TY - JOUR
AU - Phty, Jennifer A Alison, PhD, MSc, Dip
AB - Abstract Objective The purpose of this review was to determine the effect of CLA infusion post cardiac surgery on pain, time to ambulation, severe adverse events, patient satisfaction, time to extubation, length of stay in the intensive care unit and in the hospital, total narcotic consumption, and pulmonary function. Design Systematic review with meta-analysis (PROSPERO CRD42014010188). Methods We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; Allied and Complementary Medicine (AMED); and PsycINFO; as well as hand-searching cardiothoracic surgery and anesthetic journals and meeting abstracts. Results Ten eligible trials with a total of 546 participants were identified. Meta-analyses showed that CLA infusion significantly reduced the total mean visual analog pain score at 72 hours (mean difference [MD] = –14.31 mm, 95% confidence interval [CI] = –25.59 to –3.03); time to ambulation (MD = –2.81 hours, 95% CI = –5.23 to –0.4); morphine requirement (MD = –10.19 mg, 95% CI = –11.80 to –8.58) but did not reduce time to ambulate to chair (MD = –1.65 hours, 95% CI = –4.04 to 0.74); time to extubation (MD = –0.18 hours, 95% CI = –1.24 to 0.89); length of ICU stay (MD = 0.9 hours, 95% CI = –2.96 to 4.75); and hospital length of stay (MD = –0.59 days, 95% CI = –1.24 to 0.07). There were insufficient data to perform a meta-analysis on severe adverse events, patient satisfaction, or pulmonary function. Conclusions CLA infusion after cardiac surgery reduces pain score at 72 hours, shortens time to ambulation, and reduces morphine consumption at 48 hours. Cardiac Surgery, Anesthetics Local, Acute Pain and Postoperative Pain Introduction Cardiac surgery performed via median sternotomy results in pain most commonly in the sternal area [1,2], inferior third of the sternum [3], epigastric area [2], and back of shoulders [2]. The pain in the sternal, inferior third of the sternum or epigastric area is most likely due to the surgical incision itself and also the presence of chest/mediastinal tubes [2,4–6]. Pain at the back of shoulders could be due to prolonged sternal retraction [2], which may lead to costochondritis or rib joint dislocation [4]. Pain intensity is reported to be highest on postoperative day 1 and 2, with a significant decrease in intensity on day 3 and onwards [2,6,7]. Patients reported most severe pain while coughing, moving, turning in bed, getting out of bed and during deep breathing, using incentive spirometry, or sitting in a chair [7]. All of these maneuvers are a part of physiotherapy treatment to avoid postoperative pulmonary complications and early rehabilitation post–cardiac surgery. Poorly controlled pain post–cardiac surgery may contribute to pulmonary complications, reduction in pulmonary function, and increased wound infection rates [4]. Effective pain control may facilitate earlier patient ambulation and participation in physiotherapy treatments [8] and contribute to better clinical outcomes such as reduced pulmonary complications [4,9], as well as increasing patient satisfaction [4,8]. One method of improving postoperative analgesia and reducing the need for opioids for pain relief is a technique where the surgeon places one or two multihole catheters on or into the wound prior to wound closure for the continuous infusion of local anesthetic via a pump device. Continuous local anesthetic (CLA) infusion has been shown to be effective in pain relief post–laparoscopic cholecystectomy [10], open groin hernia repair [11], gynecological surgery [9–11], open colonic resection [11], and orthopedic surgery [9,11]. However, there has been no systematic review with meta-analysis on the effects of CLA infusion in cardiac surgery. The aim of this systematic review was to determine the effect of CLA infusion on pain and mobilization post–cardiac surgery via sternotomy. Methods Search Strategy This systematic review used the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines. The review protocol was registered on the PROSPERO Website (http://www.crd.york.ac.uk/PROSPERO) prior to screening and data extraction (registration No. CRD42014010188) We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue November 2013); MEDLINE (1946 to week 4 January 2014); EMBASE (1980 to 2014 February 3); CINAHL (1981 to January 2014); Allied and Complementary Medicine (AMED; 1985 to January 2014); and PsycINFO (1967 to January week 3, 2014); as well as hand-searching cardiothoracic surgery and anesthetic journals and meeting abstracts. We also used the cited/bibliography of retrieved articles to identify further relevant trials. No language restrictions were used. We reran the search on above databases for any updated trials to June–August 2016. Search terms used are shown in Supplementary Table S1. Inclusion, Exclusion, and Selection Criteria Types of Studies Randomized controlled trials (RCTs). Types of Participants Trials including patients age 18 years or older undergoing cardiac surgery, valve repair/replacement, combined coronary artery bypass graft surgery (CABG) and valve surgery, aortic arch repair, or any cardiac surgery via sternotomy and having continuous local anesthetic infusion compared with either saline infusion, no infusion, or usual care as postoperative analgesia. Types of Interventions Intervention Group. Studies were included if they were RCTs of CLA infusion in cardiac surgery performed via sternotomy. The CLA infusion must have been at the site of the sternotomy wound, either tunnelled parasternally or adjacent to the sternotomy wound. The medication for CLA infusion could be any local anesthetic agent. Other analgesic supplements such as opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) were allowed. The precise nature of anesthetic (medication, rate, dosage, location of the catheter) was recorded wherever possible. Comparator/Control Group. The comparator group could be either a placebo group with same infusion device using saline infusion or a control group using patient-controlled analgesia (PCA) with opioids or local anesthetics agents or any other method of pain relief. Types of Outcome Measures RCTs reporting any of the following primary and secondary outcomes were eligible for inclusion. Primary outcomes Pain scores at rest, during movement, during or after physiotherapy sessions, or at any other point in time Distance walked or any other measures of activity Severe adverse events, such as wound infection, deep sternal wound infection, toxicity to the infusion, postoperative complication related to the technique of insertion of the delivery device, or local anesthetics Secondary outcomes Patient satisfaction with pain management Time to extubation Length of intensive care unit (ICU) stay Length of hospital stay Total narcotic consumption, PCA usage, other pain medication Pulmonary function Selection of Studies Two review authors (SH and MM) independently coded studies identified in the literature searches for relevance by examining title, abstract, and keywords fields as follows: INCLUDE: study categorically meets all review criteria; UNCLEAR: study appears to meet some review criteria but insufficient information available to categorically determine relevance; and EXCLUDE: study does not categorically meet all review criteria. Two reviewers (SH, MM) used a full text of studies in categories 1 and 2 to decide on study inclusion. Disagreements were resolved by consensus or independent reviewer (JA). Data Extraction, Assessment, and Analysis Data Extraction and Management Data were extracted independently by two review authors using the data extraction form before being entered into RevMan (version 5) by the primary reviewer (SH), with random checks on accuracy. Data included characteristics of included studies (methods, participants, interventions, and outcomes) and results of the included studies. Where applicable, authors of included studies were contacted to verify the data extracted for their study or to provide details of missing data. Assessment of Risk Bias in Included Studies We evaluated the methodological quality of the studies by the type of randomization, sequence generation for randomization, allocation concealment, blinding, and completeness of trial data. Disagreements were resolved by consensus or third reviewer. Authors of included studies were contacted to clarify where study data were unclear. Data Synthesis We performed a test for heterogeneity of studies included in the meta-analyses. For continuous variables of pain score, walking distance, patient satisfaction, length of stay in ICU and hospital, time to extubation, total narcotic consumption or morphine equivalent, and pulmonary function, either the mean change from baseline (95% confidence interval [CI]) or the mean postintervention values and standard deviation for each group were used for the meta-analyses. Odds ratios were calculated for binary outcomes such as failure of regimen or adverse events. Subgroup analysis was conducted, if required, to explore possible sources of heterogeneity. Results Study Selection Process The flow diagram of study selection is shown in Figure 1. Of 518 possible trials, 10 studies were included in this review [1,3,8,12–18]. One study was a dissertation paper [1]. In total, 546 patients were randomized to continuous infusion of local anesthetics or placebo/usual care. Data from nine studies were included in the quantitative synthesis. Figure 1 View largeDownload slide PRISMA flow chart of the study selection process. Figure 1 View largeDownload slide PRISMA flow chart of the study selection process. Study Characteristics Characteristics of included studies are shown in Table 1. Participants’ mean age ranged from 54 to 68 years. All participants underwent elective cardiac surgery via median sternotomy. Six studies included a majority of male patients [1,8,13–16]. Table 1 Characteristics of included trials (N = 10) Authors Surgery Choice of local anesthetics Placement of catheter Intervention group Control group Outcome measures Results Dowling et al. (2003) [15] Elective CABG/CABG+TMR Ropivacaine Catheters placed anterior to the sternum, connected to elastomeric infusion pump 0.2% at 4 mL/h for 48 h 16 patients Same catheter and device, infusion with saline 19 patients Narcotic analgesia requirements; pain scores; pulmonary function; time to extubation; LOS in ICU and hospital and severe adverse events Less narcotic usage; lower VAS score; lower mean hospital LOS in ropivacaine group. No significant differences between groups in pulmonary function; time to extubation; LOS in ICU or wound infection. No drug toxicity in either group. White et al. (2003) [3] CABG, valve replacement procedures, ASD repairs, and atrial myxoma excision procedure Bupivacaine First catheter placed in the subfascial plane above sternum, and second above fascia in the subcutaneous tissue at sternotomy incision site and connected to elastomeric infusion pump 0.25% (12 patients) and 0.5% (12 patients) at 4 mL/h for 48 h Same catheter and device, infusion with saline 12 patients Pain score; opioid dosage; patient satisfaction; nausea and vomit; time to extubation; ambulation with assistance; discharge from ICU and hospital times and blood sample Significantly lower pain score, faster to ambulate in both bupivacaine groups; significantly less opioid consumption, more participant satisfaction in the 0.5% bupivacaine group; no significant differences between groups in nausea and vomit and time to extubation and ICU stay; serum concentrations were lower than toxicity level in both bupivacaine groups. Magnano et al. (2005) [17] Cardiac surgery via sternotomy Bupivacaine One catheter anterior to the sternum after sternal wiring 0.5% 5 mL/h for 36 h 23 patients Same catheter without any local anesthetic 23 patients Assisted ventilation time; pain score; location of pain; consumption of intravenous analgesic drugs Assisted ventilation time was significantly longer in bupivacaine group. No significant difference in VAS or morphine consumption in between groups. Pain was generally localized in inferior third sternum. Ghavidel et al. (2009) [16] Elective coronary artery bypass graft surgery Bupivacaine One catheter was placed in soft presternal tissue after sternal closure then connected to elastomeric infusion pump 0.25% at 2 mL/h for 72 h 20 patients No catheter, no infusion 20 patients Pain score; participant satisfaction; narcotic and analgesic dosage; duration of mechanical ventilation and intubation; LOS in ICU and hospital and wound problems Significantly lower mean VAS; higher participant satisfaction; higher rate of pain reduction and less narcotics during POD1 in bupivacaine group. No significant differences between groups in ICU and hospital LOS; mean doses of opioid during ICU stay; duration of ventilation and intubation. Nil wound problems in both groups. Langley (2009) [1] Elective CABG via sternotomy Bupivacaine 2 catheters were inserted percutaneously via subpectoral tunnelling on either side of sternum, and connected to elastomeric infusion pump 0.5% at 4 mL/h for 96 h Off-pump CABG 28 patients On-pump CABG 26 patients Same catheter and device, infusion with saline Off-pump CABG 29 patients On-pump CABG 25 patients Pain intensity; location of pain; opioid consumption; time to extubation; time to ambulate to chair; LOS in ICU and hospital and nausea and vomit Pain mostly in sternal region. Nonsignificant outcomes between groups in all of the specified outcomes. Eljezi et al. (2012) [8] CABG or valve replacement via sternotomy Ropivacaine 2 catheters tunnelled subcutaneously, below pectoral muscles over the costosternal margin parallel to the sternotomy incision and connected to elastomeric infusion pump 0.2% at 4 mL/h for 48 h 20 patients Same catheters and device, infusion with saline 19 patients Pain score; morphine consumption; patient satisfaction; nausea and vomiting; spirometry; physiotherapist perception to early mobilization; total ropivacaine plasma concentration Significantly lower pain at mobilization; significantly less morphine consumption and higher satisfaction in ropivacaine group. Significantly more participants ambulated early. No significant difference between groups in nausea and vomiting; spirometry; low total ropivacaine plasma concentration. Abbasi et al. (2012) [12] Elective off pump CABG Bupivacaine 2 catheters were placed at the median sternotomy incision site and connected to elastomeric infusion pump 0.5% at 4 mL/h for 48 h 18 patients Same catheters and device, infusion with saline 18 patients Pain relief; time to extubation; length of ICU and hospital stay; need of opioid analgesics and time to ambulate No significant difference between groups in pain relief; time to extubation and ICU LOS. Significant reduction in LOS in hospital; opioid analgesics and faster to ambulate in bupivacaine group. Agarwal et al. (2013) [13] Various cardiac surgery via sternotomy Ropivacaine 2 catheters in the sternal wound below the subcutaneous tissue, either side of the sternotomy, connected to single pump 0.3% at 4 mL/h for 64 h 44 patients Same catheter and device, infusion with normal saline 41 patients Time to extubation; LOS of ICU and hospital; pain score; opioid requirement; nausea and vomiting; pulmonary function testing and safety No significant difference between groups in all outcomes. Sternal wound infection in ropivacaine group was higher than historical institution rate. Dignan et al. (2014) [14] Elective CABG Ropivacaine 2 catheters tunnelled parasternally in a subpectoral position, connected to elastomeric infusion pump 0.5% at 4 mL/h for 96 h 26 patients Same catheters and device, infusion with saline 25 patients usual care group did not receive any intervention 24 patients Proportion of patients remaining in ICU for more than 48 hours; extubation time; ICU and hospital LOS; SAE; morphine equivalent dose; acute pain; pain scores No significant difference between groups in all outcomes. Nasr et al. (2015) [18] Elective CABG Bupivacaine 1 catheter anterior to the sternum above fascia in the subcutaneous tissue, connected to elastomeric infusion pump 0.25% at 5 mL/h for 48 h 19 patients Same catheter and device, infusion with saline 18 patients Morphine requirements; pain score; extubation time; incidence of wound infection; ICU and hospital stay and bupivacaine level in blood Significantly lower morphine requirement; pain scores; extubation time in bupivacaine group. No significant difference between groups in length of ICU and hospital stay. Plasma concentration did not reach toxic level. No incidence of sternal infection or delayed wound healing in both groups. Authors Surgery Choice of local anesthetics Placement of catheter Intervention group Control group Outcome measures Results Dowling et al. (2003) [15] Elective CABG/CABG+TMR Ropivacaine Catheters placed anterior to the sternum, connected to elastomeric infusion pump 0.2% at 4 mL/h for 48 h 16 patients Same catheter and device, infusion with saline 19 patients Narcotic analgesia requirements; pain scores; pulmonary function; time to extubation; LOS in ICU and hospital and severe adverse events Less narcotic usage; lower VAS score; lower mean hospital LOS in ropivacaine group. No significant differences between groups in pulmonary function; time to extubation; LOS in ICU or wound infection. No drug toxicity in either group. White et al. (2003) [3] CABG, valve replacement procedures, ASD repairs, and atrial myxoma excision procedure Bupivacaine First catheter placed in the subfascial plane above sternum, and second above fascia in the subcutaneous tissue at sternotomy incision site and connected to elastomeric infusion pump 0.25% (12 patients) and 0.5% (12 patients) at 4 mL/h for 48 h Same catheter and device, infusion with saline 12 patients Pain score; opioid dosage; patient satisfaction; nausea and vomit; time to extubation; ambulation with assistance; discharge from ICU and hospital times and blood sample Significantly lower pain score, faster to ambulate in both bupivacaine groups; significantly less opioid consumption, more participant satisfaction in the 0.5% bupivacaine group; no significant differences between groups in nausea and vomit and time to extubation and ICU stay; serum concentrations were lower than toxicity level in both bupivacaine groups. Magnano et al. (2005) [17] Cardiac surgery via sternotomy Bupivacaine One catheter anterior to the sternum after sternal wiring 0.5% 5 mL/h for 36 h 23 patients Same catheter without any local anesthetic 23 patients Assisted ventilation time; pain score; location of pain; consumption of intravenous analgesic drugs Assisted ventilation time was significantly longer in bupivacaine group. No significant difference in VAS or morphine consumption in between groups. Pain was generally localized in inferior third sternum. Ghavidel et al. (2009) [16] Elective coronary artery bypass graft surgery Bupivacaine One catheter was placed in soft presternal tissue after sternal closure then connected to elastomeric infusion pump 0.25% at 2 mL/h for 72 h 20 patients No catheter, no infusion 20 patients Pain score; participant satisfaction; narcotic and analgesic dosage; duration of mechanical ventilation and intubation; LOS in ICU and hospital and wound problems Significantly lower mean VAS; higher participant satisfaction; higher rate of pain reduction and less narcotics during POD1 in bupivacaine group. No significant differences between groups in ICU and hospital LOS; mean doses of opioid during ICU stay; duration of ventilation and intubation. Nil wound problems in both groups. Langley (2009) [1] Elective CABG via sternotomy Bupivacaine 2 catheters were inserted percutaneously via subpectoral tunnelling on either side of sternum, and connected to elastomeric infusion pump 0.5% at 4 mL/h for 96 h Off-pump CABG 28 patients On-pump CABG 26 patients Same catheter and device, infusion with saline Off-pump CABG 29 patients On-pump CABG 25 patients Pain intensity; location of pain; opioid consumption; time to extubation; time to ambulate to chair; LOS in ICU and hospital and nausea and vomit Pain mostly in sternal region. Nonsignificant outcomes between groups in all of the specified outcomes. Eljezi et al. (2012) [8] CABG or valve replacement via sternotomy Ropivacaine 2 catheters tunnelled subcutaneously, below pectoral muscles over the costosternal margin parallel to the sternotomy incision and connected to elastomeric infusion pump 0.2% at 4 mL/h for 48 h 20 patients Same catheters and device, infusion with saline 19 patients Pain score; morphine consumption; patient satisfaction; nausea and vomiting; spirometry; physiotherapist perception to early mobilization; total ropivacaine plasma concentration Significantly lower pain at mobilization; significantly less morphine consumption and higher satisfaction in ropivacaine group. Significantly more participants ambulated early. No significant difference between groups in nausea and vomiting; spirometry; low total ropivacaine plasma concentration. Abbasi et al. (2012) [12] Elective off pump CABG Bupivacaine 2 catheters were placed at the median sternotomy incision site and connected to elastomeric infusion pump 0.5% at 4 mL/h for 48 h 18 patients Same catheters and device, infusion with saline 18 patients Pain relief; time to extubation; length of ICU and hospital stay; need of opioid analgesics and time to ambulate No significant difference between groups in pain relief; time to extubation and ICU LOS. Significant reduction in LOS in hospital; opioid analgesics and faster to ambulate in bupivacaine group. Agarwal et al. (2013) [13] Various cardiac surgery via sternotomy Ropivacaine 2 catheters in the sternal wound below the subcutaneous tissue, either side of the sternotomy, connected to single pump 0.3% at 4 mL/h for 64 h 44 patients Same catheter and device, infusion with normal saline 41 patients Time to extubation; LOS of ICU and hospital; pain score; opioid requirement; nausea and vomiting; pulmonary function testing and safety No significant difference between groups in all outcomes. Sternal wound infection in ropivacaine group was higher than historical institution rate. Dignan et al. (2014) [14] Elective CABG Ropivacaine 2 catheters tunnelled parasternally in a subpectoral position, connected to elastomeric infusion pump 0.5% at 4 mL/h for 96 h 26 patients Same catheters and device, infusion with saline 25 patients usual care group did not receive any intervention 24 patients Proportion of patients remaining in ICU for more than 48 hours; extubation time; ICU and hospital LOS; SAE; morphine equivalent dose; acute pain; pain scores No significant difference between groups in all outcomes. Nasr et al. (2015) [18] Elective CABG Bupivacaine 1 catheter anterior to the sternum above fascia in the subcutaneous tissue, connected to elastomeric infusion pump 0.25% at 5 mL/h for 48 h 19 patients Same catheter and device, infusion with saline 18 patients Morphine requirements; pain score; extubation time; incidence of wound infection; ICU and hospital stay and bupivacaine level in blood Significantly lower morphine requirement; pain scores; extubation time in bupivacaine group. No significant difference between groups in length of ICU and hospital stay. Plasma concentration did not reach toxic level. No incidence of sternal infection or delayed wound healing in both groups. Characteristics of included trials (N = 10). ASD = atrial septal defect; CABG = coronary artery bypass graft surgery; ICU = intensive care unit; LOS = length of stay; PCA = patient-controlled analgesia; POD = postoperative day; SAE = severe adverse event; TMR = transmyocardial revascularization; VAS = visual analog scale. Table 1 Characteristics of included trials (N = 10) Authors Surgery Choice of local anesthetics Placement of catheter Intervention group Control group Outcome measures Results Dowling et al. (2003) [15] Elective CABG/CABG+TMR Ropivacaine Catheters placed anterior to the sternum, connected to elastomeric infusion pump 0.2% at 4 mL/h for 48 h 16 patients Same catheter and device, infusion with saline 19 patients Narcotic analgesia requirements; pain scores; pulmonary function; time to extubation; LOS in ICU and hospital and severe adverse events Less narcotic usage; lower VAS score; lower mean hospital LOS in ropivacaine group. No significant differences between groups in pulmonary function; time to extubation; LOS in ICU or wound infection. No drug toxicity in either group. White et al. (2003) [3] CABG, valve replacement procedures, ASD repairs, and atrial myxoma excision procedure Bupivacaine First catheter placed in the subfascial plane above sternum, and second above fascia in the subcutaneous tissue at sternotomy incision site and connected to elastomeric infusion pump 0.25% (12 patients) and 0.5% (12 patients) at 4 mL/h for 48 h Same catheter and device, infusion with saline 12 patients Pain score; opioid dosage; patient satisfaction; nausea and vomit; time to extubation; ambulation with assistance; discharge from ICU and hospital times and blood sample Significantly lower pain score, faster to ambulate in both bupivacaine groups; significantly less opioid consumption, more participant satisfaction in the 0.5% bupivacaine group; no significant differences between groups in nausea and vomit and time to extubation and ICU stay; serum concentrations were lower than toxicity level in both bupivacaine groups. Magnano et al. (2005) [17] Cardiac surgery via sternotomy Bupivacaine One catheter anterior to the sternum after sternal wiring 0.5% 5 mL/h for 36 h 23 patients Same catheter without any local anesthetic 23 patients Assisted ventilation time; pain score; location of pain; consumption of intravenous analgesic drugs Assisted ventilation time was significantly longer in bupivacaine group. No significant difference in VAS or morphine consumption in between groups. Pain was generally localized in inferior third sternum. Ghavidel et al. (2009) [16] Elective coronary artery bypass graft surgery Bupivacaine One catheter was placed in soft presternal tissue after sternal closure then connected to elastomeric infusion pump 0.25% at 2 mL/h for 72 h 20 patients No catheter, no infusion 20 patients Pain score; participant satisfaction; narcotic and analgesic dosage; duration of mechanical ventilation and intubation; LOS in ICU and hospital and wound problems Significantly lower mean VAS; higher participant satisfaction; higher rate of pain reduction and less narcotics during POD1 in bupivacaine group. No significant differences between groups in ICU and hospital LOS; mean doses of opioid during ICU stay; duration of ventilation and intubation. Nil wound problems in both groups. Langley (2009) [1] Elective CABG via sternotomy Bupivacaine 2 catheters were inserted percutaneously via subpectoral tunnelling on either side of sternum, and connected to elastomeric infusion pump 0.5% at 4 mL/h for 96 h Off-pump CABG 28 patients On-pump CABG 26 patients Same catheter and device, infusion with saline Off-pump CABG 29 patients On-pump CABG 25 patients Pain intensity; location of pain; opioid consumption; time to extubation; time to ambulate to chair; LOS in ICU and hospital and nausea and vomit Pain mostly in sternal region. Nonsignificant outcomes between groups in all of the specified outcomes. Eljezi et al. (2012) [8] CABG or valve replacement via sternotomy Ropivacaine 2 catheters tunnelled subcutaneously, below pectoral muscles over the costosternal margin parallel to the sternotomy incision and connected to elastomeric infusion pump 0.2% at 4 mL/h for 48 h 20 patients Same catheters and device, infusion with saline 19 patients Pain score; morphine consumption; patient satisfaction; nausea and vomiting; spirometry; physiotherapist perception to early mobilization; total ropivacaine plasma concentration Significantly lower pain at mobilization; significantly less morphine consumption and higher satisfaction in ropivacaine group. Significantly more participants ambulated early. No significant difference between groups in nausea and vomiting; spirometry; low total ropivacaine plasma concentration. Abbasi et al. (2012) [12] Elective off pump CABG Bupivacaine 2 catheters were placed at the median sternotomy incision site and connected to elastomeric infusion pump 0.5% at 4 mL/h for 48 h 18 patients Same catheters and device, infusion with saline 18 patients Pain relief; time to extubation; length of ICU and hospital stay; need of opioid analgesics and time to ambulate No significant difference between groups in pain relief; time to extubation and ICU LOS. Significant reduction in LOS in hospital; opioid analgesics and faster to ambulate in bupivacaine group. Agarwal et al. (2013) [13] Various cardiac surgery via sternotomy Ropivacaine 2 catheters in the sternal wound below the subcutaneous tissue, either side of the sternotomy, connected to single pump 0.3% at 4 mL/h for 64 h 44 patients Same catheter and device, infusion with normal saline 41 patients Time to extubation; LOS of ICU and hospital; pain score; opioid requirement; nausea and vomiting; pulmonary function testing and safety No significant difference between groups in all outcomes. Sternal wound infection in ropivacaine group was higher than historical institution rate. Dignan et al. (2014) [14] Elective CABG Ropivacaine 2 catheters tunnelled parasternally in a subpectoral position, connected to elastomeric infusion pump 0.5% at 4 mL/h for 96 h 26 patients Same catheters and device, infusion with saline 25 patients usual care group did not receive any intervention 24 patients Proportion of patients remaining in ICU for more than 48 hours; extubation time; ICU and hospital LOS; SAE; morphine equivalent dose; acute pain; pain scores No significant difference between groups in all outcomes. Nasr et al. (2015) [18] Elective CABG Bupivacaine 1 catheter anterior to the sternum above fascia in the subcutaneous tissue, connected to elastomeric infusion pump 0.25% at 5 mL/h for 48 h 19 patients Same catheter and device, infusion with saline 18 patients Morphine requirements; pain score; extubation time; incidence of wound infection; ICU and hospital stay and bupivacaine level in blood Significantly lower morphine requirement; pain scores; extubation time in bupivacaine group. No significant difference between groups in length of ICU and hospital stay. Plasma concentration did not reach toxic level. No incidence of sternal infection or delayed wound healing in both groups. Authors Surgery Choice of local anesthetics Placement of catheter Intervention group Control group Outcome measures Results Dowling et al. (2003) [15] Elective CABG/CABG+TMR Ropivacaine Catheters placed anterior to the sternum, connected to elastomeric infusion pump 0.2% at 4 mL/h for 48 h 16 patients Same catheter and device, infusion with saline 19 patients Narcotic analgesia requirements; pain scores; pulmonary function; time to extubation; LOS in ICU and hospital and severe adverse events Less narcotic usage; lower VAS score; lower mean hospital LOS in ropivacaine group. No significant differences between groups in pulmonary function; time to extubation; LOS in ICU or wound infection. No drug toxicity in either group. White et al. (2003) [3] CABG, valve replacement procedures, ASD repairs, and atrial myxoma excision procedure Bupivacaine First catheter placed in the subfascial plane above sternum, and second above fascia in the subcutaneous tissue at sternotomy incision site and connected to elastomeric infusion pump 0.25% (12 patients) and 0.5% (12 patients) at 4 mL/h for 48 h Same catheter and device, infusion with saline 12 patients Pain score; opioid dosage; patient satisfaction; nausea and vomit; time to extubation; ambulation with assistance; discharge from ICU and hospital times and blood sample Significantly lower pain score, faster to ambulate in both bupivacaine groups; significantly less opioid consumption, more participant satisfaction in the 0.5% bupivacaine group; no significant differences between groups in nausea and vomit and time to extubation and ICU stay; serum concentrations were lower than toxicity level in both bupivacaine groups. Magnano et al. (2005) [17] Cardiac surgery via sternotomy Bupivacaine One catheter anterior to the sternum after sternal wiring 0.5% 5 mL/h for 36 h 23 patients Same catheter without any local anesthetic 23 patients Assisted ventilation time; pain score; location of pain; consumption of intravenous analgesic drugs Assisted ventilation time was significantly longer in bupivacaine group. No significant difference in VAS or morphine consumption in between groups. Pain was generally localized in inferior third sternum. Ghavidel et al. (2009) [16] Elective coronary artery bypass graft surgery Bupivacaine One catheter was placed in soft presternal tissue after sternal closure then connected to elastomeric infusion pump 0.25% at 2 mL/h for 72 h 20 patients No catheter, no infusion 20 patients Pain score; participant satisfaction; narcotic and analgesic dosage; duration of mechanical ventilation and intubation; LOS in ICU and hospital and wound problems Significantly lower mean VAS; higher participant satisfaction; higher rate of pain reduction and less narcotics during POD1 in bupivacaine group. No significant differences between groups in ICU and hospital LOS; mean doses of opioid during ICU stay; duration of ventilation and intubation. Nil wound problems in both groups. Langley (2009) [1] Elective CABG via sternotomy Bupivacaine 2 catheters were inserted percutaneously via subpectoral tunnelling on either side of sternum, and connected to elastomeric infusion pump 0.5% at 4 mL/h for 96 h Off-pump CABG 28 patients On-pump CABG 26 patients Same catheter and device, infusion with saline Off-pump CABG 29 patients On-pump CABG 25 patients Pain intensity; location of pain; opioid consumption; time to extubation; time to ambulate to chair; LOS in ICU and hospital and nausea and vomit Pain mostly in sternal region. Nonsignificant outcomes between groups in all of the specified outcomes. Eljezi et al. (2012) [8] CABG or valve replacement via sternotomy Ropivacaine 2 catheters tunnelled subcutaneously, below pectoral muscles over the costosternal margin parallel to the sternotomy incision and connected to elastomeric infusion pump 0.2% at 4 mL/h for 48 h 20 patients Same catheters and device, infusion with saline 19 patients Pain score; morphine consumption; patient satisfaction; nausea and vomiting; spirometry; physiotherapist perception to early mobilization; total ropivacaine plasma concentration Significantly lower pain at mobilization; significantly less morphine consumption and higher satisfaction in ropivacaine group. Significantly more participants ambulated early. No significant difference between groups in nausea and vomiting; spirometry; low total ropivacaine plasma concentration. Abbasi et al. (2012) [12] Elective off pump CABG Bupivacaine 2 catheters were placed at the median sternotomy incision site and connected to elastomeric infusion pump 0.5% at 4 mL/h for 48 h 18 patients Same catheters and device, infusion with saline 18 patients Pain relief; time to extubation; length of ICU and hospital stay; need of opioid analgesics and time to ambulate No significant difference between groups in pain relief; time to extubation and ICU LOS. Significant reduction in LOS in hospital; opioid analgesics and faster to ambulate in bupivacaine group. Agarwal et al. (2013) [13] Various cardiac surgery via sternotomy Ropivacaine 2 catheters in the sternal wound below the subcutaneous tissue, either side of the sternotomy, connected to single pump 0.3% at 4 mL/h for 64 h 44 patients Same catheter and device, infusion with normal saline 41 patients Time to extubation; LOS of ICU and hospital; pain score; opioid requirement; nausea and vomiting; pulmonary function testing and safety No significant difference between groups in all outcomes. Sternal wound infection in ropivacaine group was higher than historical institution rate. Dignan et al. (2014) [14] Elective CABG Ropivacaine 2 catheters tunnelled parasternally in a subpectoral position, connected to elastomeric infusion pump 0.5% at 4 mL/h for 96 h 26 patients Same catheters and device, infusion with saline 25 patients usual care group did not receive any intervention 24 patients Proportion of patients remaining in ICU for more than 48 hours; extubation time; ICU and hospital LOS; SAE; morphine equivalent dose; acute pain; pain scores No significant difference between groups in all outcomes. Nasr et al. (2015) [18] Elective CABG Bupivacaine 1 catheter anterior to the sternum above fascia in the subcutaneous tissue, connected to elastomeric infusion pump 0.25% at 5 mL/h for 48 h 19 patients Same catheter and device, infusion with saline 18 patients Morphine requirements; pain score; extubation time; incidence of wound infection; ICU and hospital stay and bupivacaine level in blood Significantly lower morphine requirement; pain scores; extubation time in bupivacaine group. No significant difference between groups in length of ICU and hospital stay. Plasma concentration did not reach toxic level. No incidence of sternal infection or delayed wound healing in both groups. Characteristics of included trials (N = 10). ASD = atrial septal defect; CABG = coronary artery bypass graft surgery; ICU = intensive care unit; LOS = length of stay; PCA = patient-controlled analgesia; POD = postoperative day; SAE = severe adverse event; TMR = transmyocardial revascularization; VAS = visual analog scale. Study Quality and Risk of Bias The quality assessment (bias) of included studies is shown in Figure 2. All trials had low risk in selective reporting, and blinding occurred in 70% of included trials. Random sequence occurred in 60% of trials, concealed allocation occurred in 40% of the trials, and 60% of trials had low risk in incomplete data. Figure 2 View largeDownload slide Risk of bias assessment. Figure 2 View largeDownload slide Risk of bias assessment. Placement of Continuous Local Anesthetic Four studies placed two catheters parallel to the sternotomy for continuous infusion of local anesthetic [1,8,13,14]. Catheters were placed anterior to the sternum [15,17,18], at the median sternotomy site [12], at either end of the sternotomy wound [3], or on the presternal tissue [16]. Concentration of local anesthetic varied: 0.2% ropivacaine [8,15], 0.3% ropivacaine [13], 0.5% ropivacaine [14], 0.25% bupivacaine [3,16,18], or 0.5% bupivacaine [1,3,12,17]. Length of infusion time differed between studies, from 36 hours [17], 48 hours [3,8,12,15], 64 hours [13], 72 hours [16], to 96 hours [1,14]. Nine studies used infusion pumps [1,3,8,12–18]. Characteristics of Excluded Studies Data from one study [13] were not included in any of the meta-analyses due to variability in the unit measurements and times of measurements for the outcomes of interest. See Supplementary Table S2 in the appendix for characteristics of excluded studies. Effects of Interventions Pain Scores Nine studies involving 490 participants reported pain scores [1,3,8,13–18], with 234 (48%) participants in CLA infusion group and 256 (52%) participants in a control group. Due to the variability in the units of measurement and times of measurement of the pain scores, pain data from only two studies were able to be included in a meta-analysis. Both of these studies used a 0–10 visual analog scale (VAS) and reported pain scores at 72 hours [15,16]. Pooled analysis of 75 participants, with 36 allocated to a CLA infusion group and 39 to a control group, showed significantly reduced mean VAS pain score at 72 hours in the CLA infusion group compared with the control group (mean difference [MD] = –14.31 mm, 95% CI = –25.59 to –3.03) (see Figure 3A). Two studies [13,17] reported that there was no significant difference between groups in pain scores at any time points of measurement of VAS. In two studies [1,17], the location of greatest participant-reported pain was in the sternal area [1] and at the inferior third portion of the sternotomy wound [17]. Figure 3 View largeDownload slide View largeDownload slide A) Forest plot of visual analog scale pain score. B) Forest plot of time to sit up in chair. Langley et al. 2009a: off pump coronary artery bypass graft (CABG) group; Langley et al. 2009b: on pump CABG group. C) Forest plot of time to ambulate. D) Forest plot of time to extubation. Langley et al. 2009a: off pump coronary artery bypass graft group; Langley et al. 2009b: on pump CABG group. E) Forest plot of length of stay in the intensive care unit. Langley et al. 2009a: off pump coronary artery bypass graft group; Langley et al. 2009b: on pump CABG group. F) Forest plot of length of stay in the hospital. Langley et al. 2009a: off pump coronary artery bypass graft group; Langley et al. 2009b: on pump CABG group. G) Forest plot of morphine requirement. CI = confidence interval; ICU = intensive care unit; VAS = visual analog scale. Figure 3 View largeDownload slide View largeDownload slide A) Forest plot of visual analog scale pain score. B) Forest plot of time to sit up in chair. Langley et al. 2009a: off pump coronary artery bypass graft (CABG) group; Langley et al. 2009b: on pump CABG group. C) Forest plot of time to ambulate. D) Forest plot of time to extubation. Langley et al. 2009a: off pump coronary artery bypass graft group; Langley et al. 2009b: on pump CABG group. E) Forest plot of length of stay in the intensive care unit. Langley et al. 2009a: off pump coronary artery bypass graft group; Langley et al. 2009b: on pump CABG group. F) Forest plot of length of stay in the hospital. Langley et al. 2009a: off pump coronary artery bypass graft group; Langley et al. 2009b: on pump CABG group. G) Forest plot of morphine requirement. CI = confidence interval; ICU = intensive care unit; VAS = visual analog scale. Distance Walked or Any Measure of Activity Two studies [1,3] involving 132 participants, with 66 in a CLA infusion group and 66 in a control group, reported time to ambulate to chair. One study [1] measured the time when participants met the criteria for their readiness to initially ambulate a few steps to sit in a chair and actual time taken for participants to initially ambulate to the chair postoperatively. For the purpose of the meta-analysis, only the actual time from operation to when participants ambulated to the chair was used. One study [3] had three groups, which were a 0.5% bupivacaine group, a 0.25% bupivacaine group, and a control group. Unit of measurements for time to ambulate to chair and time to ambulate were in days. For the purpose of the meta-analysis, only data from the 0.25% bupivacaine group were included, and unit of days was converted to hours. Pooled analysis showed no significant difference between the CLA infusion group and control group in time to ambulate to chair (MD = –1.65 hours, 95% CI = –4.04 to 0.74) (see Figure 3B). Three studies [3,8,12] involving 99 participants, 50 in a CLA infusion group and a 49 in control group, reported the participants’ time to ambulate. Due to variability in units of measurement and measurement times, only data from two of these studies [3,12] could be used in the meta-analysis. The two included studies involved 60 participants, 30 participants in a CLA infusion group and 30 in a control group. Pooled analysis showed reduced time to ambulate in the CLA infusion group compared with the control group (MD = –2.81 hours, 95% CI = –5.23 to –0.4) (see Figure 3C). Only one study [8] reported the number of participants who complied with physiotherapy interventions on postoperative day 2; it showed that 12 out of 20 (60%) participants in a CLA infusion group complied with physiotherapy interventions compared with five out of 20 (26%) in a control group (P = 0.097). Severe Adverse Events Seven studies involving 311 participants, 156 in a CLA infusion group and 155 in a control group, reported adverse events [3,8,13–16,18]. As there were no consistent adverse events reported in the studies, no meta-analysis was performed. Four studies reported no differences in nausea [1,3,8,13] between groups, and three studies reported no difference in vomiting [3,8,13] between groups. Three studies [13,15,18] reported no drug toxicity in the CLA or control group. One study [13] reported that the sternal wound infection rate was higher than the institution’s historical rate: 9.1% of the patients receiving ropivacaine compared with historical control of 1.9% in all sternal wound infections; 6.8% of the patients receiving ropivacaine compared with historical control of 1.0% in the deep sternal wound infections. Therefore, their data safety monitoring board ended the study early. However, there were no statistically significant differences in the total number of severe adverse events (SAEs) [14] or wound infections [18] between the groups in two studies. A device-related adverse event in which a catheter tip broke during removal, requiring re-exploration of the wound, was reported by one study [3]. Patient Satisfaction with Pain Management Four studies [3,8,12,16] reported patient satisfaction with CLA infusion, involving 139 participants, 70 in a CLA infusion group and 69 in a control group. Due to variability of measurement units, the four studies could not be pooled for analysis. Three studies [3,8,16] reported that participants in the CLA infusion group were more satisfied with pain management compared with the control group (P < 0.0001, P = 0.029, and P < 0.05, respectively). Time to Extubation Nine studies with 475 participants, 243 in a CLA infusion group and 232 in a control group [1,3,12–18], reported time to extubation. Eight studies with 187 participants in a CLA infusion group and 191 participants in a control group were able to be pooled for analysis [1,3,12,14–18] and showed no difference in time to extubation between the CLA infusion group and control group (MD = –0.18 hours, 95% CI = –1.24 to 0.89) (see Figure 3D). Length of ICU Stay Eight studies [1,3,12–16,18] involving 416 participants, 208 in a CLA infusion group and 208 in a control group, reported length of stay in ICU. In one study, there were no reportable data [15], and in others, data were not able to be converted to a common measure [13,14]; therefore, five trials with 123 participants in a CLA infusion group and 122 participants in a control group could be pooled for analysis [1,3,12,16,18]. The pooled analysis showed that there was no between-group difference in length of ICU stay (MD = 0.9 hours, 95% CI = –2.96 to 4.75) (see Figure 3E). The time measurement of length of ICU stay was defined in two studies [1,3] as time of arrival in the ICU from the operating theater until discharge from the ICU. The three other studies [12,16,18] did not specify the time measurement of ICU length of stay. Length of Hospital Stay Eight studies [1,3,12–16,18] involving 416 participants reported the length of hospital stay, with 208 participants in a CLA group and 208 participants in a control group. Two studies could not be included in the meta-analysis as data could not be converted to the common outcome unit of measurement [13,14]. Six studies [1,3,12,15,16,18] with 139 participants in a CLA group and 141 participants in a control group could be pooled for analysis and showed that there was no between-group difference in the length of hospital stay (MD = –0.59 days, 95% CI = –1.24 to 0.07) (see Figure 3F). Total Narcotic Consumption Ten studies involving 514 participants, 263 participants in a CLA infusion group and 251 participants in a control group, reported total narcotic consumption. Due to variability in unit of measurements and measurement time, only two studies [8,18] with 39 participants in a CLA infusion group and 37 participants in a control group could be pooled for analysis and showed that the CLA infusion group had a significant reduction in morphine requirement at 48 hours compared with the control group (MD = –10.19 mg, 95% CI = –11.80 to –8.58) (see Figure 3G). Pulmonary Function Two studies [8,15] involving 77 participants, 36 participants in a CLA infusion group and 39 participants in a control group, reported the pulmonary function test outcomes. Due to variability in reporting measurements, the data were unable to be pooled for analysis. One study [15] reported the percentage change from baseline (measured preoperatively) for forced expiratory volume in one second (FEV1) and peak expiratory flow rate (PEFR), which was measured every four hours until discharge from the ICU, and then daily for a further three days. Another study [8] measured FEV1, FVC, FEV1/FVC ratio, inspiratory capacity (IC), tidal volume (TV), inspiratory reserve volume (IRV), and expiratory reserve volume (ERV) the mornings of postoperative day 1 and postoperative day 2. The data were presented as percentage of the preoperative value and showed no significant difference between the groups in any of the measurements (all P > 0.05). Discussion This systematic review found that participants receiving CLA infusion post–cardiac surgery had less overall pain at 72 hours, took less time to ambulate, and used less narcotics than participants in control groups. However, there were no differences between the CLA infusion group and the control group in time taken to ambulate to chair, length of ICU or hospital stay, or time to extubation. The most common area of pain after cardiac surgery is the sternal area [1,19], particularly the inferior third of the sternum [3]. This pain is most likely due to chest drains [19] and commencing daily activities and exercises such as breathing exercises, coughing, and beginning to ambulate [7]. Participants have reported that the most painful activities were coughing and getting out of bed [7] and that they limited these activities due to pain [20], which may hinder their postoperative recovery. The meta-analysis in this study demonstrated that CLA infusion in the sternal area was able to reduce the pain experienced by participants at 72 hours, suggesting that CLA may be an effective pain relief intervention in the early postoperative days. While a meta-analysis of pain score at other time points after cardiac surgery was not possible, significant reductions in pain scores in the CLA infusion group compared with the control group were shown at 24 hours after tracheal extubation [3], during the first 48 hours when taking a deep breath [18], and during mobilization at 48 hours [8]. Rehabilitation after cardiac surgery includes early ambulation [21,22], which also may help to prevent postoperative atelectasis [23]. Early ambulation after cardiac surgery is important as it promotes rapid recovery and early discharge post–cardiac surgery, in particular after coronary artery bypass graft surgery [21]. In the included studies, time to ambulation was defined either as ambulation with assistance [3] or mean time to ambulation [12]. The meta-analysis showed slightly shorter time to ambulation for those participants who had CLA infusion compared with those participants in the control group. Time to sit in a chair was defined as average time when participants walked from the bed to chair [1] or time when participants were able to sit up in a chair [3]. Our meta-analysis did not show any significant difference between the CLA infusion group and the control group in time to ambulate to a chair. The studies reported that most participants sat up in a chair with assistance either on the day of surgery or on day 1 postoperation [1], and all participants in the 0.5% bupivacaine CLA infusion group were able to sit up in a chair on the first postoperative day [3]. In addition, in a randomized controlled trial where physiotherapists were blinded to the intervention, they reported that more participants in the CLA infusion group ambulated within the first 48 hours postoperation (13 participants in the CLA infusion group compared with one participant in the control group, P < 0.000) [8]. Included studies reported the following categories of adverse events: nausea and vomiting [1,3,8,13]; serum toxicity level [3,8,13,15,18]; sternal wound infection [13,14,15,18]; and catheter-related adverse events [3,15]. Although a meta-analysis could not be performed for adverse events, studies that reported incidence of nausea and vomiting reported no between-group differences. This is different from studies in other types of surgeries such as general surgery (upper abdominal and vascular surgery), gynecological (cesarean section and abdominal hysterectomy), and urological (prostatectomy) that reported reduction in postoperative nausea and vomiting for the continuous wound catheter group compared with the control group [9], despite slight variations in the method of continuous local anesthetic delivery. Five studies [3,8,13,15,18] reported no incidence of toxicity, which is consistent with the systematic review that reported no cases of systemic toxicity when CLA infusion was used in cardiothoracic as well as other surgeries [9]. One participant was reported to have surpassed the lowest toxicity level, but there was no report of any symptoms of overdose [8]. It should be noted that one study reported that both deep sternal wound and all sternal wound infections were higher than the historical infection rate for their institution, and the study was ended early [13]. Earlier extubation allows participants to cough and walk earlier after cardiac surgery [23]. In our meta-analysis, participants receiving CLA infusion did not have a shorter time to extubation compared with the control group. Reasons for this could be that not all included studies used standardized extubation criteria and the decision to extubate may have varied based on individual clinicians’ clinical reasoning or the institution’s extubation criteria. Our meta-analysis did not show any difference between the CLA infusion group and control group in length of stay in the ICU. Length of stay in the ICU is also determined by multiple factors in the clinical setting, such as waiting for ward beds. One study [1] attempted to differentiate between the “actual” time of discharge from the ICU and time to meet “discharge criteria” from the ICU but did not show any difference between the CLA infusion group and the control group. Opioids are known to have some adverse side effects, such as respiratory depression, nausea and vomiting, and constipation [4]. Our meta-analysis showed a reduction in narcotic consumption at 48 hours [8,18]. Three studies, not included in the meta-analysis, also reported significant reduction in narcotic use in the CLA infusion group [3,12,15]. However, the other five studies not included in the meta-analysis reported that there was no significant difference between groups in total narcotic usage [1,13,14,16,17]. In these studies, the measurement times varied as follows: at 36 hours [17]; daily for 64 hours [13]; during ICU stay only [16]; at 96 hours [14]; and daily for 96 hours [1]. Some limitations of the review were that placement of the local anesthetic infusion catheters varied slightly between studies. Some studies used catheters on the wound [12], and some studies tunnelled catheters parallel to the sternotomy [1,8,13,14], using one [16–18] or two catheters [1,3,8,12,13,18]. In addition, agents of local anesthetics, dosage, and duration of CLA infusions varied between studies. Local anesthetic agents used were either ropivacaine [8,13–15] or bupivacaine [1,3,12,16–18]. Dosage between trials ranged from ropivacaine of 0.2% [8,15], 0.3% [13], 0.5% [14], and bupivacaine of 0.25% [3,16,18] and 0.5% [1,3,12,17]. Duration of the infusion varied between 36 hours [17], 48 hours [3,8,12,15,18], 64 hours [13], 72 hours [16], and 96 hours [1,14]. For the purpose of the meta-analyses, these variances were not accounted for. We were unable to determine optimal placement of catheters or optimal duration or dosage of local anesthetic infusion because of the variability in catheter placement and the dosages. In addition, trials included in this review had small sample sizes. While we performed a thorough search of published studies, we did not search the clinical trials registries for unpublished studies. If studies were unpublished due to negative findings, this could contribute to publication bias. In conclusion, this is the first systematic review with meta-analyses investigating the effectiveness of CLA infusion adjacent to the sternal wound after cardiac surgery. CLA infusion reduced pain at 72 hours, reduced the time to commencement of ambulation, and reduced morphine equivalent at 48 hours. However, it should be noted that the meta-analyses are based on the relatively small numbers of studies that could be included in the meta-analyses. CLA infusion did not reduce time to extubation or length of stay in the ICU or in hospital. CLA infusion may be an effective pain relief management in the early postoperative period; however, more data are required to analyze the effects of CLA infusion on severe adverse events, patient satisfaction, and pulmonary function. Acknowledgements The authors thank Ken Merten Library staff at Liverpool Hospital for performing the literature searches. Supplementary Data Supplementary Data may be found online at http://painmedicine.oxfordjournals.org. References 1 Langley MEP. Pain Management After Cardiac Surgery. Doctoral Dissertation, East Carolina University, Chicago and APA citation formats; 2009 . Retrieved from the Scholarship. http://hdl.handle.net/10342/1866. 2 Mueller X , Tinguely F , Tevaearai H et al. , Pain location, distribution, and intensity after cardiac surgery . Chest 2000 ; 118 : 391 – 6 . 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TI - Effect of Continuous Local Anesthetic in Post–Cardiac Surgery Patients: A Systematic Review
JF - Pain Medicine
DO - 10.1093/pm/pnx189
DA - 2017-08-16
UR - https://www.deepdyve.com/lp/oxford-university-press/effect-of-continuous-local-anesthetic-in-post-cardiac-surgery-patients-3f0zpY5OV6
SP - 1
EP - 1090
VL - Advance Article
IS - 5
DP - DeepDyve
ER -