Ann Thorac Surg 2007;84:1627-1632. doi:10.1016/j.athoracsur.2007.06.028
© 2007 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Postoperative Hypothermia and Blood Loss After the Neonatal Arterial Switch Procedure
Yusuke Iwata, MDa,
Jane W. Newburger, MDb,
David Zurakowski, PhDa,
Richard A. Jonas, MDa,*
a Department of Cardiovascular Surgery, Children’s National Medical Center, Washington, DC
b Department of Cardiology, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts
Accepted for publication June 6, 2007.
* Address correspondence to Dr Jonas, Department of Cardiovascular Surgery, Children’s National Medical Center, 111 Michigan Ave NW, Washington, DC 20010 (Email: rjonas{at}cnmc.org).
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Abstract
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Background: Numerous studies have demonstrated that mild hypothermia helps reduce hypoxic/ischemic brain injury that may occur during neonatal cardiac procedures. However, traditional intensive care practices emphasize aggressive rewarming, and the risk of excessive bleeding that may be related to hypothermia.
Methods: An analysis was conducted of prospectively collected temperature and blood loss data on 47 neonates (30 boys, 17 girls) with transposition of the great arteries who underwent an arterial switch operation at median age 6 days (range, 2 to 23 days) and a mean weight of 3.6 ± 0.6 kg. Blood loss was compared between 26 patients with mean temperatures below 35.5°C for first 6 hours after operation (mild hypothermia group) and 21 patients at 35.5°C or higher (normothermia group). Repeated-measures analysis of variance and regression modeling were used to evaluate the association between temperature and blood loss and to detect outliers.
Results: Total postoperative blood loss was 31 ± 28 mL in the first 6 hours and 61 ± 37 mL at 24 hours (range, 15 to 238 mL). Postoperative blood loss between two groups at 6 or 24 hours did not differ significantly. After two outliers were removed, no significant relationship remained between body temperature at 6 hours and cumulative blood loss at 24 hours.
Conclusions: Mild postoperative hypothermia does not increase blood loss in neonates after the arterial switch operation. Lack of a difference between the two groups is not likely due to the study being underpowered. We recommend avoidance of aggressive rewarming, which might exacerbate potential neurologic injury.
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Introduction
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Traditional intensive care practice emphasizes the importance of aggressive rewarming of neonates and young infants who are hypothermic [1–3]. The deleterious effects of perioperative hypothermia have also been well documented for cardiac and noncardiac adult surgical patients [4–9]. Cardiac surgeons have particularly emphasized the importance of hypothermia in exacerbating postbypass coagulopathy [10–13]. However, our experience with the use of postoperative hypothermia to control junctional tachycardia suggested that hypothermia had minimal impact on bleeding after neonatal and infant cardiac procedures [14–16].
Recent reports in the neuroscience literature have described the effectiveness of systemic hypothermia in reducing hypoxic/ischemic brain injury [17–20]. Our own studies on brain injury in piglets have emphasized the risk of exacerbation of brain injury by excessive rewarming above 37°C [21]. The concern is that aggressive rewarming may increase brain injury after ischemic insult, although there are no data to support this speculation in neonates undergoing cardiac operations. The aim of the study was to investigate the impact of mild postoperative hypothermia on postoperative blood loss and blood product requirements after cardiac surgical procedures in a neonatal population.
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Patients and Methods
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Analysis was performed on 47 consecutive neonates (17 girls, 30 boys) with transposition of the great arteries who were enrolled between June 2001 and April 2004 in a study of hematocrit strategy conducted at Children’s Hospital Boston. All patients underwent an arterial switch operation at median age 6 days (range, 2 to 23 days) and at a mean weight of 3.6 ± 0.6 kg. Institutional Review Board approval was obtained for the enrollment of patients in the prospective study. The need for additional patient consent for this meta-analysis was waived because no patient identifiers were available and no follow-up contact was initiated with patients or families.
The arterial switch operation was performed with cardiopulmonary bypass with a roller pump and membrane oxygenator with blood prime. Both pH and partial pressure of carbon dioxide (PCO
2) were maintained according to the pH stat strategy. The lowest hematocrit was maintained above 25% in all patients. Intraoperative blood loss was estimated and recorded. Intraoperative and postoperative management was standardized for all patients. Postoperative blood loss data were collected starting at the time of arrival in the intensive care unit (ICU). Temperature data were recorded by rectal temperature probe for at least the first 12 hours and then by rectal probe or thermometer.
Hypothermia was applied intraoperatively in all patients. Most were cooled to deep hypothermia, with 41 patients cooled to less than 18°C. Minimum rectal temperatures of another 6 patients were from 18.3° to 21.8°C. Circulatory arrest was used in 45 patients, of whom 40 were cooled to less than 18°C. Two patients who did not undergo circulatory arrest were cooled to 16.4° and 21.8°C.
After arriving at the ICU, most patients were allowed to rewarm passively. Rewarming with heating lamps and pads was used rarely, and care was taken to avoid hyperthermia. Mean body temperature for the first 6 hours after surgery, which is considered the high-risk period for excessive bleeding in this patient population, was calculated by averaging hourly body temperature in the first 6 hours from admission to ICU. For the cohort of 47 patients as a whole, mean body temperature for the first 6 hours after surgery was 35.4° ± 0.7°C (range, 33.3° to 37.2°C).
Analysis was undertaken looking at temperature both as a continuous variable and also with the patients divided into a mildly hypothermic group (n = 26) with a body temperature of less than 35.5°C and a normothermic group (n = 21) that had a body temperature of 35.5°C or higher in the first 6 hours postoperatively. The two groups were not significantly different with respect to age: the median patient age was 5 days (range, 2 to 23 days) in the mild hypothermia group and 7 days (range, 2 to 13 days) in the normothermia group (p = 0.13, Mann-Whitney U test). In addition, weight at arrival was comparable between the hypothermia and normothermia groups (3.58 ± 0.62 kg versus 3.62 ± 0.60 kg, p = 0.80, Student t test).
Blood was collected for platelet count, prothrombin time, and activated partial thromboplastin time (APTT) analysis at admission to the ICU and on the first postoperative day.
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Statistical Analysis
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Variables related to blood loss were compared between the hypothermia and normothermia temperature groups using repeated-measures mixed-model analysis of variance (ANOVA), with time as the within-subjects factor and an interaction F test for comparing slopes of cumulative blood loss during the first 6 hours and at 24 hours postoperatively between the mild hypothermia and normothermia groups. An unstructured covariance type was used in the final analyses and provided the best model fit according to Akaike’s information criteria.
Regression analysis was used to determine whether a significant linear or nonlinear relationship existed between temperature as a continuous variable and postoperative blood loss. Regression diagnostics to identify potential outliers or overly influential observations included DFBETAS [22].
Simple proportions, such as aprotinin usage between groups, were compared by the Fisher exact test. Two-tailed values of p < 0.05 were considered statistically significant. Statistical analysis was performed with SPSS 15.0 software (SPSS Inc, Chicago, IL). A retrospective power analysis was conducted to determine, on the basis of sample sizes of 26 mildly hypothermic and 21 normothermic patients, the statistical power to detect mean differences of 25 to 35 mL in cumulative blood loss in the first 6 postoperative hours (nQuery Advisor 6.0, Statistical Solutions, Saugus, MA).
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Results
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No deaths or neurologic events, as determined by clinical observation, occurred in the ICU. A comprehensive neurologic evaluation of all patients before discharge identified only minor abnormalities, such as changes in muscle tone. As summarized in Table 1, no differences were found between the mildly hypothermic and normothermic groups in any of the bypass related times, use of aprotinin, or incidence of open chest incision or reexploration. Forty-five patients, 20 in normothermic group and 25 in the mildly hypothermic group, had deep hypothermic circulatory arrest, with a mean circulatory arrest time of 19 minutes. Nine patients (35%) in the mildly hypothermic group and 14 (67%) in the normothermic group had a ventricular septal defect (p = 0.04). Figure 1
illustrates that there were no differences between the two groups in the volume of fluids or blood products infused intraoperatively or in the fluid output. Figure 2
shows that there was no significant difference in the hematocrit value after admission to the ICU between the groups, although the hematocrit value was significantly different at 2 hours after bypass.
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Fig 1. No significant differences were noted in any of the variables relating to fluid balance during the surgical procedures between the groups with mild hypothermia (clear bars) and normothermia (filled bars). Other variables included fresh frozen plasma, cryoprecipitate, and whole blood. (Error bars represent the standard error. PRBCs = packed red blood cells.)
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Fig 2. Hematocrit was comparable in the mild hypothermia (triangles) and normothermia (circles) groups before operation, induction, and end of bypass. Hematocrit was significantly higher in the mild hypothermia group 1 hour after bypass, although no differences were found between groups at admission to the intensive care unit (ICU) or on postoperative day 1. (*Statistically significant at p < 0.05 by repeated-measures analysis of variance. Error bars represent standard errors.)
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Figure 3
shows the differences in body temperature between the mildly hypothermic and normothermic groups (Fig 3, p < 0.05). Mean postoperative blood loss in the first 6 hours for both groups combined was 31 ± 28 mL (range, 5 to 189 mL) and 61 ± 37 mL (range, 15 to 238 mL) at 24 hours, with no significant differences between the two groups (Fig 4). Repeated-measures ANOVA indicated that although blood loss increased over 24 hours (F = 77.25, p < 0.0001), no significant differences in the amount of postoperative blood loss were observed between the mild hypothermia and normothermia groups in the first 6 hours (F = 0.56, p = 0.46) or at 24 hours (F = 0.42, p = 0.52). A comparison of the slopes between the two groups throughout the first 6 hours (Greenhouse-Geisser F = 0.73, p = 0.60) and throughout 24 hours (Greenhouse-Geisser F = 0.34, p = 0.64) showed that the slopes were equal, which meant hourly cumulative rate of blood loss was similar.
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Fig 3. Body temperature was comparable in the mild hypothermia (triangles) and normothermia (circles) groups at end of bypass and 1 hour after bypass. The mild hypothermia group had lower body temperature at admission to the intensive care unit (ICU) and at 1 to 6 hours in the ICU; however, no group differences were observed at 7 to 24 hours in the ICU. (*Statistically significant at p < 0.01 by repeated-measures analysis of variance. Error bars represent standard errors.)
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Fig 4. Cumulative blood loss at 24 hours after operation was not significantly different (p = 0.52) between the mild hypothermia (triangles) and normothermia (circles) groups as evaluated by repeated-measures analysis of variance (ANOVA). (Error bars represent the standard error.)
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The repeated-measures ANOVA indicated no significant differences between the two groups at any 1-hour time point throughout the first 6 hours and the 24-hour postoperative period. Our retrospective power analysis using ANOVA revealed that the sample sizes of 26 mildly hypothermic and 21 normothermic patients provided a power of 98% to detect a mean difference of 35 mL in cumulative blood loss between the two groups within the first 6 hours postoperatively, 93% power to detect a difference of 30 mL, and 82% power to detect a difference of 25 mL. Thus, it is unlikely that the lack of differences between the two groups was due to the study being underpowered because the expected probability of a type II error is less than 20%.
No significant group differences were noted in any 6-hour time period, either in blood loss or blood product usage, during the first 24 hours postoperatively (Fig 5, 6).
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Fig 5. There was no significant difference in postoperative blood loss between the mild hypothermia (clear bars) and normothermia (filled bars) groups per each 6-hour interval. (Error bars represent the standard error.)
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Fig 6. No significant difference was found in postoperative blood product requirements between the mild hypothermia (clear bars) and normothermia (filled bars) groups per each 6-hour interval. (Error bars represent the standard error.)
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Regression analysis of temperature as a continuous variable indicated an inverse relationship when all 47 neonates were evaluated together that could be characterized by a nonlinear exponential relationship, with lower temperatures associated with greater postoperative bleeding. Of the 5 patients who had a cumulative blood loss exceeding 100 mL during the first 24 hours after surgery (103, 105, 112, 140, and 238 mL), 4 were in the mild hypothermia group. However, inspection of possible outliers or overly influential observations, as flagged by DFBETA values exceeding 3, indicated that the 2 patients with the highest blood losses (140 mL at 33.3°C and 238 mL at 33.95°C) were outliers and that their inclusion in the analysis could distort the actual relationship between temperature and blood loss. These 2 patients are identified in Figure 7.
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Fig 7. Scatter plot shows body temperature at 6 hours and blood loss for the first 24 hours postoperatively. Two major outliers are indicated as white triangles: (A) was a patient with a blood loss of 140 mL at 33.3°, and (B) was a patient with a blood loss of 238 mL with a body temperature of 33.95°. After excluding these overly influential observations, no significant linear or nonlinear correlation of any kind was found between temperature and blood loss among the remaining 45 neonates.
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After removing these two observations from the regression analysis, no significant relationship of any kind (linear or nonlinear) was found among the remaining 45 patients. Therefore, the inverse relationship as suggested in Figure 7 is influenced by only two data points, both of which represent very low temperatures at 6 hours and very high amounts of blood loss at 24 hours. These two outliers clearly dominate and would lead to misleading results if left in the analysis. Furthermore, their removal improves the accuracy of the analysis, which indicates that cumulative blood loss at 24 hours is not significantly related to temperature.
The difference between the two groups for values of coagulation variables was not significant. However, although the normothermia group showed no change in mean APTT from admission to the ICU to postoperative day 1 (38.1 ± 11.1 to 39.4 ± 9.9 seconds, p = 0.79), APTT was elevated among patients in the hypothermic group at admission to the ICU and then normalized at postoperative day 1 (44.2 ± 10.6 to 38.3 ± 10.8 seconds, p = 0.07).
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Comment
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Cardiac surgeons have been aware for many years that hypothermic cardiopulmonary bypass disturbs the coagulation system, resulting in multiple abnormalities in platelet function and coagulation indices [10, 23]. Exposure of the neonate to the foreign surface of the cardiopulmonary bypass circuit is relatively greater compared with that of an adult. Neonates are particularly susceptible to coagulation abnormalities in view of their immature vitamin K hepatic synthetic mechanisms as well as the general immaturity of their coagulation system. Heat regulation is also difficult in the neonate because of the high ratio of surface area to volume. It has therefore been difficult to define the impact of postoperative hypothermia in exacerbating bleeding early postoperatively.
Some investigators have demonstrated that mild hypothermia alters coagulation enzyme activity and platelet function [24, 25]. Shimokawa and colleagues [26] emphasized that traditional coagulation tests, for example APTT, are performed at 37°C and the influence of hypothermia can thus be underestimated. They recommend that hemostatic measurements should be performed at the actual body temperature [26]. Our APTT data in the hypothermic group at admission to the ICU may have been inaccurate for this reason, thereby possibly explaining the lack of difference between our two groups.
Martini and colleagues [27] reported the notion that even a mild degree of hypothermia can significantly delay coagulation, although the effect of hypothermia in their studies using a pig trauma model were difficult to distinguish from the consequences of acidosis and massive transfusion.
Maintenance of the core temperature can require aggressive surface rewarming methods, including heating lights, warming blankets, and forced-air [1–3, 11, 13]. Hohn and coworkers [11] reported that without aggressive intraoperative warming, body temperatures in adults who underwent cardiac procedures dropped significantly after arrival in the ICU. A significant inverse relationship was noted between body temperature on arrival in the ICU and postoperative blood loss [11].
Aggressive maintenance of normothermia has been a strongly entrenched practice in both the neonatal ICU and the cardiac ICU [4, 11, 13, 28]. Normothermia is undoubtedly helpful in improving coagulation and probably in reducing the risk of infection, but it also has adverse effects [4, 8–9]. Supraventricular tachycardia is more likely to be problematic in the postoperative neonate who is at normothermia or hyperthermia. Common rhythm abnormalities such as junctional tachycardia can often be managed by the simple technique of cooling to mild hypothermia of 34.5° or 35°C [14–16].
Neurologic injury after a cerebral ischemic insult has been clearly documented to be exacerbated by hyperthermia [21, 29, 30]. A mild degree of hypothermia, such as 2° or 3°C, has been demonstrated to be highly protective in numerous animal studies, although it has been difficult to create controlled clinical studies that document equal efficacy in cardiac surgical patients. Nevertheless, the efficacy of mild hypothermia in protecting against hypoxic and ischemic brain injury has been demonstrated in the neonatal ICU [17–19]. Bissonnette and colleagues [30] reported that the actual brain temperature in infants and children who underwent cardiopulmonary bypass with usual warming techniques reached 39.6°C at 6 hours after cardiopulmonary bypass, although core temperatures by rectal, esophageal, and tympanic measurements were well correlated with actual brain temperature, albeit about 2° lower [30]. Thus, aggressive warming may not be necessary for at least the first 6 hours after cardiac procedures with circulatory arrest in infants and children, even if core temperatures using usual monitoring techniques indicate mild hypothermia.
One of the remarkable features of this study is the documentation that the total amount of blood loss in the neonate after a complex procedure such as the arterial switch procedure can be kept to a very reasonable level. The mean cumulative blood loss was 61 mL within 24 hours after surgery, representing approximately 20% of the total blood volume of the average neonate. Although this is still a significant amount of blood loss, it is much less than the amount of blood loss that often was encountered in the early years of neonatal corrective surgery. Consequently, we believe that it is reasonable to use a mild degree of hypothermia after a known cerebral ischemic insult or deep hypothermic circulatory arrest to protect against exacerbation of neurologic injury.
One of the limitations of this study is that at 6 hours, only 2 patients had body temperatures below 34°C (the two major outliers) and all of the remaining 45 patients had temperatures above 34.5°C. Because none of the patients in our study had temperatures between 34° and 34.5°C, it is not clear what amounts of blood loss can be expected within that interval. Nevertheless, among the 11 patients with temperatures at 6 hours above 34.5°C but below 35°C, the average blood loss was only 40 mL. Another limitation of the study is that sophisticated analysis of coagulation such as thromboelastograms and platelet function assays were not undertaken.
In conclusion, mild postoperative hypothermia does not increase blood loss in neonates after the arterial switch operation. We recommend avoidance of aggressive rewarming, which might exacerbate potential neurological injury.
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Acknowledgments
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This work was supported by grants HL 063411 and RR 02172 from the National Institutes of Health.
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References
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- Brink LW. Abnomalities in temperature regulationIn: Levin DL, Morriss FC, editors. Essentials of pediatric intensive care. 2nd ed.. New York, NY: Churchill Livingstone; 1997. pp. 548-555.
- Allen E. Abnormalities in temperature regulationIn: Blumer JL, editor. Pediatric intensive care. 3rd ed.. St. Louis, MO: Mosby; 1990. pp. 126-135.
- Motta P, Mossad E, Toscana D, Lozano S, Insler S. Effectiveness of a circulating-water warming garment in rewarming after pediatric cardiac surgery using hypothermic cardiopulmonary bypass J Cardiothorac Vasc Anesth 2004;18:148-151.[Medline]
- Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A. Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty Lancet 1996;347:289-292.[Medline]
- Frank SM, Fleisher LA, Breslow MJ, et al. Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events JAMA 1997;277:1127-1134.[Abstract/Free Full Text]
- Insler SR, O’Connor MS, Leventhal MJ, Nelson DR, Starr NJ. Association between postoperative hypothermia and adverse outcome after coronary artery bypass surgery Ann Thorac Surg 2000;70:175-181.[Abstract/Free Full Text]
- Sessler DI. Complications and treatment of mild hypothermia Anesthesiology 2001;95:531-543.[Medline]
- Harper CM, McNicholas TM, Gowrie-Mohan S. Maintaining perioperative normothermia BMJ 2003;326:721-722.[Free Full Text]
- Kruz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and hospitalizationStudy of Wound Infection and Temperature Group. N Engl J Med 1996;334:1209-1215.[Abstract/Free Full Text]
- Westaby S. Coagulation disturbance in profound hypothermia: the influence of anti-fibrinolytic therapy Semin Thorac Cardiovasc Surg 1997;9:246-256.[Medline]
- Hohn L, Schweizer A, Kalangos A, Morel DR, Bednarkiewigz M, Licker M. Benefits of intraoperative skin surface warming in cardiac surgical patients Br J Anaesth 1998;80:318-323.[Abstract/Free Full Text]
- Paparella D, Brister SJ, Buchanan MR. Coagulation disorders of cardiopulmonary bypass: a review Intensive Care Med 2004;30:1873-1881.[Medline]
- Hofer CK, Worn M, Tavakoli R, et al. Influence of body core temperature on blood loss and transfusion requirements during off-pump coronary artery bypass grafting: A comparison of 3 warming systems J Thorac Cardiovasc Surg 2005;129:838-843.[Abstract/Free Full Text]
- Pfammatter JP, Paul T, Ziemer G, Kallfelz HCl. Successful management of Junctional tachycardia by hypothermia after cardiac operation in infants Ann Thorac Surg 1995;60:556-560.[Abstract/Free Full Text]
- Asou T, Kado H, Shiokawa Y, Fukae K, Yasui H. Successful management of junctional tachycardia by hypothermia after a Fontan operation Ann Thorac Surg 1996;62:583-585.[Abstract/Free Full Text]
- Hoffman TM, Bush DM, Wernovsky GW, et al. Postoperative junctional ectopic tachycardia in children: incidence, risk factors, and treatment Ann Thorac Surg 2002;74:1607-1611.[Abstract/Free Full Text]
- Inder TE, Hunt RW, Morley CJ, et al. Randomized trial of systemic hypothermia selectively protects the cortex on MRI in term hypoxic-ischemic encephalopathy J Pediatr 2004;145:835-837.[Medline]
- Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy N Engl J Med 2005;353:1574-1584.[Abstract/Free Full Text]
- Adelson PD, Ragheb J, Muizelaar JP, et al. Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children Neurosurgery 2005;56:740-754.[Medline]
- du-Plessis AJ. Induced mild hypothermia: the spearhead strategy for effective neonatal neuroprotection? Pediatrics 1998;102:972-974.[Free Full Text]
- Shum-Tim D, Nagashima M, Shin’oka T, et al. Postischemic hyperthermia exacerbates neurologic injury after deep hypothermic circulatory arrest J Thorac Cardiovasc Surg 1998;116:780-792.[Abstract/Free Full Text]
- Harrell FE. Regression modeling strategies with applications to linear models, logistic regression, and survival analysisNew York, NY: Springer; 2001. pp. 74-85.
- Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass Ann Thorac Surg 2003;75:S715-S720.[Abstract/Free Full Text]
- Wolberg AS, Meng ZH, Monroe III DM, Hoffman M. Asystemic evaluation of the effect of temperature on coagulation enzyme activity and platelet function J Trauma 2004;56:1221-1228.[Medline]
- Cavallini M, Preis FWB, Casati A. Effect of mild hypothermia on blood coagulation in patients undergoing elective plastic surgery Plast Reconstr Surg 2005;116:316-321.[Medline]
- Shimokawa M, Kitaguchi K, Kawaguchi M, Skamoto T, Kakimoto M, Furuya H. The influence of induced hypothermia for hemostatic function on temperature-adjusted measurements in rabbits Anesth Analg 2003;96:1209-1213.[Abstract/Free Full Text]
- Martini WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. Independent contributions of hypothermia and acidosis to coagulopathy in swine J Trauma 2005;58:1002-1010.[Medline]
- Brauer A, Weyland W, Kazmaier S, et al. Efficacy of postoperative rewarming after cardiac surgery Ann Thorac Cardiovasc Surg 2004;10:171-177.[Medline]
- Takara I, Ohshiro M, Takechi A, Kukita I, Sugahara K. The relationship between postoperative body temperature for 24 hours and central nervous system dysfunction in patients of selective cerebral perfusion Masui 2003;52:963-966.[Medline]
- Bissonnette B, Holtby HM, Davis AJ, Pua H, Gilder FJ, Black M. Cerebral hyperthermia in children after cardiopulmonary bypass Anesthesiology 2000;93:611-618.[Medline]
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Abstract
Introduction
