Hypothermia In Patients Research Articles

Outcome from severe accidental hypothermia with cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation

PurposeThis study aimed to identify factors of neurologic prognosis in severe accidental hypothermic patients with cardiac arrest. Basic proceduresThis retrospective observational study was performed in a tertiary care university hospital in Sapporo, Japan (January 1994 to December 2012). We investigated 26 patients with accidental hypothermic cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation (ECPR). We evaluated the neurologic outcome in patients who were resuscitated with ECPR at discharge from hospital. Main findingsIn those 26 patients, their median age was 50.5 years; and 69.2% were male. The cause of hypothermia was exposure to cold air in 46.1%, submersion in 46.1%, and avalanche in 7.8%. Ten (38.5%) of these patients survived to favorable neurological outcome at discharge. Factors associated with favorable neurological outcome were a cardiac rhythm other than asystole (P = .009), nonasphyxial hypothermia (P = .006), higher pH (P = .01), and lower serum lactate (P = .01). In subgroup analyses, the patients with hypothermic cardiac arrest due to submersion or avalanche (asphyxia group) showed no factors associated with good neurological outcome, whereas the nonasphyxia group showed a significantly lower core temperature (P = .02) and a trend towards a lower serum lactate (P = .09). Principal conclusionsPatients with hypothermic cardiac arrest due to nonasphyxial hypothermia have improved neurologic outcomes when treated with ECPR compared to patients with asphyxial hypothermic cardiac arrest. Further investigation is needed to develop a prediction rule for patients with nonasphyxial hypothermic cardiac arrest to determine which patients would benefit from treatment with ECPR.

Therapeutic peritoneal lavage with warm saline solution as an option for a critical hypothermic trauma patient

In this paper, we present the case of a 63-year-old woman, who was found in her flat lying unconscious on the floor for an unknown time. At the time of admission, her core temperature was 24 °C and ventricular fibrillation was detected on the electrocardiogram (ECG). Because of the unstable conditions, the persistent nonperfusing cardiac rhythm and the dramatically inhibited coagulation cascade, a peritoneal lavage connected to a rapid infuser was performed for rewarming, instead of using a transportable heart-lung machine and a haemodialysis device. After a prolonged cardiopulmonary resuscitation (CPR), the patient could be transferred to the intensive care unit (ICU) in a stable condition. After 40 days in the ICU, recovery was fast, and another month of treatment later, she could be discharged back home without any discomfort. This report illustrates the successful use of the peritoneal lavage for rewarming a severely hypothermic patient without any extracorporeal rewarming device. Furthermore, it can be used in nearly every hospital if the necessary equipment is affordable. It is demonstrated that this technique is able to provide good outcomes for all victims of accidental hypothermia.

Preoperative patient warming in the prevention of hypothermia

Inadvertent perioperative hypothermia is associated with morbidity leading to prolonged recovery and hospitalisation, increased incidence of wound infections, increased risk of morbid cardiac events and increased bleeding during and after surgery. Guidelines for the prevention of perioperative hypothermia have been issued, but there is uncertainty as to the most effective means of preventing hypothermia in this patient population, leading to inconsistencies in clinical practice. To determine whether implementation of these guidelines would be effective in practice, the present study was designed. Different methods of pre-warming were applied and temperature measurements for patients receiving general anaesthesia during surgery were recorded. Data were collected for 47 (24.5%) of 192 patients who were enrolled in the study. The mean temperature of patients was 36.96°C (standard deviation=0.43), with a range between 36.1°C and 37.6°C, demonstrating that there were no hypothermic patients in the study. The precautionary measures taken to prevent hypothermia in this study were found to be effective, indicating that adherence to published guidelines should be encouraged in surgical practice.

The treatment of accidental hypothermia and drowning with the aid of extracorporeal circulation/ECMO

Background The Heart Centre Friesland is the youngest cardiac surgery facility in the Netherlands, starting in January 2004. It is located in the northern part of the country serving 750000 inhabitants. The environment is very water rich, with a lot of recreational activities on the water, in summer and winter time. Apart from that, there is an extensive off shore industry in our part of the North Sea. The expectation was that a certain number of hypothermic patients, with or without drowning, should be presented to our centre. This was not the case initially. A survey in the region among rescue services and hospitals showed that approximately 20 patients per year existed. Obviously, the first line rescue teams were not aware of the proper way to handle this patient category. A lot of energy was spent to inform the first line how to treat the patients and when to go to a heart centre. The initial treatment is simple, intubate the patient, start resuscitation and measure the core temperature. If the temperature is 28 °C or lower, transport to a heart centre. Any degree of hypothermia with cardiac instability, the same action, and any case with fluid aspiration too. The aim of this presentation is to show an overview of the patients we treated. One of these patients will be used as a case report to show the techniques used for treatment. Seven patients were presented to our centre in the last two years. Four of the patients were severely hypothermic, three with mild hypothermia. Six of the patients were submerged and had aspirated large volumes of water. Methods Three of the deep hypothermic patients where discharged without any morbidity, the last one was weaned from bypass, but suffered from cerebral damage due to insufficient resuscitation. All mild hypothermic patients could be weaned from bypass, but predictably suffered severe cerebral damage. One of them became a non beating donor patient after five days of ECMO. Several cannulation techniques were used, depending on logistic possibilities and the indication, cardiac or pulmonary support. In the cardiac group we used three times a heart lung machine and two times mobile device with femoral cannulation. For the pulmonary insufficiency patients the Cardiohelp with veno-venous cannulation was used. Bypass time ranged from 2 to 125 hours, depending on the recovery of the pulmonary function. The fact that all patients can be weaned from bypass taught us that drowning is not necessarily a contra indication for treatment. This case report is about a 31-year-old woman with severe hypothermia, who was presented at the OR of the Medical Centre Leeuwarden on December 10, 2010. She was found in her car under the ice, and was submersed for about 45 minutes, before the Mobile Medical Team arrived. Ventricular fibrillation occurred during intubation. Resuscitation was immediately started and continuously performed during the transport to the hospital. The patient arrived at the hospital while resuscitation was performed. At that moment her rectal temperature was 21°C and her peripheral temperature 14°C. Fulminant pulmonary oedema was present, and the patient was in her 12 week of pregnancy. We prefer to treat these patients in an OR with median sternotomy using a heart lung machine, but in this case we were forced to use the catheterisation lab to * Correspondence: cornelis.visser@live.com Heart Centre Friesland, the Netherlands Visser and Schepp Journal of Cardiothoracic Surgery 2013, 8(Suppl 1):O83 http://www.cardiothoracicsurgery.org/content/8/S1/O83

Akzidentelle Hypothermie

Uncertainty exists on how to treat patients suffering from accidental hypothermia and on the optimal transport decisions. The aim of this review is to provide an updated evidence-based reference for the pre-hospital and in-hospital management of patients with accidental hypothermia and for the transport decisions required to facilitate treatment. Advances in the efficiency and availability of rewarming techniques have improved the prognosis for patients presenting with hypothermia. For hypothermic patients with a core body temperature ≥ 28 °C without cardiac instability there is increasing evidence to support the use of active external and minimally invasive rewarming techniques (e.g. chemical, electrical or forced air heating packs, blankets and warm parenteral fluids). Hypothermic patients with cardiac instability (i.e. systolic blood pressure < 90 mmHg, ventricular arrhythmia and core body temperature < 28 °C) should be rewarmed with active external and minimally invasive rewarming techniques in a hospital which also has circulation substituting venous-arterial extracorporeal membrane oxygenation (VA-ECMO) and cardiopulmonary bypass (CBP) facilities. In cardiac arrest patients VA-ECMO may be a better treatment option than CBP and survival rates of 100 % can be achieved compared to ~ 10 % with traditional methods (e.g. body cavity lavage). Early transport to a hospital appropriately equipped for rewarming has the potential to decrease complication rates and improve survival.

Management of patients following cold water immersion

Sudden immersion in cold water results in a number of physiological changes within the human body. This disruption of homeostasis can have a detrimental effect on normal body function and lead to life-threatening consequences including drowning, hypothermia and sudden death. This article will examine the changes in physiology from the point of initial immersion through to rescue or death. Particular attention is given to the profound effects upon the respiratory, cardiovascular and neurological systems as a consequence of cold water immersion. This is then reviewed and observed from the perspective of paramedics practising within the United Kingdom, who may face challenges that arise from this phenomenon. The pre-hospital assessment of immersed patients will be discussed in order to identify and address potential and immediate life threats, with specific focus on rewarming hypothermic patients post immersion.

Abstracts from the 3rd Annual Therapeutic Hypothermia and Temperature Management ConferenceMarch 4–5, 2013Miami, FL

Abstracts from the 3rd Annual Therapeutic Hypothermia and Temperature Management ConferenceMarch 4–5, 2013Miami, FL

When should cardiopulmonary bypass be used in the setting of severe hypothermic cardiac arrest?

A best evidence topic was written according to a structured protocol. The question addressed was regarding the indication and timing of the use of cardiopulmonary bypass (CPB), following severe hypothermic cardiac arrest. A total of 284 papers were found using the reported searches, of which nine represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were survival, rewarming speed, incidence of arrhythmia during rewarming, resolution of full neurological function, long-term neurological function, evidence of damage on neurological imaging and venous metabolic parameters in hypothermic patients. The most recent of the best evidence studies, a retrospective comparative study of 68 patients, demonstrated CPB rewarming to be far superior to conventional methods of rewarming, with mortality rates of 15.8 and 53.3%, respectively. Another study of similar size, comparing CPB with extracorporeal membrane oxygenation (ECMO) for rewarming, revealed superior survival rates with ECMO, 75 vs 34%. A systematic review of 68 patients demonstrated an overall survival of 60%, and 80% of survivors returning to a previous level of activity. Two smaller observational studies reported survival rates of 73.1 and 45.5%, respectively. A retrospective study analysing long-term neurological outcomes of survivors reported normal history and physical examination in 93.3%, normal neurovascular ultrasound in 100%, normal neuropsychological findings in 93.3% and normal brain magnetic resonance imaging in 86.7%. A small comparative study demonstrated a significant survival benefit when CPB was preceded with emergency thoracotomy, internal cardiac massage and warm mediastinal irrigation compared with CPB alone. We conclude that, following deep hypothermic circulatory arrest, the urgent use of cardiopulmonary bypass is widely indicated for rewarming where it has been shown to provide good survival and neurological outcomes far superior in comparison with conventional methods of rewarming.

Clopidogrel does not work following cardiopulmonary resuscitation

Dear Sir, The platelet inhibitor clopidogrel is often part of dual antiplatelet therapy used for acute coronary syndromes. However, its effect depends on a sequential series of events, making it prone to failure [1]. The paper by Souckova et al. on the bioavailability of clopidogrel used during therapeutic hypothermia (TH) following cardiopulmonary resuscitation excellently illustrates this point, as only two of nine hypothermic patients showed adequate platelet inhibition. This was due to both delayed clopidogrel absorption and reduced bioavailability [2]. In the discussion of their findings, Souckova et al. could have lent further support for their conclusion by citing a previous larger study on clopidogrel efficacy during TH after cardiac arrest [3]. In this study, we observed that clopidogrel administered during TH was inefficacious in all 25 patients after 1 day of treatment. Moreover, only five of 16 subjects showed satisfactory clopidogrel platelet inhibition on day three. The clinical consequences are probably shown by Penela et al., who observed that stent thrombosis occurred in five out of 11 patients given percutaneous coronary intervention (16 stents were placed) and TH. This is an alarming rate compared to the 0.44 % reported for patients not treated with TH in the same period and hospital [4]. Preliminary results from a larger study presented by Ibrahim et al. at the ESC 2011 meeting also suggest a lack of clopidogrel effect during TH [5]. The conclusion from these studies is unequivocal: Clopidogrel should be replaced with an active, intravenously administrated drug in patients treated with TH.

Cardiac index during therapeutic hypothermia: which target value is optimal?

Mild therapeutic hypothermia is now recognized as standard therapy in patients resuscitated from out-of-hospital cardiac arrest (OHCA), and is recommended in comatose patients suffering from cardiac arrest related to ventricular fibrillation (VF) [1]. In these patients, maintaining an adequate tissue oxygen delivery (DO2) is crucial. However, during hypothermia, clinical signs of hypoperfusion such as cold, clammy skin and delayed capillary refill are not reliable and monitoring devices must, therefore, be used to measure or estimate the cardiac index (CI). However, there are no recommendations regarding the target value of CI in the hypothermic patient. In this article, the authors attempt to provide clinicians with some rationale to guide their therapy for the management of CI in patients treated with mild therapeutic hypothermia.

The Thermoregulation Story

Although suppression of thermoregulatory mechanisms by anesthetics is generally assumed, the extent to which thermoregulation is active during general anesthesia is not known. The only thermoregulatory responses available to anesthetized, hypothermic patients are vasoconstriction and nonshivering thermogenesis. To test anesthetic effects on thermoregulation, the authors measured skin-surface temperature gradients (forearm temperature - fingertip temperature) as an index of cutaneous vasoconstriction in unpremedicated patients anesthetized with 1% halothane and paralyzed with vecuronium during elective, donor nephrectomy. Patients were randomly assigned to undergo maximal warming (warm room, humidified respiratory gases, and warm intravenous fluids; n = 5) or standard temperature management (no special warming measures; n = 5). Skin-surface temperature gradients of 4°C or more were prospectively defined as significant vasoconstriction. Normothermic patients (average minimum esophageal temperature = 36.4° ± 0.3°C [SD]) did not demonstrate significant vasoconstriction. However, each hypothermic patient displayed significant vasoconstriction at esophageal temperatures ranging from 34.0 to 34.8°C (average temperature = 34.4° ± 0.2°C). These data indicate that active thermoregulation occurs during halothane anesthesia, but that it does not occur until core temperature is approximately 2.5°C lower than normal. In two additional hypothermic patients, increased skin-temperature gradients correlated with decreased perfusion as measured by a laser Doppler technique. Measuring skin-surface temperature gradients is a simple, noninvasive, and quantitative method of determining the thermoregulatory threshold during anesthesia.

Effects of Dexamethasone on Pulmonary Oxygenation Impairments in Therapeutic Hypothermia for Patients with Traumatic Brain Injury

Objectives: We studied retrospectively to examine differences in the occurrence rate of pneumonia and the time-course changes in pulmonary oxygenation between hypothermic and normothermic therapies with or without dexamethasone (D) administration in patients with traumatic brain injury (TBI). Design: A retrospective observational study. Setting: Two university hospitals. Subjects and Methods: In consecutive TBI patients (GCS ≤ 8) treated with hypothermic (N=23, 32-33°C) or normothermic (N=16, 36-37.5°C) therapy, the occurrence rate of pneumonia, PaO2/FIO2 (P/F) ratios and C-reactive protein (CRP) levels were examined. The comparisons were made among hypothermic and normothermic groups with or without D administration. In several patients in both groups, neutrophil functions were examined. Data were analyzed with ANOVA followed by Sheffe’s F-test, Mann-Whitney U-test, Kruskal-Wallis tests or chi-squared test (p<0.05) as appropriate. Results: The occurrence rate of pneumonia in a hypothermic group with D administration was significantly lower than in a hypothermic group without D. In the hypothermic group without D treatment, CRP elevation during the rewarming phase occurred, which was followed by more severe P/F ratio deteriorations as compared to the hypothermic group given D. Neutrophil phagocytic functions in hypothermic patients without D were activated around 35°C, which were followed by marked decreases in pulmonary oxygen. In contrast, phagocytic function in a hypothermic patient receiving D was depressed, but without P/F ratios below 280. Conclusion: This study poses hypotheses that neutrophils play a role in the pulmonary oxygenation impairment in hypothermic therapy for TBI patients, and that dexamethasone improves the pulmonary complications in therapeutic hypothermia.

Rewarming for accidental hypothermia in an urban medical center using extracorporeal membrane oxygenation.

SummaryBackground:Accidental hypothermia complicated by cardiac arrest carries a high mortality rate in urban areas. For moderate hypothermia cases conventional rewarming methods are usually adequate, however in severe cases extracorporeal membrane oxygenation (ECMO) is known to provide the most efficient rewarming with complete cardiopulmonary support. We report a case of severe hypothermia complicated by prolonged cardiac arrest successfully resuscitated using ECMO.Case Report:A 45 year old female was brought to our emergency department with a core body temperature <25°C. Shortly after arrival she had witnessed cardiac arrest in the department. Resuscitative efforts were started immediately including conventional rewarming techniques, followed by ECMO support. ECMO was used successfully in this case to resuscitate this patient from prolonged arrest (3.5 hours) when conventional techniques likely would have failed. After a prolonged hospital course this patient was discharged with her baseline mental and physical capacities intact.Conclusions:This case demonstrates the advantages of advanced internal rewarming techniques, such as ECMO, for quick and efficient rewarming of severely hypothermic patients. This case supports the use of ECMO in severely hypothermic patients as the standard of care.

The effect of admission spontaneous hypothermia on patients with severe traumatic brain injury

IntroductionRecent information has emerged regarding the harmful effects of spontaneous hypothermia at time of admission in trauma patients. However the volume of evidence regarding the role of spontaneous hypothermia in TBI patients is inadequate. MethodsWe performed secondary data analysis of 10 years of the Pennsylvania trauma outcome study (PTOS) database. Unadjusted comparisons of the association of admission spontaneous hypothermia with mortality were performed. In addition, full assessment of the association of hypothermia with mortality was conducted using multivariable logistic regressions reporting the odds ratios (OR) with the 95% confidence intervals (CI) and P-values. ResultsThere were 11,033 patients identified from the PTOS with severe TBI. There were 4839 deaths (43.9%). The proportion of deaths in hypothermic patients was higher than the proportion of deaths in normothermic patients (53.9% vs. 37.4% respectively; P value<0.001). In a multivariable logistic regression model adjusted for demographics, injury characteristics, and information at admission to the trauma centre, the odds of death among patients with hypothermia were 1.70 times the odds of death among patients with normothermia (OR 1.70, 95% CI 1.50–1.93), indicating that the probability of death was significantly higher when patients arrived hypothermic at the trauma centre. ConclusionThe presence of spontaneous hypothermia at hospital admission is associated with a significant increase in the risk of mortality in patients with severe TBI. The benefit of maintaining normothermia in severe TBI patients, the impact of prolonged re-warming in patients with established hypothermia and the introduction of prophylactic measures to complications of hypothermia are key points that require further investigation.

Acetaminophen/diphenhydramine overdose in profound hypothermia

Background. There are few reports of acetaminophen overdose in hypothermic patients and even fewer reports describing profound hypothermia. The kinetics, risk of hepatotoxicity, and the possible dose adjustments to N-acetylcysteine (NAC) therapy are not known in this setting. Case report. A 37-year-old female was found unconscious outside in December and was brought by ambulance to a tertiary care Emergency Department (ED) following a presumed overdose of acetaminophen and diphenhydramine. She later confirmed the ingestion and reported the ingestion had occurred approximately 18 hours prior to being found. On arrival, she was profoundly hypothermic, with a core rectal temperature of 17°C. Her initial serum acetaminophen concentration was 232 mcg/mL 19 hours post ingestion of a reported dose of approximately 50 grams of acetaminophen and 2.5 grams of diphenhydramine. Active rewarming was started immediately and IV NAC was initiated using the standard treatment protocol. The patient did not develop serious signs of hepatic injury or NAC toxicity. The patient's AST and ALT peaked 12 hours after admission at 84 IU/L (ref 10–37 U/L) and 104 IU/L (ref 12–78 U/L), respectively. Her INR peaked 2 hours after admission at 1.46 (ref < 1.2). Discussion. Despite the significant ingestion of acetaminophen, delayed presentation, prolonged period of decreased responsiveness, and profound hypothermia, the patient did not develop any signs/symptoms of liver injury. NAC was administered in a standard dose during her rewarming period without apparent toxicity. The patient's absorption and/or metabolism of acetaminophen were likely slowed by her hypothermia and possibly by the anticholinergic coingestant. Initiation of IV NAC at a standard dose was apparently safe and effective in preventing hepatotoxicity as the patient was rewarmed. Conclusions. Profound hypothermia may be protective of hepatic injury in acetaminophen overdose. Delayed absorption from the coingestant, diphenhydramine, may also have played a role. IV NAC was given in a standard dose without apparent toxicity in the setting of profound hypothermia. Lastly, IV NAC, in standard dosing, appeared to be effective in preventing hepatotoxicity during rewarming in a patient with a potentially hepatotoxic concentration of acetaminophen with a coingestion of the anticholinergic agent, diphenhydramine.

Abstract 311: Early Evaluation Biomarkers-Based of Neurological Prognosis in Hypothermic Post--Cardiac Arrest Patients

Early prognosis of neurological outcome in patients resuscitated from cardiac arrest (CA) is a major medical challenge. High serum levels of both serum neuron-specific enolase (NSE) and S-100B protein are related with brain damage, but the relationship with neurological outcome at hospital discharge, in hypothermic post CA patients, is uncertain. The aim of this study was to evaluate the prognostic value and cut-off values of NSE and S-100B protein in predicting neurological outcome in comatose patients after CA treated with therapeutic hypothermia (TH). Methods: We enrolled consecutive patients, between November 2010 and May 2012. NSE and S-100B values were sampled at admission and every 24 hours since discharge from intensive care unit. According to Cerebral Performance Category (CPC) scale, neurological outcome was dichotomized into good (CPC 1-2) or poor (CPC 3-5). Results: thirty-one patients (25 males; mean age 60±15years). Twenty patients had a favourable outcome. Median values of serum NSE peak and S-100B peak were 25 ug/L (interquartile range, 20.8 to 43.3 ug/L) and 0.3 ug/L (range, 0.15 to 0.7 ug/L) respectively. High peak values of NSE and S-100B were significantly associated with poor neurological outcome (p=0.015 and p=0.007 respectively). Using a regression tree model we found worst neurological recovery for NSE peak value above 64.7 ug/L or S-100B above 0.65 ug/L (p=0.01 and p=0.007 respectively). Good neurological outcome was associated with NSE peak value less than 40.5 ug/L (p=0.012) especially if S-100B was less than 0.23 ug/L (p=0.031) (figure). Conclusion: Serum peak concentrations of NSE and S-100B result to be highly predictive of neurological outcome, especially when combined. Moreover, our data demonstrate that a good neurological outcome is associated with NSE peak value minor than 40.5 ug/L especially with S-100B minor than 0.23 ug/L. On this basis, determination of NSE and S-100B peak values may be useful in the early evaluation of prognostic neurological outcome to guide clinical decision making, in hypothermic post CA patients.

Impact of prehospital hypothermia on transfusion requirements and outcomes

Prehospital hypothermia (PH) is known to increase mortality following traumatic injury. PH relationship with transfusion requirements has not been documented. The purpose of this investigation was to analyze the impact of PH on blood product requirements and subsequent outcomes. The Los Angeles County Trauma System Database was queried for all patients admitted between 2005 and 2009. Demographics, physiologic parameters, and transfusion requirements were obtained and dichotomized by admission temperatures with a core temperature of less than 36.5 °C considered hypothermic. Multivariate analysis was performed to determine factors contributing to transfusion requirements and to derive adjusted odds ratios (AORs) for mortality and rates of adult respiratory distress syndrome and pneumonia. A total of 21,023 patients were analyzed in our study with 44.6% presenting with PH. Hypothermic patients required 26% more fluid resuscitation (p < 0.001) in the emergency department and 17% more total blood products (p < 0.001) than those who were admitted with a normal temperature. There was a trend toward an increase in emergency department transfusion (8%, p = 0.06). PH was independently associated with the need for a transfusion (AOR, 1.1; p = 0.047), increased mortality (AOR, 2.0; p < 0.01), as well as incidence of adult respiratory distress syndrome (AOR, 1.8; p < 0.05) and pneumonia (AOR, 2.6; p < 0.01). PH is associated with increased transfusion and fluid requirements and subsequently worse outcomes. Interventions that correct hypothermia may decrease transfusion requirements and improve outcomes. Prospective studies investigating correction of hypothermia in trauma patients are warranted. Prognostic/epidemiologic study, level III.

Effects of Hypothermia on the Disposition of Morphine, Midazolam, Fentanyl, and Propofol in Intensive Care Unit Patients

Therapeutic hypothermia (TH) may induce pharmacokinetic changes that may affect the level of sedation. We have compared the disposition of morphine, midazolam, fentanyl, and propofol in TH with normothermia in man. Fourteen patients treated with TH following cardiac arrest (33-34°C) were compared with eight matched critically ill patients (36-38°C). Continuous infusions of morphine and midazolam were stopped and replaced with infusions of fentanyl and propofol to describe elimination and start of infusion pharmacokinetics, respectively. Serial serum and urine samples were collected for 6-8 hours for validated quantification and subsequent pharmacokinetic analysis. During TH, morphine elimination half-life (t(1/2)) was significantly higher, while total clearance (CL(tot)) was significantly lower (median [semi-interquartile range (s-iqr)]): t(1/2), 266 (43) versus 168 (11) minutes, P < 0.01; CL(tot), 1201 (283) versus 1687 (200) ml/min, P < 0.01. No significant differences were seen for midazolam. CL(tot) of fentanyl and propofol was significantly lower in hypothermic patients [median (s-iqr)]: fentanyl, 726 (230) versus 1331 (678) ml/min, P < 0.05; propofol, 2046 (305) versus 2665 (223) ml/min, P < 0.05. Compared with the matched, normothermic intensive care unit patients, t(1/2) of morphine was significantly higher during TH. CL(tot) was lower during TH for morphine, fentanyl, and propofol but not for midazolam. Reducing the infusion rates of morphine, fentanyl, and propofol during TH is encouraged.

Haemodynamic variables and functional outcome in hypothermic patients following out-of-hospital cardiac arrest

Aim of the studyTo evaluate the association between haemodynamic variables during the first 24h after intensive care unit (ICU) admission and neurological outcome in out-of-hospital cardiac arrest (OHCA) victims undergoing therapeutic hypothermia. MethodsIn a multi-disciplinary ICU, records were reviewed for comatose OHCA patients undergoing therapeutic hypothermia. The hourly variable time integral of haemodynamic variables during the first 24h after admission was calculated. Neurologic outcome was assessed at day 28 and graded as favourable or adverse based on the Cerebral Performance Category of 1–2 and 3–5. Bi- and multivariate regression models adjusted for confounding variables were used to evaluate the association between haemodynamic variables and functional outcome. Results67/134 patients (50%) were classified as having favourable outcome. Patients with adverse outcome had a higher mean heart rate (73 [62–86] vs. 66 [60–78]bpm; p=0.04) and received noradrenaline more frequently (n=17 [25.4%] vs. n=9 [6%]; p=0.02) and at a higher dosage (128 [56–1004] vs. 13 [2–162] μgh−1; p=0.03) than patients with favourable outcome. The mean perfusion pressure (mean arterial blood pressure minus central venous blood pressure) (OR=1.001, 95% CI =1–1.003; p=0.04) and cardiac index time integral (OR=1.055, 95% CI=1.003–1.109; p=0.04) were independently associated with adverse outcome at day 28. ConclusionMean perfusion pressure and cardiac index during the first 24h after ICU admission were weakly associated with neurological outcome in an OHCA population undergoing therapeutic hypothermia. Further studies need to elucidate whether norepinephrine-induced increases in perfusion pressure and cardiac index may contribute to adverse neurologic outcome following OHCA.

Update on therapeutic temperature management

It is a pleasure to announce the 2nd Innsbruck Hypothermia Symposium. We are very happy that Critical Care has agreed to publish extended abstracts submitted by invited renowned scientists from all over the world; that is, Europe, the Americas, Asia. Neuroprotection - potentially achieved by targeted temperature management (that is, therapeutic hypothermia or prophylactic controlled normothermia) - is essential in emergency and acute care management of various severe neurologic and cardiologic diseases. Beyond neuroprotection - for this aim, therapeutic hypothermia has been established after resuscitation of patients with cardiac arrest due to a shockable arrhythmia and in neonatal asphyxic encephalopathy - therapeutic hypothermia and prophylactic controlled normothermia have been published in single case reports, retrospective, open, but also in prospective randomised controlled trials in many other emergency disciplines in which both neuroprotection and protection of other organs and tissues are the target of our therapeutic endeavours. The Medical University Innsbruck, Austria, is happy to organise this conference on temperature management, therapeutic hypothermia and prophylactic normothermia respectively, to be held in Portoroz, Slovenia. In accordance with the first Meeting on Hypothermia, which was held in Miami, Florida, USA (CHilling At the Beach), we are proud to suggest the acronym CHAB standing for take Care for Heart And Brain, characterising the major target organs of therapeutic and, possibly also, prophylactic temperature management. Again, we have been able to gather most renowned scientists, neurointensivists and intensivists, emergency physicians, cardiologists and other specialists to cover the entire scientific and clinical spectrum of emergency temperature management, technical aspects of cooling and management of potential complications including shivering, but also temperature management in neurology, neurosurgery, intensive care medicine, in the operation theatre, cardiology, infectious diseases, and so forth. Beyond that we cross borders and discuss hypothermia and intracranial pressure, pharmacodynamics in hypothermic patients and the influence of hypothermia onto pharmacokinetics/pharmacodynamics, hypothermia in refractory status epilepticus or heat stroke, hypothermia and advanced neuromonitoring, hypothermia and nutrition, shivering and the critical issue of rewarming, amongst other topics. The aim of this symposium is to enhance the knowledge on temperature management, increase the readiness and stimulate the preparedness to institute therapeutic hypothermia and/or prophylactic controlled normothermia, respectively, in patients in need of tissue and organ protection, uncontrolled body temperatures possibly adding - per se - to neuronal damage. Knowing the medical literature and knowing the issue of potentially life-threatening side effects and complications incurred by this invasive therapeutic manoeuvre, it is the foremost aim of this symposium and this supplementary issue of Critical Care to discuss all these aspects of targeted temperature management in emergency, critical care and, in particular, neurocritical patients and conditions. For this reason the organisers have agreed that the discussion of these various issues, being so important for general critical care, neurocritical care and emergency medicine, must be distributed as widely as possible, making it available to critical care and neurocritical care specialists all over the world. Therefore we are extremely grateful to the Editors of Critical Care for providing a forum for all of the extended abstracts of all invited speakers, covering the entire field of adult emergency and critical care medicine. We do hope and we are convinced that this supplementary issue will be a source of inspiration and knowledge, hopefully becoming a work of reference for intensivists, neurologists, neurointensivists, cardiologists and all emergency physicians alike. It is the aim of the organisers to establish a series of such symposia within the next years in order to keep up with all the developments in this field and to maintain the highest possible level of knowledge of targeted temperature management in the community of emergency and intensive care physicians.