TY - JOUR
AU - Patzkowski, Michael S
AB - ABSTRACT Introduction Enhanced Recovery After Surgery (ERAS) protocols have shown significant benefits in multiple areas including early mobilization, improved pain control, and early oral intake. Deficient nutritional states may compromise the operative outcomes. Several essential vitamins, e.g., B12, C, D, and E, have demonstrated anti-inflammatory properties and may promote wound healing. Given the low risk of oral multivitamin supplementation and the potential benefits, we hypothesized that adding a multivitamin to our institution’s ERAS protocols would be a low-cost perioperative intervention accounting for a very small fraction of the annual pharmacy budget. Methods A cost analysis for vitamin supplementation for all adult orthopedic surgical cases for the fiscal year 2018 was conducted. To assess the potential cost for multivitamin supplementation in the perioperative period, the fiscal year 2018 pharmacy budget and current costs of multivitamins were obtained from the hospital pharmacy. Medication costs were obtained from the medical logistics ordering system at per unit (i.e., bottle) and per tablet levels for all formulary oral multivitamins. We also determined the number of adult orthopedic surgical cases for our facility in the fiscal year 2018 from our surgery scheduling system. The cost for supplementation for a single day (day of surgery), 1 week (first postoperative week), 6 weeks plus 1 week preop, and 6 months plus 1 week preop for all cases was then calculated. Results Our institution’s pharmacy budget for the fiscal year 2018 was $123 million dollars with two oral multivitamins on formulary. Prenatal tablets, containing vitamins A-E, calcium, iron, and zinc, cost $1.52 per bottle of 100 tablets and $0.0152 per tablet, while renal formulation tablets, containing water-soluble vitamins B and C, cost $2.79 per bottle of 100 tablets and $0.0279 per tablet. For one fiscal year, the medication cost to supplement every adult orthopedic surgery patient with an oral multivitamin for 1 day, 1 week, 6 weeks plus 1 week preop, and 6 months plus 1 week preop would range from $60.47 to $110.99, from $423.29 to $776.93, from $2,963.03 to $5,438.51, and from $10,582.25 to $19,423.25, respectively, depending on which multivitamin was prescribed. These costs would represent between 0.00005% and 0.00009% of the annual pharmacy budget for 1 day, between 0.0003% and 0.0006% for 1 week, between 0.00245% and 0.441% for 6 weeks plus 1 week preop, and between 0.00875% and 1.575% for 6 months plus 1 week preop, respectively. Discussion/Conclusions The relative nutrient-deficient state in the perioperative patient from decreased oral intake contributes to the metabolic derangements resulting from the surgery. The current ERAS protocols help to mitigate this with early feeding, and the addition of multivitamin supplementation may enhance this process. Multivitamins are safe, widely accessible, and inexpensive, and early investigations of pain control and healing have shown encouraging results. Further prospective studies are needed for incorporating multivitamins into ERAS protocols in order to elucidate the effective dosages, duration of treatment, and effect on outcomes. INTRODUCTION Enhanced Recovery After Surgery (ERAS) protocols were developed to improve patient recovery and safety and reduce the hospital costs. These protocols have shown significant patient benefits in multiple areas including early mobilization, improved pain alleviation with multimodal analgesia, and early oral intake.1–3 One of the challenges of this field, however, is implementing new interventions that may increase the costs. An additional challenge is identifying the interventions that are of low risk to the patient. One potential intervention that satisfies both the aforementioned challenges and is yet to be evaluated is the incorporation of multivitamin supplementation into an ERAS strategy. The literature suggests that multiple vitamins (B12, C, D, and E) may have analgesic properties, may promote wound healing, and are well-tolerated by most patients.4–24 The purpose of the current investigation was to determine the cost burden of adding a daily multivitamin to the multimodal analgesia protocol for adult orthopedic surgery patients. METHODS To assess the potential cost for multivitamin supplementation in the perioperative period, annual budgets ($131 million for the fiscal year 2019) and costs of multivitamins (prenatal, Nephro-vite) were obtained from the hospital pharmacy. Prenatal vitamins are the available multivitamins at our facility and are dispensed to adults without renal pathology. For those with kidney disease Nephro-vite is dispensed instead. The in-hospital cost for 100 prenatal vitamins is $1.52, while the cost for Nephro-vite is $2.79. The number of adult orthopedic cases for the fiscal year 2018 was then obtained from the hospital’s surgical scheduling system and determined to be 3,978. The cost for vitamin supplementation for 1 day, 1 week, 6 weeks plus 1 week preop, and 6 months plus 1 week preop for the 3,978 patients was then calculated. Of note, the active ingredients in the prenatal vitamins and in Nephro-vite are presented in Table I. TABLE I. Multivitamin Ingredients . Prenatal . Nephro-vite . Vitamin A 4,000 IU Vitamin C 100 mg 60 mg Vitamin D 400 IU Vitamin E 11 IU Vitamin B1 1.5 mg 1.5 mg Vitamin B2 1.7 mg 1.7 mg Vitamin B3 18 mg Vitamin B6 2.6 mg 10 mg Folic acid 0.8 mg 1 mg Vitamin B12 4 mcg 6 mcg Calcium 263 mg Iron 27 mg Zinc 25 mg Niacinamide 20 mg d-Biotin 300 mcg Pantothenic acid 10 mg . Prenatal . Nephro-vite . Vitamin A 4,000 IU Vitamin C 100 mg 60 mg Vitamin D 400 IU Vitamin E 11 IU Vitamin B1 1.5 mg 1.5 mg Vitamin B2 1.7 mg 1.7 mg Vitamin B3 18 mg Vitamin B6 2.6 mg 10 mg Folic acid 0.8 mg 1 mg Vitamin B12 4 mcg 6 mcg Calcium 263 mg Iron 27 mg Zinc 25 mg Niacinamide 20 mg d-Biotin 300 mcg Pantothenic acid 10 mg The table lists the active ingredients in both the prenatal vitamins and Nephro-vite. Units of measurement are as follows: international units (IU), milligrams (mg), and micrograms (mcg). Open in new tab TABLE I. Multivitamin Ingredients . Prenatal . Nephro-vite . Vitamin A 4,000 IU Vitamin C 100 mg 60 mg Vitamin D 400 IU Vitamin E 11 IU Vitamin B1 1.5 mg 1.5 mg Vitamin B2 1.7 mg 1.7 mg Vitamin B3 18 mg Vitamin B6 2.6 mg 10 mg Folic acid 0.8 mg 1 mg Vitamin B12 4 mcg 6 mcg Calcium 263 mg Iron 27 mg Zinc 25 mg Niacinamide 20 mg d-Biotin 300 mcg Pantothenic acid 10 mg . Prenatal . Nephro-vite . Vitamin A 4,000 IU Vitamin C 100 mg 60 mg Vitamin D 400 IU Vitamin E 11 IU Vitamin B1 1.5 mg 1.5 mg Vitamin B2 1.7 mg 1.7 mg Vitamin B3 18 mg Vitamin B6 2.6 mg 10 mg Folic acid 0.8 mg 1 mg Vitamin B12 4 mcg 6 mcg Calcium 263 mg Iron 27 mg Zinc 25 mg Niacinamide 20 mg d-Biotin 300 mcg Pantothenic acid 10 mg The table lists the active ingredients in both the prenatal vitamins and Nephro-vite. Units of measurement are as follows: international units (IU), milligrams (mg), and micrograms (mcg). Open in new tab RESULTS The cost to supplement an individual adult orthopedic surgery patient with a prenatal vitamin for 1 day, 1 week, 6 weeks plus 1 week preop, and 6 months plus 1 week preop would be $0.015, $0.106, $0.753, and $2.625, respectively. The total cost to supplement all adult orthopedic surgery patients during a fiscal year with a prenatal vitamin for 1 day, 1 week, 6 weeks plus 1 week preop, and 6 months plus 1 week preop would be $60.47, $423.29, $2,963.03, and $10,582.25, respectively. These costs would represent 0.00005% (1 day), 0.00035% (1 week), 0.00245% (6 weeks plus 1 week preop), and 0.00875% (6 months plus 1 week preop) of the annual budget (Table II). The cost per patient for the water-soluble Nephro-vite for 1 day, 1 week, 6 weeks plus 1 week preop, and 6 months plus 1 week preop would be $0.028, $0.195, $1.372, and $4.90, respectively. The total cost for supplementation for Nephro-vite 1 day, 1 week, 6 weeks plus 1 week preop, and 6 months plus 1 week preop would be $110.99, $776.93, $5,438.51, and $19,423.25, respectively. These costs would account for 0.00009% (1 day), 0.00063% (1 week), 0.441% (6 weeks plus 1 week preop), and 1.575% (6 months plus 1 week preop) of the annual pharmacy budget (Table II). Table 2. Cost Analysis . Cost per . . % Annual . . Patient . Annual cost . Budget . Pre-Natal One Day $0.015 $60.47 0.00005% One Week $0.106 $423.29 0.00035% Six Weeks + One Week Preop $0.735 $2,963.03 0.00245% Six Months + One Week Preop $2.625 $10,582.25 0.00875% Nephro-vite® One Day $0.028 $110.99 0.00009% One Week $0.195 $776.93 0.00063% Six Weeks + One Week Preop $1.372 $5,438.51 0.441% Six Months + One Week Preop $4.90 $19,423.25 1.575% . Cost per . . % Annual . . Patient . Annual cost . Budget . Pre-Natal One Day $0.015 $60.47 0.00005% One Week $0.106 $423.29 0.00035% Six Weeks + One Week Preop $0.735 $2,963.03 0.00245% Six Months + One Week Preop $2.625 $10,582.25 0.00875% Nephro-vite® One Day $0.028 $110.99 0.00009% One Week $0.195 $776.93 0.00063% Six Weeks + One Week Preop $1.372 $5,438.51 0.441% Six Months + One Week Preop $4.90 $19,423.25 1.575% Table 2 lists the cost per patient, the total cost for all patients and percentage of annual budget to supplement with a pre-natal vitamin and with Nephro-vite® for one day, one week, six weeks plus one week preop and six months plus one week preop. Open in new tab Table 2. Cost Analysis . Cost per . . % Annual . . Patient . Annual cost . Budget . Pre-Natal One Day $0.015 $60.47 0.00005% One Week $0.106 $423.29 0.00035% Six Weeks + One Week Preop $0.735 $2,963.03 0.00245% Six Months + One Week Preop $2.625 $10,582.25 0.00875% Nephro-vite® One Day $0.028 $110.99 0.00009% One Week $0.195 $776.93 0.00063% Six Weeks + One Week Preop $1.372 $5,438.51 0.441% Six Months + One Week Preop $4.90 $19,423.25 1.575% . Cost per . . % Annual . . Patient . Annual cost . Budget . Pre-Natal One Day $0.015 $60.47 0.00005% One Week $0.106 $423.29 0.00035% Six Weeks + One Week Preop $0.735 $2,963.03 0.00245% Six Months + One Week Preop $2.625 $10,582.25 0.00875% Nephro-vite® One Day $0.028 $110.99 0.00009% One Week $0.195 $776.93 0.00063% Six Weeks + One Week Preop $1.372 $5,438.51 0.441% Six Months + One Week Preop $4.90 $19,423.25 1.575% Table 2 lists the cost per patient, the total cost for all patients and percentage of annual budget to supplement with a pre-natal vitamin and with Nephro-vite® for one day, one week, six weeks plus one week preop and six months plus one week preop. Open in new tab DISCUSSION ERAS protocols have gained traction and interest in the recent years; out of the more than 1,600 articles related to the topic found on PubMed, over half were published since 2016.3 These protocols were compiled after the individual contributing components were rigorously investigated, the effects of metabolic derangements and physical interventions on postoperative recovery were elucidated, and the effectiveness of specific interventions on hastening the recovery process was determined.25 The relative nutrient-deficient state in the perioperative patient due to decreased oral intake contributes to the metabolic derangements resulting from the surgery. The current ERAS protocols help to mitigate this with early feeding.1,3 The addition of multivitamin supplementation may further mitigate these effects. There are a relatively large number of studies dedicated to examining the effects of vitamin augmentation on pain control and healing, most with very encouraging results.6–30 These range from meta-analysis of the literature to prospective randomized controlled trials. A recently published randomized, double-blind, placebo-controlled trial demonstrates the beneficial effects of vitamin E supplementation on wound healing and metabolic status in patients with diabetic foot ulcers.19 There are also studies demonstrating the benefits of vitamin B supplementation on a variety of pain pathologies, vitamin C supplementation on healing and pain control, and vitamin D supplementation for reduction of chronic pain with the duration of supplementation ranging from a single dose given monthly to 24 weeks of daily supplementation.4–6,8–11,15,16,21,22,24,26–30 The vitamin B complex displays display promising results in the literature regarding pain control, particularly vitamin B12 and to a lesser extent B1 and B6.26–30 Vitamin B12 has been shown to reduce neuropathic pain in rats in both an isolated and a synergistic manner with gabapentin, a commonly used perioperative pain medication.26 Moreover, vitamin B12 was shown to enhance the analgesic properties of morphine and reduce the tolerance development in rat models, suggesting a potential to decrease opioid consumption. In addition to the observed efficacy of pain reduction by vitamin B12 in animal models, several clinical studies have appreciated an effect as well. In regard to musculoskeletal pain, patients with known osteoarthritis experienced greater pain reduction when using diclofenac and vitamin B complex (B1, B3, and B12) compared to diclofenac alone.28 The data regarding perioperative vitamin B12 supplementation are sparse but promising. One study noted a decrease in opioid consumption in women status post cesarean section when taking gabapentin with vitamin B complex (B1, B2, B3, and B6) compared to gabapentin alone.29 Ponce-Monter et al. appreciated a decrease in perioperative pain scores in patients using diclofenac with vitamin B complex (B1, B6, and B12) compared to diclofenac alone in patients with lower-extremity fractures.30 The neuromodulating effects of vitamin B12 have been established at the cellular level and the existing data suggest synergistic and isolated analgesic properties; however, further clinical trials in the surgical setting are warranted.26–30 Perhaps the most well-known vitamin discussed in the orthopedic literature is vitamin C. The American Academy of Orthopaedic Surgeons recommends adjuvant treatment of distal radius fractures with vitamin C for the prevention of disproportionate pain.11 While more recent literature may suggest a controversy with regard to the efficacy of vitamin C in reducing the incidence of complex regional pain syndrome, there are numerous other studies that support its benefit in the postoperative patient.4–6,8–10 A randomized controlled trial by Li et al. in 2018 demonstrated an improved postoperative healing with postoperative vitamin C supplementation in dental implant surgery with and without the use of bone graft.21 Mohammad et al. in 2016 showed that vitamin C favorably impacts the expression of transcription factors associated with the early resolution of inflammation and tissue remodeling.22 Finally, an article published in The Journal of Foot and Ankle Surgery demonstrated a trend in vitamin C intake and faster recovery of skin integrity and strength across wounds in a guinea pig model.24 As previously mentioned, a proposed strength of this study involves the administration of relatively low-risk supplements at a low cost. Nevertheless, administration of any exogenous substrate is not entirely risk free. In regard to vitamin C, there is a concern that despite its primarily antioxidant capabilities, there is some concern for its prooxidant effects that may be detrimental to tissue healing. Yet as mentioned above, the available data largely support the role of vitamin C in would healing (i.e., increased tissue remodeling transcription factor activity, increased dental extraction wound healing, and increased wound healing in guinea pigs).21,22,24 A noted concern for vitamin A supplementation involves the decreased bone resorption and the increased risk of hip fractures as presented in the Iowa Women’s Trial where the authors noted a “small, elevated risk compared with nonusers” but delineated that the risk of all types of fractures was not increased with vitamin A supplementation.31 Additionally, there was no dose-dependent effect for vitamin A use and the risk of fracture. Furthermore, the women in the vitamin A supplement group were also more likely to be on thyrotropic medications and hormone replacement which confounds the findings. Based on the data, there would not be a large concern for the short-term vitamin A use in a similar population. Folate supplementation, in the setting of active colon cancer, has been shown to promote tumor growth, in contrast to the protection it provides in normal colonic mucosa.32 Other research evaluating cervical and breast cancer have been inconclusive regarding the effect of folate on tumor growth enhancement.33 This risk could be avoided by implementing a screening tool for active colorectal cancer as part of an exclusion criteria in the future studies. Finally, concern has been raised for a potential increased risk of lung cancer in active smokers using vitamin E. However, Huang et al. showed no increased risk in the population from a prospective trial in 2020 involving 22,781 patients, and similar results were found in a meta-analysis of 11 studies by Chen et al. in 2015.34,35 Lastly, it is known that iron-containing supplements can interfere with the absorption of certain medications including bisphosphonates, thyroid medications, and certain antibiotics. A reasonable way to avoid this would be appropriately spacing the medication administration throughout the day. While risks exist with the use of vitamin supplementation, the literature as a whole support a favorable benefit-to-risk ratio. The future looks bright for vitamin supplementation in the perioperative patient, yet there has been a recent critique of ERAS protocols for instituting additional components without sufficient robust scientific inquisition showing a statistically significant benefit and for extrapolating data to other surgical fields (original studies done in colorectal surgery).3 There is a concern that this may lead to expensive, ineffective, and potentially unsafe interventions.3 This is a valid concern. However, the multivitamins we examined are safe, sold over-the-counter, and, as we have shown, are very inexpensive. As recently discussed, there are numerous studies demonstrating the benefit of vitamin supplementation on pain control and healing.6–30 However, while many of these studies demonstrate a benefit in animal models or at a biochemical level, there is limited evidence demonstrating a clinically significant benefit in patients. Thus, further investigation in the form of prospective randomized controlled trials is warranted. CONCLUSION The current ERAS protocols help to mitigate the metabolic derangements associated with surgery and the relative nutrient-deficient state in the perioperative patient. Multivitamin supplementation may impart multiple benefits, and supplementation through the perioperative period imparts minimal financial burden. Further prospective studies are needed for incorporating multivitamins into ERAS protocols in order to elucidate the effective dosages, duration of treatment, and effect on outcomes. ACKNOWLEDGMENTS None declared. FUNDING None declared. CONFLICT OF INTEREST STATEMENT None declared. REFERENCES 1. Ljunggvist O , Scott M, Fearon KC: Enhanced recovery after surgery: a review . JAMA Surg Mar 2017 ; 152 ( 3 ): 292 - 8 . Google Scholar Crossref Search ADS PubMed WorldCat 2. Ljunggvist O : Enhanced recovery after surgery-knowing, not guessing . 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J Natl Cancer Inst 2020 Feb 1 ; 112 ( 2 ): 191 - 9 . doi: 10.1093/jnci/djz077 PMID: 31077299; PMCID: PMC7019088. Google Scholar Crossref Search ADS PubMed WorldCat 35. Chen G , Wang J, Hong X, Chai Z, Li Q: Dietary vitamin E intake could reduce the risk of lung cancer: evidence from a meta-analysis . Int J Clin Exp Med 2015 Apr 15 ; 8 ( 4 ): 6631 - 7 . PMID: 26131295; PMCID: PMC4483938. Google Scholar PubMed OpenURL Placeholder Text WorldCat Author notes Presented at the Society of Military Orthopaedic Surgeons Annual Meeting, Palm Beach Gardens, FL, December 2019. The views expressed are solely those of the authors and do not reflect the official views or policy of the Brooke Army Medical Center, the U.S. Army, the U.S. Air Force, the Defense Health Agency, or the Department of Defense. The following study did not involve the use of human subjects and did not qualify as human subjects research. Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US. This work is written by (a) US Government employee(s) and is in the public domain in the US. Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.
TI - Multivitamin Use in Enhanced Recovery After Surgery Protocols: A Cost Analysis
JF - Military Medicine
DO - 10.1093/milmed/usaa505
DA - 2021-08-28
UR - https://www.deepdyve.com/lp/oxford-university-press/multivitamin-use-in-enhanced-recovery-after-surgery-protocols-a-cost-hgXT8g0ro6
SP - e1024
EP - e1028
VL - 186
IS - 9-10
DP - DeepDyve
ER -