Thomas Uray

Efficacy and Safety of Endovascular Cooling After Cardiac Arrest. Cohort Study and Bayesian Approach

Background and Purpose— Recently 2 randomized trials in comatose survivors of cardiac arrest documented that therapeutic hypothermia improved neurological recovery. The narrow inclusion criteria resulted in an international recommendation to cool only a restricted group of primary cardiac arrest survivors. In this retrospective cohort study we investigated the efficacy and safety of endovascular cooling in unselected survivors of cardiac arrest. Methods— Consecutive comatose survivors of cardiac arrest, who were either cooled for 24 hours to 33°C with endovascular cooling or treated with standard postresuscitation therapy, were analyzed. Complication data were obtained by retrospective chart review. Results— Patients in the endovascular cooling group had 2-fold increased odds of survival (67/97 patients versus 466/941 patients; odds ratio 2.28, 95% CI, 1.45 to 3.57; P<0.001). After adjustment for baseline imbalances the odds ratio was 1.96 (95% CI, 1.19 to 3.23; P=0.008). When discounting the observational data in a Bayesian analysis by using a sceptical prior the posterior odds ratio was 1.61 (95% credible interval, 1.06 to 2.44). In the endovascular cooling group, 51/97 patients (53%) survived with favorable neurology as compared with 320/941 (34%) in the control group (odds ratio 2.15, 95% CI, 1.38 to 3.35; P=0.0003; adjusted odds ratio 2.56, 1.57 to 4.17). There was no difference in the rate of complications except for bradycardia. Conclusion— Endovascular cooling improved survival and short-term neurological recovery compared with standard treatment in comatose adult survivors of cardiac arrest. Temperature control was effective and safe with this device.

Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms

AIM Mild therapeutic hypothermia (32-34°C) improves neurological recovery and reduces the risk of death in comatose survivors of cardiac arrest when the initial rhythm is ventricular fibrillation or pulseless ventricular tachycardia. The aim of the presented study was to investigate the effect of mild therapeutic hypothermia (32-34°C for 24h) on neurological outcome and mortality in patients who had been successfully resuscitated from non-ventricular fibrillation cardiac arrest. METHODS In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest with asystole or pulseless electric activity as the first documented rhythm. Data were collected from 1992 to 2009. Main outcome measures were neurological outcome within six month and mortality after six months. RESULTS Three hundred and seventy-four patients were analysed. Hypothermia was induced in 135 patients. Patients who were treated with mild therapeutic hypothermia were more likely to have good neurological outcomes in comparison to patients who were not treated with hypothermia with an odds ratio of 1.84 (95% confidence interval: 1.08-3.13). In addition, the rate of mortality was significantly lower in the hypothermia group (odds ratio: 0.56; 95% confidence interval: 0.34-0.93). CONCLUSION Treatment with mild therapeutic hypothermia at a temperature of 32-34°C for 24h is associated with improved neurological outcome and a reduced risk of death following out-of-hospital cardiac arrest with non-shockable rhythms.

Out-of-hospital surface cooling to induce mild hypothermia in human cardiac arrest: a feasibility trial.

AIM The earliest initiation of mild hypothermia after resuscitation from cardiac arrest is crucial. This study aimed to evaluate the feasibility and safety of out-of-hospital surface cooling in such cases. METHODS Cooling pads stored below 0 degrees C in the ambulance were applied as soon as possible after restoration of spontaneous circulation in the out-of-hospital setting. This continued in the emergency department until an oesophageal temperature of 34 degrees C was reached, when the pads were removed. A target temperature of 33 degrees C was maintained for 24 h. Results are given as median and interquartile range. RESULTS From September 2006 to January 2007, 15 victims of cardiac arrest were included. Cooling was initiated at 12 (8.5-15) min after restoration of spontaneous circulation. Oesophageal temperatures decreased from 36.6 (36.2-36.6) degrees C to 33 degrees C within 70 (55-106) min. Hospital admission was at 45 (34-52) min, with oesophageal temperatures of 35.4 (34.6-35.9) degrees C; the target 33 degrees C was achieved 50 (29-82) min after admission. No skin lesions were observed. CONCLUSION Non-invasive surface cooling immediately after resuscitation from cardiac arrest, in the out-of-hospital setting, proved to be feasible, fast and safe. Whether early cooling will improve neurological outcome needs to be determined in future studies.

Hypothermia after cardiac arrest: a treatment that works

Purpose of reviewSudden death from cardiac arrest is a major health problem that still receives too little publicity. Current therapy after cardiac arrest concentrates on resuscitation efforts because, until now, no specific therapy for brain protection after restoration of spontaneous circulation was available. Therapeutic mild or moderate resuscitative hypothermia is a novel therapy with multifaceted chemical and physical effects by preventing or mitigating the derangements seen in the postresuscitation syndrome. Recent findings and summaryIn 2002, two prospective, randomized studies reported improved outcomes when deliberate hypothermia was induced in comatose survivors after resuscitation from cardiac arrest. However, several issues with regard to resuscitative cooling are still unanswered and should be studied further. These include the optimal timing to initiate cooling, the optimal cooling period, the optimal temperature level, and rewarming strategy. Even important questions, such as which cooling technique will be available in the near future that would combine ease of use with high efficacy, are not answered yet.

Hemostasis in cardiac arrest patients treated with mild hypothermia initiated by cold fluids

AIM OF THE STUDY Application of mild hypothermia (32-33 degrees C) has been shown to improve neurological outcome in patients with cardiac arrest. However, hypothermia affects hemostasis, and even mild hypothermia is associated with bleeding and increased transfusion requirements in surgery patients. On the other hand, crystalloid hemodilution has been shown to induce a hypercoagulable state. The study aim was to elucidate in which way the induction of mild therapeutic hypothermia by a bolus infusion of cold crystalloids affects the coagulation system of patients with cardiac arrest. METHODS This was a prospective pilot study in 18 patients with cardiac arrest and return of spontaneous circulation (ROSC). Mild hypothermia was initiated by a bolus infusion of cold 0.9% saline fluid (4 degrees C; 30ml/kg/30min) and maintained for 24h. At 0h (before hypothermia), 1, 6 and 24h we assessed coagulation parameters (PT, APPT), platelet count and performed thrombelastography (ROTEM) after in vitro addition of heparinase. RESULTS A total amount of 2528 (+/-528)ml of 0.9% saline fluid was given. Hematocrit (p<0.01) and platelet count (-27%; p<0.05) declined, whereas APTT increased (2.7-fold; p<0.01) during the observation period. All ROTEM parameters besides clotting time (CT) after 1h (-20%; p<0.05) did not significantly change. CONCLUSION Mild hypothermia only slightly prolonged clotting time as measured by rotation thrombelastography. Therefore, therapeutic hypothermia initiated by cold crystalloid fluids has only minor overall effects on coagulation in patients with cardiac arrest.

Factors associated with a change in functional outcome between one month and six months after cardiac arrest A retrospective cohort study

AIM OF THE STUDY The appropriate time point of evaluation of functional outcome in cardiac arrest survivors remains a matter of debate. In this cohort study we posed the hypothesis that there are no significant changes in Cerebral Performance Categories (CPC) between one month and six months after out-of hospital cardiac arrest. If changes were present we aimed to identify reasons for these changes. METHODS Based on a cardiac arrest registry, a potential change in CPC and mortality between one month and six months after cardiac arrest was analysed. Variables that were associated with these changes were identified. RESULTS Thirty percent of 681 patients showed a significant change in functional outcome and mortality between one month and six months after out-of hospital cardiac arrest, 12% improved in CPC, 1% deteriorated, 17% died. The only factor that was associated with an improvement in CPC in the multivariate analysis was time to restoration of spontaneous circulation (ROSC) (RRR 1.04, 95% CI 1.01-1.06, per minute). We could not find any significant factors associated with a deterioration of CPC. Factors that were associated with mortality were age (RRR 1.03, 95% CI 1.01-1.06) and ventricular fibrillation as initial cardiac rhythm (RRR 0.34, 95% CI 0.16-0.71). CONCLUSIONS There is a relevant change of functional outcome even one month after out-of hospital cardiac arrest. Especially when studies compare patient groups with unequal arrest times, and an unequal distribution of initial cardiac rhythms a follow-up period longer than one month should be considered for the final outcome evaluation after cardiac arrest.

Thoracic impedance changes measured via defibrillator pads can monitor ventilation in critically ill patients and during cardiopulmonary resuscitation.

Objective:Monitoring of ventilation performance during cardiopulmonary resuscitation would be desirable to improve the quality of cardiopulmonary resuscitation. To investigate the potential for measuring ventilation rate and inspiration time, we calculated the correlation in waveform between transthoracic impedance measured via defibrillator pads and tidal volume given by a ventilator. Design:Clinical study. Setting:Emergency department of a tertiary care university hospital. Patients:A convenience sample of mechanical ventilated patients (n = 32), cardiac arrest patients (n = 20), and patients after restoration of spontaneous circulation (n = 31) older than 18 were eligible. Interventions:The Heartstart 4000SP defibrillator (Laerdal Medical Cooperation, Stavanger, Norway) with additional capabilities of recording thoracic impedance changes was used. Measurements and Main Results:The relationship between impedance change and tidal volume (impedance coefficient) was calculated. The mean (sd) correlations between the impedance waveform and the tidal volume waveform in the patient groups studied were .971 (.027), .969 (.032), and .967 (.035), respectively. The mean (sd) impedance coefficient for all patients in the study was .00194 (.0078) &OHgr;/mL, and the mean (sd) specific (weight-corrected) impedance coefficient was .152 (.048) &OHgr;/kg/mL. The measured thorax impedance change for different tidal volumes (400–1000 mL) was approximately linear. Conclusions:The impedance sensor of a defibrillator is accurate in identifying tidal volumes, when chest compressions are interrupted. This also allows quantifying ventilation rates and inspiration times. However this technology, at its present state, provides only limited practical means for exact tidal volume estimation.

Gender modifies the influence of age on outcome after successfully resuscitated cardiac arrest: a retrospective cohort study.

Abstract: Age is an important risk factor for mortality and unfavorable outcome after successfully resuscitated cardiac arrest. Other risk factors may interact with this relationship. We conducted the current study to quantify the influence of age on mortality and unfavorable neurologic outcome of patients surviving out-of-hospital cardiac arrest, and to determine the role of other confounding variables. This study was based on a cardiac arrest registry comprising all patients with witnessed out-of-hospital cardiac arrest of cardiac origin after successful resuscitation admitted to a department of emergency medicine between September 1991 and December 2004. We assessed the association between age and mortality and the degree of neurologic impairment, adjusting for multiple risk factors. We tested for interaction between age and all other risk factors with outcome. With each year of age the adjusted odds ratio for in-hospital death increased by 1.05 (95% confidence interval [CI], 1.04-1.07), and the adjusted odds ratio for an unfavorable neurologic outcome increased by 1.04 (95% CI, 1.03-1.06). Interaction between age and sex was present, and the analysis was stratified to sex. For men we found a steep risk increase for death and unfavorable outcome after being resuscitated from cardiac arrest, with the highest risk in the oldest age quartile. For women we observed only a slight risk increase for death and almost no risk increase for unfavorable outcome. Age is a strong independent risk factor for mortality and neurologic impairment after successfully resuscitated cardiac arrest. The risk increase with advancing age is much greater in men than in women. Therefore, in women, the influence of age on prognosis after cardiac arrest may not be very important, while in men it still plays an important role. This should be considered especially when treating successfully resuscitated women and discussing the prognosis with the medical team or the patients family. Abbreviations: CI = confidence intervals, CPC = cerebral performance category, IQR = interquartile range, SD = standard deviation.

Pronounced platelet hyperfunction in patients with cardiac arrest achieving restoration of spontaneous circulation

Objective:Markers of platelet activation are increased in patients undergoing cardiopulmonary resuscitation. Hyperfunctional platelets may contribute to impairment of microcirculatory function and overall poor outcome despite restoration of spontaneous circulation (ROSC). Patients with myocardial infarction have hyperfunctional platelets, which predict the degree of myocardial necrosis. Thus, we hypothesized that platelets may be even more activated in patients whose myocardial infarction leads to cardiac arrest and compared them with patients whose cardiac arrest was due to a noncardiac origin. Design:Prospective observational study. Setting:Emergency department of a tertiary care hospital. Patients:One hundred four patients with witnessed cardiac arrest who achieved ROSC. Interventions:Blood sampling. Measurements and Main Results:We assessed collagen adenosine diphosphate closure time with the platelet function analyzer-100, and measured plasma levels of von Willebrand factor: ristocetin cofactor activity levels by turbidometry. Independent physicians diagnosed the origin of cardiac arrest. The majority of cardiac arrests were caused by myocardial ischemia. Invariably, collagen adenosine diphosphate closure time values (55 seconds; 95% confidence interval: 52–58 seconds) were much shorter in these patients compared with patients with other causes of cardiac arrest (110 seconds; 95% confidence interval: 84–135 seconds, p < 0.001). von Willebrand factor: ristocetin cofactor activity plasma levels were more than three-fold above normal values in both groups. Conclusions:Patients with myocardial ischemia-triggered cardiac arrest had the highest degree of platelet hyperfunction under high shear rates, which was not solely due to increased von Willebrand factor. Future trials are necessary to clarify whether rapid, more aggressive antiplatelet therapy improves outcome after cardiac arrest.

Surface Cooling for Rapid Induction of Mild Hypothermia After Cardiac Arrest: Design Determines Efficacy

OBJECTIVES Recently, a novel cooling pad was developed for rapid induction of mild hypothermia after cardiac arrest. The aim of this study was to evaluate the cooling efficacy of three different pad designs for in-hospital cooling. METHODS Included in this prospective interventional study were patients with esophageal temperature (Tes) > 34 degrees C on admission. The cooling pad consists of multiple cooling units, filled with a combination of graphite and water, which is precooled to -18 degrees C (design A) or to -9 degrees C (designs B and C) before use. The designs of the cooling pad differed in number, shape, and thickness of the cooling units, with weights of 9.7 kg (design A), 5.3 kg (design B), and 6.2 kg (design C). All three designs were tested in sequential order and were changed according to the results found in the previous trial. Cooling was started after admission until Tes = 34 degrees C, when the cooling pad was removed. The target temperature of Tes = 32-34 degrees C was maintained for 24 hours. Data are presented as medians and interquartile ranges (IQRs = 25%-75%) or proportions. RESULTS Cooling rates were 3.4 degrees C/hour (IQR = 2.5-3.7) with design A (n = 12), 2.8 degrees C/hour (IQR = 1.6-3.3) with design B (n = 7), and 2.9 degrees C/hour (IQR = 1.9-3.6) with design C (n = 10; p = 0.5). To reach 34 degrees C, the cooling pad had to be exchanged with a new one due to melting and therefore depleting cooling capacity in three patients with design A, in five patients with design B, and in no patient with design C (p = 0.004). CONCLUSIONS With adequate design and storage temperature, the cooling pad proved to be efficient for rapid in-hospital cooling of patients resuscitated from cardiac arrest.