We read with great interest the article recently published by Margarit et al.1 on the influence of total intravenous anaesthesia and isoflurane anaesthesia on plasma interleukin-6 and interleukin-10 concentrations after colorectal surgery for cancer. In this randomised controlled trial, the authors have compared the effects of total intravenous anaesthesia and isoflurane anaesthesia on plasma concentrations of interleukin-6 and interleukin-10 in 60 patients who underwent surgery for colorectal cancer. In their study, they tried to control most factors that could affect perioperative immune function, such as age, sex, American Society of Anaesthesiologists classification, weight, anaesthesia time, surgical time and so on. In addition, many other parameters such as immune disorders or immunosuppressive therapy, asthma and so on were also included. However, to better eliminate the effect of confounding factors on the final experimental results and to obtain an optimal comparison, several other important issues should have been considered in this study.
Firstly, although many physiological parameters were described, the type of intraoperative infusion, the antibiotic administration and the parenteral nutrition support were not clearly mentioned in the article. All of these unconsidered conditions may have, in our opinion, a nonnegligible effect on the immunity of the patients. Indeed, different volume replacement regimens may provoke different immunological responses during surgical procedures.2 Animal studies and experiments in isolated cell cultures showed that hypertonic saline suppressed several neutrophil functions and at the same time upregulated T-lymphocyte function.3,4 Lawrence and Schell5 also found that both saline and hydroxyethyl starches inhibited cell-mediated immunity, but hydroxyethyl starches were more suppressive than saline in mice. However, in a clinical trial, acute hypervolaemic haemodilution with hydroxyethyl starches was reported to be helpful in improving immune function during total hip replacement.6 In addition, prophylactic antibiotics in open colorectal surgery have been used to decrease the incidence of superficial and deep surgical site infections.7 Antibiotics are critical to immune function, as the microbiota play a fundamental role in the induction and function of the host immune system.8 It is therefore necessary to report on injection dosage, administration time and class of antibiotic used. Furthermore, total parenteral nutrition support cannot be ignored after colorectal surgery, because total parenteral nutrition was reported to likely have a deleterious effect on immune function.9
More importantly, when the authors are talking about the type of surgery, only colectomy (right/left) and anterior rectal resection are mentioned. We think this is insufficient to conclude that both the total intravenous anaesthesia and isoflurane anaesthesia groups were comparable concerning surgical stress. According to the guidelines of colon and rectal cancer surgery,10 the selection of different surgical techniques should be based on the radial margin of cancer, colorectal cancer location and so on. As mentioned in their article,1 there were five patients who had an anterior rectal resection in the total intravenous anaesthesia group and eight in the isoflurane anaesthesia group. Nevertheless, some important information was missing, including how many patients had low or high rectal cancer, how many underwent anus-saving surgery and how many had a Brooke ileostomy. As we know, the serum expression levels of particular cytokines and chemokines can vary a lot in different surgery and trauma circumstances. The effect of the anaesthetic technique on cytokine expressions may be very weak in comparison with surgical stress during the perioperative period. Thus, more specific surgical techniques should have been taken into consideration.
In addition, although patients without signs of local invasion or distant metastases at preoperative evaluation using imaging studies were included, some factors such as the tumour differentiation, disease types and the preoperative carcinoembryonic antigen (CEA) level are believed to be related to the patients’ immune response, thereby affecting their prognosis. Finally, we are confused about the patient numbers in Table 1. The total number of patients should be 31, not 30 as indicated in their article, because the sum of three (ASA I), 25 (ASA II) and three (ASA III) patients is equal to 31.
In summary, on the basis of the arguments above, we think that the results presented in the study by Margarit et al.1 would have been more convincing and reliable if all these factors had been taken into account.
Acknowledgments relating to this article
Assistance with the letter: none.
Financial support and sponsorship: the work is supported by the National Natural Science Foundation of China (Grant No.81172200).
Conflicts of interest: none.
1. Margarit SC, Vasian HN, Balla E, et al. The influence of total intravenous anaesthesia and isoflurane anaesthesia on plasma interleukin-6 and interleukin-10 concentrations after colorectal surgery for cancer: a randomised controlled trial. Eur J Anaesthesiol
2. Westphal M, James MF, Kozek-Langenecker S, et al. Hydroxyethyl starches: different products – different effects. Anesthesiology
3. Loomis WH, Namiki S, Ostrom RS, et al. Hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation. J Biol Chem
4. Pascual JL, Ferri LE, Seely AJ, et al. Hypertonic saline resuscitation of hemorrhagic shock diminishes neutrophil rolling and adherence to endothelium and reduces in vivo vascular leakage. Ann Surg
5. Lawrence DA, Schell RF. Influence of hydroxyethyl starch on humoral and cell-mediated immune responses in mice. Transfusion
6. Tang QF, Hao YF, Qian YN, et al. Effects of acute hypervolaemic haemodilution on the expression of plasma interferon-inducible protein-10 and bactericidal/permeability-increasing protein in patients undergoing total hip replacement. J Int Med Res
7. Nelson RL, Glenny AM, Song F. Antimicrobial prophylaxis for colorectal surgery. Cochrane Database Syst Rev
8. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell
9. Gogos CA, Kalfarentzos F. Total parenteral nutrition and immune system activity: a review. Nutrition
10. Nelson H, Petrelli N, Carlin A, et al. National Cancer Institute Expert Panel. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst