Therapeutic Temperature Modulation Research Articles

Outcome and prognostication after cardiac arrest.

The outcome after out-of-hospital cardiac arrest has historically been grim at best. The current overall survival rate of patients admitted to a hospital is approximately 10%, making cardiac arrest one of the leading causes of death in the United States. The situation is improving with the incorporation of therapeutic temperature modulation, aggressive prevention of secondary brain injury, and improved access to advanced cardiovascular support, all of which have decreased mortality and allowed for better outcomes. Mortality after cardiac arrest is often the direct result of active withdrawal of life-sustaining therapy based on the perception that neurological recovery is not possible. This reality highlights the importance of providing accurate estimates of neurological prognosis to decision makers when discussing goals of care. The current standard of care for assessing neurological status in patients with hypoxic-ischemic encephalopathy emphasizes a multimodal approach that includes five elements: (1) neurological examination off sedation, (2) continuous electroencephalography, (3) serum neuron-specific enolase levels, (4) magnetic resonance brain imaging, and (5) somatosensory-evoked potential testing. Sophisticated decision support systems that can integrate these clinical, imaging, and biomarker and neurophysiologic data and translate it into meaningful projections of neurological outcome are urgently needed.

Therapeutic temperature modulation in severe or moderate traumatic brain injury: a propensity score analysis of data from the Nationwide Japan Neurotrauma Data Bank.

In patients with severe traumatic brain injury (TBI), a randomized controlled trial revealed that outcomes did not significantly improve after therapeutic hypothermia (TH) or normothermia (TN). However, avoiding pyrexia, which is often associated with intracranial disorders, might improve clinical outcomes. The objective of this study was to compare neurological outcomes among patients with moderate and severe TBI after therapeutic temperature modulation (TTM) in the absence of other interventions. Data from 1091 patients were obtained from the Japan Neurotrauma Data Bank Project 2009, a cohort observational study. Patients with cardiac arrest, those with a Glasgow Coma Scale score of 3 and dilated fixed pupils, and those whose cause of death was injury to another area of the body were excluded, leaving 687 patients aged 16 years or older in this study. The patients were divided into 2 groups: the TTM group underwent TN (213 patients) or TH (82 patients), and the control group (392 patients) did not receive TTM. The primary end point for this study was the rate of poor outcome at hospital discharge, and the secondary end point was in-hospital death. Out of the 208 total items in the database, 29 variables that could potentially affect outcome were matched using the propensity score (PS) method in order to reduce selection bias and balance the baseline characteristics. From each group, 141 patients were extracted using the PS-matching process. Among the patients in the TTM group, 29 had undergone TH and 112 had undergone TN. In a log-rank test using Kaplan-Meier survival curves, no significant differences in patient outcome or death were observed between the 2 groups (poor outcome, p = 0.83; death, p = 0.18). A Cox proportional-hazards regression analysis established the HR for poor outcome and mortality at 1.03 (95% CI 0.78-1.36, p = 0.83) and 1.34 (95% CI 0.87-2.07, p = 0.18), respectively. There was no clear improvement in neurological outcomes after TTM in patients with moderate or severe TBI. To elucidate the role of TTM in patients with these injuries, a prospective study is needed with long-term follow-up using specific target temperatures.

Heat Transfer in Health and Healing.

Our bodies depend on an exquisitely sensitive and refined temperature control system to maintain a state of health and homeostasis. The exceptionally broad range of physical activities that humans engage in and the diverse array of environmental conditions we face require remarkable strategies and mechanisms for regulating internal and external heat transfer processes. On the occasions for which the body suffers trauma, therapeutic temperature modulation is often the approach of choice for reversing injury and inflammation and launching a cascade of healing. The focus of human thermoregulation is maintenance of the body core temperature within a tight range of values, even as internal rates of energy generation may vary over an order of magnitude, environmental convection, and radiation heat loads may undergo large changes in the absence of any significant personal control, surface insulation may be added or removed, all occurring while the body's internal thermostat follows a diurnal circadian cycle that may be altered by illness and anesthetic agents. An advanced level of understanding of the complex physiological function and control of the human body may be combined with skill in heat transfer analysis and design to develop life-saving and injury-healing medical devices. This paper will describe some of the challenges and conquests the author has experienced related to the practice of heat transfer for maintenance of health and enhancement of healing processes.

Therapeutic temperature modulation is associated with pulmonary complications in patients with severe traumatic brain injury.

To examine complications associated with the use of therapeutic temperature modulation (mild hypothermia and normothermia) in patients with severe traumatic brain injury (TBI). One hundred and fourteen charts were reviewed. Inclusion criteria were: severe TBI with Glasgow Coma Scale (GCS) < 9, intensive care unit (ICU) stay > 24 h and non-penetrating TBI. Patients were divided into two cohorts: the treatment group received therapeutic temperature modulation (TTM) with continuous surface cooling and indwelling bladder temperature probes. The control group received standard treatment with intermittent acetaminophen for fever. Information regarding complications during the time in the ICU was collected as follows: Pneumonia was identified using a combination of clinical and laboratory data. Pulmonary embolism, pneumothorax and deep venous thrombosis were identified based on imaging results. Cardiac arrhythmias and renal failure were extracted from the clinical documentation. acute respiratory distress syndrome and acute lung injury were determined based on chest imaging and arterial blood gas results. A logistic regression was conducted to predict hospital mortality and a multiple regression was used to assess number and type of clinical complications. One hundred and fourteen patients were included in the analysis (mean age = 41.4, SD = 19.1, 93 males), admitted to the Jackson Memorial Hospital Neuroscience ICU and Ryder Trauma Center (mean GCS = 4.67, range 3-9), were identified and included in the analysis. Method of injury included motor vehicle accident (n = 29), motor cycle crash (n = 220), blunt head trauma (n = 212), fall (n = 229), pedestrian hit by car (n = 216), and gunshot wound to the head (n = 27). Ethnicity was primarily Caucasian (n = 260), as well as Hispanic (n = 227) and African American (n = 223); four patients had unknown ethnicity. Patients received either TTM (43) or standard therapy (71). Within the TTM group eight patients were treated with normothermia after TBI and 35 patients were treated with hypothermia. A logistic regression predicting in hospital mortality with age, GCS, and TM demonstrated that GCS (Beta = 0.572, P < 0.01) and age (Beta = -0.029) but not temperature modulation (Beta = 0.797, ns) were significant predictors of in-hospital mortality [χ(2) (3) = 22.27, P < 0.01] A multiple regression predicting number of complications demonstrated that receiving TTM was the main contributor and was associated with a higher number of pulmonary complications (t = -3.425, P = 0.001). Exposure to TTM is associated with an increase in pulmonary complications. These findings support more attention to these complications in studies of TTM in TBI patients.

Pharmacologic evaluation of shivering management in neurologically injured patients utilizing therapeutic normothermia

Uncontrolled shivering may have negative consequences by increasing metabolic demand and subsequently neutralize the benefits of therapeutic normothermia [1]. Previous anti-shivering protocols that utilize the least sedation have been described in therapeutic temperature modulation (TTM) [2]. Our aim is to describe and evaluate an anti-shivering protocol that emphasizes the least sedating regimen with the least number of pharmacologic agents for patients undergoing therapeutic normothermia.

Therapeutic Temperature Modulation for Fever After Intracerebral Hemorrhage

We sought to determine whether therapeutic temperature modulation (TTM) to treat fever after intracerebral hemorrhage (ICH) is associated with improved hospital complications and discharge outcomes. We performed a retrospective case-control study of patients admitted with spontaneous ICH having two consecutive fevers ≥38.3 °C despite acetaminophen administration. Cases were enrolled from a prospective database of patients receiving TTM from 2006 to 2010. All cases received TTM for fever control with goal temperature of 37 °C with a shiver-control protocol. Controls were matched in severity by ICH score and retrospectively obtained from 2001 to 2004, before routine use of TTM for ICH. Primary outcome was discharge-modified Rankin score. Forty patients were enrolled in each group. Median admission ICH Score, ICH volume, and GCS were similar. TTM was initiated with a median of 3 days after ICH onset and for a median duration of 7 days. Mean daily T max was significantly higher in the control group over the first 12 days (38.1 vs. 38.7 °C, p ≤ 0.001). The TTM group had more days of IV sedation (median 8 vs. 1, p < 0.001) and mechanical ventilation (18 vs. 9, p = 0.003), and more frequently underwent tracheostomy (55 vs. 23 %, p = 0.005). Mean NICU length of stay was longer for TTM patients (15 vs. 11 days, p = 0.007). There was no difference in discharge outcomes between the two groups (overall mortality 33 %, moderate or severe disability 67 %). Therapeutic normothermia is associated with increased duration of sedation, mechanical ventilation, and NICU stay, but is not clearly associated with improved discharge outcome.

Influence of baseline magnesium concentrations on shivering in therapeutic temperature modulation

Therapeutic temperature modulation (TTM) is widely used in the care setting to improve outcomes of patients with traumatic brain injury (TBI). Through fever prevention, both oxygen utilization and caloric expenditure are reduced, so metabolic efficiency can be maximized [1]. However, patient cooling is not without consequences and shivering is experienced by more than 70% of patients achieving TTM. Because shivering triggers an increase in metabolic demand, causing additional oxygen consumption and the promotion of catabolism, its prevention is ideal [2]. We set out to review the data surrounding the anti-shivering component of a normothermia protocol in the surgical ICU (SICU) of one Minnesota hospital.

Assessment of a Patient's Shivering

Therapeutic temperature management (TTM) is also known as therapeutic hypothermia or therapeutic temperature modulation. This therapy has become a standard of care for patients who are comatose after cardiac arrest. It is also used for comatose patients with acute liver failure and brain injury patients with persistent elevated intracranial pressure.1Patients receiving TTM therapy must be monitored for a variety of side effects including fluid and electrolyte alterations, hemodynamic instability, respiratory insufficiency, and shivering. Shivering is an involuntary response designed to generate heat and increase body temperature. It is difficult to identify but can have devastating effects in these already critically ill patients. An assessment tool, such as the Bedside Shivering Assessment Scale (BSAS), will help quickly identify patients who are shivering, and alllow for early intervention to limit the consequences of the shivering response.2

Therapeutic Hypothermia for Traumatic Brain Injury

Experimental evidence demonstrates that therapeutic temperature modulation with the use of mild induced hypothermia (MIH, defined as the maintenance of body temperature at 32-35 °C) exerts significant neuroprotection and attenuates secondary cerebral insults after traumatic brain injury (TBI). In adult TBI patients, MIH has been used during the acute "early" phase as prophylactic neuroprotectant and in the sub-acute "late" phase to control brain edema. When used to control brain edema, MIH is effective in reducing elevated intracranial pressure (ICP), and is a valid therapy of refractory intracranial hypertension in TBI patients. Based on the available evidence, we recommend: applying standardized algorithms for the management of induced cooling; paying attention to limit potential side effects (shivering, infections, electrolyte disorders, arrhythmias, reduced cardiac output); and using controlled, slow (0.1-0.2 °C/h) rewarming, to avoid rebound ICP. The optimal temperature target should be titrated to maintain ICP <20 mmHg and to avoid temperatures <35 °C. The duration of cooling should be individualized until the resolution of brain edema, and may be longer than 48 h. Patients with refractory elevated ICP following focal TBI (e.g. hemorrhagic contusions) may respond better to MIH than those with diffuse injury. Randomized controlled trials are underway to evaluate the impact of MIH on neurological outcome in adult TBI patients with elevated ICP. The use of MIH as prophylactic neuroprotectant in the early phase of adult TBI is not supported by clinical evidence and is not recommended.

Shivering Management During Therapeutic Temperature Modulation: Nurses’ Perspective

Therapeutic temperature modulation, which incorporates mild hypothermia and maintenance of normothermia, is being used to manage patients resuscitated after cardiac arrest. Methods of modulating temperature include intravenous infusion of cold fluids and surface or endovascular cooling. During this therapy, the shiver response is activated as a defense mechanism in response to an altered set-point temperature and causes metabolic and hemodynamic stress for patients. Recognition of shivering according to objective and subjective assessments is vital for early detection of the condition. Once shivering is detected, treatment is imperative to avoid deleterious effects. The Bedside Shivering Assessment Scale can be used to determine the efficacy of interventions intended to blunt thermoregulatory defenses and can provide continual evaluation of patients' responses to the interventions. Nurses' knowledge and understanding of the harmful effects of shivering are important to effect care and prevent injury associated with uncontrolled shivering.

Prevention of Shivering During Therapeutic Temperature Modulation: The Columbia Anti-Shivering Protocol

As the practice of aggressive temperature control has become more commonplace, new clinical problems are arising, of which shivering is the most common. Treatment for shivering while avoiding the negative consequences of many anti-shivering therapies is often difficult. We have developed a stepwise protocol that emphasizes use of the least sedating regimen to achieve adequate shiver control. All patients treated with temperature modulating devices in the neurological intensive care unit were prospectively entered into a database. Baseline demographic information, daily temperature goals, best daily GCS, and type and cumulative dose of anti-shivering agents were recorded. We collected 213 patients who underwent 1388 patient days of temperature modulation. Eighty-nine patients underwent hypothermia and 124 patients underwent induced normothermia. In 18% of patients and 33% of the total patient days only none-sedating baseline interventions were needed. The first agent used was most commonly dexmeditomidine at 50% of the time, followed by an opiate and increased doses of propofol. Younger patients, men, and decreased BSA were factors associated with increased number of anti-shivering interventions. A significant proportion of patients undergoing temperature modulation can be effectively treated for shivering without over-sedation and paralysis. Patients at higher risk for needing more interventions are younger men with decreased BSA.

Metabolic benefits of surface counter warming during therapeutic temperature modulation*

To determine the impact of counter warming (CW) with an air circulating blanket on shivering and metabolic profile during therapeutic temperature modulation (TTM). A prospective observational study. An 18-bed neurologic intensive care unit. Fifty mechanically ventilated patients with brain injury undergoing TTM with automated surface and intravascular devices. Fifty indirect calorimetry (IDC) measurements with and without CW during TTM. IDC was continuously performed for 10-15 minutes at baseline with CW (phase I), off CW (phase II), and again after the return of CW (phase III). Shivering severity during each phase was scored on a scale of 0-3 using the Bedside Shivering Assessment Scale (BSAS). Resting energy expenditure (REE), oxygen consumption, and carbon dioxide production were determined by IDC; 56% were women, with mean age 61 +/- 15 years. At the time of IDC, 72% of patients had signs of shivering (BSAS >0). All measures of basal metabolism increased after removal of the air warming blanket (from phases I and II); REE increased by 27% and oxygen consumption by 29% (both p < 0.002). A one-point increase in baseline BSAS was noted in 55% (n = 23/42) of patients from phase I to phase II. In a multivariate analysis, sedative use (p = 0.03), baseline moderate to severe shivering (p = 0.04), and lower serum magnesium levels (p = 0.01) were associated with greater increases in REE between phase I and phase II of CW. Phase III of CW was associated with a reversal in the increases in all metabolic variables. Surface CW provides beneficial control of shivering and improves the metabolic profile during TTM.

Metabolic Impact of Shivering During Therapeutic Temperature Modulation

Therapeutic temperature modulation is widely used in neurocritical care but commonly causes shivering, which can hamper the cooling process and result in increases in systemic metabolism. We sought to validate a grading scale to assist in the monitoring and control of shivering. A simple 4-point Bedside Shivering Assessment Scale was validated against continuous assessments of resting energy expenditure, oxygen consumption, and carbon dioxide production as measured by indirect calorimetry. Therapeutic temperature modulation for fever control or the induction of hypothermia was achieved with the use of a surface or endovascular device. Expected energy expenditure was calculated using the Harris-Benedict equation. A hypermetabolic index was calculated from the ratio of resting of energy expenditure to energy expenditure. Fifty consecutive cerebrovascular patients underwent indirect calorimetry between January 2006 and June 2007. Fifty-six percent were women, and mean age 63+/-16 years. The majority underwent fever control (n=40 [80%]) with a surface cooling device (n=44 [87%]) and had signs of shivering (Bedside Shivering Assessment Scale >0, 64% [n=34 of 50]). Low serum magnesium was independently associated with the presence of shivering (Bedside Shivering Assessment Scale >0; OR, 6.8; 95% CI, 1.7 to 28.0; P=0.01). The Bedside Shivering Assessment Scale was independently associated with the hypermetabolic index (W=16.3, P<0.001), oxygen consumption (W=26.3, P<0.001), resting energy expenditure (W=27.2, P<0.001), and carbon dioxide production (W=18.2, P<0.001) with a high level of interobserver reliability (kappa(w)=0.84, 95% CI, 0.81 to 0.86). The Bedside Shivering Assessment Scale is a simple and reliable tool for evaluating the metabolic stress of shivering.

Therapeutic temperature modulation in neurocritical care

The ability to effectively achieve and maintain long-term temperature control is an important goal that has been previously unachievable in the neurocritical care setting. Previous attempts have been limited by the inability to overcome physiologic defense mechanisms, short duration of action, or significant adverse effects. Recent advances in technology have made therapeutic temperature modulation feasible. In this review, current concepts of therapeutic temperature modulation are presented. New advances in technology may provide an important breakthrough in the ability to reduce fever-associated morbidity in neurocritically ill patients. What remains to be seen is whether the advantages of these technologies will outweigh the risks associated with therapeutic temperature modulation.

Therapeutic Hypothermia.

Mayo Clinic, Rochester, Minnesota. weglinski.margaret@mayo.eduTherapeutic Hypothermia. Edited by Stephan A. Mayer, M.D., and Daniel I. Sessler, M.D. New York, Marcel Dekker, 2005. Pages: 648. Price: $149.95.For many years, the therapeutic use of induced hypothermia was largely limited to cardiopulmonary bypass–facilitated cardiac—and less commonly, cerebrovascular—surgery. That all changed in the mid 1980s, when several laboratories demonstrated in animal models that mild hypothermia (33°–35°C) resulted in protection of the brain against ischemic and traumatic injuries. These discoveries rapidly led to the application of mild to moderate hypothermia in various clinical situations, including operative neurosurgery, stroke, cardiac arrest, and head trauma. Numerous uncontrolled studies began to appear in the literature. Other studies suggested that mild perioperative hypothermia was associated with an increased incidence of bleeding, infectious, and cardiovascular complications. Despite these conflicting study results, a 2003 survey from Great Britain and Ireland reported that hypothermia was being used in more than 50% of patients undergoing cerebral aneurysm surgery.It is against this historical backdrop that Therapeutic Hypothermia arrives on the scene. As the editors mention in the preface, one of the reasons therapeutic hypothermia has attracted such intense interest is because pharmacologic interventions have consistently failed to improve outcome after various neurologic injuries. As more is learned about the mechanisms of hypothermia-induced neuroprotection, physicians are becoming more inclined to treat body temperature like other physiologic variables and optimize it for each individual patient. This constitutes a new field of medicine that influences many areas of clinical practice: neurologic and cardiac surgery, critical care medicine, emergency medicine, neurology, and neurosurgery. Therapeutic Hypothermia is meant to be a comprehensive reference on this emerging field of medicine. It consists of 17 chapters written by an international collection of 26 authors. The chapters are grouped into four sections: Thermoregulation, Consequences of Hypothermia, Therapeutic Temperature Modulation, and Clinical Applications of Therapeutic Hypothermia. Chapters within the first three sections lay the scientific groundwork to better explain how and why hypothermia has been used in the clinical arena. I found that, throughout the book, each chapter provided enough background information on its topic to allow it to stand alone and therefore allow me to read the chapters that interested me first and then fill in my knowledge gaps by perusing the supporting chapters later. As with any multiauthor textbook, there is a small amount of repetition among the chapters, but for the most part, readers are appropriately referred to other chapters to avoid this. The text is easy to read, but some of the black-and-white figures are small and often dwarfed by their accompanying legends.The editors, Stephan A. Mayer, M.D. (Columbia University, New York, New York), and Daniel I. Sessler, M.D. (University of Louisville, Louisville, Kentucky), should be commended for having the foresight to publish a book that attempts to summarize all that is currently known about therapeutic hypothermia. The book does an excellent job of organizing and synthesizing the multitude of studies performed in this rapidly growing field, many of which come to conflicting conclusions. It belongs in the reference library of every department of anesthesiology, critical care medicine, neurosurgery, cardiac surgery, emergency medicine, and neurology. It is a book that will no doubt require future editions to keep current with all that is being published in the field. This is probably best demonstrated by the fact that the results of the Intraoperative Hypothermia for Aneurysm Surgery Trial, Part 2 (IHAST2), were not yet published at the time this book went to press and so are not included in the text (although they are alluded to in the foreword by Michael Todd, M.D., The University of Iowa, Iowa City, Iowa). I am hoping the next edition will include not only the IHAST2 results, but reports of yet more intriguing research in this promising field.Mayo Clinic, Rochester, Minnesota. weglinski.margaret@mayo.edu