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Comparison of propofol and sevoflurane anesthesia on human cellular immunity in patients undergoing total hip arthroplasty

XIULAI ZHANG MD, HAIYAN ZHOU MD, YI WANG MD, GANG CHEN MD, LINGLING FANG MD

Department of Anesthesiology, Second Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, P.R. China

Keywords: propofol; sevoflurane; anesthesia; cellular immunity; total hip arthroplasty

Abstract

Study Objective: To compare the effect of propofol and sevoflurane anesthesia on human cellular immunity in patients undergoing total hip arthroplasty.

Patients: 26 ASA physical status?and ? patients scheduled for total hip arthroplasty.

Interventions: Patients were randomly divided into two groups: propofol group (n=13), total intravenous general anesthesia maitained with propofol was conducted; sevoflurane group (n=13), combined intravenous–inhalation general anesthesia maitained with sevoflurane was conducted.

Measurements: Blood samples were obtained before induction of anesthesia, 1 h after anesthesia and at the end of operation. Blood hydrocortisone were investigated by radioimmunoassay; peripheral nature killer (NK) cells and T lymphocyte subpopulations (CD3??CD4??CD8?cells) were investigated by flow cytometry.

Main Results: Blood hydrocortisone increased significantly while CD3??CD4? T lymphocytes and CD4?/CD8? ratio decreased after induction of anesthesia. The changes in propofol group were more significantly than those in sevoflurane group.

Conclusion: Total intravenous general anesthesia maitained with propofol induced more significant suppression of cellular immunity compared with combined intravenous–inhalation general anesthesia maitained with sevoflurane.

1. INTRODUCTION

General anesthesia and surgical stress are know to interfere with patients’ cellular immunity through several mechanisms such as hydrocortisone increase, inhibition of NK cell and changes of T lymphocyte subpopulations. In the present study, we compared the effect of propofol and sevoflurane anesthesia on human cellular immunity in patients undergoing total hip arthroplasty through investigation of blood hydrocortisone, peripheral nature killer (NK) cells and T lymphocyte subpopulations.

2. PATIENTS AND METHODS

26 ASA physical status?and ? patients of both sexes scheduled for total hip arthroplasty were randomly divided into two groups: propofol group (n=13), total intravenous general anesthesia maitained with propofol was conducted; sevoflurane group (n=13), combined intravenous–inhalation general anesthesia maitained with sevoflurane was conducted. The patients were otherwise healthy without immune or blood system disease. Patients who had fever, infection or had received immunoregulatory drugs were also excluded.

All patients were premedicated with oral estazolam 15?20 mg. Anesthesia and surgical procedures were started at the same time in the morning. General anesthesia was induced with midazolam 0.15?0.20 mg/kg?fentanyl 5μg/kg and vecuronium 0.15 mg/kg body wt. Additional bolus injection of fentanyl or vecuronium was given during operation if needed. Anesthesia was maitained with propofol 6.0?8.0mg/kg.h iv injection in propofol group whereas sevoflurane at an expiratory concentration of 1.0%?1.2% in sevoflurane group. ECG, blood pressure and hemoglobin oxygen saturation were monitored in each patients.

Blood samples were obtained from peripheral vein before induction of anesthesia, 1 h after anesthesia and at the end of operation. Blood hydrocortisone was determined by radioimmunoassay (RIA). Peripheral nature killer (NK) cells and T lymphocyte subpopulations (CD3??CD4??CD8?cells) were investigated by FACSCalibur flow cytometer (USA BD Company) and data were evaluated using CELLQuest 3.1f supplied with the instrument.

2.1. Statistical analysis

The results were expressed as means ± SD. The Analysis of Variance was used for statistical evaluation. P<0.01 indicates that the difference is significant.

3. RESULTS

The general status of the patients are shown in Table 1. There was no significant difference of patients’ ages, body weights, operation time and the dosage of fentanyl consumed between two groups. No patients in the two groups received blood transfusion during operation. Blood hydrocortisone increased significantly after induction of anesthesia while the increase in propofol group was more significantly than in sevoflurane group (Table 2).

Significant decrease in CD3??CD4? T lymphocytes and CD4?/CD8? ratio were found after induction and the changes in propofol group were more significantly than those in sevoflurane group. CD8? cells remained statistically unaffected in both two groups. The percentage of NK cells decreased significantly after induction but there was no significant difference between two groups. The changes in NK cells and T lymphocyte subpopulations in the peripheral blood after induction of anesthesia are shown in Table 3.

Table 1 General status of the patients in two groups?x(_)±s?

Group	n	age?y?	weight?kg)	Operation time?min?
propofol	13	54±8	62±9	140±35
sevoflurane	13	52±9	60±10	137±33

Table 2 Changes in blood hydrocortisone in two groups ?ug/L, x(_)±s?

Group (n=13)

blood hydrocortisone

preinduction 1 h after anesthesia at the end of operation

propofol

384±103 684±82 ?? 691±91??

sevoflurane

379±98 540±101? 600±84?

?P<0.05, vs preinduction. ?P<0.05, vs sevoflurane group.

Table 3 Changes in peripheral NK cells and T lymphocyte subpopulations(x(_)±s)

	Group (n=13)	preinduction	1 h after anesthesia	at the end of operation
CD3????	propofol group	72.2±6.5	56.6±5.2??	53.0±6.0??
	sevoflurane group	71.3±5.8	63.4±6.2?	62.6±5.9?
CD4????	propofol group	48.8±6.0	36.0±5.5??	36.2±5.3??
	sevoflurane group	48.0±5.8	42.1±5.2?	42.7±5.2?
CD8????	propofol group	22.1±5.4	22.6±6.1	23.0±5.8
	sevoflurane group	22.7±5.3	22.4±5.8	21.3±5.8
CD4?/CD8?	propofol group	2.2±0.3	1.5±0.2??	1.5±0.2??
	sevoflurane group	2.3±0.3	1.9±0.3?	1.9±0.2?
NK???	propofol group	22.3±4.8	17.2±4.8?	17.5±4.3?
	sevoflurane group	22.9±5.2	17.0±5.6?	17.2±5.2?

?P<0.05, vs preinduction. ?P<0.05, vs sevoflurane group.

4. DISCUSSION

General anesthesia and surgical stress are know to influence patients’ cellular immunity [1-3]. The ratio of CD4?/CD8? is regarded as a common measure of immune system status in healthy individuals and also commonly assessed in the diagnosis and staging of diseases affecting the immune system [4,5]. NK cells are major cytokine( producers during bacterial sepsis and activation of NK cells improves bacterial clearance by priming macrophages to help clear a subsequent bacterial challenge [6]. In this study we have shown that two different anesthetic techniques: total intravenous general anesthesia maitained with propofol and combined intravenous–inhalation general anesthesia maitained with sevoflurane lead to immunosuppression during total hip arthroplasty, as shown through the imbalance in immune cell composition of the peripheral blood, including CD3??CD4? and NK cells as well as CD4?/CD8? ratio.

After anesthesia and operation we observed increase of blood hydrocortisone. Hydrocortisone is synthesized in the cortex of the adrenal gland, where it is released into the blood stream. The effect of endocrine stress response on anesthesia and operation are always mediated by glucocorticoid hormone such as hydrocortisone [7]. The increase of hydrocortisone in group of total intravenous general anesthesia was more significantly than in group of combined intravenous–inhalation general anesthesia, indicating that combined intravenous–inhalation general anesthesia maitained with sevoflurane attenuate the endocrine stress response better than total intravenous general anesthesia maitained with propofol.

There have been reports that opiate drugs and intravenous and inhaled anesthestic have been shown to contribute to imunosuppression [8,9]. Mustafa et al compared immunosuppressive effects of propofol and thiopentan and found propofol to have greater effect [10]. They attribute it to chemical structure of the propofol and indirectly cytokines mediated by the agents. The general status and surgical injury between two groups had nonsignificant difference so that influences to the observed changes by factors besides anesthesia are basically equal. In this study we also found that the immunosuppression in group of total intravenous general anesthesia was more significant than that in group of combined intravenous–inhalation general anesthesia, it may be related to the effect of propofol. Besides, the more significant effect on endocrine stress response and release of hydrocortisone in propofol group may take action simultaneously. There have already been investigates about the relationship between the cortisol response and immune changes in the perioperative period and it was found that increase of stress hormone suppressed T lymphocytes responses to surgery [11,12].

This study showed that cellular immunity was interfered during general anesthesia in total hip arthroplasty. Total intravenous general anesthesia maitained with propofol induced more significant suppression of cellular immunity compared with combined intravenous–inhalation general anesthesia maitained with sevoflurane.

REFERENCES

[1] Brand JM, Kirchner H, Poppe C, et al. The effects of general anesthesia on human peripheral immune cell distribution and cytokine production. Clin Immunol Immunopathol, 1997; 83:190-4.

[2]Hory Y, Ibuki T, Hosokawa T, et al. The effect of neurosurgical stress on peripheral lymphocyte subpopulations. J Clin Anesth; 2003; 15:1-8.

[3]Procopio MA, Rassias AJ, DeLeo JA, et al. The in vivo effects of general and epidural anesthesia on human immune function. Anesth Analg, 2001; 93: 460-5.

[4]Syrijala H, Surcal HM, Ilonen J. Low CD4?/CD8? T lymphocyte ratio in acute myocardial infarction. Clin Exp Immunol, 1991; 83:326-8.

[5]Li T, Qiu Z, Han Y, et al. Rapid loss of both CD4+ and CD8+ T lymphocyte subsets during the acute phase of severe acute respiratory syndrome. Chin Med J, 2003; 116:985-7.

[6]Scott MJ, Hoth JJ, Gardner SA, ET AL. Natural killer cell activation primes macrophages to clear bacterial infection. Am Surg, 2003; 69: 679-86.

[7]le Roux CW, Chapman GA, Kong WM, et al. Free cortisol index is better than serum total cortisol in determining hypothalamic-pituitary-adrenal status in patients undergoing surgery. J Clin Endocrinol Metab, 2003; 88:2045-8.

[8]Welters I. Opioids and immunosuppression. Clinical relevance? Anaesthesist, 2003; 52: 442-52.

[9]Puig NR, Ferrero P, Bay ML,et al. Effects of sevoflurane general anesthesia: immunological studies in mice. Int Immunopharmacol, 2002; 2: 95-104.

[10]Mustafa Alt?ndi?, Emel Türk Ar?ba?, Ali Kart, et al. Comparison of Immunological Effect of Propofol and Thiopentone on the Immune System. Journal of Turgut Özal Medical Center, 1997; 4: 187-92.

[11]Jameson P, Desborough JP, Bryant AE, et al. The effect of cortisol suppression on interleukin-6 and white blood cell responses to surgery. Acta Anaesthesiol Scand, 1997; 41: 304-8.

[12]Januszkiewicz A, Essen P, McNurlan MA, et al. A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers. Metabolism, 2001; 50: 1308-14.

First Published April 27th 2007

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