Original Article. Postoperative hypothermia and patient outcomes after major elective non-cardiac surgery. Abstract

Transcription

1 Original Article doi: /anae Postoperative and patient outcomes after major elective non-cardiac surgery D. Karalapillai, 1 D. Story, 2 G. K. Hart, 3 M. Bailey, 4 D. Pilcher, 5 A. Schneider, 6 M. Kaufman, 7 D. J. Cooper 8 and R. Bellomo 9 1 Consultant Anaesthetist and Intensivist, 2 Associate Professor and Head of Research, Department of Anaesthesia, 3 Associate Professor and Director, 6 Research Fellow, 7 Registrar, 9 Professor and Head of Intensive Care Research, Department of Intensive Care, Austin Health, Melbourne, Vic., Australia 4 Associate Professor, Senior Statistical Consultant, ANZIC-Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia 5 Director Adult Patient Database, ANZICS Centre for Outcome and Resources Evaluation, Melbourne, Vic., Australia 8 Professor and Head of Intensive Care Research, Alfred Hopital, Melbourne, Vic., Australia Abstract Using a multicentre adult patient database from Australia and New Zealand, we obtained the lowest and highest temperature in the first 24 h after admission to the intensive care unit after elective non-cardiac surgery. Hypothermia was defined as core temperature < 36 C; transient as a temperature < 36 C that was corrected within 24 h, and persistent as not corrected within 24 h. We studied patients. Hypothermia occurred in (46%) patients, was transient in (45%), and was persistent in 608 (1.2%) patients. On multivariate analysis, neither transient (OR = 1.07, 95% CI ) nor persistent (OR = % CI ) was independently associated with increased hospital mortality.... Correspondence: D. Karalapillai dharshi.karalapillai@austin.org.au Accepted: 16 November 2012 Unintentional is common in the early postoperative period [1 5]. Current evidence, including small randomised trials, suggests that a decrease in tympanic temperature of 1 3 C is associated with physiological derangements and complications that may be reduced by active warming [6 13]. This evidence has led many anaesthetists to strive to maintain normothermia for patients in the peri-operative period. Despite this being common practice, there are only a few studies of the epidemiology of [2 5] and those that exist are limited in scope and external validity by being single centre in nature. To our knowledge, no large epidemiological multicentre studies of postoperative in the intensive care unit (ICU) have been conducted among patients after non-cardiac surgery. We considered the hypothesis that, in patients admitted to the ICU after all types of major elective non-cardiac surgery, might be both common and independently associated with increased mortality, and that this Anaesthesia 2013 The Association of Anaesthetists of Great Britain and Ireland 605

2 Karalapillai et al. Hypothermia and major non-cardiac surgery association would apply to both transient and persistent. We used data from a large, Australian and New Zealand multicentre ICU database to test this hypothesis [14]. Methods We performed a retrospective observational study of prospectively collected postoperative ICU data. The study data were collected and submitted to the Australian and New Zealand Intensive Care Society (ANZ- ICS) database by participating units after collection by trained data collectors (ANZICS Clinical Outcome Research and Evaluation (CORE) Adult Patient Database, ANZICS, Melbourne, Australia). The ANZICS CORE Management Committee granted access to the data in accordance with standing protocols. Data were collected under the Quality Assurance Legislation of the Commonwealth of Australia (Part VC Health Insurance Act 1973, Commonwealth of Australia) with government support and funding. Each hospital allows the data to be used for appropriate research, governed by the ANZICS CORE terms of reference. The ANZICS CORE database is a high-quality national database of patients admitted to ICU from more than 100 ICUs in Australia and New Zealand [14]. It is the repository of prospectively collected illness severity data on the day of admission, information on ICU and hospital outcome and specific physiological data, including the highest and lowest temperature recorded in the first 24 h of admission. In addition, it identifies patients according to the source of admission and, in case of patients admitted to the ICU after surgery, according to whether their surgery was elective or unplanned. Data were retrieved for the prospectively collected database with focus on patients admitted to ICUs over an eight-year period between 2000 and Data included patients from rural, private, metropolitan and tertiary hospitals. We included all consecutive patients whose admission source was the operating room after elective non-cardiac surgery. Postoperative temperatures were measured using infrared tympanic thermometers, as is common in ICUs in Australia and New Zealand. Normothermia was defined as a lowest temperature 36 C, as is consistent with previous studies [2, 3]. Measurements were recorded at intervals of 1 4 h. We did not study patients with a temperature > 38 C and patients who were re-admitted, because of the known association between fever and increased mortality [15] and because we wanted to focus on our comparison of and normothermia. We used the lowest and highest temperature within the first 24 h of ICU admission as the primary study variables. In-hospital mortality was the primary outcome measure. Secondary outcome measures were ICU mortality as well as ICU and hospital length of stay. With ethical approval, to assess the temporal relationship of the lowest temperature in the first 24 h relative to the time of ICU admission, we retrospectively collected additional detailed data on a subgroup of 100 consecutive patients of a single tertiary centre, which contributed to the database, and which was also the hospital of the primary authors. We reviewed all recorded temperatures in these patients to assess the timing of the lowest recorded temperature relative to ICU admission. We compared the characteristics and outcomes of three groups: 1 Patients without : 36 C (referred to as normothermia). 2 Patients whose lowest temperature was < 36 C, but whose highest temperature was 36 C (referred to as transient ). 3 Patients who had both lowest and highest temperatures < 36 C (referred to as persistent ). Univariate comparisons for overall group differences were performed using chi-squared tests for equal proportion, ANOVA for continuously normally distributed variables and Kruskal Wallis test otherwise. We determined the relationships between temperature and mortality using logistic regression analysis adjusting for age, sex, illness severity, type of surgery, level of ICU and presence of mechanical ventilation. As the most accurate measure of illness severity (APACHE III score) contains a temperature component, an adjusted APACHE III score (corrected APACHE III score) was derived whereby the temperature component of the APACHE III score was removed [16]. Both hospital and ICU lengths of stay were found to be well approxi- 606 Anaesthesia 2013 The Association of Anaesthetists of Great Britain and Ireland

3 Karalapillai et al. Hypothermia and major non-cardiac surgery Anaesthesia 2013, 68, mated by log-normal distributions. As a consequence, they were log-transformed and assessed using multiple linear regression analysis. A two-sided p value of 0.05 was considered statistically significant for main effects, but to account for multiple comparisons created by three group comparisons, a Bonferroni correction was applied in which a reduced p value of p = (0.05/ 3) was used to indicated statistical significance for posthoc comparisons. All analyses were performed using SAS version 9.1 (SAS Institute Inc., Cary, NC, USA). Results We studied patients admitted to 118 ICUs in Australia and New Zealand after elective non-cardiac surgery between 2000 and 2008 (Table 1). The largest surgical groups were: general surgery (41%); vascular surgery 9631 (19%); neurosurgery 9124 (19%); and thoracic surgery 5069 (10%). The mean lowest temperature was 35.9 (0.8) C and the mean highest temperature was 37.1 (0.5) C. In total, (46%) patients experienced in the 24 h after ICU admission. Of these, (45%) had transient and only 608 (1.2%) had persistent. Persistently hypothermic patients were older and had higher corrected APACHE scores than normothermic patients (Table 1). Hospital length of stay was similar for the normothermic and for the transient groups; however, it was significantly lower for those with persistent (Table 1). After multivariate adjustment for age, sex, surgery type, patient severity of illness, hospital type, ventilation and year, a similar trend remained for normothermia with a geometric mean of 216 (95% CI ) h for transient with a geometric mean of 214 (95% CI ) h and for persistent with a geometric mean of 185 (95% CI ) h (p < 0.001). When considering survivors only, the results remained very similar: normothermia: 213 (95% CI ) h; transient : 217 Table 1 Baseline data of patients admitted to ICU after elective non-cardiac surgery between 2000 and 2008 in 118 centres in Australia and New Zealand. Values are mean (SD), number (proportion) or median (IQR [range]). Total (n = ) Normothermia (n = ) Transient (n = ) Persistent (n = 608) p value Age; years 65 (16) 63 (16) 68 (15) 68 (14) Male (58%) (58%) (58%) 359 (59%) 0.94 Surgery type General (41%) (41%) 9023 (40%) 225 (37%) Neurosurgery 9124 (18%) 5505 (20%) 3609 (16%) 97 (16%) Orthopaedics 4055 (8%) 2202 (8%) 1805 (8%) 49 (8%) 0.50 Plastics/maxillofacial/ENT 507 (1%) 275 (1%) 226 (1%) 6 (1%) 0.07 Thoracic 5069 (10%) 2477 (9%) 2256 (10%) 67 (11%) Vascular 9631 (19%) 4404 (16%) 4737 (21%) 122 (20%) Others 2534 (5%) 1376 (5%) 902 (4%) 43 (7%) Hospital type Rural 3548 (7%) 2202 (8%) 5865 (26%) 195 (32%) Metropolitan 8617 (17%) 4679 (17%) 3609 (16%) 127 (21%) Tertiary (30%) 9358 (34%) (51%) 255 (42%) Private (46%) (41%) 226 (7%) 43 (7%) APACHE III score 42 (17) 38 (15) 46 (17) 47 (17) Corrected APACHE III score 37 (16) 35 (16) 40 (17) 39 (18) Highest temperature; C 37.1 (0.5) 37.2 (0.4) 36.9 (0.5) (0.4) Lowest temperature; C 35.9 (0.7) 36.3 (0.3) 35.3 (0.3) 34.8 (1.0) Controlled ventilation 7096 (14%) 3303 (2%) 3835 (17%) 61 (10%) Hospital LOS; h 216 ( [ ]) 214 ( [ ]) 219 ( [ ]) 193 ( [5 4728]) ENT, ear, nose and throat; APACHE, acute physiology and chronic health evaluation (corrected, with temperature component removed); LOS, length of stay Anaesthesia 2013 The Association of Anaesthetists of Great Britain and Ireland 607

4 Karalapillai et al. Hypothermia and major non-cardiac surgery (95% CI ) h; and persistent hypothermic: 193 (95% CI h (p = 0.001)). Overall, 1388 of the patients died in hospital (2.7%). Mortality in the temperature groups was: 638 of (2.3%) for normothermia; 722 of (3.2%) for transient ; and 28 of 610 (4.6%) for persistent (p = 0.001). The characteristics of non-survivors are displayed in Table 2. These patients were older, had higher corrected APACHE scores, were more likely to have undergone general, plastics/maxillofacial/ear, nose and throat and were likely to have lower body temperatures (Table 2). Relating to normothermia on univariate analysis, transient (OR = 1.41, 95% CI ) Table 2 Characteristics of survivors and non-survivors in patients who underwent non-cardiac surgery in 118 ICUs in Australia and New Zealand between 2000 and Values are mean (SD) or number (proportion). Survivors (n = ) Discussion We conducted a multicentre retrospective data analysis of more than patients undergoing major elec- Nonsurvivors (n = 1388) p value Age; years 65 (0.1) 74 (0.3) Male (58%) 861 (62%) APACHE III score 41 (0.1) 63 (0.6) Corrected 36 (0.1) 58 (0.6) APACHE III score Type of surgery General (40%) 708 (51%) Vascular 9367 (19%) 278 (20%) Thoracic 4437 (9%) 139 (10%) Neurosurgery 8874 (18%) 125 (9%) Orthopaedics 3944 (8%) 97 (7%) Plastics/other* 2465 (0.5%) 14 (1%) Others 1972 (4%) 14 (1%) Hospital type Rural 3451 (7%) 125 (9%) Metropolitan 7888 (16%) 305 (22%) Tertiary (30%) 555 (40%) Private (46%) 403 (29%) Controlled ventilation 6902 (14%) 500 (36%) Lowest 35.5 (0.02) 35.7 (0.03) temperature; C Highest 36.9 (0.003) 36.9 (0.002) 0.37 temperature; C Normothermia (55%) 638 (46%) Transient (44%) 722 (52%) Persistent 493 (1%) 28 (2%) 0.02 APACHE, acute physiology and chronic health evaluation (corrected, with temperature component removed). *includes maxillofacial and ear, nose and throat. and persistent (OR = 1.89, 95% CI ) were associated with increased hospital mortality. On multivariate logistic regression analysis (Table 3), however, transient and persistent were not significantly independently associated with increased hospital mortality. Several other variables were identified as independent predictors of hospital mortality: age; male sex; corrected APACHE III score; hospital type; controlled ventilation; and type of surgery. The details of the subgroup of 100 patients whose temperature was analysed in detail are displayed in Table 4. The average temperature was lowest on arrival in the ICU and was, on average, normalised within 1 h of ICU admission and remained so thereafter (Fig. 1). On admission to ICU, 44% of patients in this cohort were hypothermic and the peak incidence of (47%) occurred 1 h after ICU admission (Fig. 2). Table 3 Results of multivariate analysis for hospital mortality in patients who underwent non-cardiac surgery between 2000 and 2008 in 118 ICUs in Australia and New Zealand. Odds ratio (95% CI) p value Age; per year 1.03 ( ) Male 1.12 ( ) Corrected APACHE III 1.05 ( ) Transient 1.07 ( ) vs normothermia Persistent vs normothermia 1.50 ( ) Hospital type (reference = private) Rural 1.78 ( ) Metropolitan 1.68 ( ) Tertiary 1.76 ( ) Surgical group (reference = vascular) General 1.63 ( ) Neurosurgery 1.69 ( ) Orthopaedics 1.37 ( ) Others 0.89 ( ) Plastics/maxillofacial/ENT 1.02 ( ) Thoracic 1.95 ( ) Controlled ventilation 1.61 ( ) APACHE, acute physiology and chronic health evaluation (corrected, with temperature component removed). ENT, ear, nose and throat. 608 Anaesthesia 2013 The Association of Anaesthetists of Great Britain and Ireland

5 Karalapillai et al. Hypothermia and major non-cardiac surgery Anaesthesia 2013, 68, Table 4 Characteristics of a subgroup of 100 patients from the database. Values are mean (SD), number or median (IQR [range]). Age; years 65 (15) Male 61 APACHE III score 57 (18) Tracheal intubation 65 Controlled ventilation 8(0 22 [0 330]) duration; h Hospital death 16 ICU death 6 Type of surgery General 38 Vascular 20 Thoracic 17 Neurosurgery 15 Plastics/maxillofacial/ENT 1 Orthopaedic 6 Others 3 Lowest temperature; C 35.7 (0.94) Highest temperature; C 37.3 (0.6) ICU length of stay; h 50 (41 94 [24 477) Hospital length of stay; h 357 ( [ ]) APACHE, acute physiology and chronic health evaluation; ICU, intensive care unit. tive non-cardiac surgery to determine the incidence of transient and persistent and to assess the independent relationship of with outcome. We found that, consistent with our first hypothesis, nearly half of all patients experienced in the first 24 h in ICU. In most of these patients, however, was transient and resolved within 24 h of ICU admission. Additionally, in a cohort of patients in whom we studied in the first 24 h in detail, we found that was short-lived with resolution within 3 h of ICU admission in more than 80% of patients. Finally, contrary to our hypothesis, was not independently associated with increased hospital mortality. To our knowledge, this is the largest study of after major elective non-cardiac surgery among patients admitted to ICU. The reported incidence of of 46% is lower than the estimate obtained from previous smaller, single-centre studies of non-cardiac surgery patients by Slotman et al. (53%), Konsayereepong et al. (57%) and Abelha et al. (58%) [4 6]. The largest of these studies included fewer than 200 patients [5]. Our lower incidence of Temperature ºC Hours post ICU admission Figure 1 Mean patient temperature against time after ICU admission (hours) in a sample of 100 patients from one Australian metropolitan centre participating in the Australian and New Zealand Intensive Care Society database. Error bars are SD. % of patients with temperature < 36 ºC Hours post ICU admission Figure 2 Percentage of patients with temperature <36 C against time in hours after ICU admission in a sample of 100 patients from one Australian metropolitan centre participating in the Australian and New Zealand Intensive Care Society database. Error bars are SD. occurred despite our study s including patients undergoing more complex surgery that may be expected to be associated with increased risk of postoperative. Our finding that neither transient nor persistent was independently associated with increased mortality, however, contrasts with our previous single-centre study of 5000 surgical patients [3] undergoing both cardiac and non-cardiac surgery, which found that a single temperature < 36 C was independently associated with increased hospital mortality. However, while in our previous study [3] we corrected for illness severity by using an APACHE III score, we did not also test the APACHE III score without the temperature component. Furthermore, we did Anaesthesia 2013 The Association of Anaesthetists of Great Britain and Ireland 609

6 Karalapillai et al. Hypothermia and major non-cardiac surgery not estimate the likely duration of and included patients who had undergone cardiac surgery [3], as a significant confounder. In a recent study of over cardiac surgery patients, we found that persistent in the early postoperative period was associated with increased hospital mortality [17]. These contrasting findings may reflect differences between cardiac and non-cardiac surgery with regard to temperature control and the different physiological implications of persistent despite rewarming after cardiopulmonary bypass. Our study indicates that mild is common in the early postoperative period after major noncardiac surgery and highlights that, while normothermia is regarded as an important physiological goal in the management of surgical patients, it is not achieved in nearly 50% of patients admitted to ICU. On univariate analysis, we found both transient and persistent to be associated with increased hospital mortality. However, after correction for age, corrected APACHE III score with the temperature component removed, hospital level, and type of surgery, there was no independent association between and mortality. This suggests that early may simply be a marker of illness severity rather than a mediator of unfavourable outcome. Previous work has suggested that even mild perioperative may be associated with increased morbidity after surgery [10 13]. Due to the limitations of our database, we could not directly assess for differences in postoperative complications. In this regard, previous randomised controlled trials of specific surgical populations have described reduced cardiac complications, blood loss and requirement for transfusion, as well as decreased wound infection and hospital stay with peri-operative warming [10 13]. Therefore, to make an indirect assessment of differences in morbidity, we used hospital length of stay as a surrogate marker. Hospital length of stay was not found to be significantly increased in hypothermic patients even if correction was delayed. Our finding that postoperative is not associated with increased hospital mortality or length of stay relative to patients who were normothermic suggests that delayed correction of early postoperative by a few hours is unlikely to be a major independent contributor to morbidity and mortality. It may simply be a marker of illness severity or type and duration of surgery, or both. This study has several strengths. First, it is large (more than patients) and multicentre in nature involving more than 100 hospitals. Second, patient temperatures were not recorded to demonstrate any specific association with, reducing the risk of bias. Third, with patients, our study has the statistical power to detect even relatively weak independent associations (as shown for each increase in age by 1 year). Fourth, by additionally providing a 100 patients cohort with detailed information, we confirmed that in the first 24 h is typically seen on arrival from the operating room and that, in most patients, (> 80%) it has resolved by 2 3 h after admission to ICU. This study also has several limitations. First, it is retrospective. Second, infrared tympanic thermometers were used to measure patient temperatures, a flaw shared with other studies of [2 6]. Using Bland Altman analyses to compare the gold standard of a pulmonary artery catheter thermistor to infrared tympanic thermometers, the tympanic thermometers have a bias of (mean difference) of % less than thermistors [18]. Therefore, they may overestimate the frequency of as well as being less precise than thermistors [19]. A further limitation of this study is that temperature measurements were not protocol-based and only peak and lowest temperatures were recorded in the database, irrespective of the number of measurements taken. However, such data are more complete than previous studies, where only ICU admission temperatures were recorded and are seen as representative of overall temperature control as shown by the detailed analysis of 100 database patients. The precise timing within the first 24 h in which the lowest and highest temperatures occurred was also not specified in the database. However, on more detailed analysis of a subgroup of 100 patients, we found that the average temperature was lowest on arrival in the ICU and peaked within the first 2 h after admission. Other limitations relate to deficiencies of our collected data, which did not include factors such as the duration of surgery, assessment for complications such as cardiac events, wound infection or red 610 Anaesthesia 2013 The Association of Anaesthetists of Great Britain and Ireland

7 Karalapillai et al. Hypothermia and major non-cardiac surgery Anaesthesia 2013, 68, cell transfusion, the use of intra-operative temperature monitoring or details of postoperative rewarming in the ICU (passive or active). Early in postoperative non-cardiac surgery patient after major elective surgery is common, but is not independently associated with increased hospital length of stay or mortality. Confirmation of these findings by other large national ICU databases would be desirable. Competing interests No external funding and no competing interests declared. References 1. Peres Bota D, Lopes Ferreira F, et al. Body temperature alterations in the critically ill. Intensive Care Medicine 2004; 30: Karalapillai D, Story D. Hypothermia on arrival in the intensive care unit after surgery. Critical Care and Resuscitation 2008; 10: Karalapillai D, Story D, Calzavacca P, et al. Inadvertent and mortality in postoperative ICU patients. Anaesthesia 2009; 64: Abelha FJ, Castro MA, Neves AM, Landeiro NM, Santos CC. Hypothermia in a surgical intensive care unit. BMC Anesthesiology 2005; 5: Kongsayreepong S, Chaibundit C, Chadpaibool J, et al. Predictor of core and the surgical intensive care unit. Anesthesia and Analgesia 2003; 96: Slotman GJ, Jed EH, Burchard KW. Adverse effects of in postoperative patients. American Journal of Surgery 1985; 149: Bush HL, Hydo LJ, Fischer E, et al. Hypothermia during elective abdominal aortic aneurysm repair: the high price of avoidable morbidity. Journal of Vascular Surgery 1995; 21: Berry JM, Garrett K, Clifton GL. Post operative in a tertiary care hospital. Anesthesiology 1999; 91 (Suppl.): A Frank SM, Higgins MS, Breslow MJ, et al. The catecholamine, cortisol, and hemodynamic response to mild : a randomized controlled trial. Anesthesiology 1995; 82: Frank SM, Fleisher LA, Breslow MJ, et al. Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial. Journal of the American Medical Association 1997; 277: Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A. Mild increases blood loss and transfusion requirements during total hip arthroplasty. Lancet 1996; 347: Lenhardt R, Marker E, Goll V, et al. Mild intraoperative prolongs postanesthetic recovery. Anesthesiology 1997; 87: Kurz A, Sessler DI, Lenhardt RA. Study of wound infections and temperature group: perioperative normothermia to reduce incidence of surgical wound infection and shorten hospitalization. New England Journal of Medicine 1996; 334: Stow PJ, Hart GK, Higlett T, et al. Development and implementation of a high quality clinical database: the Australian and New Zealand Intensive Care Society adult Patient database. Journal of Critical Care 2006; 21: Hannan EL, Samdashvil Z, Wechsler A, et al. The relationship between perioperative temperature and adverse outcomes after off pump coronary bypass graft surgery. Journal of Thoracic and Cardiovascular Surgery 2010; 139: Knaus WA, Draper EA, Wagner DP, et al. APACHE II:a severity of disease classification. Critical Care Medicine 1985; 13: Karalapillai D, Story D, Hart GK, et al. Postoperative and patients outcomes after elective cardiac surgery. Anaesthesia 2011; 66: Nierman DM. Tools that we use: If you cant measure it, you cant manage it. Critical Care Medicine 2007; 35: Moran JL, Peter JV, Solomon PJ, et al. Tympanic temperature measurements: are they reliable in critically ill? A clinical study of measures of agreement. Critical Care Medicine 2007; 35: Anaesthesia 2013 The Association of Anaesthetists of Great Britain and Ireland 611