Kees H. Polderman

Mechanisms of action, physiological effects, and complications of hypothermia.

Background:Mild to moderate hypothermia (32–35°C) is the first treatment with proven efficacy for postischemic neurological injury. In recent years important insights have been gained into the mechanisms underlying hypothermias protective effects; in addition, physiological and pathophysiological changes associated with cooling have become better understood. Objective:To discuss hypothermias mechanisms of action, to review (patho)physiological changes associated with cooling, and to discuss potential side effects. Design:Review article. Interventions:None. Main Results:A myriad of destructive processes unfold in injured tissue following ischemia–reperfusion. These include excitotoxicty, neuroinflammation, apoptosis, free radical production, seizure activity, blood–brain barrier disruption, blood vessel leakage, cerebral thermopooling, and numerous others. The severity of this destructive cascade determines whether injured cells will survive or die. Hypothermia can inhibit or mitigate all of these mechanisms, while stimulating protective systems such as early gene activation. Hypothermia is also effective in mitigating intracranial hypertension and reducing brain edema. Side effects include immunosuppression with increased infection risk, cold diuresis and hypovolemia, electrolyte disorders, insulin resistance, impaired drug clearance, and mild coagulopathy. Targeted interventions are required to effectively manage these side effects. Hypothermia does not decrease myocardial contractility or induce hypotension if hypovolemia is corrected, and preliminary evidence suggests that it can be safely used in patients with cardiac shock. Cardiac output will decrease due to hypothermia-induced bradycardia, but given that metabolic rate also decreases the balance between supply and demand, is usually maintained or improved. In contrast to deep hypothermia (≤30°C), moderate hypothermia does not induce arrhythmias; indeed, the evidence suggests that arrhythmias can be prevented and/or more easily treated under hypothermic conditions. Conclusions:Therapeutic hypothermia is a highly promising treatment, but the potential side effects need to be properly managed particularly if prolonged treatment periods are required. Understanding the underlying mechanisms, awareness of physiological changes associated with cooling, and prevention of potential side effects are all key factors for its effective clinical usage.

Induced hypothermia and fever control for prevention and treatment of neurological injuries

Increasing evidence suggests that induction of mild hypothermia (32-35 degrees C) in the first hours after an ischaemic event can prevent or mitigate permanent injuries. This effect has been shown most clearly for postanoxic brain injury, but could also apply to other organs such as the heart and kidneys. Hypothermia has also been used as a treatment for traumatic brain injury, stroke, hepatic encephalopathy, myocardial infarction, and other indications. Hypothermia is a highly promising treatment in neurocritical care; thus, physicians caring for patients with neurological injuries, both in and outside the intensive care unit, are likely to be confronted with questions about temperature management more frequently. This Review discusses the available evidence for use of controlled hypothermia, and also deals with fever control. Besides discussing the evidence, the aim is to provide information to help guide treatments more effectively with regard to timing, depth, duration, and effective management of side-effects. In particular, the rate of rewarming seems to be an important factor in establishing successful use of hypothermia in the treatment of neurological injuries.

European society of intensive care medicine study of therapeutic hypothermia (32-35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial)

BackgroundTraumatic brain injury is a major cause of death and severe disability worldwide with 1,000,000 hospital admissions per annum throughout the European Union.Therapeutic hypothermia to reduce intracranial hypertension may improve patient outcome but key issues are length of hypothermia treatment and speed of re-warming. A recent meta-analysis showed improved outcome when hypothermia was continued for between 48 hours and 5 days and patients were re-warmed slowly (1°C/4 hours). Previous experience with cooling also appears to be important if complications, which may outweigh the benefits of hypothermia, are to be avoided.Methods/designThis is a pragmatic, multi-centre randomised controlled trial examining the effects of hypothermia 32-35°C, titrated to reduce intracranial pressure <20 mmHg, on morbidity and mortality 6 months after traumatic brain injury. The study aims to recruit 1800 patients over 41 months. Enrolment started in April 2010.Participants are randomised to either standard care or standard care with titrated therapeutic hypothermia. Hypothermia is initiated with 20-30 ml/kg of intravenous, refrigerated 0.9% saline and maintained using each centres usual cooling technique. There is a guideline for detection and treatment of shivering in the intervention group. Hypothermia is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to maintain intracranial pressure <20 mmHg. Intracranial hypertension is defined as an intracranial pressure >20 mmHg in accordance with the Brain Trauma Foundation Guidelines, 2007.DiscussionThe Eurotherm3235Trial is the most important clinical trial in critical care ever conceived by European intensive care medicine, because it was launched and funded by the European Society of Intensive Care Medicine and will be the largest non-commercial randomised controlled trial due to the substantial number of centres required to deliver the target number of patients. It represents a new and fundamental step for intensive care medicine in Europe. Recruitment will continue until January 2013 and interested clinicians from intensive care units worldwide can still join this important collaboration by contacting the Trial Coordinating Team via the trial website http://www.eurotherm3235trial.eu.Trial registrationCurrent Controlled Trials ISRCTN34555414

Accuracy and reliability of APACHE II scoring in two intensive care units Problems and pitfalls in the use of APACHE II and suggestions for improvement.

Acute Physiology and Chronic Health Evaluation (APACHE) II scoring is widely used as an index of illness severity, for outcome prediction, in research protocols and to assess intensive care unit performance and quality of care. Despite its widespread use, little is known about the reliability and validity of APACHE II scores generated in everyday clinical practice. We retrospectively re‐assessed APACHE II scores from the charts of 186 randomly selected patients admitted to our medical and surgical intensive care units. These ‘new’ scores were compared with the original scores calculated by the attending physician. We found that most scores calculated retrospectively were lower than the original scores; 51% of our patients would have received a lower score, 26% a higher score and only 23% would have remained unchanged. Overall, the original scores changed by an average of 6.4 points. We identified various sources of error and concluded that wide variability exists in APACHE II scoring in everyday clinical practice, with the score being generally overestimated. Accurate use of the APACHE II scoring system requires adherence to strict guidelines and regular training of medical staff using the system.

Neuroprotection in acute brain injury: An up-to-date review

Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.

Equipment review: Cooling catheters to induce therapeutic hypothermia?

There is growing acceptance within the medical community of induced (therapeutic) hypothermia as a tool to achieve neuroprotection and/or cardioprotection. Although much work remains to be done in identifying those clinical situations in which hypothermia can be effective, there is now sufficient evidence to regard it as a standard of care, at least for some indications such as selected patients with postanoxic encephalopathy. Thus, attention is now partly shifting from assessment of the clinical evidence of efficacy to technical and implementation issues. This review provides a list of criteria by which cooling devices can be judged, and specifically it discusses one of the new cooling devices: the Alsius CoolGard 3000® device and CoolLine® catheter. General aspects and advantages/disadvantages of surface versus core cooling are discussed, as are potential side effects, device-specific pros and cons, and cost-effectiveness issues. In addition, the current state of the evidence for use of induced hypothermia for various indications is briefly reviewed.

Emergency Neurological Life Support: Resuscitation Following Cardiac Arrest

Cardiac arrest is the most common cause of death in North America. Neurocritical care interventions, including therapeutic hypothermia (TH), have significantly improved neurological outcomes in patients successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an Emergency Neurological Life Support protocol. Patients remaining comatose following resuscitation from cardiac arrest and who are not bleeding are potential candidates for TH. This protocol will review induction, maintenance, and re-warming phases of TH, along with management of TH side effects. Aggressive shivering suppression is necessary with this treatment to ensure the maintenance of a target temperature. Ancillary testing, including electrocardiography, computed tomography imaging of the brain, continuous electroencephalography, monitoring, and correction of electrolyte, blood gas, and hematocrit changes are also necessary to optimize outcomes.

Automated peritoneal lavage: an extremely rapid and safe way to induce hypothermia in post-resuscitation patients

See related letter by Esnault et al.,http://ccforum.com/content/17/3/431IntroductionMild therapeutic hypothermia (MTH) is a worldwide used therapy to improve neurological outcome in patients successfully resuscitated after cardiac arrest (CA). Preclinical data suggest that timing and speed of induction are related to reduction of secondary brain damage and improved outcome.MethodsAiming at a rapid induction and stable maintenance phase, MTH induced via continuous peritoneal lavage (PL) using the Velomedix® Inc. automated PL system was evaluated and compared to historical controls in which hypothermia was achieved using cooled saline intravenous infusions and cooled blankets.ResultsIn 16 PL patients, time to reach the core target temperature of 32.5°C was 30 minutes (interquartile range (IQR): 19 to 60), which was significantly faster compare to 150 minutes (IQR: 112 to 240) in controls. The median rate of cooling during the induction phase in the PL group of 4.1°C/h (IQR: 2.2 to 8.2) was significantly faster compared to 0.9°C/h (IQR: 0.5 to 1.3) in controls. During the 24-hour maintenance phase mean core temperature in the PL patients was 32.38 ± 0.18°C (range: 32.03 to 32.69°C) and in control patients 32.46 ± 0.48°C (range: 31.20 to 33.63°C), indicating more steady temperature control in the PL group compared to controls. Furthermore, the coefficient of variation (VC) for temperature during the maintenance phase was lower in the PL group (VC: 0.5%) compared to the control group (VC: 1.5%). In contrast to 23% of the control patients, none of the PL patients showed an overshoot of hypothermia below 31°C during the maintenance phase. Survival and neurological outcome was not different between the two groups. Neither shivering nor complications related to insertion or use of the PL method were observed.ConclusionsUsing PL in post-CA patients results in a rapidly reached target temperature and a very precise maintenance, unprecedented in clinical studies evaluating MTH techniques. This opens the way to investigate the effects on neurological outcome and survival of ultra-rapid cooling compared to standard cooling in controlled trials in various patient groups.Trial RegistrationClinicalTrials.gov: NCT01016236

How to Stay Cool in the Intensive Care Unit? Endovascular Versus Surface Cooling

Dozens of observational studies published over the past two decades have shown that fever in patients with acute neurologic injury, regardless of its cause, is independently linked to higher mortality, poor neurologic outcome, and increased length of stay in the intensive care unit (ICU) and hospital. This has been demonstrated for traumatic brain injury, acute ischemic stroke (AIS), subarachnoid haemorrhage, intracranial haemorrhage, and cardiac arrest (CA). 1,2 Therefore, therapeutic temperature management (TTM) is a key goal of care in all patients with acute brain injury. In most cases the goal is strict fever control, i.e. controlled normothermia; in patients with post-hypoxic injuries the goals is often to achieve below-normal core temperature, i.e. to induce therapeutic hypothermia (TH).

How to Stay Cool in the ICU? Endovascular vs. Surface Cooling

Dozens of observational studies published over the past two decades have shown that fever in patients with acute neurologic injury, regardless of its cause, is independently linked to higher mortality, poor neurologic outcome, and increased length of stay in the intensive care unit (ICU) and hospital. This has been demonstrated for traumatic brain injury, acute ischemic stroke (AIS), subarachnoid haemorrhage, intracranial haemorrhage, and cardiac arrest (CA). 1,2 Therefore, therapeutic temperature management (TTM) is a key goal of care in all patients with acute brain injury. In most cases the goal is strict fever control, i.e. controlled normothermia; in patients with post-hypoxic injuries the goals is often to achieve below-normal core temperature, i.e. to induce therapeutic hypothermia (TH).