Surgical Support Protocol

Postoperative Care

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Dr. Christopher Knee, ND

Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

A
Systematic review or meta-analysis of human trials
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study

Physiological responses to surgical procedures impact various outcomes such as length of hospital stay and risk of postoperative complications. (6)(12)(18) Targeting mechanisms that help regulate inflammation and immune function is key to an integrative treatment plan. 

Regulation of post-surgical immune function and inflammation may be achieved through decreasing pro-inflammatory cytokines, such as tumor necrosis factor (TNFα) and interleukins. (9)(24)(19) It is hypothesized that gene expressions of TNF and interleukin-6 (IL-6) are correlated with the gene expression of suppressor of cytokine stimulation-3 (SOCS3), providing insight into the possible mechanism through which decreased inflammation is achieved. (6)

Decreasing oxidative stress may also improve the inflammatory response. Focusing on maintaining adequate plasma and RBC glutathione levels, as well as a favorable glutathione to glutathione disulfide ratio, assists in the attenuated loss of antioxidants. (4) Additionally, interventions aimed at improving neutrophil phagocytosis show potential in upregulating immune function post-operatively. (1)

The ingredients presented in the protocol below reflect research findings that demonstrate the efficacy of dietary supplements when used to support physiological function following surgical interventions.

Probiotics

Specific probiotics strains may reduce the incidence of common postoperative complications such as infection. However, outcomes are dependent on type of surgery, demographic, strain, and dosing. Listed below are three possible strain combinations with associated outcomes. (2)(7)(10)(24)

Strain combination 1

30 billion CFU of Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei subsp, Lactobacillus lactis, twice per month, 6 months beginning 4 weeks post-surgery

  • Scenario: postoperative complications in colorectal cancer (24)
    • Reduced inflammation, demonstrated by decreased serum levels of TNFα and interleukins IL-6, IL-10, IL-12, IL-17A, IL-17C, and IL-22 when compared to placebo
Probiotic strain combination 1 in the Fullscript catalog

Strain combination 2

5.5 billion CFU probiotic containing Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii, once per day, 14 days starting on the day of surgery

  • Scenario: postoperative complications in colorectal cancer (6)
    • Decreased rate of colorectal surgery complications by 20.2%, including the rate of postoperative pneumonia by 8.9%, surgical site infection by 12.9%, and anastomotic leakage by 7.6% when compared to placebo
      Length of hospital stay shortened by two days in patients receiving probiotics
    • Length of hospital stay shortened by two days in patients receiving probiotics
Probiotic strain combination 2 in the Fullscript catalog

Strain combination 3

4 billion CFU probiotic containing Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus casei, Bifidobacterium bifidum and 100 mg of fructooligosaccharides, twice a day, 14 days perioperatively

  • Scenario: postoperative complications in periampullary neoplasm (18)
    • Reduced the rate of postoperative infection incidence by 43.5% when compared to placebo
    • Decreased mean length of hospital stay from 23 days to 12 days
    • Reduced postoperative mortality; no occurrences of death were experienced in the probiotic group when compared to 6 deaths recorded in the placebo group
Probiotic strain combination 3 in the Fullscript catalog

Magnesium

800 mg magnesium oxide (240 mg elemental magnesium), once per day, from admission to discharge, or 2 g (or 5-50 mg/kg) of intravenous magnesium in the form of levulinate, gluconate, sulfate, or chloride, on day of surgery (3)(8)(11)(12)

  • Incidences of hypomagnesemia, associated with high occurrences in cardiac surgery, were decreased by 29.3% in oral magnesium oxide supplementation, demonstrating an overall decrease in postoperative complications; additionally, reduced gastrointestinal incidences of nausea, vomiting, and constipation in postoperative coronary artery bypass graft surgery when compared to control (12)
  • Decreased postoperative ventricular dysrhythmias, ventilatory support, and increased stroke volume in postoperative cardiac patients treated with intravenous magnesium chloride (3)
  • Systematic review of 14 randomized trials found perioperative magnesium supplementation decreased the risk of postoperative shivering (11)
  • Meta-analysis of 5 randomized controlled trials found magnesium supplementation in pediatric patients undergoing cardiopulmonary bypass decreased incidence of arrhythmia postoperatively (8)
Magnesium in the Fullscript catalog

Glutamine

 0.18-0.4 g/kg, once per day, 1-7 days subsequent to surgery (1)(16)(22)

  • Improved immune function as demonstrated by increased neutrophil phagocytosis, as well as maintained muscular protein synthesis as measured by muscular ribosomal concentration, which is typically reduced following surgical trauma in postoperative colorectal cancer patients (1)
  • Increased T-cell DNA synthesis, indicating enhancement of T-cell function in postoperative colorectal resection (16)
  • Improved immunodepression and nutrition response as well as decreased inflammation in gastrointestinal surgery (22)
  • Attenuated loss of antioxidants, demonstrated by maintenance of plasma and RBC glutathione levels and glutathione to glutathione disulfide ratio in patients undergoing elective abdominal surgery; additionally, length of hospital stay decreased (4)
Glutamine in the Fullscript catalog

Omega-3 fatty acids

0.1-0.2 g/kg once per day of omega-3 fatty acids, seven days subsequent to surgery (1)(9)

Note: Changes in blood flow or coagulation related to altered levels of fibrinogen, factor V, and triglycerides may occur in select populations (13)(14)(20)

  • Neutrophil phagocytosis increased for postoperative colorectal cancer patients whose standard total parenteral nutrition was supplemented with omega-3 fatty acids
  • Postoperative immune function improved and inflammation as indicated by lower levels of IL-6, TNFα, and C-reactive protein in postoperative colorectal cancer patients who had a radical resection; additionally, length of hospital stay decreased (9)
  • Meta-analysis of 16 randomized controlled trials found omega-3 fatty acid emulsion improved immune function, inflammation, and postoperative curative effect in postoperative gastrointestinal cancer (25)
  • Decreased risk of olfactory loss in patients undergoing endoscopic resection for sellar or parasellar tumors (21)
Omega-3 fatty acids in the Fullscript catalog

Branched-chain amino acids

4.74-5.56 g branched-chain amino acids (BCAAs), 2-3 times per day, starting two weeks prior to surgery, and continued for three to six months subsequent to surgery (5)(15)

  • Compared to a control group, individuals receiving BCAA supplementation demonstrated anti-catabolic effects leading to improved metabolic status, which was indicated by improved BCAA-to-tyrosine ratio and favorable levels of retinol-binding protein (23)
  • Decreased mean length of hospital stays from 19 days to 17 days and overall incidence of postoperative complications by 26.9% when compared to placebo (15)(17)
  • Events of hepatic recurrence were decreased by 17.5% postoperatively and decreased morbidity after liver resection for hepatocellular carcinoma; additionally, hospital stay decreased (17)
  • Ameliorated mental stress and decreased risk of intrahepatic recurrence and complications after radiofrequency ablation for hepatocellular carcinoma (15)
  • Decreased recurrence of hepatic resection and decreased tumor markers AFP and PIVKA-II compared to control after hepatic resection in patients with hepatocellular carcinoma (5)
Branched-chain amino acids in the Fullscript catalog

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

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References

  1. Aliyazicioglu, T., Cantürk, N. Z., Simsek, T., Kolayli, F., & Çekmen, M. (2013). Effects of standard and/or glutamine dipeptide and/or omega-3 fatty acid-supplemented parenteral nutrition on neutrophil functions, interleukin-8 level and length of stay–A double blind, controlled randomised study. East African Medical Journal, 90(2), 59–66. https://pubmed.ncbi.nlm.nih.gov/26866103/ (C)
  2. Bajramagic, S., Hodzic, E., Mulabdic, A., Holjan, S., Smajlovic, S. V., & Rovcanin, A. (2019). Usage of Probiotics and its Clinical Significance at Surgically Treated Patients Sufferig from Colorectal Carcinoma. Medieval Archaeology, 73(5), 316–320. https://pubmed.ncbi.nlm.nih.gov/31819304/ (C)
  3. England, M. R., Gordon, G., Salem, M., & Chernow, B. (1992). Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial. JAMA: The Journal of the American Medical Association, 268(17), 2395–2402. https://pubmed.ncbi.nlm.nih.gov/1404796/ (B)
  4. Fan, Y.-P., Yu, J.-C., Kang, W.-M., & Zhang, Q. (2009). Effects of glutamine supplementation on patients undergoing abdominal surgery. Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K’o Hsueh Tsa Chih / Chinese Academy of Medical Sciences, 24(1), 55–59. https://pubmed.ncbi.nlm.nih.gov/19382426/ (C)
  5. Ichikawa, K., Okabayashi, T., Maeda, H., Namikawa, T., Iiyama, T., Sugimoto, T., Kobayashi, M., Mimura, T., & Hanazaki, K. (2013). Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study. Surgery Today, 43(7), 720–726. https://pubmed.ncbi.nlm.nih.gov/22890582/ (C)
  6. Kotzampassi, K., Stavrou, G., Damoraki, G., Georgitsi, M., Basdanis, G., Tsaousi, G., & Giamarellos-Bourboulis, E. J. (2015). A Four-Probiotics Regimen Reduces Postoperative Complications After Colorectal Surgery: A Randomized, Double-Blind, Placebo-Controlled Study. World Journal of Surgery, 39(11), 2776–2783. https://pubmed.ncbi.nlm.nih.gov/25894405/ (B)
  7. Lederer, A.-K., Pisarski, P., Kousoulas, L., Fichtner-Feigl, S., Hess, C., & Huber, R. (2017). Postoperative changes of the microbiome: are surgical complications related to the gut flora? A systematic review. BMC Surgery, 17(1), 125. https://pubmed.ncbi.nlm.nih.gov/29202875/ (A)
  8. Lee, H. Y., Ghimire, S., & Kim, E. Y. (2013). Magnesium supplementation reduces postoperative arrhythmias after cardiopulmonary bypass in pediatrics: a metaanalysis of randomized controlled trials. Pediatric Cardiology, 34(6), 1396–1403. https://pubmed.ncbi.nlm.nih.gov/23443885/ (A)
  9. Liang, B., Wang, S., Ye, Y.-J., Yang, X.-D., Wang, Y.-L., Qu, J., Xie, Q.-W., & Yin, M.-J. (2008). Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients. World Journal of Gastroenterology: WJG, 14(15), 2434–2439. https://pubmed.ncbi.nlm.nih.gov/18416476/ (C)
  10. Liu, Z., Qin, H., Yang, Z., Xia, Y., Liu, W., Yang, J., Jiang, Y., Zhang, H., Yang, Z., Wang, Y., & Zheng, Q. (2011). Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and post-operative infectious complications in colorectal cancer surgery – a double-blind study. Alimentary Pharmacology & Therapeutics, 33(1), 50–63. https://pubmed.ncbi.nlm.nih.gov/21083585/ (C)
  11. Lysakowski, C., Dumont, L., Czarnetzki, C., & Tramèr, M. R. (2007). Magnesium as an adjuvant to postoperative analgesia: a systematic review of randomized trials. Anesthesia and Analgesia, 104(6), 1532–1539, table of contents. https://pubmed.ncbi.nlm.nih.gov/17513654/ (A)
  12. Moradian, S. T., Ghiasi, M. S., Mohamadpour, A., & Siavash, Y. (2017). Oral magnesium supplementation reduces the incidence of gastrointestinal complications following cardiac surgery: a randomized clinical trial. Magnesium Research: Official Organ of the International Society for the Development of Research on Magnesium, 30(1), 28–34. https://pubmed.ncbi.nlm.nih.gov/28417897/ (C)
  13. Mundal, H. H., Meltzer, H. M., & Aursnes, I. (1994). Bleeding times related to serum triglyceride levels in healthy young adults. Thrombosis Research, 75(3), 285–291. https://pubmed.ncbi.nlm.nih.gov/7992239/ (C)
  14. Newens, K. J., Thompson, A. K., Jackson, K. G., Wright, J., & Williams, C. M. (2011). DHA-rich fish oil reverses the detrimental effects of saturated fatty acids on postprandial vascular reactivity. The American Journal of Clinical Nutrition, 94(3), 742–748. https://pubmed.ncbi.nlm.nih.gov/21831993/ (C)
  15. Nojiri, S., Fujiwara, K., Shinkai, N., Iio, E., & Joh, T. (2017). Effects of branched-chain amino acid supplementation after radiofrequency ablation for hepatocellular carcinoma: A randomized trial. Nutrition , 33, 20–27. https://pubmed.ncbi.nlm.nih.gov/27908546/ (C)
  16. O’Riordain, M. G., Fearon, K. C., Ross, J. A., Rogers, P., Falconer, J. S., Bartolo, D. C., Garden, O. J., & Carter, D. C. (1994). Glutamine-supplemented total parenteral nutrition enhances T-lymphocyte response in surgical patients undergoing colorectal resection. Annals of Surgery, 220(2), 212–221. https://pubmed.ncbi.nlm.nih.gov/8053744/ (C)
  17. Okabayashi, T., Nishimori, I., Sugimoto, T., Maeda, H., Dabanaka, K., Onishi, S., Kobayashi, M., & Hanazaki, K. (2008). Effects of branched-chain amino acids-enriched nutrient support for patients undergoing liver resection for hepatocellular carcinoma. Journal of Gastroenterology and Hepatology, 23(12), 1869–1873. https://pubmed.ncbi.nlm.nih.gov/18717761/ (C)
  18. Sommacal, H. M., Bersch, V. P., Vitola, S. P., & Osvaldt, A. B. (2015). Perioperative synbiotics decrease postoperative complications in periampullary neoplasms: a randomized, double-blind clinical trial. Nutrition and Cancer, 67(3), 457–462. https://pubmed.ncbi.nlm.nih.gov/25803626/ (C)
  19. Sugawara, G., Nagino, M., Nishio, H., Ebata, T., Takagi, K., Asahara, T., Nomoto, K., & Nimura, Y. (2006). Perioperative synbiotic treatment to prevent postoperative infectious complications in biliary cancer surgery: a randomized controlled trial. Annals of Surgery, 244(5), 706–714. https://pubmed.ncbi.nlm.nih.gov/17060763/ (C)
  20. Vanschoonbeek, K., Feijge, M. A. H., Paquay, M., Rosing, J., Saris, W., Kluft, C., Giesen, P. L. A., de Maat, M. P. M., & Heemskerk, J. W. M. (2004). Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(9), 1734–1740. https://pubmed.ncbi.nlm.nih.gov/15217806/ (C)
  21. Yan, C. H., Rathor, A., Krook, K., Ma, Y., Rotella, M. R., Dodd, R. L., Hwang, P. H., Nayak, J. V., Oyesiku, N. M., DelGaudio, J. M., Levy, J. M., Wise, J., Wise, S. K., & Patel, Z. M. (2020). Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial. Neurosurgery, 87(2), E91–E98. https://pubmed.ncbi.nlm.nih.gov/31950156/ (C)
  22. Yeh, C.-N., Lee, H.-L., Liu, Y.-Y., Chiang, K.-C., Hwang, T.-L., Jan, Y.-Y., & Chen, M.-F. (2008). The role of parenteral glutamine supplement for surgical patient perioperatively: result of a single center, prospective and controlled study. Langenbeck’s Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie, 393(6), 849–855. https://pubmed.ncbi.nlm.nih.gov/18712409/ (C)
  23. Yoshida, R., Yagi, T., Sadamori, H., Matsuda, H., Shinoura, S., Umeda, Y., Sato, D., Utsumi, M., Nagasaka, T., Okazaki, N., Date, A., Noguchi, A., Tanaka, A., Hasegawa, Y., Sakamoto, Y., & Fujiwara, T. (2012). Branched-chain amino acid-enriched nutrients improve nutritional and metabolic abnormalities in the early post-transplant period after living donor liver transplantation. Journal of Hepato-Biliary-Pancreatic Sciences, 19(4), 438–448. https://pubmed.ncbi.nlm.nih.gov/21947604/ (C)
  24. Zaharuddin, L., Mokhtar, N. M., Muhammad Nawawi, K. N., & Raja Ali, R. A. (2019). A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer. BMC Gastroenterology, 19(1), 131. https://pubmed.ncbi.nlm.nih.gov/31340751/ (B)
  25. Zhao, Y., & Wang, C. (2018). Effect of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on inflammatory and immune function in postoperative patients with gastrointestinal malignancy: A meta-analysis of randomized control trials in China. Medicine, 97(16), e0472. https://pubmed.ncbi.nlm.nih.gov/29668624/ (A)

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