Continuous versus intermittent neuromuscular blockade in patients during targeted temperature management after resuscitation from cardiac arrest-A randomized, double blinded, double dummy, clinical trial.

AIM OF THE STUDY: Current guidelines recommend targeted temperature management to improve neurological outcome after cardiac arrest. Evidence regarding an ideal sedative/analgesic regimen including skeletal muscle paralysis is limited. METHODS: Patients were randomized to either a continuous administration of rocuronium (continuous-NMB-group) or to a continuous administration of saline supplemented by rocuronium bolus administration if demanded (bolus-NMB-group). The primary outcome was the number of shivering episodes. Secondary outcomes included survival and neurological status one year after cardiac arrest, time to awakening, length of stay as well as required cumulative dose of rocuronium, midazolam and fentanyl. RESULTS: Sixty-three patients (32 continuous-NMB-group; 31 bolus-NMB-group) were enrolled. Differences in baseline characteristics were not significant. Shivering episodes were detected in 94% of the patients in the bolus-NMB-group compared to 25% of the patients receiving continuous rocuronium infusion (p<0.01). The continuous-NMB-group received significant lower doses of midazolam (4.3±0.8mg/kg vs. 5.1±0.9mg/kg, p<0.01) and fentanyl (62±14µg/kg vs. 71±7µg/kg, p<0.01), but higher cumulative doses of rocuronium (7.8±1.8mg/kg vs. 2.3±1.6mg/kg, p<0.01). Earlier awakening (2 [IQR 2;3] vs. 4 [IQR 2;7.5] days, p=0.04) and decreased length of stay at the ICU (6 [IQR 3;5.9] vs. 10 [IQR 5;15] days, p=0.03) were observed in the continuous-NMB-group. There were no significant differences in survival and quality of life 12 months after cardiac arrest. CONCLUSIONS: Continuous neuromuscular blockade during the first day after resuscitation reduced shivering, midazolam and fentanyl requirement, time to awakening and discharge from intensive care unit. There were no differences in overall survival, cooling rate and time to target temperature.

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.

Neurologic causes of cardiac arrest and outcomes.

BACKGROUND: Sudden cardiac arrest as a complication of neurologic disorders is rare, occasionally acute neurologic events present with cardiac arrest as initial manifestation. OBJECTIVE: Our aim was to describe neurologic disorders as a cause of cardiac arrest in order to enable better recognition. METHODS: We retrospectively analyzed prospectively collected resuscitation data of all patients treated between 1991 and 2011 at the emergency department after cardiac arrest caused by a neurologic event, including diagnosis, therapy, and outcomes. RESULTS: Over 20 years, 154 patients suffered cardiac arrest as a result of a neurologic event. Out-of-hospital cardiac arrest occurred in 126 (82%) patients, 78 (51%) were male, median age was 51 years (interquartile range 17 to 89 years). As initial electrocardiogram rhythm, pulseless electrical activity was found in 77 (50%) cases, asystole in 61 (40%), and ventricular fibrillation in 16 (10%) cases. The most common cause was subarachnoid hemorrhage in 74 (48%) patients, 33 (21%) patients had intracerebral hemorrhage, 23 (15%) had epileptic seizure, 11 (7%) had ischemic stroke, and 13 (8%) had other neurologic diseases. Return of spontaneous circulation was achieved in 139 (90%) patients. Of these, 22 (14%) were alive at follow-up after 6 months, 14 (9%) with favorable neurologic outcome, 8 of these with epileptic seizure, and most of them with history of epilepsy. CONCLUSIONS: Subarachnoidal hemorrhage is the leading neurologic cause of cardiac arrest. Most of the patients with cardiac arrest caused by neurologic disorder have a very poor prognosis.

Cardiac arrest caused by acute intoxication-insight from a registry.

INTRODUCTION: The aim of the study was to evaluate the epidemiology and outcome after cardiac arrest caused by intoxication. METHODS: A retrospective analysis of 1991 to 2010 medical record of patients experiencing cardiac arrest caused by self-inflicted, intentional intoxication was performed. The setting was an emergency department of a tertiary care university hospital. The primary end point was the presentation of epidemiologic data in relation to favorable neurologic outcome, defined as cerebral performance categories 1 or 2 and 180-day survival. Furthermore, the patients were subdivided into a single-substance and polysubstance group, depending on the substances causing the intoxication. RESULTS: Of 3644 patients admitted to our department, 99 (2.7%) with a median age of 26 (interquartile range, 19-42) years (37% female) were included. Cardiac arrest was witnessed in 62 cases (63%). Eleven patients (11%) received basic life support by bystanders, and 11 (11%) had a shockable rhythm in the initial electrocardiogram. The combined end point "good survival" was achieved by 34 patients (34%). Cardiac arrest occurred out of hospital in 73 patients (74%) and in-hospital in 26 patients (26%). A single substance causing the intoxication was found in 56 patients (56%). Opiates were the leading substance, with 25 patients (25%) using them. CONCLUSION: Cardiac arrest caused by intoxication is found predominately in young patients. Overall, favorable neurologic survival was achieved in 34%. Opiate-related cardiac arrest was associated with poor survival and a high incidence of neurologic deficits.

Strategic target temperature management in myocardial infarction--a feasibility trial.

OBJECTIVE: The purpose of this study was to demonstrate the feasibility of a combined cooling strategy started out of hospital as an adjunctive to percutaneous coronary intervention (PCI) in the treatment of ST-elevation acute coronary syndrome (STE-ACS). DESIGN: Non-randomised, single-centre feasibility trial. SETTING: Department of emergency medicine of a tertiary-care facility, Medical University of Vienna, Vienna, Austria. In cooperation with the Municipal ambulance service of the city of Vienna. PATIENTS: Consecutive patients with STE-ACS presenting to the emergency medical service within 6 h after symptom onset. INTERVENTIONS: Cooling was initiated with surface cooling pads in the out-of-hospital setting, followed by the administration of 1000-2000 mL of cold saline at hospital arrival and completed by endovascular cooling in the catheterisation laboratory. MAIN OUTCOME MEASURES: Feasibility of lowering core temperature below 35.0°C prior to immediately performed revascularisation. Safety and tolerability of the cooling procedure. RESULTS: In enrolled 19 patients (one woman, median age 51 years (IQR 45-59)), symptom onset to first medical contact (FMC) was 45 min (IQR 31-85). A core temperature below 35.0°C at reperfusion of the culprit lesion was achieved in 11 patients (78%) within 100 min (IQR 90-111) after FMC without any cooling-related serious adverse event. Temperature could be lowered from baseline 36.4°C (IQR 36.2-36.5°C) to 34.4°C (IQR 34.1-35.0°C) at the time of reperfusion. CONCLUSIONS: With limitations an immediate out-of-hospital therapeutic hypothermia strategy was feasible and safe in patients with STE-ACS undergoing primary PCI. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov/ct2/show/NCT01864343; clinical trials unique identifier: NCT01864343.

Dispatchers impression plus Medical Priority Dispatch System reduced dispatch centre times in cases of out of hospital cardiac arrest. Pre-alert--a prospective, cluster randomized trial.

AIM OF THE STUDY: Dispatch centre processing times for out-of-hospital cardiac arrest or critically ill patients should be as short as possible. A modified 'pre-alert' dispatch workflow might be able to improve the processing time. METHODS: Between October 2010 and May 2011 dispatch events, suspicious for cardiac arrest, were prospectively randomized in 24h clusters. The emergency medical service of the intervention group got, based on the dispatchers impression, a 'pre-alert' alarm-message followed by the standard Medical Priority Dispatch System query whereas the control group did not. RESULTS: In 225 clusters 1500 events were eligible for analysis. Data are presented as median and 25-75 interquartile ranges. Per-protocol analysis demonstrated for the intervention group on 'pre-alert' days a median processing time of 143 s (109-187; n=256) versus 198 s (167-255; n=502) in the control group on non 'pre-alert' days, with a difference of 0.23 log-seconds (p<0.001; 95% CI 0.74-0.28). In critical ill patients, intention-to-treat analysis showed for the intervention group a median of 168 s (131-264; n=153) versus 239 s (176-309; n=164) in the control group, with a difference of 1.4 log-seconds (p<0.001; 95% CI 1.25-1.55). CONCLUSION: Dispatch times can effectively be reduced in cases of out-of-hospital cardiac arrest or critical ill patients with a 'pre-alert' dispatch workflow in combination with the Medical Priority Dispatch System protocol. This might play an important role in improving patient care.

Out of hospital cardiac arrest in Vienna: incidence and outcome.

AIM OF THE STUDY: To determine the incidence of out-of-hospital cardiac arrest and the survival rate of those patients who received CPR in the city of Vienna. METHODS: A cohort of patients with out-of-hospital cardiac arrests and who were treated by the Vienna Ambulance Service between January 1, 2009, and December 31, 2010, were followed up until either death or hospital discharge. The associations of survival and neurological outcome with their potential predictors were analysed using simple logistic regression models. Odds ratios were estimated for each factor. RESULTS: During the observation period, a total of 7030 (206.8/100,000 inhabitants/year) patients without signs of circulation were assessed by teams of the Vienna Ambulance Service, and 1448 adult patients were resuscitated by emergency medical service personnel. A sustained return of spontaneous circulation was reported in 361 (24.9%) of the treated patients, and in all 479 (33.0%) of the patients were taken to the emergency department. A total of 164 (11.3%) of the patients were discharged from the hospital alive, and 126 (8.7%) of the patients showed cerebral performance categories of 1 or 2 at the time of discharge. Younger age, an arrest in a public area, a witnessed arrest and a shockable rhythm were associated with a higher probability of survival to hospital discharge. CONCLUSION: Survival rates for out-of-hospital cardiac arrests remain low. Efforts should be focused on rapidly initiating basic life support, early defibrillation, and high-quality CPR by emergency medical services and state-of-the art post-resuscitation care.

Emergency cardio-pulmonary bypass in cardiac arrest: seventeen years of experience.

AIM: Emergency cardiopulmonary bypass (E-CPB) is an advanced and rarely used procedure for patients in cardiac arrest that do not regain restoration of spontaneous circulation with standard resuscitation methods. The feasibility, safety and outcome of the intervention with E-CPB in cardiac arrest situations at our department have been evaluated. METHODS: Clinical presentation, time intervals, diagnosis and outcome of all patients who received E-CPB at an emergency department of a tertiary care university hospital were evaluated. Patient charts were reviewed regarding cardiac arrest variables and treatment data of all patients from 1993 to 2010. RESULTS: E-CPB was performed in 55 patients. Of all patients, 33 (60%) were male and the median age was 32 years (IQR 24-44). In all cases cardiac arrest was witnessed. The first recorded ECG rhythm showed pulseless electric activity in 23 (42%), ventricular fibrillation in 21 (38%) and asystole in 11 (20%) patients. Cardiac arrest occurred out-of-hospital in 33 (60%) patients. The median duration of CPR before performing E-CPB was 86 min (IQR 69-121). The median 'cannulation'-time was 33 min (IQR 21-45) and the duration on bypass was 311 min (IQR 161-953). Cardiac causes of arrest were found in 19 (35%) patients. Eight patients (15%) survived to 6 months with good neurological outcome. CONCLUSION: E-CPB for cardiac arrest is feasible and safe. In this seemingly desperate patient population after prolonged cardiac arrest, we observed a high survival rate of 15%. E-CPB is a meaningful treatment option, which should be considered more often and earlier.

The effect of percutaneous coronary intervention in patients suffering from ST-segment elevation myocardial infarction complicated by out-of-hospital cardiac arrest on 30 days survival.

AIM OF THE STUDY: To question the beneficial effects of the recommended early percutaneous coronary intervention (PCI) after out-of-hospital cardiac arrest on 30-day survival with favourable neurological outcome. METHODS: Prospectively collected data of 1277 out of hospital cardiac arrest patients between 2005 and 2010 from a registry at a tertiary care university hospital were used for a cohort study. RESULTS: In 494 (39%) arrest patients ST-segment elevation was identified in 249 (19%). Within 12h after restoration of spontaneous circulation catheter laboratory investigations were initiated in 197 (79%) and PCI in 183 (93%) (78% got PCI in less than 180 min). Adjustment for a cumulative time without chest compressions <2 min, initial shockable rhythm, cardiac arrest witnessed by healthcare professionals, and a higher core temperature at time of hospitalization reduced the effect of PCI on favourable neurological outcome at 30 days (OR 1.40; 95% CI, 0.53-3.7) compared to the univariate analysis (OR 2.52; 95% CI, 1.42-4.48). CONCLUSION: This cohort study failed to demonstrate the beneficial effects of PCI as part of post-resuscitation care on 30-day survival with a favourable neurological outcome.

Mild therapeutic hypothermia improves outcomes compared with normothermia in cardiac-arrest patients--a retrospective chart review.

OBJECTIVE: Studies showing the effectiveness of therapeutic hypothermia (32-34°C) in postcardiac arrest patients have been criticized because of patients with elevated body temperature (>37.5°C) in the noncooled control group. Thus, the effects of spontaneous normothermia (<37.5°C) compared with mild therapeutic hypothermia were studied. DESIGN: Retrospective chart review from 1991 to 2010. PATIENTS: Witnessed out-of-hospital arrest, presumed to be of cardiac origin, aged 18 to 80 yrs and with a Glassgow Coma Scale score of <8 at admission. INTERVENTIONS: Patients with sustained restoration of spontaneous circulation who did not receive therapeutic hypothermia and never exceeded 37.5°C during the 36 hrs postcardiac arrest were compared with patients who received mild therapeutic hypothermia. MEASUREMENTS AND MAIN RESULTS: The primary end point was a favorable neurological outcome, defined as Cerebral Performance Categories 1 or 2; the secondary end point was overall survival to 180 days. Significantly more patients in the hypothermia group had Cerebral Performance Categories 1 or 2 (hypothermia: 256 of 467 [55%] vs. normothermia: 69 of 165 [42%]) and survived for >180 days (hypothermia: 315 of 467 [67%] vs. normothermia: 79 of 165 [48%]). The propensity score adjusted risk ratio for good neurological outcome of patients undergoing hypothermia treatment was 1.37 (confidence interval 1.09-1.72, p≤.01) and for dying within 180 days was 0.57 (confidence interval 0.44-0.73, p≤.01) compared to normothermia. CONCLUSIONS: Therapeutic hypothermia is associated with significantly improved neurological outcome and 180-day survival compared to spontaneous normothermia in cardiac-arrest patients.

The beneficial effect of mild therapeutic hypothermia depends on the time of complete circulatory standstill in patients with cardiac arrest.

AIM: Mild therapeutic hypothermia has shown to improve long-time survival as well as favorable functional outcome after cardiac arrest. Animal models suggest that ischemic durations beyond 8 min results in progressively worse neurologic deficits. Based on these considerations, it would be obvious that cardiac arrest survivors would benefit most from mild therapeutic hypothermia if they have reached a complete circulatory standstill of more than 8 min. 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, which remain comatose after restoration of spontaneous circulation. Data were collected from 1992 to 2010. We investigated the interaction of 'no-flow' time on the association between post arrest mild therapeutic hypothermia and good neurological outcome. 'No-flow' time was categorized into time quartiles (0, 1-2, 3-8, >8 min). RESULTS: One thousand-two-hundred patients were analyzed. Hypothermia was induced in 598 patients. In spite of showing a statistically significant improvement in favorable neurologic outcome in all patients treated with mild therapeutic hypothermia (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.14-1.93) this effect varies with 'no-flow' time. The effect is significant in patients with 'no-flow' times of more than 2 min (OR: 2.72; CI: 1.35-5.48) with the maximum benefit in those with 'no-flow' times beyond 8 min (OR: 6.15; CI: 2.23-16.99). CONCLUSION: The beneficial effect of mild therapeutic hypothermia increases with cumulative time of complete circulatory standstill in patients with witnessed out-of-hospital cardiac arrest.

Post-resuscitation care at the emergency department with critical care facilities--a length-of-stay analysis.

AIM OF THE STUDY: An emergency department providing critical care will have an effect on outcome and intensive-care-units' resources by avoiding unnecessary or futile intensive-care admissions and thereby save hospital expenses. The study focussed on this result. METHODS: The study employed a retrospective analysis of prospectively collected data of out-of-hospital cardiac arrest patients with return of spontaneous circulation, comatose on arrival. Outcomes and length of stay of patients who either stayed at the 'emergency department only' or were 'transferred in addition to an intensive care unit' were compared. Linear regression with log length of stay as outcome and 'emergency department only' as predictor with covariates was used for modelling. RESULTS: From 1991 to 2008, out of 1236 patients (age 57 ± 15 years, female 31%), the 'emergency department only' group (n=349 (28%)) survived to discharge in 81(23%) cases, with a median length-of-stay in critical care of 1.7 (interquartile range 0.8; 3.1) days. The patients 'transferred in addition to an intensive care unit' (n=887 (72%)), with a survival rate of 55% (n=486, p<0.001) stayed 10 (5; 18) days (p<0.001). The length-of-stay in hospital was significantly shorter if patients were treated in the 'emergency department only' independent of other cardiac-arrest-related factors (regression coefficient -1.42, confidence interval -1.60 to -1.24). CONCLUSIONS: An emergency department with critical care prevents admissions to intensive care units in 28% of patients with out-of-hospital cardiac arrest. It saves intensive-care-unit resources and shortens length of stay for comatose out-of-hospital cardiac-arrest survivors, regardless of their outcome.