Asian Cardiovasc Thorac Ann 2006;14:505-510
© 2006 Asia Publishing EXchange Ltd
Minor Infection Encouraged by Steroid Administration During Cardiac Surgery
Tetsuro Sano, MD,
Shigeki Morita, MD,
Munetaka Masuda, MD,
Hisataka Yasui, MD
Department of Cardiovascular Surgery, Graduate School of Medical Sciences, The Kyushu University, Fukuoka, Japan
For reprint information contact: Tetsuro Sano, MD Tel: 81 92 642 5557 Fax: 81 92 642 5566 Email: tsanokyu{at}yahoo.co.jp, Department of Cardiovascular Surgery, Graduate School of Medical Sciences, The Kyushu University, 3-1-1 Maidashi Higashi-ku Fukuoka 812-8582, Japan.
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ABSTRACT
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The aim of this study was to investigate whether steroid administration would increase the risk of postoperative infection. Sixty adults who underwent elective cardiac surgery under cardiopulmonary bypass were prospectively randomized into two groups. Thirty-one patients received hydrocortisone (50 mg·kg–1) before and after cardiopulmonary bypass, the other 29 served as controls. Various hemodynamic and pulmonary measurements were obtained perioperatively, and the white blood cell counts and levels of C-reactive protein were checked up to the 14th postoperative day. Steroid administration did not have any favorable effects during the perioperative period. Re-administration of antibiotics was needed in 7 patients (22.6%) after the 7th postoperative day in the steroid group, and in 3 (10.3%) in the control group. The peak white cell counts and C-reactive protein levels after the 7th postoperative day were significantly higher in the steroid group. Steroid administration offered no clinical benefit to patients undergoing cardiac surgery with cardiopulmonary bypass, and it may encourage minor infections in the late postoperative period.
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INTRODUCTION
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It is well known that cardiac surgery under cardiopulmonary bypass (CPB) induces a systemic inflammatory response.1 This is thought to cause postoperative organ dysfunction. Steroids have been used during open heart surgery to reduce the inflammatory response during CPB and preserve organ function.2 Many investigators have reported favorable effects of steroid administration during open heart surgery.3–9 However, some recent studies have showed detrimental effects of steroids.10–13 The aim of this study was to investigate whether this retardation of recovery of adaptive immunity induced by steroid administration would increase the risk of infection after open heart surgery.
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PATIENTS AND METHODS
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Sixty adults who underwent elective cardiac surgery with CPB at Kyushu University Hospital were prospectively randomized into two groups by our operation-registry staff who were not involved in this study. The study protocol was approved by our institutional review board. Thirty-one patients received hydrocortisone (50 mg·kg–1) before and after CPB (steroid group). The other 29 patients received saline as controls (non-steroid group). All patients gave their written informed consent. They had no major complications such as kidney or liver dysfunction. The profiles of each group are given in Table 1
. Intraoperative management involved standard anesthetics (fentanyl 50 µg·kg–1, midazolam 1–2 mg, pancuronium 0.1 mg·kg–1) and routine monitoring techniques (electrocardiogram, central venous or pulmonary arterial pressure, urine output, bladder and skin temperature) in all patients. The cardiac output was examined 10 min after insertion of a Swan-Ganz catheter, after terminating CPB, and every hour after coming off CPB. Blood gases, electrolytes, and serum glucose levels were assessed every 30 min during the operation. The extracorporeal circuit consisted of a hollow-fiber membrane oxygenator with a heat exchanger (D903; Dideco, Mirandola, Italy), polyvinyl chloride tubing (Baxter, Irvine, CA, USA), and silicone rubber pump tubing (Sumitomo, Tokyo, Japan). The circuit was primed with 1,600 mL of Ringer’s lactate solution, 100 mL of 25% human albumin, 45 mEq of sodium bicarbonate, 1,000 mg of vitamin C, 150 mL of 20% mannitol, 4,500 U of heparin, and 1 g of cefazolin. Before the institution of CPB, heparin was administered (300 IU·kg–1) and the activated coagulation time was kept at > 400 sec. A CPB flow rate of 2.5 L·min–1·m–2 was maintained, and bladder temperature was kept at 30°C. Myocardial protection was accomplished using intermittent antegrade cold potassium crystalloid cardioplegia. Ice slush was placed around the heart to keep the myocardial temperature at 4°C or less. The blood pressure was kept above 50 mm Hg using phenylephrine. Protamine was given (300 IU·kg–1) at the end of CPB. Coronary bypass grafts comprised left internal thoracic arteries, left radial arteries, and right gastroepiploic arteries. The mean number of grafts per patient was 2.7 ± 0.84 in the steroid group and 2.8 ± 0.92 in the non-steroid group.
In the intensive care unit (ICU), all patients were mechanically ventilated on postoperative day (POD) 1. The respiratory rate was adjusted to keep the PCO2 between 30 and 40 mm Hg. The fraction of inspired oxygen was adjusted to keep PO2 between 100 and 200 mm Hg under a positive end-expiratory pressure of 5 mm Hg. Criteria for extubation in our ICU include alert consciousness, hemodynamic stability, and adequate pulmonary function (PO2 > 100 mm Hg with a fraction of inspired oxygen of 0.4, positive end-expiratory pressure < 5 mm Hg, PCO2 < 45 mm Hg without mechanical support). Ten percent glucose solution (800 mL·m–2 daily) was used as a standard infusion. Dopamine and dobutamine were administered to keep the mean arterial pressure > 70 mm Hg. Patients were sedated with propofol (1–3 mg·kg–1·hr–1) if needed. Blood gases, electrolytes, and serum glucose levels were examined every 1–2 hr in the ICU. Blood samples to check the postoperative course were taken routinely on POD 1, 2, 3, 5, 7, and 14. If needed, additional blood samples were taken. Antibiotics (cefazolin plus amikacin) were given intravenously to all patients by POD 3. If an increase in white blood cell (WBC) count or C-reactive protein (CRP) recurred, or fever > 38°C was found after POD 5, additional antibiotics were administered intravenously for 1 to 3 days.
Fisher’s exact test was applied to categorical data. Comparison of the patient characteristics, perioperative WBC count, and CRP levels were made with the Student t test. A probability value < 0.05 was considered significant. All data were computed with Stat View version 5.0 (SAS Institute, Cary, NC, USA).
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RESULTS
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Table 1
shows the clinical characteristics of the patients. There were no significant differences in patient profiles between groups. Table 2 shows the hemodynamic data during the perioperative period. There was no significant difference in these data. Table 3 shows the perioperative lung function data, blood glucose levels, and body weights. The pulmonary function in terms of oxygenation of blood, carbon dioxide excretion, and intubation time was not significantly different between the two groups. The blood glucose level in the steroid group on arrival in the ICU was significantly higher than in the non-steroid group. The dose of insulin was also greater in the steroid group on ICU arrival.
There was no incidence of major wound infection such as mediastinitis in either group. There were minor complications: atrial flutter in 8, ventricular tachycardia in 1, pericardial effusion in 1, acute renal failure in 2, pneumothorax in 1, and enteritis in 1 in the steroid group; while in the non-steroid group there was atrial flutter in 6, pericardial effusion in 3, and pneumonia in 1. The peak WBC counts in POD 1–3, POD 4–6, and after POD 7 in the steroid group were significantly higher than those in the non-steroid group (Table 4, Figure 1). The peak value of CRP in POD 1–3 was significantly greater in the non-steroid group. However, the levels of CRP rapidly decreased in the non-steroid group and the peak value of CRP after POD 7 was significantly lower than that in the steroid group (Table 4, Figure 1). The numbers of days when the patient’s fever was more than 37.5°C showed a similar trend to the CRP level, although the differences between the groups did not reach statistical significance (Table 4). Seven patients received antibiotics intravenously after POD 7 in the steroid group, while only 3 in the non-steroid group required antibiotics (Table 4; p = 0.019). The lengths of hospital stay were not significantly different between the groups.
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Figure 1. Postoperative inflammatory response. White columns indicate the steroid group and black columns indicate the non-steroid group. Error bars indicate the standard deviations. *p < 0.05, **p < 0.01 vs non-steroid group. CRP = C-reactive protein, WBC = white blood cell.
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DISCUSSION
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Many investigators have reported that steroid administration benefits patients undergoing open heart surgery; however, some recent reports have shown that steroids had no favorable effect on the postoperative course, but rather retarded extubation.3–9,11–13 The issue has been extensively reviewed.14 From our department, Mayumi and colleagues10 reported that steroid administration and CPB synergistically suppressed the immune response after open heart surgery. Thus, we changed from using methylprednisolone (biological half-life, 12–36 hr) to hydrocortisone (biological half-life, 8–12 hr) to reduce the impairment of cellular immunity.
Major infections such as mediastinitis are rare events (approximately 0.5% in our institute). It is very difficult to detect a difference in such a relatively rare endpoint, so we used parametric variables (WBC count and CRP). We found that these inflammatory parameters were transiently increased in some patients after POD 5, and we assumed that this reflected the incidence of minor infection after surgery. Since the timing of the transient increase of inflammatory parameters was different from patient to patient, we compared the maximum values.
We administer antibiotics intravenously to avoid infection when we observe a recurrent increase of inflammatory parameters or fever higher than 38°C after POD 5. Seven patients were given antibiotics intravenously after POD 7 in the steroid group vs only 3 in the non-steroid group. There was also a tendency towards a slower decrease of inflammatory parameters in the steroid group. As a result of this slow decrease, the peak WBC count and CRP level after POD 7 were significantly greater in the steroid group than in the non-steroid group. Taking these data together, it is conceivable that steroid administration may promote minor infections in the late phase of the postoperative period. Glucocorticoid itself induces granulocytosis, so the significantly higher WBC count in the steroid group seen by POD 3 was probably due to the effect of the steroid. This granulocytosis induced by glucocorticoid ends by 48 hr.15 Therefore, the significantly higher WBC count after POD 3 in the steroid group cannot be explained merely by the effect of the steroid.
In the healthy subject, inflammatory responses help adaptive immunity and synergistically work against various pathogens. Thus, the inflammatory response itself is not necessarily an adverse response so long as it is not excessive. In some reports, steroid administration strongly inhibited the increase of cytokines such as interleukin-6 and -8.6–9 This strong inhibition may interfere with preparation of the immune system for infection after surgery. In view of this, steroid administration would not have any advantage in routine open heart surgery, and we and other investigators could not find any favorable effect of steroid on organ function during the perioperative period (Tables 2 and 3).16–19 There was no increase in the incidence of major infection in our patients given steroids during CPB. In patients with normal immunity, partially impaired adaptive immunity may be sufficient to prevent major infection. These days, there are more patients with advanced age, and they frequently have subnormal immunity. In such patients, retardation of recovery of adaptive immunity by steroid administration may increase the possibility of a major infection. Off-pump surgery should be performed in such patients if possible.
It was concluded from this study that steroid administration offered no clinical benefit to patients undergoing cardiac surgery with CPB in the early phase of the postoperative period, and may promote minor infection in the late phase of the postoperative period.
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ABSTRACT
INTRODUCTION
