Hypothermia as a Risk Factor for Pediatric Cardiothoracic Surgical Site Infection

To investigate whether deep hypothermia is associated with pediatric cardiothoracic surgical site infection, we performed a retrospective study evaluating many variables thought to be related to postoperative wound infection. Lowest core body temperature was the clinical factor most strongly associated with increased risk of infection and was the sole controlling factor in a multivariate analysis. Although many risk factors have been reported for cardiothoracic surgical site infections in adult populations, 1 studies specific to such infections in pediatrics are scarce, and pediatric risk factors are not as well-characterized. 2, 3 A major difference between pediatric and adult cardiothoracic surgery is the use of deep hypothermia in pediatric cases. Hypothermia protects against ischemic damage by lowering tissue oxygen demands during a time when perfusion is significantly reduced or even halted to allow for a dry operating field. Clinical evidence for an association between hypothermia and increased risk of infections has been demonstrated by a retrospective study of children kept hypothermic (30°C) to control cerebral edema after drowning or Reye’s syndrome. 4 These children were at a markedly increased risk of various infectious complications compared with a control group. More recently a randomized clinical trial in adult colorectal surgery patients demonstrated that patients whose core body temperatures were allowed to drop by ∼2°C were three times more likely to develop surgical site infections than patients who were kept normothermic. 5 Given these findings and the far greater depths of hypothermia that pediatric cardiothoracic surgical patients are subjected to, we hypothesized that deep hypothermia would be associated with cardiothoracic surgical site infections in these patients. We conducted an epidemiologic study to investigate this association in a population of pediatric cardiothoracic surgical patients at a tertiary care center in Denver. A case-control design was used, with 25 cases of cardiothoracic surgical site infections drawn from all pediatric cardiothoracic surgery patients with operation dates between December, 1991, and January, 1995, for whom medical records were available for review. The case definition for infection was modified slightly from that described in the Centers for Disease Control National Nosocomial Infection Survey 6 and included patients who developed wound infections documented in the surgical service’s morbidity and mortality database; or whose surgical sites yielded pathogens on culture and had clinical signs of infection documented in their charts. Patients whose infections developed >1 month after surgery were excluded. Patients were also excluded if more than one operation requiring opening of the mediastinum was performed within 1 month before documentation of infection. Controls (n = 54) were selected at random from the remaining population of cardiothoracic surgery patients during this period. A ratio of two controls per case was used, with extra sampling of controls to account for potential exclusion of controls or inaccessibility of medical records. Any patients who exhibited signs of cardiothoracic surgical site infections but met the exclusion criteria for cases were excluded from the control group. All data were abstracted from patient medical records. Demographic variables included age, sex and race. Preoperative health status was measured using the American Society of Anesthesiologists (ASA) score. Operative duration was measured in minutes. Intraoperative hypothermia was measured as the lowest core body temperature (°C). Other intraoperative variables included whether cardiopulmonary bypass was used, critical care pathway (an index of severity/complexity of procedure, with higher letters representing more complex cases), and standardized antibiotic units. This last variable adjusted intraoperative antibiotic doses for the weight of the patient, the duration of the operation and the recommended prophylactic dose for the given chemotherapeutic agent. Postoperative cardiac output status was determined by examining several clinical variables (vital signs, urine output, venous oxygen saturation, pulse pressures and administration of inotropic therapies) for the first 24 postoperative hours. In univariate analyses of continuous variables approximating a normal distribution, Student’s t test was used; the Wilcoxon rank sum test was used if continuous variables did not approximate a normal distribution. The chi square test was used for categorical variables. Lowest core body temperature was analyzed as a categorical variable (by quartile of all subjects combined) and as a continuous variable. Multivariate analyses were performed using multiple logistic regression. Only ASA score significantly altered the association between lowest core body temperature and cardiothoracic surgical site infections. Thus the final model contained only these two predictor variables. All analyses were performed using the SAS System, Version 6.12. A comparison of cases and controls by study variables is shown in Table 1. Cases were significantly (P < 0.05) more likely than controls to be infants, of Hispanic ethnicity, have a higher ASA score, have undergone deep hypothermia and be on cardiopulmonary bypass. The mean value of standardized antibiotic units was lower for cases than for controls, but this difference was not statistically significant.Table 1: Comparison of cases and controls by study variablesThe most significant risk factor for cardiothoracic surgical site infections was deep hypothermia. The range of lowest core body temperature for cases was 11.0–36.3°C and 14.0–37.1°C for controls. For cases, the mean ± sd was 22.1 ± 7.3°C; for controls the mean ± sd was 28.0 ± 6.0°C (P < 0.001). Ranges and odds ratios for lowest core body temperature quartiles are shown in Table 2. Quartile 1 (least hypothermic) served as the referent group, with Quartile 4 comprising patients subjected to the greatest depth of hypothermia. No significant increase in risk was seen for Quartiles 2 and 3; however, Quartile 4 displayed a significant increase in risk [odds ratio, 19.50; 95% confidence interval (CI), 3.38–112.45].Table 2: Quartiles of lowest core body temperature and risk of cardiothoracic surgical site infection per quartileLowest core body temperature Quartile 4 was chosen as the primary term in the multiple logistic regression model, because it conveyed by far the strongest and most significant risk. Multivariate analysis of the risk for Quartile 4 (adjusting for ASA score) yielded an odds ratio of 5.80 (95% CI 1.69–19.93). Further adjustment for age, gender, race, operative duration, cardiopulmonary bypass, critical care pathway, intraoperative standardized antibiotic units or postoperative cardiac output deficiency did not significantly affect the risk of cardiothoracic surgical site infection conveyed by hypothermia. Analyzing lowest core body temperature as a continuous variable yielded an unadjusted odds ratio per °C of 1.15 (95% CI 1.06–1.24). Adjusting for ASA score yielded an odds ratio per °C of 1.11 (95% CI 1.02–1.21). Comment. Surgical site infections have a complex etiology. Host, agent and environmental factors combine to render a patient susceptible to infection. Several risk factors were found by univariate analysis to be associated with cardiothoracic surgical site infections in our study population; however, by multivariate analysis only deep hypothermia retained a significant association. Sensitive analyses of the interaction between hypothermia and other risk factors were not possible because of the small sample size of this study. Nonetheless these findings suggest that deep hypothermia has a primary role within the etiology of pediatric cardiothoracic surgical site infections. The increased risk of infection associated with hypothermia has been postulated to be the result of its immunosuppressive effect on neutrophils (PMN), coincident to the introduction of pathogenic bacteria through invasive surgical procedures. Several in vitro studies have demonstrated that hypothermia affects various PMN functions, including chemotaxis, endothelial adhesion, phagocytosis and generation of reactive oxygen intermediates. 7–15In vivo studies have demonstrated similar effects on PMN release from bone marrow, chemotaxis and generation of reactive oxygen intermediates. 7, 13–15 Hypothermia also reduces macrophage motility and antibody production. 5 Recently it has been suggested that granulocyte colony-stimulating factor might improve outcome in infections after hypothermia. 16 The retrospective nature of this study leaves unanswered several questions regarding the influence of hypothermia on the risk of cardiothoracic surgical site infections in pediatric patients. Our data were not sufficient to investigate whether the duration of hypothermia interacted with the depth of hypothermia to influence the risk of cardiothoracic surgical site infections. Despite the modest dose response demonstrated, our data analyzed by quartile suggest a threshold effect, with a significant increase in risk seen only after the core body temperature was dropped by ∼17°C in this population. Although this threshold effect may be an artifact of the small sample size of this study, a number of recent studies suggest that this effect may be limited to deep hypothermia in that mild decreases in intraoperative temperature did not increase the risk of infection. 17–21 A larger, prospective study addressing these issues and incorporating a bioassay method for measuring PMN function may provide further clues into the complex etiology of surgical site infections. In addition decreased body temperature may have other infection-promoting effects. 22 The benefits of hypothermia in pediatric cardiothoracic surgery outweigh the risks. By reducing ischemic injury to the brain and other tissues, hypothermia allows the correction of complex cardiac defects that would otherwise not be possible. The findings of this study indicate that the risk of pediatric cardiothoracic surgical site infections related to hypothermia may warrant greater supplementation of antibacterial defenses, including ensuring adequate intraoperative antibiotic coverage and/or postoperative stimulation of leukocyte response. 16 Acknowledgments. We thank Esther Carpenter, R.N. and Susan Dolan, R.N., M.S. for their technical assistance in this study.