Hypothermia In Post-cardiac Arrest Patients Research Articles

Effectiveness of Induced Hypothermia on the Prognosis of Post-cardiac Arrest Patients: A Scoping Literature Review.

Cardiac arrest (CA) is one of the leading causes of death worldwide. Therapeutic hypothermia (TH) is hypothesized to be a reliable practice for better prognosis in post-cardiac arrest (PCA) patients.Medical subject headings (MeSH) terminology was used to search PubMed Central, Medline, and PubMed databases for articles on the use of hypothermia in PCA patients. We selected various clinical trials, meta-analyses and review articles with complete texts in the English language. PCA syndrome occurs after a CA where the body experiences a state of global ischemia and multi-system dysfunction due to the release of reactive oxygen species (ROS) and inflammatory mediators. Hypothermia slows down enzymatic reactions, reduces free radical production, conserves energy, and prevents the accumulation of metabolic waste products. Delaying the time to initiate targeted temperature management (TTM) increases the mortality of patients, the appropriate temperature for TTM has always been debatable. TTM also has various deleterious effects on various organ systems from shivering, and arrhythmias to life-threatening infections but the risks outweigh the benefits for the patients when hypothermia is introduced in PCA care. Our study compares the different modalities to initiate hypothermia from surface cooling devices to intravascular cooling devices, and the adverse effects of each method compared to another.

Thermoregulation: A journey from physiology to computational models and the intensive care unit.

Thermoregulation plays a vital role in homeostasis. Many species of animals as well as humans have evolved various physiological mechanisms for body temperature control, which are characteristically flexible and enable a fine-tuned spatial and temporal regulation of body temperature in different environmental conditions and circumstances. Human beings normally maintain a core body temperature at around 37°C, and maintenance of this relatively high temperature is critical for survival. Therefore, principles of thermoregulatory control have also important clinical implications. Infections can cause the body temperature to rise internally and several diseases can cause a dysfunction of thermoregulatory mechanisms. Moreover, the utilization of thermotherapies in treating various diseases has been known for thousands of years with a recent resurgence of interest. An increasing amount of research suggests that targeted temperature management is of paramount importance to patient outcomes in certain clinical scenarios. We provide a concise summary of the basic concepts of thermoregulation. Emphasis is given to the principles of thermoregulation in humans in basic pathological states and to targeted temperature management strategies in the clinical environment, with special attention on therapeutic hypothermia in postcardiac arrest patients. Finally, the discussion is focused on the potential offered by computational thermophysiological models for predicting thermal responses of patients in various clinical circumstances, for proposing new perspectives in the design of novel thermal therapies, and to optimize targeted temperature management strategies. This article is categorized under: Cardiovascular Diseases > Cardiovascular Diseases>Computational Models Cardiovascular Diseases > Cardiovascular Diseases>Environmental Factors Cardiovascular Diseases > Cardiovascular Diseases>Biomedical Engineering.

Thermodynamic assessment of therapeutic hypothermia techniques for rehabilitation of post-cardiac arrest patients

A comparative study of the three main methods for inducing hypothermia in post-cardiac arrest patients is performed. A human thermal model from the literature is adapted to simulate an average adult during treatment using intravascular cooling, extracorporeal cooling, or a combination of both. The investigation is carried out using the temperature profile that best represents the hypothalamus temperature, and uses the destroyed exergy as a quality index. Each of these techniques is modeled by an equation for the exergy efficiency. As a result of the better stability and control of the patient's core temperature, as well as a reduction of destroyed exergy, the model that makes use of both techniques simultaneously proves to be, from a thermodynamic perspective, superior to the others, although each has advantages and disadvantages.

Outcomes and Utilization of Therapeutic Hypothermia in Post-Cardiac Arrest Patients in Teaching Versus Non-Teaching Hospitals: Retrospective Study of the Nationwide Inpatient Sample Database (2016).

BackgroundUsing therapeutic hypothermia (TH) reduces the core body temperature of survivors of cardiac arrest to minimize the neurological damage caused by severe hypoxia. The TH protocol is initiated following return of spontaneous circulation (ROSC) in non-responsive patients. Clinical trials examining this technique have shown significant improvement in neurological function among survivors of cardiac arrests. Though there is strong evidence to support TH use to improve the neurologic outcomes in shockable and nonshockable rhythms, predictors of TH utilization are not well-characterized. Our study tried to evaluate TH utilization, as well as the effect of the teaching status of hospitals, on outcomes, including mortality, length of stay, and total hospitalization charges.MethodWe conducted a retrospective analysis of the Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (HCUP-NIS) database. Patients with an admitting diagnosis of cardiac arrest, as identified by the corresponding International Classification of Disease, 10th Revision (ICD-10) code for the year 2016 were analyzed. In addition, we identified TH using the ICD-10 procedure code. A weighted descriptive analysis was performed to generate national estimates. Groups of patients admitted to teaching hospitals were compared to those admitted in non-teaching hospitals. Patients were stratified by age, sex, race, and demographic and clinical data, including the Charlson Comorbidity Index (CCI), for these two groups, and statistical analysis was done for the primary outcome, in-hospital mortality, as well as the secondary outcomes, including length of stay (LOS) and total hospitalization charges. Fisher’s exact test was used to compare proportions and student’s t-test for continuous variables. Statistical analysis was completed by linear regression analysis.ResultsA total of 13,780 patients met the inclusion criteria for cardiac arrest admission. The number of patients with cardiac arrest admitted to a teaching hospital was 9285. A total of 670 patients received TH, with 495 admissions to teaching hospitals. The population of females in the hypothermia group was 270. The mean age of patients received TH was 59.4 years. In patients who received TH, 65% were Caucasians followed by Hispanics (16%), with no significant statistical racial differences in groups (p=0.30). The majority of patients with TH in both groups (teaching vs. non-teaching admissions) had Medicare (58.8% vs 49.5%; p=0.75). Hospitals in the southern region had the most admissions in both groups (45.7% and 31.3%), with the northeast region having the least non-teaching hospital admissions (8.5%) and approximately similar teaching hospital admissions in other regions (~22%) (p=0.27). The total number of deaths in this group was 510, out of which 370 were in a teaching hospital. After adjusting for age, sex, race, income, the CCI, hospital location, and bed size, mortality was not significantly different between these two groups (p=0.797). We found increased LOS in patients admitted to teaching hospitals (p=0.021). With a p-value of 0.097, there were no differences in total hospitalization charges in both groups.ConclusionThere were no significant differences in mortality or total hospitalization charge between patients admitted with cardiac arrest to a teaching hospital and received TH as compared to a non-teaching hospital although patients admitted to teaching hospitals stayed longer.

Intracranial Pressure Increases During Rewarming Period After Mild Therapeutic Hypothermia in Postcardiac Arrest Patients.

Elevation of intracranial pressure (ICP) may worsen brain injury and neurological outcome. Studies on the use of therapeutic hypothermia (TH) for traumatic brain injury suggests that rapid rewarming from TH is associated with elevated ICP and poorer outcomes. However, few studies describe the time course of ICP changes during TH/rewarming after cardiac arrest (CA). In this study, we observed the changes in ICP during mild TH and rewarming after CA. Secondarily, we examined whether ICP is related to outcome. We studied comatose patients resuscitated from CA, who were treated with TH and who had ICP monitored. Target core temperature was 34°C for 24 h and target rewarming rate was 0.25°C/h. ICP and cerebral perfusion pressure (CPP) were monitored during the period. Outcome was rated as cerebral performance category. In nine patients, ICP increased during TH and rewarming (6.0 [4.0-9.0] mmHg to 16.0 [12.0-26.0] mmHg, p = 0.008). CPP did not change during the period (83.3 [80.1-91.0] mmHg to 74.3 [52.0-87.3] mmHg). Higher ICP was associated with worse outcomes (p = 0.009). All the cases with ICP >25 mmHg or CPP <40 mmHg died. Major ICP increment was observed during the rewarming period, although, some increase of ICP occurred even during the mild TH. ICP increment was higher in patients with worse outcomes.

Targeted temperature management: a health economic perspective

More and more limited financial resources in the health care sector call for an economic evaluation of potential new therapies. The economic evaluation of a new therapy is complex and depends not only on the perspective of the various stakeholders, but also on the country-specific characteristics of various reimbursement systems. From the patient perspective, the costs for new therapies might not be a concern, as long as the insurance system covers the costs. From the hospital perspective, a new therapy which reduces the length of stay might be worthwhile in a DRG-based reimbursement system, but not in a pay-per-patient-day reimbursement system. To respect the perspective of the society, a cost-effectiveness analysis could be expressed in terms of a ratio where the denominator is a gain in quality-adjusted life years (QALY) and the numerator is the cost associated with the health gain. QALY is a measure of disease burden and takes into account the quality of life measured as the Health Utility Index (HUI, dead = 0 and perfect health = 1) and quantity of life lived measured as survival time: QALY = survival time × HUI (for example, 4 years survival with HUI 0.5 = 2 QALY, or 2 years survival with HUI 1 = 2 QALY). Previous studies reported that mild therapeutic hypothermia improves neurologic recovery and survival in patients resuscitated from cardiac arrest. The estimated number needed to treat is only six patients; nevertheless, target temperature management has hardly been implemented in post-cardiac arrest treatment. The aim of the current study was to evaluate the cost-effectiveness of therapeutic hypothermia in post-cardiac arrest patients. The QALY–cost ratio was chosen as the primary outcome. To assess the cost-effectiveness of temperature management, data from a Cochrane review about mild hypothermia after cardiac arrest including 398 patients were analyzed. The QALY–cost ratio was calculated based on the cerebral performance score and total treatment costs after cardiac arrest. The assumed costs included potential cooling procedure, hospital stay, rehabilitation, and potential defibrillation implantation in Austria. Total treatment costs per 100 patients were €4.1 million for patients treated with mild hypothermia, and €3.7 million for patients with standard care. Post-arrest patients receiving mild hypothermia gained an average of 1.11 QALY compared with conventional care. This resulted in a cost-effectiveness ratio of €3.827 per QALY. Targeted temperature management at 32 to 34°C after cardiac arrest seems to be a very cost-effective treatment, with €3.827 per QALY far below commonly used benchmarks for assessing the cost-effectiveness of an intervention. These results may provide an economic rationale for implementing targeted temperature management as a standard treatment after cardiac arrest.

Accuracy of continuous thermodilution cardiac output monitoring by pulmonary artery catheter during therapeutic hypothermia in post-cardiac arrest patients

PurposeThermodilution continuous cardiac output measurements (TDCCO) by pulmonary artery catheter (PAC) have not been validated during therapeutic hypothermia in post-cardiac arrest patients. The calculated cardiac output based on the indirect Fick principle (FCO) using pulmonary artery blood gas mixed venous oxygen saturation (FCO-BG-SvO2) is considered as the gold standard. Continuous SvO2 by PAC (PAC-SvO2) has also not been validated previously during hypothermia. The aims of this study were (1) to compare FCO-BG-SvO2 with TDCCO, (2) to compare PAC-SvO2 with BG-SvO2 and finally (3) to compare FCO with SvO2 obtained via PAC or blood gas. MethodsWe analyzed 102 paired TDCCO/FCO-BG-SvO2 and 88 paired BG-SvO2/PAC-SvO2 measurements in 32 post-cardiac arrest patients during therapeutic hypothermia. ResultsTDCCO was significantly although poorly correlated with FCO-BG-SvO2 (R2 0.21, p<0.01) without systematic bias (−0.15±1.76l/min). Analysis according to Bland and Altman however showed broad limits of agreement ([−3.61; 3.45]l/min) and an unacceptable high percentage error (105%). None of the criteria for clinical interchangeability were met. Concordance analysis showed that TDCCO had limited trending ability (R2 0.03). FCO based on PAC-SvO2 was highly correlated with FCO-BG-SvO2 (R2 0.72) with a small bias (−0.08±0.72l/min) and slightly too high percentage error (44%). ConclusionOur results show an extreme inaccuracy of TDCCO by PAC in post-cardiac arrest patients during therapeutic hypothermia. We found a reasonable correlation between BG-SvO2 and PAC-SvO2 and subsequently between FCO calculated with SvO2 obtained either via blood gas or PAC. The decision to start or titrate inotropics should therefore not be guided by TDCCO in this setting.

Cardiovascular effects of mild hypothermia in post-cardiac arrest patients by beat-to-beat monitoring. A single centre pilot study

Data on the hemodynamic and cardiovascular effects of hypothermia in patients with cardiac arrest are scarce. The aim of this study was to evaluate the hemodynamic changes induced by hypothermia by means of Most Care(®) (pressure recording analytical method, PRAM methodology), a beat-to-beat hemodynamic monitoring method. We enrolled 20 patients with cardiac arrest (CA) consecutively admitted to our intensive cardiac care unit and treated with mild hypothermia (TH). While non-survivors showed no changes in haemodynamic variables throughout the study period, survivors exhibited a significant increase in systemic vascular resistance indexed during hypothermia and a trend towards lower values of heart rate and higher levels of mean arterial pressure. According to our data, PRAM methodology proved to be a feasible and clinically useful tool in CA patients treated with TH since it provides continuous beat-to-beat haemodynamic monitoring that is based on assessment of several haemodynamic variables. Moreover, we observed that survivors showed a different haemodynamic behaviour during hypothermia in respect to patients who died. However, further studies, performed in larger cohorts, are needed to better elucidate the haemodynamic effects of hypothermia in CA patients by means of PRAM methodology.

Neurological outcome and time to target temperature during therapeutic hypothermia in post-cardiac arrest patients

Method: We conducted a database study at Cochin hospital in Paris, France. Between December 2006 and January 2010, we included 381 patients who were all resuscitated from an OHCA (excepted those with a primary neurological cause or moribunds). A moderate glycemic control was applied in all patients (aiming to maintain glycemia between 5.1 and 7.7mmol/l). BG was measured every 3h during the first 48h. The median glycemia and the largest delta were assessed. Amultivariate analysis was performed to determine parameters that independently influenced the main outcome (CPC level at ICU discharge). Results: 136/381 patients (36%) had a favorable outcome (CPC 1–2). Median BG level was 7.6mmol/l [6.3–9.8] in patients with a favorable outcome compared to 9.0mmol/l (IQR: 7.1–10.6) for patientswithanunfavorableneurologic outcome (p 8.4mmol/l) was found to be an independent predictor of poor neurological issue (OR=0.43; 95% CI [0.24–0.78], p=0.006). Other predictive factors of poor outcome were an unshockable rhythm, cardiac arrest location, a no flow >4min and a low flow >15min. Finally an increase in median BG was associated with an increase in the proportion of patients with a poor neurological outcome (Fig. 1). Conclusion: Even after adjustment with usual prognostic factors, an increase in glycemia during the first 48h is associated with an unfavorable neurological outcome.

Cerebral tissue oxygen saturation during therapeutic hypothermia in post-cardiac arrest patients

Aim of the studyThis observational study was performed to assess the cerebral tissue oxygen saturation during and after therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest. MethodsWe performed a prospective observational study on the cerebral tissue oxygen saturation (SctO2) in post-cardiac arrest patients treated with therapeutic hypothermia (TH) between March 2011 and April 2012. SctO2 (measured by near-infrared spectroscopy) was non-invasively and continuously measured in 28 post-cardiac arrest patients during hypothermia and active rewarming. ResultsAt the start of mechanically induced TH, SctO2 was 68% (65–72) and PaCO2 was 47.2mmHg (36.9–51.4). SctO2 and PaCO2 significantly decreased to 59% (57–64; p=0.006) and 36.6mmHg (33.9–44.7; p=0.002), respectively, within the first 3h of mechanically induced TH. Cerebral tissue oxygen saturation was significantly lower in non-survivors (n=10) compared with survivors (n=18) at 3h after induction of hypothermia (p=0.02) while the decrease in PaCO2 was similar in both groups. During TH maintenance, SctO2 gradually returned to baseline values (69% (63–72)) at 24h, with no differences between survivors and non-survivors (p=0.65). Carbon dioxide remained within the range of mild hypocapnia (32–38mmHg) throughout the hypothermic period. During rewarming, SctO2 further increased to 71% (67–78). ConclusionsInduction of TH in comatose post-CA patients changes the balance between oxygen delivery and supply. The decrease in SctO2 was less pronounced in patients surviving to hospital discharge.

An audit to assess the effectiveness of therapeutic hypothermia for post-cardiac arrest patients: The outcome of therapeutic hypothermia in post-cardiac arrest patients between October 2010 and October 2011 in Broomfield Hospital, Chelmsford, UK

Therapeutic Hypothermia (TH) is a recognized treatment as part of the post-cardiac arrest management for comatose patients by the UK Resuscitation Council since 2005. The purpose of TH is to minimize secondary phase injury following reperfusion injuries to the brain.1–4

Use of Therapeutic Hypothermia in Postcardiac Arrest Patients by Emergency Departments

Since 2003, resuscitation guidelines have recommended the use of induced hypothermia as a therapy for patients who achieve return of spontaneous circulation after cardiac arrest from ventricular fibrillation. The aim of this study was to survey emergency physicians across the United States on their use of therapeutic hypothermia (TH) after cardiac arrest. An 18-question survey was e-mailed to a sample of emergency physicians. Fifty-eight respondents completed the survey. Most (71%) were associated with an emergency medicine residency training program. Annual census ranged from 12,000 to >170,000 visits. TH is used by the majority (69%) of respondents, 79% of which report the presence of a formal institutional protocol. The majority of respondents use TH in arrest rhythms including but not limited to ventricular fibrillation, and 21% begin the process in the prehospital setting. To induce hypothermia, a majority of respondents use commercial cooling products. The average time to target temperature was 95 minutes. The majority of respondents report a goal temperature between 32°C and 34°C. A shivering protocol is used by 76% of respondents, and as a first line medication, 46% use benzodiazepines. For those who do not use TH or do not have a protocol in place, the reasons cited include "too expensive," "too difficult to implement," and "not enough science to warrant it." In this sample of practicing emergency physicians, TH after cardiac arrest is not being used as described in the original literature. Although awareness and implementation of TH have increased, there appears to be a wide variation in the application of this therapy.

A knowledge translation collaborative to improve the use of therapeutic hypothermia in post-cardiac arrest patients: protocol for a stepped wedge randomized trial

BackgroundAdvances in resuscitation science have dramatically improved survival rates following cardiac arrest. However, about 60% of adults that regain spontaneous circulation die before leaving the hospital. Recently it has been shown that inducing hypothermia in cardiac arrest survivors immediately following their arrival in hospital can dramatically improve both overall survival and neurological outcomes. Despite the strong evidence for its efficacy and the apparent simplicity of this intervention, recent surveys show that therapeutic hypothermia is delivered inconsistently, incompletely, and often with delay.Methods and designThis study will evaluate a multi-faceted knowledge translation strategy designed to increase the utilization rate of induced hypothermia in survivors of cardiac arrest across a network of 37 hospitals in Southwestern Ontario, Canada. The study is designed as a stepped wedge randomized trial lasting two years. Individual hospitals will be randomly assigned to four different wedges that will receive the active knowledge translation strategy according to a sequential rollout over a number of time periods. By the end of the study, all hospitals will have received the intervention. The primary aim is to measure the effectiveness of a multifaceted knowledge translation plan involving education, reminders, and audit-feedback for improving the use of induced hypothermia in survivors of cardiac arrest presenting to the emergency department. The primary outcome is the proportion of eligible OHCA patients that are cooled to a body temperature of 32 to 34°C within six hours of arrival in the hospital. Secondary outcomes will include process of care measures and clinical outcomes.DiscussionInducing hypothermia in cardiac arrest survivors immediately following their arrival to hospital has been shown to dramatically improve both overall survival and neurological outcomes. However, this lifesaving treatment is frequently not applied in practice. If this trial is positive, our results will have broad implications by showing that a knowledge translation strategy shared across a collaborative network of hospitals can increase the number of patients that receive this lifesaving intervention in a timely manner.Trial RegistrationClinicalTrials.gov Trial Identifier: NCT00683683

A rapid, safe, and low-cost technique for the induction of mild therapeutic hypothermia in post-cardiac arrest patients

Aim of studyThe benefits of inducing mild therapeutic hypothermia (MTH) in cardiac arrest patients are well established. Timing and speed of induction have been related to improved outcomes in several animal trials and one human study. We report the results of an easily implemented, rapid, safe, and low-cost protocol for the induction of MTH. MethodsAll in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA) patients admitted to an intensive care unit meeting inclusion criteria were cooled using a combination modality of rapid, cold saline infusion (CSI), evaporative surface cooling, and ice water gastric lavage. Cooling tasks were performed with a primary emphasis on speed. The main endpoints were the time intervals between return of spontaneous circulation (ROSC), initiation of hypothermia (IH), and achievement of target temperature (TT). Results65 patients underwent MTH during a 3-year period. All patients reached target temperature. Median ROSC–TT was 134min. Median ROSC–IH was 68min. Median IH–TT was 60min. IH–TT cooling rate was 2.6°C/h. Complications were similar to that of other large trials. 31% of this mixed population of IHCA and OHCA patients recovered to a Pittsburgh cerebral performance score (CPC) of 1 or 2. ConclusionA protocol using a combination of core and surface cooling modalities was rapid, safe, and low cost in achieving MTH. The cooling rate of 2.6°C/h was superior to most published protocols. This method uses readily available equipment and reduces the need for costly commercial devices.

Therapeutic hypothermia after cardiac arrest

Over recent years there has been growing evidence to support the use of hypothermia in post-cardiac arrest patients. Therapeutic hypothermia is now part of the UK Resuscitation Council guidelines in cardiac arrest, and has become part of many hospitals’ postcardiac arrest algorithm.

A low-tech and no-cost approach to induce mild hypothermia in postcardiac arrest patients

A low-tech and no-cost approach to induce mild hypothermia in postcardiac arrest patients