Limited effect of mild therapeutic hypothermia on outcome after prolonged resuscitation.

BACKGROUND: Mild therapeutic hypothermia interferes with multiple cascades of the ischaemia/reperfusion injury that is known as primary mechanism for brain damage after cardiac arrest. First resuscitation attempts and the duration of resuscitation efforts will initiate and aggravate this pathophysiology. Therefore we investigated the interaction between the duration of basic and advanced life support and outcome after cardiac arrest in patients treated with or without mild therapeutic hypothermia. METHODS: This retrospective cohort study included patients 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest with presumed cardiac cause, which remained comatose after restoration of spontaneous circulation. The basic and advanced life support 'low-flow' time, categorized into four quartiles (0-11, 12-17, 18-28, ≥ 29 min), was correlated with neurological outcome. RESULTS: Out of 1103 patients 613 were cooled to a target temperature of 33 ± 1 °C for 24h. In the three quartiles with 'low-flow' time up to 28 min cooling was associated with >2-fold odds of favourable neurological outcome. In the fourth quartile with 'low-flow' time of ≥ 29 min cooling had no influence on neurological outcome (OR: 0.73; 95% CI: 0.38-1.4, test for interaction p<0.01). CONCLUSION: The duration of resuscitation efforts, defined as 'low-flow' time, influences the effectiveness of mild therapeutic hypothermia in terms of neurologic outcome. Patients with low to moderate 'low-flow' time benefit most from this treatment.

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.

Non-invasive continuous cerebral temperature monitoring in patients treated with mild therapeutic hypothermia: an observational pilot study.

AIM OF THE STUDY: To investigate if body temperature as measured with a prototype of a non-invasive continuous cerebral temperature sensor using the zero-heat-flow method to reflect the oesophageal temperature (core temperature) during mild therapeutic hypothermia after cardiac arrest. METHODS: In patients over 18 years old with restoration of spontaneous circulation after cardiac arrest, a temperature sensor that uses the zero-heat-flow principle was placed on the forehead during the periods of cooling and re-warming. This temperature was compared to oesophageal temperature as the primary temperature-monitoring site. To assess agreement, we used the Bland-Altman approach and Lin's concordance correlation coefficient. RESULTS: From September 2008 to April 2009, data from 19 patients were analysed. The median time from restoration of spontaneous circulation until temperature sensor application was 53min (interquartile range, 31; 96). All sensors were removed when a core temperature of 36 degrees C was reached. These measurements were in agreement with oesophageal temperature measurements. No allergic reaction, rash or other irritation occurred on the skin around or under the probes. Bland-Altman results showed a bias of -0.12 degrees C and 95% limits of agreement of -0.59 and +0.36 degrees C. Lin's concordance correlation coefficient was 0.98. CONCLUSIONS: Body temperature measurements using a non-invasive continuous cerebral temperature sensor prototype that uses the zero-heat-flow method accurately reflected oesophageal temperature measurements during mild therapeutic hypothermia in patients with restoration of spontaneous circulation after 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.

Safety, feasibility, and hemodynamic and blood flow effects of active compression-decompression of thorax and abdomen in patients with cardiac arrest.

OBJECTIVE: During closed chest compression for cardiac arrest, any increase in coronary perfusion pressure accounts for a proportional increase in myocardial blood flow and therefore the resuscitability of the patient. The objectives of this study were to evaluate the safety, feasibility, and hemodynamic effects of phased chest and abdominal compression-decompression and to compare it with mechanical chest compression during cardiopulmonary resuscitation. DESIGN: In this prospective, single-center, phase II study, we compared patients treated with the Datascope Lifestick Resuscitator with patients who had been treated with mechanical precordial compression. SETTING: Emergency department of a tertiary care university hospital. PATIENTS: We included 31 patients with cardiac arrest who had received cardiopulmonary resuscitation in the emergency department. INTERVENTIONS: The Lifestick device was used in 20 patients. In 11 patients, mechanical chest compression with the Thumper device was used as a control intervention. MEASUREMENTS AND MAIN RESULTS: We evaluated the safety, feasibility, and hemodynamic effects of both interventions and observed, with the help of echocardiography, the mechanisms through which blood flow was generated. We found no significant difference between the use of the Lifestick device and standard chest compression with the Thumper device in resuscitations. Most operators regarded the Lifestick as a feasible alternative to the Thumper. We could observe a mean increase in coronary perfusion pressure of 9.33 mm Hg (interquartile range, 1.96-14.36; p = .08) and an increase of end-tidal CO2 of 10 mm Hg (interquartile range, 5-16; p = .003) (1333Pa [interquartile range, 665-2133]) during resuscitation with the Lifestick compared with using the Thumper. CONCLUSION: In this preliminary study, resuscitation with the Lifestick was found to be safe and feasible. The design of the study and small number of patients included in it limit the conclusions about the hemodynamic effects of the Lifestick.

Mild hyperhomocysteinemia is associated with a decreased fibrinolytic activity in patients after ST-elevation myocardial infarction.

BACKGROUND: Elevated homocysteine (Hcy) levels have been associated with increased risk for cardiovascular disease and it has been shown that hyperhomocysteinemia is associated with increased levels of t-PA antigen in individuals without evidence for coronary artery disease (CAD). The aim of this study was to examine if Hcy plasma levels are associated with plasma levels of fibrinolytic factors in patients with CAD and a history of acute myocardial infarction. METHODS: We measured in 56 patients with CAD, 1 month after their first ST-elevation myocardial infarction, plasma levels of Hcy, the fibrinolytic parameters tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-type-1 (PAI-1), and t-PA-PAI-1 complexes. RESULTS: Hcy plasma levels inversely correlated with t-PA activity (r=-0.303, p<0.05). Patients with mild hyperhomocysteinemia (Hcy>15 micromol/L, n=8) showed significantly lower plasma levels of t-PA activity (p<0.05). Regression analysis revealed that out of cardiovascular risk factors and medical treatment only Hcy was significantly associated with t-PA activity. CONCLUSIONS: Patients with CAD after a first myocardial infarction and hyperhomocysteinemia show a reduced t-PA activity independently from cardiovascular risk factors and medical treatment. Homocysteine lowering therapies may increase fibrinolytic activity and thereby may help to avoid atherothrombotic events in patients with CAD after a first myocardial infarction.

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 degrees 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. CONCLUSIONS: 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.

An increase of C-reactive protein is associated with enhanced activation of endogenous fibrinolysis at baseline but an impaired endothelial fibrinolytic response after venous occlusion.

OBJECTIVES: The goal of this study was to determine whether chronic inflammation of the vascular wall may be associated with an impaired activation of the fibrinolytic system. BACKGROUND: Inflammation plays an important role in the initiation and progression of atherosclerosis, and the fibrinolytic system may prevent local thrombus formation. METHODS: We included 50 patients six months after their first myocardial infarction. Plasma levels of the inflammatory marker C-reactive protein (CRP) were determined at basal conditions, and the fibrinolytic parameters tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were measured at basal conditions and after a standardized venous occlusion (VO) of the forearm. RESULTS: Patients with high CRP levels (> or =3 mg/l) showed a significantly higher t-PA activity at baseline compared with patients with medium (1 to 2.9 mg/l) and low (<1 mg/l) CRP levels (p <0.005). In contrast, patients with low CRP levels showed a higher increase of t-PA activity (p <0.05) and a higher reduction of PAI-1 activity during VO (p <0.05) compared with patients with medium and high CRP levels. A multivariate analysis that included cardiovascular risk factors and medical treatment showed that CRP is an independent predictor of the t-PA response after a standardized VO. CONCLUSIONS: Chronic low-grade inflammation is associated with enhanced activation of endogenous fibrinolysis at baseline but a reduced fibrinolytic response to VO. This impaired endogenous fibrinolytic capacity might be an important contributor to the increased coronary event rate associated with elevated CRP levels.

Serial lactate determinations for prediction of outcome after cardiac arrest.

We investigated the relationship between lactate clearance and outcome in patients surviving the first 48 hours after cardiac arrest. We conducted the study in the emergency department of an urban tertiary care hospital. We analyzed the data for all 48-hour survivors after successful resuscitation from cardiac arrest during a 10-year period. Serial lactate measurements, demographic data, and key cardiac arrest data were correlated to survival and best neurologic outcome within 6 months after cardiac arrest. Parameters showing significant results in univariate analysis were tested for significance in a logistic regression model. Of 1502 screened patients, 394 were analyzed. Survivors (n = 194, 49%) had lower lactate levels on admission (median, 7.8 [interquartile range, 5.4-10.8] vs 9 [6.6-11.9] mmol/L), after 24 hours (1.4 [1-2.5] vs 1.7 [1.1-3] mmol/L), and after 48 hours (1.2 [0.9-1.6] vs 1.5 [1.1-2.3] mmol/L). Patients with favorable neurologic outcome (n = 186, 47%) showed lower levels on admission (7.6 [5.4-10.3] vs 9.2 [6.7-12.1] mmol/L) and after 48 hours (1.2 [0.9-1.6] vs 1.5 [1-2.2] mmol/L). In multivariate analysis, lactate levels at 48 hours were an independent predictor for mortality (odds ratio [OR]: 1.49 increase per mmol/L, 95% confidence interval [CI]: 1.17-1.89) and unfavorable neurologic outcome (OR: 1.28 increase per mmol/L, 95% CI: 1.08-1.51). Lactate levels higher than 2 mmol/L after 48 hours predicted mortality with a specificity of 86% and poor neurologic outcome with a specificity of 87%. Sensitivity for both end points was 31%. Lactate at 48 hours after cardiac arrest is an independent predictor of mortality and unfavorable neurologic outcome. Persisting hyperlactatemia over 48 hours predicts a poor prognosis.

The effect of mild therapeutic hypothermia on renal function after cardiopulmonary resuscitation in men.

BACKGROUND: Mild therapeutic hypothermia (MTH) improves neurological outcome in patients after cardiac arrest. From animal and human studies it appears that hypothermia impairs renal function. The aim of this study was to examine the effects of MTH on renal function in humans. METHODS: Patients were participants recruited in one of the centres of the hypothermia after cardiac arrest-multicenter trial. We measured serum creatinine and creatinine clearance (C(Cr)) within 24 h of MTH, at 4 hourly intervals. Patients were followed for acute renal failure and need for renal supportive therapy for 28 days. RESULTS: We included 60 patients (32 hypothermic, 28 normothermic). Median serum creatinine on admission was [[119 micromol/l (IQR 108-133)] [1.35 mg/dl (IQR 1.22-1.50)]] in hypothermic and [[114 micromol/l (IQR 99-131)] [1.29 mg/dl (IQR 1.12-1.48)]] in normothermic patients, and decreased to [[69 micromol/l (IQR 62-84)] [0.78 mg/dl (IQR 0.70-0.95)]] in the hypothermic group and to [[88 micromol/l (IQR 71-123)] [1.00 mg/dl (IQR 0.80-1.39)]] in the normothermic group within 24h. C(Cr) was decreased on admission. Within 24 h C(Cr) improved to normal values in normothermic patients [1.53 ml/s (IQR 1.15-2.35) [92 ml/min (IQR 69-141)]] and remained low in hypothermic patients [0.88 ml/s (IQR 0.63-1.38) [53 ml/min (IQR 38-83)]] (P = 0.0006). No difference was found between the groups in the development of acute renal failure or the need for renal supportive therapy. CONCLUSION: Twenty four hours of MTH was associated with a delayed improvement in renal function. This was not reflected in the serum creatinine values, which were low in the hypothermic group. This transient impaired renal function appeared to be completely reversible within 4 weeks.

Hypothermia after cardiac arrest: a treatment that works.

PURPOSE OF REVIEW: Sudden 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 SUMMARY: In 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.