 = no signs to 3 = marked signs Total score = 9 Week 1 Week 7 No hypnosis or support 3.07 2.72 Hypnosis 2.89 1.28 P < 0.01 Week 1 Week 7 Supportive attention 3.47 1.94 Hypnosis 2.89 1.28 P < 0.01 Rao (2008)20 Interval before suture removal Number of days 4 weeks Supportive therapy and exercise rehabilitation 13.7 ± 5.3 Yoga program 10.8 ± 3.3 P = 0.03 Drain retention Number of days Variable 6.79 ± 2.4 4.8 ± 1.5 P = 0.001 Pereira (2016)21 Push Ranging from 0-4; 0 = no exudate/scarring tissue 4 = abundant exudate, necrotic tissue 1 month Routinely standardised information 0.4 Empathic patient-centred interview 0.1 P < 0.005 Anxiety level Y (STAY-Y): 20 item self-report instrument which includes separate measures of state and trait anxiety, each subtest ranging from 20 to 80, higher scores indicating greater anxiety Before interview After interview After surgery 38.7 38.5 37.9 33.9 31.6 30.7 P = 0.001 Study Outcome Outcome measurement Follow up time Result control group Result intervention group P-value Systemic treatments Vaxman (1995)10 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Placebo 38 ± 2 29 ± 1 Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid 39 ± 1 29 ± 1 “ns” “ns” Fibroblast count Mean number of Fibroblasts per optical field in skin and scar 8 days 21 days 26 ± 2 83 ± 6 28 ± 2 91 ± 7 “ns” “ns” Vaxman (1996)9 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Oral 0.2 g/day Pantothenic acid and 1.0 g/day Ascorbic acid 39 ± 6 27 ± 6 Oral 0.9 g/day Pantothenic acid and 3 g/day Ascorbic acid 36 ± 4 25 ± 8 “ns” “ns” Fibroblast count n/field 8 days 21 days 28 ± 7 90 ± 31 19 ± 7 80 ± 30 “ns” “ns” Levandovski (2008)11 SSI = either of two distinct criteria for diagnosis: 1. pus could be expressed from the incision; 2. incisional or organ space; with a diagnostic period up to 30 days Yes or no (number of SSI) 30 days Placebo 16/26 Oral 10 mg diazepam 4/61 P = 0.00 State-trait anxiety inventory (STAI): The preoperative score were measured just before surgery; The postoperative anxiety was defined as the average of the score obtained at 6 and 24 hours following surgery Anxiety point scale 0 (no anxiety) - 45.5 (most anxiety) points Patients in the highest quartile were classified as High anxiety and patients in the lowest or equal to the quartile were classifies as Low anxiety 24 hours 41.91 ± 8.88 38.13 ± 6.94 P = 0.01 Künzli (2013)12 Postoperative wound infection (SSI) ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks 30 days (9/178) (22/182) FAS P = 0.018 ITT P = 0.248 Wound healing assessed by treating surgeon? 100 mm visual analog scale (VAS) 0 mm = extremely bad and 100 mm extremely good healing 30 days FAS 90 (80-100) ITT 86 (30-98) 88 (75-100) 80 (17-96) P = 0.147 P = 0.217 Postoperative pain VAS score (0, extremely bad; 100, extremely good). 30 days The median (interquartile range) FAS 3.5 (0–12) ITT 10 (0-35) 7 (0-20) 13 (0-57) P = 0.045 P = 0.092 Melling (2001)13 Wound infection Antibiotics ASEPSIS wound score: purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks 6 weeks Nonwarmed group 19 (14%) Local warming 5 (4%) Systemic warming 8 (6%) All warmed patients (Local+systemic) 13 (5%) P = 0.003 P = 0.026 P = 0.001 Systemic warming 8 (6%) Local warming 5 (4%) “ns” Nonwarmed group 22 (16%) All warmed patients (local+systemic) 18 (57%) P = 0.002 Topical application Zampieri (2010)14 Cosmetic results 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dyschromic signs), 2 = good (flared margins, no dyschromic signs), 3 = very good (excellent cosmetic results, no visible scars) 6 months Petrolatum-based emollient (two independent reviewers?) Poor 7%-5% Fairly good 15%-18% Good 0% Very good 78%-77% Topical vitamin E (two independent reviewers?) Poor 0% Fairly good 0% Good 4%-5% Very good 96%-95% P < 0.05 Psychological interventions Robles (2007)15 TEWL (transepidermal water loss) g/m2h 2 hour No stress 18.64 ± 9.71 Stress 21.81 ± 14.06 Stress + support 21.98 ± 6.83 “ns” Koschwanez (2013)16 Reepithelialisation % 7 days 11 days 14 days 17 days 21 days Write about time management 10% 42.1% 90% 95% 100% Write about traumatic experience 27% 76.2% 90% 100% 100% “ns” P = 0.028 “ns” “ns” “ns” Weinman (2008)17 Wound diameter mm 7 days 14 days 21 days Write about time management 4.15 ± 0.48 mm 3.67 ± 0.56 mm 3.27 ± 0.54 mm Write about traumatic experience 4.10 ± 0.62 mm 3.28 ± 0.44 mm 2.98 ± 0.39 mm “ns” P < 0.05 “ns” Broadbent (2012)18 Hydroxyproline level μg/cm of tubing 7 days Normal care 13.56 ± 6.04 Psychological relaxing intervention 22.35 ± 17.48 P = 0.02 Ginandes (2003)19 Doctor’s WAI rating Edema (1-3), erythema (1-3), exudates (1-3); 0 = no signs to 3 = marked signs Total score = 9 Week 1 Week 7 No hypnosis or support 3.07 2.72 Hypnosis 2.89 1.28 P < 0.01 Week 1 Week 7 Supportive attention 3.47 1.94 Hypnosis 2.89 1.28 P < 0.01 Rao (2008)20 Interval before suture removal Number of days 4 weeks Supportive therapy and exercise rehabilitation 13.7 ± 5.3 Yoga program 10.8 ± 3.3 P = 0.03 Drain retention Number of days Variable 6.79 ± 2.4 4.8 ± 1.5 P = 0.001 Pereira (2016)21 Push Ranging from 0-4; 0 = no exudate/scarring tissue 4 = abundant exudate, necrotic tissue 1 month Routinely standardised information 0.4 Empathic patient-centred interview 0.1 P < 0.005 Anxiety level Y (STAY-Y): 20 item self-report instrument which includes separate measures of state and trait anxiety, each subtest ranging from 20 to 80, higher scores indicating greater anxiety Before interview After interview After surgery 38.7 38.5 37.9 33.9 31.6 30.7 P = 0.001 FAS, full-analysis set; ITT, intention to treat; ns, not significant; SSI, surgical site infections; STAI, state-trait anxiety inventory; TEWL, transepidermal water loss; VAS, visual analog scale; WAI, wound assessment inventory. View Large Systemic Treatments Five articles describing systemic preoperative interventions have been found, three of which resulted in significantly improved wound healing. Vitamin Suppletion In the first two studies, Vaxman investigated the effect of ascorbic acid (also called vitamin C or VC) and pantothenic acid (also called vitamin B5 or VB5) on wound healing in patients undergoing surgery for tattoo removal.9,10 The intervention group received either VC or VB5 and the control group received a placebo. The used dosage differed between the two studies. In the first study, the intervention group received 1.0 g vitamin C and 0.2 g vitamin B5 orally. In the second study, the intervention group received 3 g vitamin C and 0.9 g vitamin B5 orally. The quality of wound healing was assessed by measuring hypertrophy, rigidity, collared, elastic stiffness, and stress. As an index of collagen in tissues, hydroxyproline levels were measured. The protocol included four stages with a total follow up of 80 days. On day 1, the patients started taking the vitamin or placebo. On day 8, a first partial tattoo removal was carried out and skin samples were taken. On day 21, a second resection was performed of the tattoo and the first scar. The patients stopped taking vitamin supplements/placebos at this point. On day 80, the second scars were removed and examined. In both studies, no significant differences were found. In conclusion: no benefit of using ascorbic acid and pantothenic acid preoperatively on wound healing has been found. Lowering Anxiety Levels In the third article in this group, Levandovski et al investigated whether increased anxiety levels may be associated with a higher risk of surgical site infections (SSI).11 The authors postulate that the use of diazepam could reduce the risk of infection by promoting the inflammatory response. This study evaluated whether use of 10 mg diazepam reduced the postoperative SSI and the anxiety levels. Patients were randomly assigned to receive either 10 mg diazepam or placebo orally the night before and 1 hour prior to abdominal hysterectomy surgery. Pre- and postoperative anxiety levels were measured with the State-trait anxiety inventory (STAI). The SSI was diagnosed according to the criteria of the Centers for Disease Control and Prevention with standard follow up of 30 days. Both variables were significantly reduced (SSI P = 0.00, STAI P = 0.01). In conclusion: the use of 10 mg diazepam preoperatively has been found to lower anxiety levels and reduce SSI. Increasing Body Temperature In the last two articles, Künzli12 and Melling13 tested the impact of warming the skin on wound healing. The Künzli study used water-filtered infrared A irradiation (wIRA). wIRA is a special form of heat radiation with high tissue penetration and a low thermal load to the skin surface. This article claimed that thermal heat preoperatively decreases the chance of SSI and that a major advantage of the wIRA vs the application of warming blankets lies in the effective penetration of the applied wIRA energy to the deep subcutaneous tissue up to depths of 2 to 3 cm. The wIRA would also cause higher arterial oxygen tension levels, decreasing surgical wound infections from 11% to 5%. Primary outcome parameters were postoperative wound infection (SSI), wound healing, and postoperative pain after 30 days. The study physician and patient judged the degrees of healing separately, on a 100 mm visual analog scale (VAS), 0 mm = extremely bad and 100 mm extremely good. Subjective wound assessment was performed by the study physician through the ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks. Evaluation of pain was daily measured by VAS scores (0, extremely bad; 100, extremely good). Four hundred (400) patients were included and randomly assigned to groups A or B. Group A received standard preoperative care plus an additional exposure to the hydrosun radiator for 20 minutes. Prophylactic antibiotics were given to both groups at least 30 min. before surgery. Exactly the same procedure was performed for patients assigned to control group B, excepting that the patients received only visible light (sham lamp). Primary efficacy analysis was carried out on the basis of an intention-to-treat (ITT) population and a full-analysis set (FAS). The ITT analysis, considering all randomized individuals by conservatively replacing dropouts as occurred SSI. The ITT shows no significant difference between groups A or B on postoperative wound pain, SSI and wound healing 30 days after surgery. The FAS analysis shows significantly less SSI (P = 0.018) and less postoperative pain (P = 0.045) in group A after 30 days. The Melling study used forced-air warming blankets and noncontact, radiant heat dressings to warm the patients. Four hundred sixteen (416) patients were selected and divided into three groups. The first group received standard care and served as control group. The second group was is the systemic group, receiving standard care plus the addition of a minimum of 30 minutes preoperative warming to the whole body using a forced-air warming blanket. The third group received standard care plus local warming by means of noncontact, radiant heat dressing, applied to the planned wound area 30 minutes before surgery. Wounds were classified as infected if there had been a purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks. All wounds were scored using an adapted version of the AEPSIS wound scoring system. The local warming group (P = 0.003) and the systemic warming group (P = 0.026) showed better wound healing compared to the nonwarmed group. The nonwarmed group needed significantly more antibiotics postoperatively than the warmed groups (P = 0.002). No significant difference has been found between the systemic and local warming groups. In conclusion: these studies found that actively warming the patient’s body preoperatively benefits wound healing. Topical Application Only one study describing topical interventions met the inclusion requirements of this review, which found a positive effect of the studied intervention. Vitamin Suppletion Zampieri et al postulate that topical application of vitamin E has been promoted to help wound healing and reduce both fibroblast proliferation and inflammation.14 A total of 428 Caucasian children who were undergoing inguinal surgery were randomly divided in two groups. In one group, topical vitamin E was applied, triwe daily for 15 days prior to surgery and twice daily for 30 days after surgery. The other group received topical petrolatum-based ointment during the same time frame and served as the control group. A four-point scale was used to rate wound healing: 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dichromic signs), 2 = good (flared margins, no dichromic signs), 3 = very good (excellent cosmetic results, no visible scars). The assessments of the cosmetic results were performed by the patients’ parents and by a blinded independent surgeon. After a 6-month follow-up period, the children who received preoperative topical vitamin E had shown significantly better wound healing and better cosmetic results than patients who had received topical petrolatum-based ointments (P < 0.05). In conclusion: topical application of vitamin E preoperatively was found to benefit wound healing. Psychological Interventions Seven articles describing the influence of psychological interventions on wound healing were identified, four of them found psychologigal interventions to be beneficial. These studies all aimed at lowering the stress level in different ways. It is said that psychological stress can affect the wound healing, by triggering the inflammatory response and enhancing production of proinflammatory cytokines.22,23 The exact mechanism behind this is still unclear. Social Support Robles examined the effect of a brief laboratory stressor and social support before the stressor on cardiovascular and cortisol responses, and skin barrier recovery after skin disruption.15 Healthy volunteers were randomly assigned to one of three groups. The first group performed a no-stress reading task (control group). The second group performed a Trier social stress test consisting of a 5-minute presentation (control group). The third group received the same stress test and additional support from a confederate before the stressor (intervention group). The intervention took place one hour prior to a tape stripping procedure that disrupted normal skin barrier function. Skin barrier recovery was measured by transepidermal water loss (TEWL, g/m2h) two hours after skin disruption. Increased TEWL reflects decreased barrier function, and decreased TEWL postdisruption indicates increased barrier function. Outcomes in both control groups did not significantly differ from the intervention group. In conclusion: this study found that social support before the stressor did not have an influence on wound healing. Expressive Writing Weinman et al and Koschwanez et al examined whether preoperative expressive writing could result in better wound healing.16,17 The authors suggest that disclosure of traumatic experiences can result in lower stress levels and thereby influence the immune system. In both studies patients were asked to write about a traumatic experience preoperatively for 20 minutes. Surgery consisted of a 4 mm punch biopsy. The wounds were created in the inner, upper arm. The outcomes were differently assessed between the studies. In the Weinman study, wound healing was determined by measuring the wound diameter for 3 weeks. In the Koschwanez study, photographs were taken at different time points for a period of 21 days. A dermatologist scored the amount of reepithelialisation. Although the Weinman study showed slightly smaller wounds in the intervention group than the control group on day 7 and 21 after surgery, these differences were not significant. In the Koschwanez study, the intervention group showed significantly more complete reepithelialisation than the control group on day 11 only. On days 7, 14, 17, and 21 there were no significant differences between the groups. In conclusion: no advantage of preoperative expressive writing aimed at lowering stress levels to increase wound healing has been found. Relaxation Exercises Three studies tried to increase the relaxation levels through using relaxation exercises.18-20 Broadbent et al attempted to achieve this by deep breathing techniques. The intervention group met with a health psychologist for 45 minutes, who instructed the participants in deep breathing techniques. Each patient was asked to take a CD home with recordings of the script and listen to it every day, starting three days prior to surgery (laparoscopic cholecystectomy), until seven days after. The control group received standard care. The authors measured the hydroxyproline and stress levels. Both were measured before and after the procedure. The intervention group showed significantly higher hydroxyproline levels than the control group. However, changes in perceived stress were not significantly correlated with hydroxyproline deposition. The authors notice that lack of an association between change in stress with hydroxyproline suggests that the effects of the intervention are not simply due to stress reduction. In conclusion: no association between perceived stress and hydroxyproline levels have been found following deep breathing exercises. Ginandes et al attempted to increase relaxation levels by a hypnotic intervention before surgery in patients with macromastia who needed a mammaplasty. Three groups were formed. The first group received hypnotic intervention during 8 half-hour weekly sessions with the study clinician commencing 2 weeks prior to surgery and continuing through 6 weeks postoperatively. The second group received supportive attention concerning the operation prior and postsurgery at the same time points as the first group. The third group served as a control group and received usual care. The quality of the wound healing was measured by the WAI (wound assessment inventory) rating by three blinded independent surgeons. After 7 weeks of follow up, the hypnosis group scored significantly lower on the WAI rating, denoting the greatest healing over time, followed by the supportive attention group. The usual care control group obtained the highest WAI scores indicating the smallest degree of healing. In conclusion: additional hypnotic intervention has been found to show improved healing over time compared to usual care. Rao et al evaluated the effect of a yoga intervention on postoperative wound healing in patients who were recently diagnosed with breast cancer and who received surgery as primary treatment and needed a mastectomy. Two groups were randomly formed: an intervention group who received a yoga program 1 day prior to surgery and 3 times a week postsurgery for the duration of 4 weeks. The control group received supportive therapy and exercise rehabilitation instead. The postoperative outcome was the interval for suture removal and the number of days before drain removal. The sutures were removed when the approximated margins of the wound were closed and the drain was removed when production reduced to <50 cc/48 hours. In both outcomes measures, the intervention group scored significantly better than the control group (P = 0.001 for drain removal, P = 0.03 for suture removal). In conclusion: this study found a yoga program starting before surgery to benefit wound healing. Providing Empathic Patient-Centered Information In the last study of this group, Pereira et al investigated the influence of an empathic patient-centered approach of providing information about the scheduled surgery on wound healing in ambulatory surgery.21 One month prior to surgery, the intervention group received personalized information about the operation through an empathic patient-centered interview, which consisted of eliciting and exploring patients concerns about the surgery for 15 minutes. The control group received the routinely delivered standardized information in the same time frame as the intervention group. The surgical wound healing was measured through PUSH and the state of anxiety was assessed with the state-trait anxiety inventory form Y (STAY-Y). One month after surgery, the intervention group showed significantly better wound tissue than the control group (P < 0.005) and also significantly lower levels of anxiety than the control group (P = 0.001). In conclusion: an empathic patient-centered approach of providing information has been found to benefit wound healing and lower the anxiety level. DISCUSSION Based on the available literature, little attention has historically been paid to the influence of preoperative interventions on wound healing and scar formation. Most published studies could not be included because they focused on intra- or postoperative interventions, or on known risk factors, such as smoking and diabetes. Interestingly, only 13 studies have been found on preoperative interventions that met the selection criteria. This may be indicative of a general historical lack of interest in the topic, despite of the possible advantages of more extensive knowledge in daily patient care. Both in the literature and surgical practice, most attention is paid to intraoperative and postoperative interventions. Classic postoperative wound management consists of different types of dressings, antibiotic treatment, and debridement. Relatively new treatments, such as negative pressure wound therapy (NPWT) and oxygen therapy (though still controversial) have improved treatment of poorly healing wounds.24 Preoperative wound management has focused on prevention of SSI and excessive scar formation. Classic preoperative management involves antibiotic prophylaxis (depending on the type of operation, given <120 min before the incision), surgical hand preparation by scrubbing (with a suitable antimicrobial soap and water or using a suitable alcohol based hand rub), and maintaining the least possible contamination of the surgical field.25 The limited number and quality of the studies included in this review limit the strength of the results found. Moreover, the great heterogeneity of the included patient groups (ie, different interventions, age ranging from 2 to 87 years) and the broad spectrum of outcome measurements made it impossible to compare the findings of different studies. Nevertheless, evidence that preoperative interventions have a positive influence on wound healing has been found. Individually, the studies allow for some interesting observations to be made, as eight of the 13 studies show a significantly better wound healing after the investigated preoperative intervention. Five studies described systemic interventions. Four of the five studies showed a significantly better wound healing for the intervention group. In the first study, Levandovski et al postulate that increased anxiety levels cause significantly more surgical site infections (SSI). The authors hypothesize that diazepam use could therefore reduce the risk of infection. Diazepam modulates the immune system involved in the attenuation of behavioral stress response induced by corticotrophin releasing hormone (CRH), responsible for immune suppression, but the correlation between anxiety and better wound healing would prove that lowering the anxiety level itself will benefit the wound healing. Flores et al state that mild perioperative hypothermia is associated with infection of the surgical wound and its prevention is therefore justified.26 Bacterial destruction depends on adequate tissue perfusion. Perioperative hypothermia causes vasoconstriction, reducing nutrient and oxygen supply to wounds and increasing frequency of surgical wound infection. To combat hypothermia three different effective ways have been identified: local water-filtered infrared and irradiation; forced-air warming blankets; and local noncontact, radiant heat dressing. More studies must be done to compare the different interventions and cost-effectiveness analyses must also be carried out. Only one study described topical application of an agent at the surgery site. This study showed that preoperatively applied topical vitamin E indeed improved the wound healing in Caucasian children. This may be a safe and beneficial addition to usual patient preparation. No studies have been found indicating a similar effect in adults and no cost-effectiveness analysis was carried out. In the literature, debate remains as to the effect of topical vitamin E on wound healing. A lot of research has been done on its effect when applied after surgery or the effect of topical vitamin E on burn victims.27 Seven studies have been found in the psychological intervention group. Four of these seven show significant differences. Recent research shows extended knowledge about the negative effects of stress on health outcomes. Stress affects the wound healing, by triggering the glucocorticoids and inflammatory response and enhancing production of cortisol/corticosterone and proinflammatory cytokines.22,23 These two primary pathways affect the progress of the normal stages of wound healing.28 The included studies show that lower anxiety levels and a relaxed preoperative state of mind may benefit wound healing. Successful ways to achieve this may be yoga intervention (Rao), deep breathing techniques (Broadbent), hypnotic intervention (Ginandes), or better empathic-centered approach to the patient (Pereira). In all these studies there were two potential confounders, the small sample size and the intrinsic belief in the therapeutic benefits of the studied interventions. Both historically and presently, surgical patient care has been focused on intra- and postoperative phases. This review shows that wound healing after surgery can be improved by focusing on preoperative care to adequately prepare the patient for surgery. CONCLUSION Surprisingly, little attention has historically been paid to the influence of preoperative interventions on wound healing following surgery. These interventions may however indeed have a positive effect on wound healing. In selected cases, wound healing has been found to benefit from a higher preoperative body temperature, topical vitamin E application, and low patient stress levels. However, additional prospective studies will be needed to further identify preoperative interventions that are beneficial for the improvement of wound healing and scar formation in the general patient population. Supplementary Material This article contains supplementary material located online at www.aestheticsurgeryjournal.com. Disclosures The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. Funding The authors received no financial support for the research, authorship, and publication of this article. REFERENCES 1. Atiyeh BS , Ioannovich J , Al-Amm CA , El-Musa KA , Dham R . Improving scar quality: a prospective clinical study . Aesthetic Plast Surg . 2002 ; 26 ( 6 ): 470 - 476 . Google Scholar CrossRef Search ADS PubMed 2. van der Veer WM , Bloemen MC , Ulrich MM et al. Potential cellular and molecular causes of hypertrophic scar formation . Burns . 2009 ; 35 ( 1 ): 15 - 29 . Google Scholar CrossRef Search ADS PubMed 3. Gill JF , Yu SS , Neuhaus IM . Tobacco smoking and dermatologic surgery . J Am Acad Dermatol . 2013 ; 68 ( 1 ): 167 - 172 . Google Scholar CrossRef Search ADS PubMed 4. Poetker DM , Reh DD . A comprehensive review of the adverse effects of systemic corticosteroids . Otolaryngol Clin North Am . 2010 ; 43 ( 4 ): 753 - 768 . Google Scholar CrossRef Search ADS PubMed 5. Powers JG , Higham C , Broussard K , Phillips TJ . Wound healing and treating wounds: Chronic wound care and management . J Am Acad Dermatol . 2016 ; 74 ( 4 ): 607 - 25; quiz 625 . Google Scholar CrossRef Search ADS PubMed 6. Kanasi E , Ayilavarapu S , Jones J . The aging population: demographics and the biology of aging . Periodontol 2000 . 2016 ; 72 ( 1 ): 13 - 18 . Google Scholar CrossRef Search ADS PubMed 7. Hagen KS , Treston-Aurand J . A comparison of two skin preps used in cardiac surgical procedures . AORN J . 1995 ; 62 ( 3 ): 393 - 402 . Google Scholar CrossRef Search ADS PubMed 8. Ueno C , Hunt TK , Hopf HW . Using physiology to improve surgical wound outcomes . Plast Reconstr Surg . 2006 ; 117 ( 7 Suppl ): 59S - 71S . Google Scholar CrossRef Search ADS PubMed 9. Vaxman F , Olender S , Lambert A , Nisand G , Grenier JF . Can the wound healing process be improved by vitamin supplementation? Experimental study on humans . Eur Surg Res . 1996 ; 28 ( 4 ): 306 - 314 . Google Scholar CrossRef Search ADS PubMed 10. Vaxman F , Olender S , Lambert A et al. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial . Eur Surg Res . 1995 ; 27 ( 3 ): 158 - 166 . Google Scholar CrossRef Search ADS PubMed 11. Levandovski R , Ferreira MB , Hidalgo MP , Konrath CA , da Silva DL , Caumo W . Impact of preoperative anxiolytic on surgical site infection in patients undergoing abdominal hysterectomy . Am J Infect Control . 2008 ; 36 ( 10 ): 718 - 726 . Google Scholar CrossRef Search ADS PubMed 12. Künzli BM , Liebl F , Nuhn P , Schuster T , Friess H , Hartel M . Impact of preoperative local water-filtered infrared A irradiation on postoperative wound healing: a randomized patient- and observer-blinded controlled clinical trial . Ann Surg . 2013 ; 258 ( 6 ): 887 - 894 . Google Scholar CrossRef Search ADS PubMed 13. Melling AC , Ali B , Scott EM , Leaper DJ . Effects of preoperative warming on the incidence of wound infection after clean surgery: a randomised controlled trial . Lancet . 2001 ; 358 ( 9285 ): 876 - 880 . Google Scholar CrossRef Search ADS PubMed 14. Zampieri N , Zuin V , Burro R , Ottolenghi A , Camoglio FS . A prospective study in children: Pre- and post-surgery use of vitamin E in surgical incisions . J Plast Reconstr Aesthet Surg . 2010 ; 63 ( 9 ): 1474 - 1478 . Google Scholar CrossRef Search ADS PubMed 15. Robles TF . Stress, social support, and delayed skin barrier recovery . Psychosom Med . 2007 ; 69 ( 8 ): 807 - 815 . Google Scholar CrossRef Search ADS PubMed 16. Koschwanez HE , Kerse N , Darragh M , Jarrett P , Booth RJ , Broadbent E . Expressive writing and wound healing in older adults: a randomized controlled trial . Psychosom Med . 2013 ; 75 ( 6 ): 581 - 590 . Google Scholar CrossRef Search ADS PubMed 17. Weinman J , Ebrecht M , Scott S , Walburn J , Dyson M . Enhanced wound healing after emotional disclosure intervention . Br J Health Psychol . 2008 ; 13 ( Pt 1 ): 95 - 102 . Google Scholar CrossRef Search ADS PubMed 18. Broadbent E , Kahokehr A , Booth RJ et al. A brief relaxation intervention reduces stress and improves surgical wound healing response: a randomised trial . Brain Behav Immun . 2012 ; 26 ( 2 ): 212 - 217 . Google Scholar CrossRef Search ADS PubMed 19. Ginandes C , Brooks P , Sando W , Jones C , Aker J . Can medical hypnosis accelerate post-surgical wound healing? Results of a clinical trial . Am J Clin Hypn . 2003 ; 45 ( 4 ): 333 - 351 . Google Scholar CrossRef Search ADS PubMed 20. Rao RM , Nagendra HR , Raghuram N et al. Influence of yoga on postoperative outcomes and wound healing in early operable breast cancer patients undergoing surgery . Int J Yoga . 2008 ; 1 ( 1 ): 33 - 41 . Google Scholar CrossRef Search ADS PubMed 21. Pereira L , Figueiredo-Braga M , Carvalho IP . Preoperative anxiety in ambulatory surgery: The impact of an empathic patient-centered approach on psychological and clinical outcomes . Patient Educ Couns . 2016 ; 99 ( 5 ): 733 - 738 . Google Scholar CrossRef Search ADS PubMed 22. McGhee LL , Maani CV , Garza TH , DeSocio PA , Gaylord KM , Black IH . The relationship of intravenous midazolam and posttraumatic stress disorder development in burned soldiers . J Trauma . 2009 ; 66 ( 4 Suppl ): S186 - S190 . Google Scholar CrossRef Search ADS PubMed 23. Zhou D , Kusnecov AW , Shurin MR , DePaoli M , Rabin BS . Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis . Endocrinology . 1993 ; 133 ( 6 ): 2523 - 2530 . Google Scholar CrossRef Search ADS PubMed 24. Rabello FB , Souza CD , Farina Júnior JA . Update on hypertrophic scar treatment . Clinics (Sao Paulo) . 2014 ; 69 ( 8 ): 565 - 573 . Google Scholar CrossRef Search ADS PubMed 25. Allegranzi B , Bischoff P , de Jonge S et al. ; WHO Guidelines Development Group . New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective . Lancet Infect Dis . 2016 ; 16 ( 12 ): e276 - e287 . Google Scholar CrossRef Search ADS PubMed 26. Flores-Maldonado A , Medina-Escobedo CE , Ríos-Rodríguez HM , Fernández-Domínguez R . Mild perioperative hypothermia and the risk of wound infection . Arch Med Res . 2001 ; 32 ( 3 ): 227 - 231 . Google Scholar CrossRef Search ADS PubMed 27. Khoosal D , Goldman RD . Vitamin E for treating children’s scars. Does it help reduce scarring ? Can Fam Physician . 2006 ; 52 : 855 - 856 . Google Scholar PubMed 28. Christian LM , Graham JE , Padgett DA , Glaser R , Kiecolt-Glaser JK . Stress and wound healing . Neuroimmunomodulation . 2006 ; 13 ( 5-6 ): 337 - 346 . Google Scholar CrossRef Search ADS PubMed © 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Aesthetic Surgery Journal Oxford University Press

The Influence of Preoperative Interventions on Postoperative Surgical Wound Healing in Patients Without Risk Factors: A Systematic Review

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© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com
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Abstract

Abstract Background Poor wound healing and scar formation remain critical problems in daily surgical practice. Generally, most attention is paid to intra- and postoperative interventions to improve wound healing after surgery, while preoperative interventions remain unsatisfactorily explored. Objectives In this systematic review, the available literature on the beneficial effects of preoperative interventions on wound healing and scar formation have been summarized and compared. Methods A comprehensive and systematic search has been conducted in MEDLINE, Pubmed, Embase, Web of Science, and Cochrane, supplemented by reference and citation tracking. All preoperative interventions and all clinically relevant outcome parameters have been considered for inclusion, due to the expected limited availability of literature. Results A total of 13 studies were included, which were all randomized trials. No cohort studies or retrospective studies have been identified. All studies described different preoperative interventions and outcome parameters and could hence not be pooled and compared. Eight studies showed significantly better wound healing after a preoperative intervention. The individual studies have been summarized in this review. Conclusions This systemic review shows that preoperative interventions can be beneficial in improving wound healing and scar formation. In selected cases, wound healing was found to benefit from a higher preoperative body temperature, topical vitamin E application, and low patient stress levels. Level of Evidence: 2 Poor wound healing remains a critical problem in daily surgical practice, concerning either impaired healing or excessive scarring.1,2 The normal stages involved in wound healing seem to fail to progress. Processes during haemostasis, inflammation, epithelialization, connective tissue deposition, and contraction can either independently, or in combination, be responsible for impaired healing. Known risk factors for poor wound healing are smoking, corticosteroid use, advanced age, and diabetes.3-6 In patients with these risk factors, more complications occur and both the healing process and hospital stay take longer. Moreover, in patients without these risk factors, there is a typical risk of excessive scarring, infections, or dehiscence after surgical interventions. Surgical site infections (SSI) and excessive scar formation have major implications that affect patient morbidity and mortality rates as well as quality of life, and add to unnecessary hospital costs. Preventing poor wound healing is hence of great value to ensure good quality patient care and to control patient care costs.7 Here lies a challenge for the surgeon and the whole team involved in patient cure and care. There is much awareness of the positive effects of intra- and postoperative interventions on wound healing exists, such as antimicrobial agents, antiseptic dressings, and negative pressure wound therapy (NPWT). Nevertheless, impaired wound healing remains a common complication of surgery.8 Much less attention is generally paid to the influence of preoperative interventions in patients without risk factors on wound healing in order to prepare a patient for surgery and to minimize postoperative complications. This systematic review of the available literature has focused on the beneficial effects of any preoperative interventions on the wound healing and scar formation sequence after surgery. METHODS The search strategy has focused on patients who underwent elective operations during which a skin wound was made. The influence of additional preoperative interventions on wound healing was studied (ie, healing rate, dehiscence, infection rate, or scar tissue). Preoperative interventions have here been defined as all interventions the patient underwent before entering the operation room in addition to the usual care. Search Methods for Identification of Studies A comprehensive and systematic search has been conducted in MEDLINE, PubMed, Embase, Web of Science, and Cochrane up to May 2017. The search strategy is given in Appendices A1 to A5. During each search, Appendix A1 was combined with the search strategy of Appendices A2, A3, A4, or A5. No restriction was made in regard to patient age or publication date. Only articles written in English have been considered for inclusion. References from the included studies have been also screened in order to identify additional primary studies, which had not previously been identified. Two review authors (N.G. and M.Z.), working independently from one another, examined titles and abstracts from the electronic search. Full articles were obtained if necessary. The third and fourth review authors (J.H. and F.N.) have been consulted if consensus was not reached. Inclusion Criteria References have been selected if they met all of the following inclusion criteria: • The study design was either a randomized controlled trial, a nonrandomized study with a control group, or a case series. • A minimum of ten patients was included. • The included patients underwent elective operations during which a skin wound was made. • The study evaluated the results of any preoperative intervention which aimed at improving wound healing and the reduction of any wound healing complications (eg, dehiscence, infection rate, scar tissue). • The criteria for inclusion were explicit (eg, type of surgery, interventions). • The number of patients deceased or lost to follow up was reported. • Clear descriptions of intervention and follow up were given and results were provided for each distinct treatment in the study. • The outcome(s) included at least one clinically relevant/measurable outcome (eg, reduced infections/dehiscence rate or scar formation). Exclusion Criteria • The study described patients with active infections before surgical intervention. • The study included patients with known risk factors for poor wound healing. • The study described pressure ulcers, chronic skin wounds, and traumatic skin wounds. • Prophylactic antibiotics have already widely been examined, and therefore, were not a topic of this review. Assessment of Risk of Bias for the Included Studies Two review authors (N.G. and M.Z.) working independently from each other conducted the risk-of-bias assessment and data extraction. Risk-of-bias of the individual studies was assessed with methodology scores based on the type of study concerned: Cochrane form II for randomized controlled trial (RCTs) and Cochrane form III for cohort studies. The authors added a number of items. Items were scored positive if they fulfilled the criteria, negative when bias was likely, or marked as inconclusive if there was insufficient information. Differences in the scoring of the risk-of-bias assessment and data extraction were discussed during a consensus meeting. If an item was scored positive, one point was awarded. The number of positively scored items has been summed per study. Data Collection and Analysis The data have been extracted onto separate, predeveloped forms. From each study, basic information has been gathered concerning authors (affiliation, sponsoring), methods (study design, sample size), patients (selection criteria and diagnoses), treatments (preoperative interventions), and outcome variables with results. With sufficient clinically and statistically homogeneous and comparable reported outcomes, data were planned to be pooled. For continuous outcomes, a mean difference (MD) was planned to be calculated. For dichotomous outcomes, relative risks (RR) were planned to be calculated. For each outcome, a 95% confidence interval (95% CI) was planned to be computed. RESULTS The initial search yielded 3448 unique references. A total of only 13 studies were eventually identified, which were all randomized controlled trials (Figure 1). The main reasons for exclusion were that interventions were not carried out preoperatively (but intra- or postoperatively); patients with known risk factors were described; no clinically relevant/measurable outcome parameter was described; or there was no surgical wound involved. The main characteristics of the included studies are given in Table 1. The PRISMA Checklist is provided in Appendix B. Figure 1. View largeDownload slide Flowchart for study inclusion. Figure 1. View largeDownload slide Flowchart for study inclusion. Table 1. Characteristics of Included Studies Study Inclusion criteria Exclusion criteria Intervention group Control group Age Time of intervention Sample size (female) Systemic treatments Vaxman (1995)10 Tattoo removal Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR >165/90 mmHg, no respect of procedure, blood concentrations of transferrin <2 g/L, prealbumin <100mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12g/dL Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid (n = 18) Placebo (n = 22) 28.5 Once a day for 21 days, started 8 days prior to surgery 40 (13) Vaxman (1996)9 Tattoo (too big to be removed by single resection), 18-40 years Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR > 165/90 mmHg, blood concentrations of transferrin <2 g/L, prealbumin <100 mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12 g/dL Oral 0.9 g Pantothenic acid and 3 g Ascorbic acid (n = 10) 0.2 g Pantothenic acid and 1 g Ascorbic acid (n = 17) 28.5 Once a day, started 8 days prior to surgery and continued until 13 days after 27 (-) Levandovski (2008)11 Patients undergoing abdominal hysterectomy Contraindications to regional anesthesia, mental impairment, chronic pain, history of congestive heart failure, valvular heart disease, renal or hepatic disease, psychotropic drug, language/communication difficulties, BMI >35 kg/m2, history of psychiatric disorders Oral 10 mg diazepam (n = 61) Placebo (n = 62) Between 19–60 years 1 night before and one hour prior to surgery 123 (123) Künzli (2013)12 Age 25-90 years, all aseptic operations with median or transverse laparotomy Laparoscopic operations, apparent infection before operation, MRSA infection, body temperature >38°C for more than 5 days preoperatively, myocardial infarction within 6 weeks before operation, radio- and/or chemotherapy within 4 weeks before surgery, Albumin <3.3 g/dL, leucocytes < 2.0 G/L, inadvertent loss of weight >10% within 6 months before operation Exposure to the hydrosun radiator for 20 minutes and prophylactic antibiotics (n = 178) Receiving only visible light (sham lamp) for 20 minutes and prophylactic antibiotics (n = 182) Between 25-90 years Same day of surgery 360 (77) Melling (2001)13 >18 years, having an elective hernia repair, varicose vein surgery, or breast surgery that would result in scar >3 cm Pregnant, taking long-term oral steroids, received radiotherapy (at incision site) or chemotherapy during the last 4 weeks, or had an infection at the time of surgery Systemic warming group received standard care, plus warming the whole body using a forced-air, warming blanket. (n = 139) Local warming group received standard care, plus warming to just the planned wound area using a noncontact, radiant heat dressing. (n = 138) Received standard care only, not including any active temperature control. (n = 139) Average 50.03 (SD 14.36) At least 30 min before surgery 242 (174) Topical application Zampieri (2010)14 Need for elective inguinal surgery (no previous or abdominal surgery), no keloids due to previous trauma, no systemic diseases, no skin diseases nor infections, no previous use of topical steroids or drugs Atopic eczema and napkin dermatitis Topical vitamin E (n = 228) Petrolatum-based emollient (n = 200) Between 2 and 9 years Trice daily for 15 days prior to surgery and twice daily for 30 days after surgery 428 (109) Psychological interventions Robles (2007)15 Healthy volunteers, 18-44 years Pregnancy, medical conditions or medications with obvious immunological, dermatological or endocrinological consequences, smoking and excessive caffeine or alcohol use Trier social stress test plus support (n = 27) Trier social stress test (n = 31) No stress (n = 27) 22.6 (4.41) 1 hour prior to surgery 85 (44) Koschwanez (2013)16 >60 years, able to write in English Smoking, significant skin disease, allergic to lignocaine, or clinically depressed Writing about a traumatic experience (n = 26) Writing about time management without mentioning emotions, opinions, or beliefs. (n = 23) 78.8 (7.2) 20 minutes daily, started 2 weeks prior to surgery and stopped 1 day prior to surgery 49 (28) Weinman (2008)17 Healthy volunteers, 18-40 years >15 cigarettes per week, skin complaint (ie, eczema or psoriasis), glucocorticoid medication use during last month, chronic inflammatory disorders, allergic rhinitis, or allergic asthma, clinical depression, acute illness, family history of keloid scarring Writing about a traumatic experience (n = 18) Writing about time management (n = 18) 22.2 (4.08) 20 minutes for three days, 2 weeks prior to surgery 36 (0) Broadbent (2012)18 Undergoing elective laparoscopic cholecystectomy, >18 years, able to read and write English - Brief relaxation intervention (n = 37) No stress (read an article silently and alone, no following test) (n = 38) 51.3 (16.8) 3 days prior to surgery and 7 days after 45 (30) Ginandes(2003) 19 Healthy women with macromastia Systemic illness, medications ,and/or behaviours affecting wound healing (diabetes, immune compromise, prescribed steroids, cigarette smoking), psychological conditions, language barriers Hypnosis (n = 6) supportive attention (n = 6) No hypnosis or support (n = 6) 38.9 (8.7) 8 half-hour weekly for 2 weeks prior to surgery 18 (18) Rao (2008)20 Recently diagnosed breast cancer, mastectomy as primary treatment, 30-70 years, Zubrod’s performance status 0-2 (ambulatory >50% of time), high school education Concurrent medical condition likely to interfere with treatment, any major psychiatric, neurological illness or autoimmune disorders, secondary malignancy, presented with infections or history of recent infections in the past month Yoga program (n = 24) Supportive therapy and exercise rehabilitation (n = 28) 49.2 (9.6) 1 hour prior to surgery and daily 3 times a week postsurgery 52 (52) Pereira (2016)21 Undergoing general ambulatory surgery Major psychiatric or neurologic pathologies Empathic personal information about surgery (n = 52) Standardized information about hospitalization norms and description of the surgical procedures (n = 52) 44.2 (14.6) One month prior to surgery 104 (35) Study Inclusion criteria Exclusion criteria Intervention group Control group Age Time of intervention Sample size (female) Systemic treatments Vaxman (1995)10 Tattoo removal Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR >165/90 mmHg, no respect of procedure, blood concentrations of transferrin <2 g/L, prealbumin <100mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12g/dL Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid (n = 18) Placebo (n = 22) 28.5 Once a day for 21 days, started 8 days prior to surgery 40 (13) Vaxman (1996)9 Tattoo (too big to be removed by single resection), 18-40 years Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR > 165/90 mmHg, blood concentrations of transferrin <2 g/L, prealbumin <100 mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12 g/dL Oral 0.9 g Pantothenic acid and 3 g Ascorbic acid (n = 10) 0.2 g Pantothenic acid and 1 g Ascorbic acid (n = 17) 28.5 Once a day, started 8 days prior to surgery and continued until 13 days after 27 (-) Levandovski (2008)11 Patients undergoing abdominal hysterectomy Contraindications to regional anesthesia, mental impairment, chronic pain, history of congestive heart failure, valvular heart disease, renal or hepatic disease, psychotropic drug, language/communication difficulties, BMI >35 kg/m2, history of psychiatric disorders Oral 10 mg diazepam (n = 61) Placebo (n = 62) Between 19–60 years 1 night before and one hour prior to surgery 123 (123) Künzli (2013)12 Age 25-90 years, all aseptic operations with median or transverse laparotomy Laparoscopic operations, apparent infection before operation, MRSA infection, body temperature >38°C for more than 5 days preoperatively, myocardial infarction within 6 weeks before operation, radio- and/or chemotherapy within 4 weeks before surgery, Albumin <3.3 g/dL, leucocytes < 2.0 G/L, inadvertent loss of weight >10% within 6 months before operation Exposure to the hydrosun radiator for 20 minutes and prophylactic antibiotics (n = 178) Receiving only visible light (sham lamp) for 20 minutes and prophylactic antibiotics (n = 182) Between 25-90 years Same day of surgery 360 (77) Melling (2001)13 >18 years, having an elective hernia repair, varicose vein surgery, or breast surgery that would result in scar >3 cm Pregnant, taking long-term oral steroids, received radiotherapy (at incision site) or chemotherapy during the last 4 weeks, or had an infection at the time of surgery Systemic warming group received standard care, plus warming the whole body using a forced-air, warming blanket. (n = 139) Local warming group received standard care, plus warming to just the planned wound area using a noncontact, radiant heat dressing. (n = 138) Received standard care only, not including any active temperature control. (n = 139) Average 50.03 (SD 14.36) At least 30 min before surgery 242 (174) Topical application Zampieri (2010)14 Need for elective inguinal surgery (no previous or abdominal surgery), no keloids due to previous trauma, no systemic diseases, no skin diseases nor infections, no previous use of topical steroids or drugs Atopic eczema and napkin dermatitis Topical vitamin E (n = 228) Petrolatum-based emollient (n = 200) Between 2 and 9 years Trice daily for 15 days prior to surgery and twice daily for 30 days after surgery 428 (109) Psychological interventions Robles (2007)15 Healthy volunteers, 18-44 years Pregnancy, medical conditions or medications with obvious immunological, dermatological or endocrinological consequences, smoking and excessive caffeine or alcohol use Trier social stress test plus support (n = 27) Trier social stress test (n = 31) No stress (n = 27) 22.6 (4.41) 1 hour prior to surgery 85 (44) Koschwanez (2013)16 >60 years, able to write in English Smoking, significant skin disease, allergic to lignocaine, or clinically depressed Writing about a traumatic experience (n = 26) Writing about time management without mentioning emotions, opinions, or beliefs. (n = 23) 78.8 (7.2) 20 minutes daily, started 2 weeks prior to surgery and stopped 1 day prior to surgery 49 (28) Weinman (2008)17 Healthy volunteers, 18-40 years >15 cigarettes per week, skin complaint (ie, eczema or psoriasis), glucocorticoid medication use during last month, chronic inflammatory disorders, allergic rhinitis, or allergic asthma, clinical depression, acute illness, family history of keloid scarring Writing about a traumatic experience (n = 18) Writing about time management (n = 18) 22.2 (4.08) 20 minutes for three days, 2 weeks prior to surgery 36 (0) Broadbent (2012)18 Undergoing elective laparoscopic cholecystectomy, >18 years, able to read and write English - Brief relaxation intervention (n = 37) No stress (read an article silently and alone, no following test) (n = 38) 51.3 (16.8) 3 days prior to surgery and 7 days after 45 (30) Ginandes(2003) 19 Healthy women with macromastia Systemic illness, medications ,and/or behaviours affecting wound healing (diabetes, immune compromise, prescribed steroids, cigarette smoking), psychological conditions, language barriers Hypnosis (n = 6) supportive attention (n = 6) No hypnosis or support (n = 6) 38.9 (8.7) 8 half-hour weekly for 2 weeks prior to surgery 18 (18) Rao (2008)20 Recently diagnosed breast cancer, mastectomy as primary treatment, 30-70 years, Zubrod’s performance status 0-2 (ambulatory >50% of time), high school education Concurrent medical condition likely to interfere with treatment, any major psychiatric, neurological illness or autoimmune disorders, secondary malignancy, presented with infections or history of recent infections in the past month Yoga program (n = 24) Supportive therapy and exercise rehabilitation (n = 28) 49.2 (9.6) 1 hour prior to surgery and daily 3 times a week postsurgery 52 (52) Pereira (2016)21 Undergoing general ambulatory surgery Major psychiatric or neurologic pathologies Empathic personal information about surgery (n = 52) Standardized information about hospitalization norms and description of the surgical procedures (n = 52) 44.2 (14.6) One month prior to surgery 104 (35) BMI, body mass index. View Large Table 1. Characteristics of Included Studies Study Inclusion criteria Exclusion criteria Intervention group Control group Age Time of intervention Sample size (female) Systemic treatments Vaxman (1995)10 Tattoo removal Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR >165/90 mmHg, no respect of procedure, blood concentrations of transferrin <2 g/L, prealbumin <100mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12g/dL Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid (n = 18) Placebo (n = 22) 28.5 Once a day for 21 days, started 8 days prior to surgery 40 (13) Vaxman (1996)9 Tattoo (too big to be removed by single resection), 18-40 years Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR > 165/90 mmHg, blood concentrations of transferrin <2 g/L, prealbumin <100 mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12 g/dL Oral 0.9 g Pantothenic acid and 3 g Ascorbic acid (n = 10) 0.2 g Pantothenic acid and 1 g Ascorbic acid (n = 17) 28.5 Once a day, started 8 days prior to surgery and continued until 13 days after 27 (-) Levandovski (2008)11 Patients undergoing abdominal hysterectomy Contraindications to regional anesthesia, mental impairment, chronic pain, history of congestive heart failure, valvular heart disease, renal or hepatic disease, psychotropic drug, language/communication difficulties, BMI >35 kg/m2, history of psychiatric disorders Oral 10 mg diazepam (n = 61) Placebo (n = 62) Between 19–60 years 1 night before and one hour prior to surgery 123 (123) Künzli (2013)12 Age 25-90 years, all aseptic operations with median or transverse laparotomy Laparoscopic operations, apparent infection before operation, MRSA infection, body temperature >38°C for more than 5 days preoperatively, myocardial infarction within 6 weeks before operation, radio- and/or chemotherapy within 4 weeks before surgery, Albumin <3.3 g/dL, leucocytes < 2.0 G/L, inadvertent loss of weight >10% within 6 months before operation Exposure to the hydrosun radiator for 20 minutes and prophylactic antibiotics (n = 178) Receiving only visible light (sham lamp) for 20 minutes and prophylactic antibiotics (n = 182) Between 25-90 years Same day of surgery 360 (77) Melling (2001)13 >18 years, having an elective hernia repair, varicose vein surgery, or breast surgery that would result in scar >3 cm Pregnant, taking long-term oral steroids, received radiotherapy (at incision site) or chemotherapy during the last 4 weeks, or had an infection at the time of surgery Systemic warming group received standard care, plus warming the whole body using a forced-air, warming blanket. (n = 139) Local warming group received standard care, plus warming to just the planned wound area using a noncontact, radiant heat dressing. (n = 138) Received standard care only, not including any active temperature control. (n = 139) Average 50.03 (SD 14.36) At least 30 min before surgery 242 (174) Topical application Zampieri (2010)14 Need for elective inguinal surgery (no previous or abdominal surgery), no keloids due to previous trauma, no systemic diseases, no skin diseases nor infections, no previous use of topical steroids or drugs Atopic eczema and napkin dermatitis Topical vitamin E (n = 228) Petrolatum-based emollient (n = 200) Between 2 and 9 years Trice daily for 15 days prior to surgery and twice daily for 30 days after surgery 428 (109) Psychological interventions Robles (2007)15 Healthy volunteers, 18-44 years Pregnancy, medical conditions or medications with obvious immunological, dermatological or endocrinological consequences, smoking and excessive caffeine or alcohol use Trier social stress test plus support (n = 27) Trier social stress test (n = 31) No stress (n = 27) 22.6 (4.41) 1 hour prior to surgery 85 (44) Koschwanez (2013)16 >60 years, able to write in English Smoking, significant skin disease, allergic to lignocaine, or clinically depressed Writing about a traumatic experience (n = 26) Writing about time management without mentioning emotions, opinions, or beliefs. (n = 23) 78.8 (7.2) 20 minutes daily, started 2 weeks prior to surgery and stopped 1 day prior to surgery 49 (28) Weinman (2008)17 Healthy volunteers, 18-40 years >15 cigarettes per week, skin complaint (ie, eczema or psoriasis), glucocorticoid medication use during last month, chronic inflammatory disorders, allergic rhinitis, or allergic asthma, clinical depression, acute illness, family history of keloid scarring Writing about a traumatic experience (n = 18) Writing about time management (n = 18) 22.2 (4.08) 20 minutes for three days, 2 weeks prior to surgery 36 (0) Broadbent (2012)18 Undergoing elective laparoscopic cholecystectomy, >18 years, able to read and write English - Brief relaxation intervention (n = 37) No stress (read an article silently and alone, no following test) (n = 38) 51.3 (16.8) 3 days prior to surgery and 7 days after 45 (30) Ginandes(2003) 19 Healthy women with macromastia Systemic illness, medications ,and/or behaviours affecting wound healing (diabetes, immune compromise, prescribed steroids, cigarette smoking), psychological conditions, language barriers Hypnosis (n = 6) supportive attention (n = 6) No hypnosis or support (n = 6) 38.9 (8.7) 8 half-hour weekly for 2 weeks prior to surgery 18 (18) Rao (2008)20 Recently diagnosed breast cancer, mastectomy as primary treatment, 30-70 years, Zubrod’s performance status 0-2 (ambulatory >50% of time), high school education Concurrent medical condition likely to interfere with treatment, any major psychiatric, neurological illness or autoimmune disorders, secondary malignancy, presented with infections or history of recent infections in the past month Yoga program (n = 24) Supportive therapy and exercise rehabilitation (n = 28) 49.2 (9.6) 1 hour prior to surgery and daily 3 times a week postsurgery 52 (52) Pereira (2016)21 Undergoing general ambulatory surgery Major psychiatric or neurologic pathologies Empathic personal information about surgery (n = 52) Standardized information about hospitalization norms and description of the surgical procedures (n = 52) 44.2 (14.6) One month prior to surgery 104 (35) Study Inclusion criteria Exclusion criteria Intervention group Control group Age Time of intervention Sample size (female) Systemic treatments Vaxman (1995)10 Tattoo removal Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR >165/90 mmHg, no respect of procedure, blood concentrations of transferrin <2 g/L, prealbumin <100mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12g/dL Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid (n = 18) Placebo (n = 22) 28.5 Once a day for 21 days, started 8 days prior to surgery 40 (13) Vaxman (1996)9 Tattoo (too big to be removed by single resection), 18-40 years Pervious scar on tattoo site, pregnancy, any disease state, drug intake, RR > 165/90 mmHg, blood concentrations of transferrin <2 g/L, prealbumin <100 mg/L, glucose >6.10 mmol/L, urea >8.20, bilirubin >20.5 μmol/L, haemoglobin <12 g/dL Oral 0.9 g Pantothenic acid and 3 g Ascorbic acid (n = 10) 0.2 g Pantothenic acid and 1 g Ascorbic acid (n = 17) 28.5 Once a day, started 8 days prior to surgery and continued until 13 days after 27 (-) Levandovski (2008)11 Patients undergoing abdominal hysterectomy Contraindications to regional anesthesia, mental impairment, chronic pain, history of congestive heart failure, valvular heart disease, renal or hepatic disease, psychotropic drug, language/communication difficulties, BMI >35 kg/m2, history of psychiatric disorders Oral 10 mg diazepam (n = 61) Placebo (n = 62) Between 19–60 years 1 night before and one hour prior to surgery 123 (123) Künzli (2013)12 Age 25-90 years, all aseptic operations with median or transverse laparotomy Laparoscopic operations, apparent infection before operation, MRSA infection, body temperature >38°C for more than 5 days preoperatively, myocardial infarction within 6 weeks before operation, radio- and/or chemotherapy within 4 weeks before surgery, Albumin <3.3 g/dL, leucocytes < 2.0 G/L, inadvertent loss of weight >10% within 6 months before operation Exposure to the hydrosun radiator for 20 minutes and prophylactic antibiotics (n = 178) Receiving only visible light (sham lamp) for 20 minutes and prophylactic antibiotics (n = 182) Between 25-90 years Same day of surgery 360 (77) Melling (2001)13 >18 years, having an elective hernia repair, varicose vein surgery, or breast surgery that would result in scar >3 cm Pregnant, taking long-term oral steroids, received radiotherapy (at incision site) or chemotherapy during the last 4 weeks, or had an infection at the time of surgery Systemic warming group received standard care, plus warming the whole body using a forced-air, warming blanket. (n = 139) Local warming group received standard care, plus warming to just the planned wound area using a noncontact, radiant heat dressing. (n = 138) Received standard care only, not including any active temperature control. (n = 139) Average 50.03 (SD 14.36) At least 30 min before surgery 242 (174) Topical application Zampieri (2010)14 Need for elective inguinal surgery (no previous or abdominal surgery), no keloids due to previous trauma, no systemic diseases, no skin diseases nor infections, no previous use of topical steroids or drugs Atopic eczema and napkin dermatitis Topical vitamin E (n = 228) Petrolatum-based emollient (n = 200) Between 2 and 9 years Trice daily for 15 days prior to surgery and twice daily for 30 days after surgery 428 (109) Psychological interventions Robles (2007)15 Healthy volunteers, 18-44 years Pregnancy, medical conditions or medications with obvious immunological, dermatological or endocrinological consequences, smoking and excessive caffeine or alcohol use Trier social stress test plus support (n = 27) Trier social stress test (n = 31) No stress (n = 27) 22.6 (4.41) 1 hour prior to surgery 85 (44) Koschwanez (2013)16 >60 years, able to write in English Smoking, significant skin disease, allergic to lignocaine, or clinically depressed Writing about a traumatic experience (n = 26) Writing about time management without mentioning emotions, opinions, or beliefs. (n = 23) 78.8 (7.2) 20 minutes daily, started 2 weeks prior to surgery and stopped 1 day prior to surgery 49 (28) Weinman (2008)17 Healthy volunteers, 18-40 years >15 cigarettes per week, skin complaint (ie, eczema or psoriasis), glucocorticoid medication use during last month, chronic inflammatory disorders, allergic rhinitis, or allergic asthma, clinical depression, acute illness, family history of keloid scarring Writing about a traumatic experience (n = 18) Writing about time management (n = 18) 22.2 (4.08) 20 minutes for three days, 2 weeks prior to surgery 36 (0) Broadbent (2012)18 Undergoing elective laparoscopic cholecystectomy, >18 years, able to read and write English - Brief relaxation intervention (n = 37) No stress (read an article silently and alone, no following test) (n = 38) 51.3 (16.8) 3 days prior to surgery and 7 days after 45 (30) Ginandes(2003) 19 Healthy women with macromastia Systemic illness, medications ,and/or behaviours affecting wound healing (diabetes, immune compromise, prescribed steroids, cigarette smoking), psychological conditions, language barriers Hypnosis (n = 6) supportive attention (n = 6) No hypnosis or support (n = 6) 38.9 (8.7) 8 half-hour weekly for 2 weeks prior to surgery 18 (18) Rao (2008)20 Recently diagnosed breast cancer, mastectomy as primary treatment, 30-70 years, Zubrod’s performance status 0-2 (ambulatory >50% of time), high school education Concurrent medical condition likely to interfere with treatment, any major psychiatric, neurological illness or autoimmune disorders, secondary malignancy, presented with infections or history of recent infections in the past month Yoga program (n = 24) Supportive therapy and exercise rehabilitation (n = 28) 49.2 (9.6) 1 hour prior to surgery and daily 3 times a week postsurgery 52 (52) Pereira (2016)21 Undergoing general ambulatory surgery Major psychiatric or neurologic pathologies Empathic personal information about surgery (n = 52) Standardized information about hospitalization norms and description of the surgical procedures (n = 52) 44.2 (14.6) One month prior to surgery 104 (35) BMI, body mass index. View Large Risk-of-Bias Assessments The results of the risk-of-bias assessments are shown in Table 2. The 13 RCTs were scored on a 10-point scale (0 being worst, 10 excellent quality). Table 2. Results of Risk-of-Bias Assessment of the RCTs Randomized controlled trials Vaxman (1995)10 Vaxman (1996)9 Levandovski (2008)11 Künzli (2013)12 Melling (2001)13 Zampieri (2010)14 Robles (2007)15 Koschwanez (2013)16 Weinman (2008)17 Broadbent (2012)18 Ginandes (2003)19 Rao (2008)20 Pereira (2014)21 Clear study objective + + + + + + + + + + + + + Criteria for inclusion explicit + + + + + + + + + + + + + Comparable groups apart from the intervention - - + + + + + + + + + + + Number of men and women + - + + + + + + + + + + + Outcome valid and clinically relevant + + + + + + + + + + + + + Randomized trial + + + + + + + + + + + + + Patient blinded for treatment + + + + - + - - + - - - - Clinician blinded for treatment + + + + + - - + - + + - - Assessors blinded for treatment - - + - + + + + - + + + - Complete follow up of each patient + + + - + + + + + + + + + Conclusion 8/10 7/10 10/10 8/10 9/10 9/10 8/10 9/10 8/10 9/10 9/10 8/10 7/10 Randomized controlled trials Vaxman (1995)10 Vaxman (1996)9 Levandovski (2008)11 Künzli (2013)12 Melling (2001)13 Zampieri (2010)14 Robles (2007)15 Koschwanez (2013)16 Weinman (2008)17 Broadbent (2012)18 Ginandes (2003)19 Rao (2008)20 Pereira (2014)21 Clear study objective + + + + + + + + + + + + + Criteria for inclusion explicit + + + + + + + + + + + + + Comparable groups apart from the intervention - - + + + + + + + + + + + Number of men and women + - + + + + + + + + + + + Outcome valid and clinically relevant + + + + + + + + + + + + + Randomized trial + + + + + + + + + + + + + Patient blinded for treatment + + + + - + - - + - - - - Clinician blinded for treatment + + + + + - - + - + + - - Assessors blinded for treatment - - + - + + + + - + + + - Complete follow up of each patient + + + - + + + + + + + + + Conclusion 8/10 7/10 10/10 8/10 9/10 9/10 8/10 9/10 8/10 9/10 9/10 8/10 7/10 RCT, randomized controlled trial. View Large Table 2. Results of Risk-of-Bias Assessment of the RCTs Randomized controlled trials Vaxman (1995)10 Vaxman (1996)9 Levandovski (2008)11 Künzli (2013)12 Melling (2001)13 Zampieri (2010)14 Robles (2007)15 Koschwanez (2013)16 Weinman (2008)17 Broadbent (2012)18 Ginandes (2003)19 Rao (2008)20 Pereira (2014)21 Clear study objective + + + + + + + + + + + + + Criteria for inclusion explicit + + + + + + + + + + + + + Comparable groups apart from the intervention - - + + + + + + + + + + + Number of men and women + - + + + + + + + + + + + Outcome valid and clinically relevant + + + + + + + + + + + + + Randomized trial + + + + + + + + + + + + + Patient blinded for treatment + + + + - + - - + - - - - Clinician blinded for treatment + + + + + - - + - + + - - Assessors blinded for treatment - - + - + + + + - + + + - Complete follow up of each patient + + + - + + + + + + + + + Conclusion 8/10 7/10 10/10 8/10 9/10 9/10 8/10 9/10 8/10 9/10 9/10 8/10 7/10 Randomized controlled trials Vaxman (1995)10 Vaxman (1996)9 Levandovski (2008)11 Künzli (2013)12 Melling (2001)13 Zampieri (2010)14 Robles (2007)15 Koschwanez (2013)16 Weinman (2008)17 Broadbent (2012)18 Ginandes (2003)19 Rao (2008)20 Pereira (2014)21 Clear study objective + + + + + + + + + + + + + Criteria for inclusion explicit + + + + + + + + + + + + + Comparable groups apart from the intervention - - + + + + + + + + + + + Number of men and women + - + + + + + + + + + + + Outcome valid and clinically relevant + + + + + + + + + + + + + Randomized trial + + + + + + + + + + + + + Patient blinded for treatment + + + + - + - - + - - - - Clinician blinded for treatment + + + + + - - + - + + - - Assessors blinded for treatment - - + - + + + + - + + + - Complete follow up of each patient + + + - + + + + + + + + + Conclusion 8/10 7/10 10/10 8/10 9/10 9/10 8/10 9/10 8/10 9/10 9/10 8/10 7/10 RCT, randomized controlled trial. View Large Study Comparison A wide variety of patients, interventions, and outcome parameters were used to assess wound healing. Because of this heterogeneity, no pooling, comparisons, or statistical analyses were possible between the included studies. The included articles individually, however, do allow for some interesting observations to be made. The main findings were grouped into three main categories: systemic treatments (n = 5), topical application (n = 1), and psychological interventions (n = 7). The main findings (Table 3) of the studies are summarized and reported below. Table 3. Outcome of Data Extraction Study Outcome Outcome measurement Follow up time Result control group Result intervention group P-value Systemic treatments Vaxman (1995)10 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Placebo 38 ± 2 29 ± 1 Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid 39 ± 1 29 ± 1 “ns” “ns” Fibroblast count Mean number of Fibroblasts per optical field in skin and scar 8 days 21 days 26 ± 2 83 ± 6 28 ± 2 91 ± 7 “ns” “ns” Vaxman (1996)9 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Oral 0.2 g/day Pantothenic acid and 1.0 g/day Ascorbic acid 39 ± 6 27 ± 6 Oral 0.9 g/day Pantothenic acid and 3 g/day Ascorbic acid 36 ± 4 25 ± 8 “ns” “ns” Fibroblast count n/field 8 days 21 days 28 ± 7 90 ± 31 19 ± 7 80 ± 30 “ns” “ns” Levandovski (2008)11 SSI = either of two distinct criteria for diagnosis: 1. pus could be expressed from the incision; 2. incisional or organ space; with a diagnostic period up to 30 days Yes or no (number of SSI) 30 days Placebo 16/26 Oral 10 mg diazepam 4/61 P = 0.00 State-trait anxiety inventory (STAI): The preoperative score were measured just before surgery; The postoperative anxiety was defined as the average of the score obtained at 6 and 24 hours following surgery Anxiety point scale 0 (no anxiety) - 45.5 (most anxiety) points Patients in the highest quartile were classified as High anxiety and patients in the lowest or equal to the quartile were classifies as Low anxiety 24 hours 41.91 ± 8.88 38.13 ± 6.94 P = 0.01 Künzli (2013)12 Postoperative wound infection (SSI) ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks 30 days (9/178) (22/182) FAS P = 0.018 ITT P = 0.248 Wound healing assessed by treating surgeon? 100 mm visual analog scale (VAS) 0 mm = extremely bad and 100 mm extremely good healing 30 days FAS 90 (80-100) ITT 86 (30-98) 88 (75-100) 80 (17-96) P = 0.147 P = 0.217 Postoperative pain VAS score (0, extremely bad; 100, extremely good). 30 days The median (interquartile range) FAS 3.5 (0–12) ITT 10 (0-35) 7 (0-20) 13 (0-57) P = 0.045 P = 0.092 Melling (2001)13 Wound infection Antibiotics ASEPSIS wound score: purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks 6 weeks Nonwarmed group 19 (14%) Local warming 5 (4%) Systemic warming 8 (6%) All warmed patients (Local+systemic) 13 (5%) P = 0.003 P = 0.026 P = 0.001 Systemic warming 8 (6%) Local warming 5 (4%) “ns” Nonwarmed group 22 (16%) All warmed patients (local+systemic) 18 (57%) P = 0.002 Topical application Zampieri (2010)14 Cosmetic results 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dyschromic signs), 2 = good (flared margins, no dyschromic signs), 3 = very good (excellent cosmetic results, no visible scars) 6 months Petrolatum-based emollient (two independent reviewers?) Poor 7%-5% Fairly good 15%-18% Good 0% Very good 78%-77% Topical vitamin E (two independent reviewers?) Poor 0% Fairly good 0% Good 4%-5% Very good 96%-95% P < 0.05 Psychological interventions Robles (2007)15 TEWL (transepidermal water loss) g/m2h 2 hour No stress 18.64 ± 9.71 Stress 21.81 ± 14.06 Stress + support 21.98 ± 6.83 “ns” Koschwanez (2013)16 Reepithelialisation % 7 days 11 days 14 days 17 days 21 days Write about time management 10% 42.1% 90% 95% 100% Write about traumatic experience 27% 76.2% 90% 100% 100% “ns” P = 0.028 “ns” “ns” “ns” Weinman (2008)17 Wound diameter mm 7 days 14 days 21 days Write about time management 4.15 ± 0.48 mm 3.67 ± 0.56 mm 3.27 ± 0.54 mm Write about traumatic experience 4.10 ± 0.62 mm 3.28 ± 0.44 mm 2.98 ± 0.39 mm “ns” P < 0.05 “ns” Broadbent (2012)18 Hydroxyproline level μg/cm of tubing 7 days Normal care 13.56 ± 6.04 Psychological relaxing intervention 22.35 ± 17.48 P = 0.02 Ginandes (2003)19 Doctor’s WAI rating Edema (1-3), erythema (1-3), exudates (1-3); 0 = no signs to 3 = marked signs Total score = 9 Week 1 Week 7 No hypnosis or support 3.07 2.72 Hypnosis 2.89 1.28 P < 0.01 Week 1 Week 7 Supportive attention 3.47 1.94 Hypnosis 2.89 1.28 P < 0.01 Rao (2008)20 Interval before suture removal Number of days 4 weeks Supportive therapy and exercise rehabilitation 13.7 ± 5.3 Yoga program 10.8 ± 3.3 P = 0.03 Drain retention Number of days Variable 6.79 ± 2.4 4.8 ± 1.5 P = 0.001 Pereira (2016)21 Push Ranging from 0-4; 0 = no exudate/scarring tissue 4 = abundant exudate, necrotic tissue 1 month Routinely standardised information 0.4 Empathic patient-centred interview 0.1 P < 0.005 Anxiety level Y (STAY-Y): 20 item self-report instrument which includes separate measures of state and trait anxiety, each subtest ranging from 20 to 80, higher scores indicating greater anxiety Before interview After interview After surgery 38.7 38.5 37.9 33.9 31.6 30.7 P = 0.001 Study Outcome Outcome measurement Follow up time Result control group Result intervention group P-value Systemic treatments Vaxman (1995)10 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Placebo 38 ± 2 29 ± 1 Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid 39 ± 1 29 ± 1 “ns” “ns” Fibroblast count Mean number of Fibroblasts per optical field in skin and scar 8 days 21 days 26 ± 2 83 ± 6 28 ± 2 91 ± 7 “ns” “ns” Vaxman (1996)9 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Oral 0.2 g/day Pantothenic acid and 1.0 g/day Ascorbic acid 39 ± 6 27 ± 6 Oral 0.9 g/day Pantothenic acid and 3 g/day Ascorbic acid 36 ± 4 25 ± 8 “ns” “ns” Fibroblast count n/field 8 days 21 days 28 ± 7 90 ± 31 19 ± 7 80 ± 30 “ns” “ns” Levandovski (2008)11 SSI = either of two distinct criteria for diagnosis: 1. pus could be expressed from the incision; 2. incisional or organ space; with a diagnostic period up to 30 days Yes or no (number of SSI) 30 days Placebo 16/26 Oral 10 mg diazepam 4/61 P = 0.00 State-trait anxiety inventory (STAI): The preoperative score were measured just before surgery; The postoperative anxiety was defined as the average of the score obtained at 6 and 24 hours following surgery Anxiety point scale 0 (no anxiety) - 45.5 (most anxiety) points Patients in the highest quartile were classified as High anxiety and patients in the lowest or equal to the quartile were classifies as Low anxiety 24 hours 41.91 ± 8.88 38.13 ± 6.94 P = 0.01 Künzli (2013)12 Postoperative wound infection (SSI) ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks 30 days (9/178) (22/182) FAS P = 0.018 ITT P = 0.248 Wound healing assessed by treating surgeon? 100 mm visual analog scale (VAS) 0 mm = extremely bad and 100 mm extremely good healing 30 days FAS 90 (80-100) ITT 86 (30-98) 88 (75-100) 80 (17-96) P = 0.147 P = 0.217 Postoperative pain VAS score (0, extremely bad; 100, extremely good). 30 days The median (interquartile range) FAS 3.5 (0–12) ITT 10 (0-35) 7 (0-20) 13 (0-57) P = 0.045 P = 0.092 Melling (2001)13 Wound infection Antibiotics ASEPSIS wound score: purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks 6 weeks Nonwarmed group 19 (14%) Local warming 5 (4%) Systemic warming 8 (6%) All warmed patients (Local+systemic) 13 (5%) P = 0.003 P = 0.026 P = 0.001 Systemic warming 8 (6%) Local warming 5 (4%) “ns” Nonwarmed group 22 (16%) All warmed patients (local+systemic) 18 (57%) P = 0.002 Topical application Zampieri (2010)14 Cosmetic results 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dyschromic signs), 2 = good (flared margins, no dyschromic signs), 3 = very good (excellent cosmetic results, no visible scars) 6 months Petrolatum-based emollient (two independent reviewers?) Poor 7%-5% Fairly good 15%-18% Good 0% Very good 78%-77% Topical vitamin E (two independent reviewers?) Poor 0% Fairly good 0% Good 4%-5% Very good 96%-95% P < 0.05 Psychological interventions Robles (2007)15 TEWL (transepidermal water loss) g/m2h 2 hour No stress 18.64 ± 9.71 Stress 21.81 ± 14.06 Stress + support 21.98 ± 6.83 “ns” Koschwanez (2013)16 Reepithelialisation % 7 days 11 days 14 days 17 days 21 days Write about time management 10% 42.1% 90% 95% 100% Write about traumatic experience 27% 76.2% 90% 100% 100% “ns” P = 0.028 “ns” “ns” “ns” Weinman (2008)17 Wound diameter mm 7 days 14 days 21 days Write about time management 4.15 ± 0.48 mm 3.67 ± 0.56 mm 3.27 ± 0.54 mm Write about traumatic experience 4.10 ± 0.62 mm 3.28 ± 0.44 mm 2.98 ± 0.39 mm “ns” P < 0.05 “ns” Broadbent (2012)18 Hydroxyproline level μg/cm of tubing 7 days Normal care 13.56 ± 6.04 Psychological relaxing intervention 22.35 ± 17.48 P = 0.02 Ginandes (2003)19 Doctor’s WAI rating Edema (1-3), erythema (1-3), exudates (1-3); 0 = no signs to 3 = marked signs Total score = 9 Week 1 Week 7 No hypnosis or support 3.07 2.72 Hypnosis 2.89 1.28 P < 0.01 Week 1 Week 7 Supportive attention 3.47 1.94 Hypnosis 2.89 1.28 P < 0.01 Rao (2008)20 Interval before suture removal Number of days 4 weeks Supportive therapy and exercise rehabilitation 13.7 ± 5.3 Yoga program 10.8 ± 3.3 P = 0.03 Drain retention Number of days Variable 6.79 ± 2.4 4.8 ± 1.5 P = 0.001 Pereira (2016)21 Push Ranging from 0-4; 0 = no exudate/scarring tissue 4 = abundant exudate, necrotic tissue 1 month Routinely standardised information 0.4 Empathic patient-centred interview 0.1 P < 0.005 Anxiety level Y (STAY-Y): 20 item self-report instrument which includes separate measures of state and trait anxiety, each subtest ranging from 20 to 80, higher scores indicating greater anxiety Before interview After interview After surgery 38.7 38.5 37.9 33.9 31.6 30.7 P = 0.001 FAS, full-analysis set; ITT, intention to treat; ns, not significant; SSI, surgical site infections; STAI, state-trait anxiety inventory; TEWL, transepidermal water loss; VAS, visual analog scale; WAI, wound assessment inventory. View Large Table 3. Outcome of Data Extraction Study Outcome Outcome measurement Follow up time Result control group Result intervention group P-value Systemic treatments Vaxman (1995)10 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Placebo 38 ± 2 29 ± 1 Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid 39 ± 1 29 ± 1 “ns” “ns” Fibroblast count Mean number of Fibroblasts per optical field in skin and scar 8 days 21 days 26 ± 2 83 ± 6 28 ± 2 91 ± 7 “ns” “ns” Vaxman (1996)9 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Oral 0.2 g/day Pantothenic acid and 1.0 g/day Ascorbic acid 39 ± 6 27 ± 6 Oral 0.9 g/day Pantothenic acid and 3 g/day Ascorbic acid 36 ± 4 25 ± 8 “ns” “ns” Fibroblast count n/field 8 days 21 days 28 ± 7 90 ± 31 19 ± 7 80 ± 30 “ns” “ns” Levandovski (2008)11 SSI = either of two distinct criteria for diagnosis: 1. pus could be expressed from the incision; 2. incisional or organ space; with a diagnostic period up to 30 days Yes or no (number of SSI) 30 days Placebo 16/26 Oral 10 mg diazepam 4/61 P = 0.00 State-trait anxiety inventory (STAI): The preoperative score were measured just before surgery; The postoperative anxiety was defined as the average of the score obtained at 6 and 24 hours following surgery Anxiety point scale 0 (no anxiety) - 45.5 (most anxiety) points Patients in the highest quartile were classified as High anxiety and patients in the lowest or equal to the quartile were classifies as Low anxiety 24 hours 41.91 ± 8.88 38.13 ± 6.94 P = 0.01 Künzli (2013)12 Postoperative wound infection (SSI) ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks 30 days (9/178) (22/182) FAS P = 0.018 ITT P = 0.248 Wound healing assessed by treating surgeon? 100 mm visual analog scale (VAS) 0 mm = extremely bad and 100 mm extremely good healing 30 days FAS 90 (80-100) ITT 86 (30-98) 88 (75-100) 80 (17-96) P = 0.147 P = 0.217 Postoperative pain VAS score (0, extremely bad; 100, extremely good). 30 days The median (interquartile range) FAS 3.5 (0–12) ITT 10 (0-35) 7 (0-20) 13 (0-57) P = 0.045 P = 0.092 Melling (2001)13 Wound infection Antibiotics ASEPSIS wound score: purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks 6 weeks Nonwarmed group 19 (14%) Local warming 5 (4%) Systemic warming 8 (6%) All warmed patients (Local+systemic) 13 (5%) P = 0.003 P = 0.026 P = 0.001 Systemic warming 8 (6%) Local warming 5 (4%) “ns” Nonwarmed group 22 (16%) All warmed patients (local+systemic) 18 (57%) P = 0.002 Topical application Zampieri (2010)14 Cosmetic results 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dyschromic signs), 2 = good (flared margins, no dyschromic signs), 3 = very good (excellent cosmetic results, no visible scars) 6 months Petrolatum-based emollient (two independent reviewers?) Poor 7%-5% Fairly good 15%-18% Good 0% Very good 78%-77% Topical vitamin E (two independent reviewers?) Poor 0% Fairly good 0% Good 4%-5% Very good 96%-95% P < 0.05 Psychological interventions Robles (2007)15 TEWL (transepidermal water loss) g/m2h 2 hour No stress 18.64 ± 9.71 Stress 21.81 ± 14.06 Stress + support 21.98 ± 6.83 “ns” Koschwanez (2013)16 Reepithelialisation % 7 days 11 days 14 days 17 days 21 days Write about time management 10% 42.1% 90% 95% 100% Write about traumatic experience 27% 76.2% 90% 100% 100% “ns” P = 0.028 “ns” “ns” “ns” Weinman (2008)17 Wound diameter mm 7 days 14 days 21 days Write about time management 4.15 ± 0.48 mm 3.67 ± 0.56 mm 3.27 ± 0.54 mm Write about traumatic experience 4.10 ± 0.62 mm 3.28 ± 0.44 mm 2.98 ± 0.39 mm “ns” P < 0.05 “ns” Broadbent (2012)18 Hydroxyproline level μg/cm of tubing 7 days Normal care 13.56 ± 6.04 Psychological relaxing intervention 22.35 ± 17.48 P = 0.02 Ginandes (2003)19 Doctor’s WAI rating Edema (1-3), erythema (1-3), exudates (1-3); 0 = no signs to 3 = marked signs Total score = 9 Week 1 Week 7 No hypnosis or support 3.07 2.72 Hypnosis 2.89 1.28 P < 0.01 Week 1 Week 7 Supportive attention 3.47 1.94 Hypnosis 2.89 1.28 P < 0.01 Rao (2008)20 Interval before suture removal Number of days 4 weeks Supportive therapy and exercise rehabilitation 13.7 ± 5.3 Yoga program 10.8 ± 3.3 P = 0.03 Drain retention Number of days Variable 6.79 ± 2.4 4.8 ± 1.5 P = 0.001 Pereira (2016)21 Push Ranging from 0-4; 0 = no exudate/scarring tissue 4 = abundant exudate, necrotic tissue 1 month Routinely standardised information 0.4 Empathic patient-centred interview 0.1 P < 0.005 Anxiety level Y (STAY-Y): 20 item self-report instrument which includes separate measures of state and trait anxiety, each subtest ranging from 20 to 80, higher scores indicating greater anxiety Before interview After interview After surgery 38.7 38.5 37.9 33.9 31.6 30.7 P = 0.001 Study Outcome Outcome measurement Follow up time Result control group Result intervention group P-value Systemic treatments Vaxman (1995)10 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Placebo 38 ± 2 29 ± 1 Oral 1.0 g Ascorbic acid and 0.2 g Pantothenic Ascorbic acid 39 ± 1 29 ± 1 “ns” “ns” Fibroblast count Mean number of Fibroblasts per optical field in skin and scar 8 days 21 days 26 ± 2 83 ± 6 28 ± 2 91 ± 7 “ns” “ns” Vaxman (1996)9 Hydroxyproline level μg/mg fry tissue weight 8 days 21 days Oral 0.2 g/day Pantothenic acid and 1.0 g/day Ascorbic acid 39 ± 6 27 ± 6 Oral 0.9 g/day Pantothenic acid and 3 g/day Ascorbic acid 36 ± 4 25 ± 8 “ns” “ns” Fibroblast count n/field 8 days 21 days 28 ± 7 90 ± 31 19 ± 7 80 ± 30 “ns” “ns” Levandovski (2008)11 SSI = either of two distinct criteria for diagnosis: 1. pus could be expressed from the incision; 2. incisional or organ space; with a diagnostic period up to 30 days Yes or no (number of SSI) 30 days Placebo 16/26 Oral 10 mg diazepam 4/61 P = 0.00 State-trait anxiety inventory (STAI): The preoperative score were measured just before surgery; The postoperative anxiety was defined as the average of the score obtained at 6 and 24 hours following surgery Anxiety point scale 0 (no anxiety) - 45.5 (most anxiety) points Patients in the highest quartile were classified as High anxiety and patients in the lowest or equal to the quartile were classifies as Low anxiety 24 hours 41.91 ± 8.88 38.13 ± 6.94 P = 0.01 Künzli (2013)12 Postoperative wound infection (SSI) ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks 30 days (9/178) (22/182) FAS P = 0.018 ITT P = 0.248 Wound healing assessed by treating surgeon? 100 mm visual analog scale (VAS) 0 mm = extremely bad and 100 mm extremely good healing 30 days FAS 90 (80-100) ITT 86 (30-98) 88 (75-100) 80 (17-96) P = 0.147 P = 0.217 Postoperative pain VAS score (0, extremely bad; 100, extremely good). 30 days The median (interquartile range) FAS 3.5 (0–12) ITT 10 (0-35) 7 (0-20) 13 (0-57) P = 0.045 P = 0.092 Melling (2001)13 Wound infection Antibiotics ASEPSIS wound score: purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks 6 weeks Nonwarmed group 19 (14%) Local warming 5 (4%) Systemic warming 8 (6%) All warmed patients (Local+systemic) 13 (5%) P = 0.003 P = 0.026 P = 0.001 Systemic warming 8 (6%) Local warming 5 (4%) “ns” Nonwarmed group 22 (16%) All warmed patients (local+systemic) 18 (57%) P = 0.002 Topical application Zampieri (2010)14 Cosmetic results 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dyschromic signs), 2 = good (flared margins, no dyschromic signs), 3 = very good (excellent cosmetic results, no visible scars) 6 months Petrolatum-based emollient (two independent reviewers?) Poor 7%-5% Fairly good 15%-18% Good 0% Very good 78%-77% Topical vitamin E (two independent reviewers?) Poor 0% Fairly good 0% Good 4%-5% Very good 96%-95% P < 0.05 Psychological interventions Robles (2007)15 TEWL (transepidermal water loss) g/m2h 2 hour No stress 18.64 ± 9.71 Stress 21.81 ± 14.06 Stress + support 21.98 ± 6.83 “ns” Koschwanez (2013)16 Reepithelialisation % 7 days 11 days 14 days 17 days 21 days Write about time management 10% 42.1% 90% 95% 100% Write about traumatic experience 27% 76.2% 90% 100% 100% “ns” P = 0.028 “ns” “ns” “ns” Weinman (2008)17 Wound diameter mm 7 days 14 days 21 days Write about time management 4.15 ± 0.48 mm 3.67 ± 0.56 mm 3.27 ± 0.54 mm Write about traumatic experience 4.10 ± 0.62 mm 3.28 ± 0.44 mm 2.98 ± 0.39 mm “ns” P < 0.05 “ns” Broadbent (2012)18 Hydroxyproline level μg/cm of tubing 7 days Normal care 13.56 ± 6.04 Psychological relaxing intervention 22.35 ± 17.48 P = 0.02 Ginandes (2003)19 Doctor’s WAI rating Edema (1-3), erythema (1-3), exudates (1-3); 0 = no signs to 3 = marked signs Total score = 9 Week 1 Week 7 No hypnosis or support 3.07 2.72 Hypnosis 2.89 1.28 P < 0.01 Week 1 Week 7 Supportive attention 3.47 1.94 Hypnosis 2.89 1.28 P < 0.01 Rao (2008)20 Interval before suture removal Number of days 4 weeks Supportive therapy and exercise rehabilitation 13.7 ± 5.3 Yoga program 10.8 ± 3.3 P = 0.03 Drain retention Number of days Variable 6.79 ± 2.4 4.8 ± 1.5 P = 0.001 Pereira (2016)21 Push Ranging from 0-4; 0 = no exudate/scarring tissue 4 = abundant exudate, necrotic tissue 1 month Routinely standardised information 0.4 Empathic patient-centred interview 0.1 P < 0.005 Anxiety level Y (STAY-Y): 20 item self-report instrument which includes separate measures of state and trait anxiety, each subtest ranging from 20 to 80, higher scores indicating greater anxiety Before interview After interview After surgery 38.7 38.5 37.9 33.9 31.6 30.7 P = 0.001 FAS, full-analysis set; ITT, intention to treat; ns, not significant; SSI, surgical site infections; STAI, state-trait anxiety inventory; TEWL, transepidermal water loss; VAS, visual analog scale; WAI, wound assessment inventory. View Large Systemic Treatments Five articles describing systemic preoperative interventions have been found, three of which resulted in significantly improved wound healing. Vitamin Suppletion In the first two studies, Vaxman investigated the effect of ascorbic acid (also called vitamin C or VC) and pantothenic acid (also called vitamin B5 or VB5) on wound healing in patients undergoing surgery for tattoo removal.9,10 The intervention group received either VC or VB5 and the control group received a placebo. The used dosage differed between the two studies. In the first study, the intervention group received 1.0 g vitamin C and 0.2 g vitamin B5 orally. In the second study, the intervention group received 3 g vitamin C and 0.9 g vitamin B5 orally. The quality of wound healing was assessed by measuring hypertrophy, rigidity, collared, elastic stiffness, and stress. As an index of collagen in tissues, hydroxyproline levels were measured. The protocol included four stages with a total follow up of 80 days. On day 1, the patients started taking the vitamin or placebo. On day 8, a first partial tattoo removal was carried out and skin samples were taken. On day 21, a second resection was performed of the tattoo and the first scar. The patients stopped taking vitamin supplements/placebos at this point. On day 80, the second scars were removed and examined. In both studies, no significant differences were found. In conclusion: no benefit of using ascorbic acid and pantothenic acid preoperatively on wound healing has been found. Lowering Anxiety Levels In the third article in this group, Levandovski et al investigated whether increased anxiety levels may be associated with a higher risk of surgical site infections (SSI).11 The authors postulate that the use of diazepam could reduce the risk of infection by promoting the inflammatory response. This study evaluated whether use of 10 mg diazepam reduced the postoperative SSI and the anxiety levels. Patients were randomly assigned to receive either 10 mg diazepam or placebo orally the night before and 1 hour prior to abdominal hysterectomy surgery. Pre- and postoperative anxiety levels were measured with the State-trait anxiety inventory (STAI). The SSI was diagnosed according to the criteria of the Centers for Disease Control and Prevention with standard follow up of 30 days. Both variables were significantly reduced (SSI P = 0.00, STAI P = 0.01). In conclusion: the use of 10 mg diazepam preoperatively has been found to lower anxiety levels and reduce SSI. Increasing Body Temperature In the last two articles, Künzli12 and Melling13 tested the impact of warming the skin on wound healing. The Künzli study used water-filtered infrared A irradiation (wIRA). wIRA is a special form of heat radiation with high tissue penetration and a low thermal load to the skin surface. This article claimed that thermal heat preoperatively decreases the chance of SSI and that a major advantage of the wIRA vs the application of warming blankets lies in the effective penetration of the applied wIRA energy to the deep subcutaneous tissue up to depths of 2 to 3 cm. The wIRA would also cause higher arterial oxygen tension levels, decreasing surgical wound infections from 11% to 5%. Primary outcome parameters were postoperative wound infection (SSI), wound healing, and postoperative pain after 30 days. The study physician and patient judged the degrees of healing separately, on a 100 mm visual analog scale (VAS), 0 mm = extremely bad and 100 mm extremely good. Subjective wound assessment was performed by the study physician through the ASEPSIS wound score: following criteria such as serous exudate, erythema, pus formation and drainage, and deep wound cracks. Evaluation of pain was daily measured by VAS scores (0, extremely bad; 100, extremely good). Four hundred (400) patients were included and randomly assigned to groups A or B. Group A received standard preoperative care plus an additional exposure to the hydrosun radiator for 20 minutes. Prophylactic antibiotics were given to both groups at least 30 min. before surgery. Exactly the same procedure was performed for patients assigned to control group B, excepting that the patients received only visible light (sham lamp). Primary efficacy analysis was carried out on the basis of an intention-to-treat (ITT) population and a full-analysis set (FAS). The ITT analysis, considering all randomized individuals by conservatively replacing dropouts as occurred SSI. The ITT shows no significant difference between groups A or B on postoperative wound pain, SSI and wound healing 30 days after surgery. The FAS analysis shows significantly less SSI (P = 0.018) and less postoperative pain (P = 0.045) in group A after 30 days. The Melling study used forced-air warming blankets and noncontact, radiant heat dressings to warm the patients. Four hundred sixteen (416) patients were selected and divided into three groups. The first group received standard care and served as control group. The second group was is the systemic group, receiving standard care plus the addition of a minimum of 30 minutes preoperative warming to the whole body using a forced-air warming blanket. The third group received standard care plus local warming by means of noncontact, radiant heat dressing, applied to the planned wound area 30 minutes before surgery. Wounds were classified as infected if there had been a purulent discharge or a painful erythema that lasted for 5 days and was treated with antibiotics within 6 weeks. All wounds were scored using an adapted version of the AEPSIS wound scoring system. The local warming group (P = 0.003) and the systemic warming group (P = 0.026) showed better wound healing compared to the nonwarmed group. The nonwarmed group needed significantly more antibiotics postoperatively than the warmed groups (P = 0.002). No significant difference has been found between the systemic and local warming groups. In conclusion: these studies found that actively warming the patient’s body preoperatively benefits wound healing. Topical Application Only one study describing topical interventions met the inclusion requirements of this review, which found a positive effect of the studied intervention. Vitamin Suppletion Zampieri et al postulate that topical application of vitamin E has been promoted to help wound healing and reduce both fibroblast proliferation and inflammation.14 A total of 428 Caucasian children who were undergoing inguinal surgery were randomly divided in two groups. In one group, topical vitamin E was applied, triwe daily for 15 days prior to surgery and twice daily for 30 days after surgery. The other group received topical petrolatum-based ointment during the same time frame and served as the control group. A four-point scale was used to rate wound healing: 0 = poor (keloids, wound infection, bleeding), 1 = fairly good (flat scar, scab, hyperpigmentation dichromic signs), 2 = good (flared margins, no dichromic signs), 3 = very good (excellent cosmetic results, no visible scars). The assessments of the cosmetic results were performed by the patients’ parents and by a blinded independent surgeon. After a 6-month follow-up period, the children who received preoperative topical vitamin E had shown significantly better wound healing and better cosmetic results than patients who had received topical petrolatum-based ointments (P < 0.05). In conclusion: topical application of vitamin E preoperatively was found to benefit wound healing. Psychological Interventions Seven articles describing the influence of psychological interventions on wound healing were identified, four of them found psychologigal interventions to be beneficial. These studies all aimed at lowering the stress level in different ways. It is said that psychological stress can affect the wound healing, by triggering the inflammatory response and enhancing production of proinflammatory cytokines.22,23 The exact mechanism behind this is still unclear. Social Support Robles examined the effect of a brief laboratory stressor and social support before the stressor on cardiovascular and cortisol responses, and skin barrier recovery after skin disruption.15 Healthy volunteers were randomly assigned to one of three groups. The first group performed a no-stress reading task (control group). The second group performed a Trier social stress test consisting of a 5-minute presentation (control group). The third group received the same stress test and additional support from a confederate before the stressor (intervention group). The intervention took place one hour prior to a tape stripping procedure that disrupted normal skin barrier function. Skin barrier recovery was measured by transepidermal water loss (TEWL, g/m2h) two hours after skin disruption. Increased TEWL reflects decreased barrier function, and decreased TEWL postdisruption indicates increased barrier function. Outcomes in both control groups did not significantly differ from the intervention group. In conclusion: this study found that social support before the stressor did not have an influence on wound healing. Expressive Writing Weinman et al and Koschwanez et al examined whether preoperative expressive writing could result in better wound healing.16,17 The authors suggest that disclosure of traumatic experiences can result in lower stress levels and thereby influence the immune system. In both studies patients were asked to write about a traumatic experience preoperatively for 20 minutes. Surgery consisted of a 4 mm punch biopsy. The wounds were created in the inner, upper arm. The outcomes were differently assessed between the studies. In the Weinman study, wound healing was determined by measuring the wound diameter for 3 weeks. In the Koschwanez study, photographs were taken at different time points for a period of 21 days. A dermatologist scored the amount of reepithelialisation. Although the Weinman study showed slightly smaller wounds in the intervention group than the control group on day 7 and 21 after surgery, these differences were not significant. In the Koschwanez study, the intervention group showed significantly more complete reepithelialisation than the control group on day 11 only. On days 7, 14, 17, and 21 there were no significant differences between the groups. In conclusion: no advantage of preoperative expressive writing aimed at lowering stress levels to increase wound healing has been found. Relaxation Exercises Three studies tried to increase the relaxation levels through using relaxation exercises.18-20 Broadbent et al attempted to achieve this by deep breathing techniques. The intervention group met with a health psychologist for 45 minutes, who instructed the participants in deep breathing techniques. Each patient was asked to take a CD home with recordings of the script and listen to it every day, starting three days prior to surgery (laparoscopic cholecystectomy), until seven days after. The control group received standard care. The authors measured the hydroxyproline and stress levels. Both were measured before and after the procedure. The intervention group showed significantly higher hydroxyproline levels than the control group. However, changes in perceived stress were not significantly correlated with hydroxyproline deposition. The authors notice that lack of an association between change in stress with hydroxyproline suggests that the effects of the intervention are not simply due to stress reduction. In conclusion: no association between perceived stress and hydroxyproline levels have been found following deep breathing exercises. Ginandes et al attempted to increase relaxation levels by a hypnotic intervention before surgery in patients with macromastia who needed a mammaplasty. Three groups were formed. The first group received hypnotic intervention during 8 half-hour weekly sessions with the study clinician commencing 2 weeks prior to surgery and continuing through 6 weeks postoperatively. The second group received supportive attention concerning the operation prior and postsurgery at the same time points as the first group. The third group served as a control group and received usual care. The quality of the wound healing was measured by the WAI (wound assessment inventory) rating by three blinded independent surgeons. After 7 weeks of follow up, the hypnosis group scored significantly lower on the WAI rating, denoting the greatest healing over time, followed by the supportive attention group. The usual care control group obtained the highest WAI scores indicating the smallest degree of healing. In conclusion: additional hypnotic intervention has been found to show improved healing over time compared to usual care. Rao et al evaluated the effect of a yoga intervention on postoperative wound healing in patients who were recently diagnosed with breast cancer and who received surgery as primary treatment and needed a mastectomy. Two groups were randomly formed: an intervention group who received a yoga program 1 day prior to surgery and 3 times a week postsurgery for the duration of 4 weeks. The control group received supportive therapy and exercise rehabilitation instead. The postoperative outcome was the interval for suture removal and the number of days before drain removal. The sutures were removed when the approximated margins of the wound were closed and the drain was removed when production reduced to <50 cc/48 hours. In both outcomes measures, the intervention group scored significantly better than the control group (P = 0.001 for drain removal, P = 0.03 for suture removal). In conclusion: this study found a yoga program starting before surgery to benefit wound healing. Providing Empathic Patient-Centered Information In the last study of this group, Pereira et al investigated the influence of an empathic patient-centered approach of providing information about the scheduled surgery on wound healing in ambulatory surgery.21 One month prior to surgery, the intervention group received personalized information about the operation through an empathic patient-centered interview, which consisted of eliciting and exploring patients concerns about the surgery for 15 minutes. The control group received the routinely delivered standardized information in the same time frame as the intervention group. The surgical wound healing was measured through PUSH and the state of anxiety was assessed with the state-trait anxiety inventory form Y (STAY-Y). One month after surgery, the intervention group showed significantly better wound tissue than the control group (P < 0.005) and also significantly lower levels of anxiety than the control group (P = 0.001). In conclusion: an empathic patient-centered approach of providing information has been found to benefit wound healing and lower the anxiety level. DISCUSSION Based on the available literature, little attention has historically been paid to the influence of preoperative interventions on wound healing and scar formation. Most published studies could not be included because they focused on intra- or postoperative interventions, or on known risk factors, such as smoking and diabetes. Interestingly, only 13 studies have been found on preoperative interventions that met the selection criteria. This may be indicative of a general historical lack of interest in the topic, despite of the possible advantages of more extensive knowledge in daily patient care. Both in the literature and surgical practice, most attention is paid to intraoperative and postoperative interventions. Classic postoperative wound management consists of different types of dressings, antibiotic treatment, and debridement. Relatively new treatments, such as negative pressure wound therapy (NPWT) and oxygen therapy (though still controversial) have improved treatment of poorly healing wounds.24 Preoperative wound management has focused on prevention of SSI and excessive scar formation. Classic preoperative management involves antibiotic prophylaxis (depending on the type of operation, given <120 min before the incision), surgical hand preparation by scrubbing (with a suitable antimicrobial soap and water or using a suitable alcohol based hand rub), and maintaining the least possible contamination of the surgical field.25 The limited number and quality of the studies included in this review limit the strength of the results found. Moreover, the great heterogeneity of the included patient groups (ie, different interventions, age ranging from 2 to 87 years) and the broad spectrum of outcome measurements made it impossible to compare the findings of different studies. Nevertheless, evidence that preoperative interventions have a positive influence on wound healing has been found. Individually, the studies allow for some interesting observations to be made, as eight of the 13 studies show a significantly better wound healing after the investigated preoperative intervention. Five studies described systemic interventions. Four of the five studies showed a significantly better wound healing for the intervention group. In the first study, Levandovski et al postulate that increased anxiety levels cause significantly more surgical site infections (SSI). The authors hypothesize that diazepam use could therefore reduce the risk of infection. Diazepam modulates the immune system involved in the attenuation of behavioral stress response induced by corticotrophin releasing hormone (CRH), responsible for immune suppression, but the correlation between anxiety and better wound healing would prove that lowering the anxiety level itself will benefit the wound healing. Flores et al state that mild perioperative hypothermia is associated with infection of the surgical wound and its prevention is therefore justified.26 Bacterial destruction depends on adequate tissue perfusion. Perioperative hypothermia causes vasoconstriction, reducing nutrient and oxygen supply to wounds and increasing frequency of surgical wound infection. To combat hypothermia three different effective ways have been identified: local water-filtered infrared and irradiation; forced-air warming blankets; and local noncontact, radiant heat dressing. More studies must be done to compare the different interventions and cost-effectiveness analyses must also be carried out. Only one study described topical application of an agent at the surgery site. This study showed that preoperatively applied topical vitamin E indeed improved the wound healing in Caucasian children. This may be a safe and beneficial addition to usual patient preparation. No studies have been found indicating a similar effect in adults and no cost-effectiveness analysis was carried out. In the literature, debate remains as to the effect of topical vitamin E on wound healing. A lot of research has been done on its effect when applied after surgery or the effect of topical vitamin E on burn victims.27 Seven studies have been found in the psychological intervention group. Four of these seven show significant differences. Recent research shows extended knowledge about the negative effects of stress on health outcomes. Stress affects the wound healing, by triggering the glucocorticoids and inflammatory response and enhancing production of cortisol/corticosterone and proinflammatory cytokines.22,23 These two primary pathways affect the progress of the normal stages of wound healing.28 The included studies show that lower anxiety levels and a relaxed preoperative state of mind may benefit wound healing. Successful ways to achieve this may be yoga intervention (Rao), deep breathing techniques (Broadbent), hypnotic intervention (Ginandes), or better empathic-centered approach to the patient (Pereira). In all these studies there were two potential confounders, the small sample size and the intrinsic belief in the therapeutic benefits of the studied interventions. Both historically and presently, surgical patient care has been focused on intra- and postoperative phases. This review shows that wound healing after surgery can be improved by focusing on preoperative care to adequately prepare the patient for surgery. CONCLUSION Surprisingly, little attention has historically been paid to the influence of preoperative interventions on wound healing following surgery. These interventions may however indeed have a positive effect on wound healing. In selected cases, wound healing has been found to benefit from a higher preoperative body temperature, topical vitamin E application, and low patient stress levels. However, additional prospective studies will be needed to further identify preoperative interventions that are beneficial for the improvement of wound healing and scar formation in the general patient population. Supplementary Material This article contains supplementary material located online at www.aestheticsurgeryjournal.com. Disclosures The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. Funding The authors received no financial support for the research, authorship, and publication of this article. REFERENCES 1. Atiyeh BS , Ioannovich J , Al-Amm CA , El-Musa KA , Dham R . Improving scar quality: a prospective clinical study . Aesthetic Plast Surg . 2002 ; 26 ( 6 ): 470 - 476 . Google Scholar CrossRef Search ADS PubMed 2. van der Veer WM , Bloemen MC , Ulrich MM et al. Potential cellular and molecular causes of hypertrophic scar formation . Burns . 2009 ; 35 ( 1 ): 15 - 29 . Google Scholar CrossRef Search ADS PubMed 3. Gill JF , Yu SS , Neuhaus IM . Tobacco smoking and dermatologic surgery . J Am Acad Dermatol . 2013 ; 68 ( 1 ): 167 - 172 . Google Scholar CrossRef Search ADS PubMed 4. Poetker DM , Reh DD . A comprehensive review of the adverse effects of systemic corticosteroids . Otolaryngol Clin North Am . 2010 ; 43 ( 4 ): 753 - 768 . Google Scholar CrossRef Search ADS PubMed 5. Powers JG , Higham C , Broussard K , Phillips TJ . Wound healing and treating wounds: Chronic wound care and management . J Am Acad Dermatol . 2016 ; 74 ( 4 ): 607 - 25; quiz 625 . Google Scholar CrossRef Search ADS PubMed 6. Kanasi E , Ayilavarapu S , Jones J . The aging population: demographics and the biology of aging . Periodontol 2000 . 2016 ; 72 ( 1 ): 13 - 18 . Google Scholar CrossRef Search ADS PubMed 7. Hagen KS , Treston-Aurand J . A comparison of two skin preps used in cardiac surgical procedures . AORN J . 1995 ; 62 ( 3 ): 393 - 402 . Google Scholar CrossRef Search ADS PubMed 8. Ueno C , Hunt TK , Hopf HW . Using physiology to improve surgical wound outcomes . Plast Reconstr Surg . 2006 ; 117 ( 7 Suppl ): 59S - 71S . Google Scholar CrossRef Search ADS PubMed 9. Vaxman F , Olender S , Lambert A , Nisand G , Grenier JF . Can the wound healing process be improved by vitamin supplementation? Experimental study on humans . Eur Surg Res . 1996 ; 28 ( 4 ): 306 - 314 . Google Scholar CrossRef Search ADS PubMed 10. Vaxman F , Olender S , Lambert A et al. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial . Eur Surg Res . 1995 ; 27 ( 3 ): 158 - 166 . Google Scholar CrossRef Search ADS PubMed 11. Levandovski R , Ferreira MB , Hidalgo MP , Konrath CA , da Silva DL , Caumo W . Impact of preoperative anxiolytic on surgical site infection in patients undergoing abdominal hysterectomy . Am J Infect Control . 2008 ; 36 ( 10 ): 718 - 726 . Google Scholar CrossRef Search ADS PubMed 12. Künzli BM , Liebl F , Nuhn P , Schuster T , Friess H , Hartel M . Impact of preoperative local water-filtered infrared A irradiation on postoperative wound healing: a randomized patient- and observer-blinded controlled clinical trial . Ann Surg . 2013 ; 258 ( 6 ): 887 - 894 . Google Scholar CrossRef Search ADS PubMed 13. Melling AC , Ali B , Scott EM , Leaper DJ . Effects of preoperative warming on the incidence of wound infection after clean surgery: a randomised controlled trial . Lancet . 2001 ; 358 ( 9285 ): 876 - 880 . Google Scholar CrossRef Search ADS PubMed 14. Zampieri N , Zuin V , Burro R , Ottolenghi A , Camoglio FS . A prospective study in children: Pre- and post-surgery use of vitamin E in surgical incisions . J Plast Reconstr Aesthet Surg . 2010 ; 63 ( 9 ): 1474 - 1478 . Google Scholar CrossRef Search ADS PubMed 15. Robles TF . Stress, social support, and delayed skin barrier recovery . Psychosom Med . 2007 ; 69 ( 8 ): 807 - 815 . Google Scholar CrossRef Search ADS PubMed 16. Koschwanez HE , Kerse N , Darragh M , Jarrett P , Booth RJ , Broadbent E . Expressive writing and wound healing in older adults: a randomized controlled trial . Psychosom Med . 2013 ; 75 ( 6 ): 581 - 590 . Google Scholar CrossRef Search ADS PubMed 17. Weinman J , Ebrecht M , Scott S , Walburn J , Dyson M . Enhanced wound healing after emotional disclosure intervention . Br J Health Psychol . 2008 ; 13 ( Pt 1 ): 95 - 102 . Google Scholar CrossRef Search ADS PubMed 18. Broadbent E , Kahokehr A , Booth RJ et al. A brief relaxation intervention reduces stress and improves surgical wound healing response: a randomised trial . Brain Behav Immun . 2012 ; 26 ( 2 ): 212 - 217 . Google Scholar CrossRef Search ADS PubMed 19. Ginandes C , Brooks P , Sando W , Jones C , Aker J . Can medical hypnosis accelerate post-surgical wound healing? Results of a clinical trial . Am J Clin Hypn . 2003 ; 45 ( 4 ): 333 - 351 . Google Scholar CrossRef Search ADS PubMed 20. Rao RM , Nagendra HR , Raghuram N et al. Influence of yoga on postoperative outcomes and wound healing in early operable breast cancer patients undergoing surgery . Int J Yoga . 2008 ; 1 ( 1 ): 33 - 41 . Google Scholar CrossRef Search ADS PubMed 21. Pereira L , Figueiredo-Braga M , Carvalho IP . Preoperative anxiety in ambulatory surgery: The impact of an empathic patient-centered approach on psychological and clinical outcomes . Patient Educ Couns . 2016 ; 99 ( 5 ): 733 - 738 . Google Scholar CrossRef Search ADS PubMed 22. McGhee LL , Maani CV , Garza TH , DeSocio PA , Gaylord KM , Black IH . The relationship of intravenous midazolam and posttraumatic stress disorder development in burned soldiers . J Trauma . 2009 ; 66 ( 4 Suppl ): S186 - S190 . Google Scholar CrossRef Search ADS PubMed 23. Zhou D , Kusnecov AW , Shurin MR , DePaoli M , Rabin BS . Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis . Endocrinology . 1993 ; 133 ( 6 ): 2523 - 2530 . Google Scholar CrossRef Search ADS PubMed 24. Rabello FB , Souza CD , Farina Júnior JA . Update on hypertrophic scar treatment . Clinics (Sao Paulo) . 2014 ; 69 ( 8 ): 565 - 573 . Google Scholar CrossRef Search ADS PubMed 25. Allegranzi B , Bischoff P , de Jonge S et al. ; WHO Guidelines Development Group . New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective . Lancet Infect Dis . 2016 ; 16 ( 12 ): e276 - e287 . Google Scholar CrossRef Search ADS PubMed 26. Flores-Maldonado A , Medina-Escobedo CE , Ríos-Rodríguez HM , Fernández-Domínguez R . Mild perioperative hypothermia and the risk of wound infection . Arch Med Res . 2001 ; 32 ( 3 ): 227 - 231 . Google Scholar CrossRef Search ADS PubMed 27. Khoosal D , Goldman RD . Vitamin E for treating children’s scars. Does it help reduce scarring ? Can Fam Physician . 2006 ; 52 : 855 - 856 . Google Scholar PubMed 28. Christian LM , Graham JE , Padgett DA , Glaser R , Kiecolt-Glaser JK . Stress and wound healing . Neuroimmunomodulation . 2006 ; 13 ( 5-6 ): 337 - 346 . Google Scholar CrossRef Search ADS PubMed © 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Aesthetic Surgery JournalOxford University Press

Published: Mar 27, 2018

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