The impact of therapeutic hypothermia as adjunctive therapy in a regional primary PCI program

Background

Therapeutic hypothermia (TH) is associated with improved neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). There are currently limited data on the outcomes of patients presenting with resuscitated OHCA in the setting of ST-segment elevation myocardial infarction (STEMI). We conducted a retrospective study to determine the outcomes of patients treated with TH for OHCA in a large regionalized STEMI program.

Methods

Patients referred for primary PCI and TH between July 2004 and April 2011 were identified from the University of Ottawa Heart Institute STEMI database. The primary endpoint was survival to hospital discharge with sufficient neurologic recovery to enable discharge home.

Results

Among 2467 consecutive patients referred for primary PCI, we identified 50 patients treated with TH following OHCA. Forty-nine underwent PCI, of which 47 (96%) received a stent. Median door-to-balloon time was 113 min (IQR 91–151). Patients with good neurologic recovery were younger, mean 51 ± 9 years versus 64 ± 12, p < 0.001, and had higher baseline creatinine clearance, 70 ± 19 mL/min/1.73 m² versus 53 ± 23 mL/min/1.73 m², p = 0.007. The primary endpoint of survival with sufficient neurologic recovery to enable discharge home was reached in 30 patients (60%). Four survivors required levels of assistance that precluded discharge home.

Conclusions

Therapeutic hypothermia in conjunction with primary PCI is associated with a favorable neurologic outcome in the majority of STEMI patients surviving OHCA. Our results suggest that TH is an important adjunctive therapy for STEMI patients suffering OHCA.     

A history of smoking is associated with improved survival in patients treated with mild therapeutic hypothermia following cardiac arrest

Objectives

To assess the association between smoking and survival with a good neurologic outcome in patients following cardiac arrest treated with mild therapeutic hypothermia (TH).

Methods

We conducted a retrospective observational study of a prospectively collected cohort of 188 consecutive patients following cardiac arrest treated with TH between May 2007 and January 2012. Smoking status was retrospectively collected via chart review and was classified as “ever” or “never”. Primary endpoint was survival to hospital discharge with a good neurologic outcome and was compared between smokers and nonsmokers. Logistic regression analysis was used to assess the association between smoking status and neurologic outcome at hospital discharge; adjusting for age, initial rhythm, time to return of spontaneous circulation (ROSC), bystander CPR, and time to initiation of TH.

Results

Smokers were significantly more likely to survive to hospital discharge with good neurologic outcome compared to nonsmokers (50% vs. 28%, p = 0.003). After adjusting for age, initial rhythm, time to ROSC, bystander CPR, and time to initiation of TH, a history of smoking was associated with increased odds of survival to hospital discharge with good neurologic outcome (OR 3.54, 95% CI 1.41–8.84, p = 0.007).

Conclusions

Smoking is associated with improved survival with good neurologic outcome in patients following cardiac arrest. We hypothesize that our findings reflect global ischemic conditioning caused by smoking.     

The prognostic value of continuous amplitude-integrated electroencephalogram applied immediately after return of spontaneous circulation in therapeutic hypothermia-treated cardiac arrest patients

Introduction

The purpose of this study was to examine the prognostic value of continuous amplitude-integrated electroencephalogram (aEEG) applied immediately after return of spontaneous circulation (ROSC) in therapeutic hypothermia (TH)-treated cardiac arrest patients.

Methods

From September 2010 to August 2011, we prospectively studied comatose patients treated with TH after cardiac arrest who were monitored with aEEG. Monitoring at the forehead was applied as soon as possible after ROSC in the emergency department and continued until recovery of consciousness, death, or 72 h after ROSC. Neurological outcome was assessed with the Cerebral Performance Category (CPC) scale at hospital discharge, and good neurological outcome was defined as a CPC score of 1 or 2.

Results

A total of 55 TH-treated patients were included. Monitoring started at a median of 96 min after ROSC (interquartile range, 49–174). At discharge, 28 patients had a CPC of 1–2, and 27 patients had a CPC of 3–5. Seventeen patients had a continuous normal voltage (CNV) trace at the start of monitoring, and this voltage was strongly associated with a good outcome (16/17 [94.1%]; sensitivity and specificity of 57.1 and 96.3%, respectively). No development of a CNV trace within the recorded period accurately predicted a poor outcome (21/21 [100%]; sensitivity and specificity of 77.8 and 100%, respectively).

Conclusions

An initial CNV trace in aEEG applied to forehead immediately after ROSC is a good early predictor of a good outcome in TH-treated cardiac arrest patients. Conversely, no development of a CNV trace within 72 h is an accurate and reliable predictor of a poor outcome with a false-positive rate of 0%.     

Emergency Department inter-hospital transfer for post-cardiac arrest care: Initial experience with implementation of a regional cardiac resuscitation center in the United States

Objective

The American Heart Association recently recommended regional cardiac resuscitation centers (CRCs) for post-resuscitation care following out-of-hospital cardiac arrest (OHCA). Our objective was to describe initial experience with CRC implementation.

Methods

Prospective observational study of consecutive post-resuscitation patients transferred from community Emergency Departments (EDs) to a CRC over 9 months. Transfer criteria were: OHCA, return of spontaneous circulation (ROSC), and comatose after ROSC. Incoming patients were received and stabilized in the ED of the CRC where advanced therapeutic hypothermia (TH) modalities were applied. Standardized post-resuscitation care included: ED evaluation for cardiac catheterization, TH (33–34 °C) for 24 h, 24 h/day critical care physician support, and evidence-based neurological prognostication. Prospective data collection utilized the Utstein template. The primary outcome was survival to hospital discharge with good neurological function [Cerebral Performance Category 1 or 2].

Results

Twenty-seven patients transferred from 11 different hospitals were included. The majority (21/27 [78%]) had arrest characteristics suggesting poor prognosis for survival (i.e. asystole/pulseless electrical activity initial rhythm, absence of bystander cardiopulmonary resuscitation, or an unwitnessed cardiac arrest). The median (IQR) time from transfer initiation to reaching TH target temperature was 7 (5–13) h. Ten (37%) patients survived to hospital discharge, and of these 9/10 (90% of survivors, 33% of all patients) had good neurological function.

Conclusions

Despite a high proportion of patients with cardiac arrest characteristics suggesting poor prognosis for survival, we found that one-third of CRC transfers survived with good neurological function. Further research to determine if regional CRCs improve outcomes after cardiac arrest is warranted.     

Therapeutic hypothermia and vasopressor dependency after cardiac arrest

Objective

Clinical trials of therapeutic hypothermia (TH) after cardiac arrest excluded patients with persistent hemodynamic instability after return of spontaneous circulation (ROSC), and thus equipoise may exist regarding use of TH in these patients. Our objective was to determine if TH is associated with worsening hemodynamic instability among patients who are vasopressor-dependent after ROSC.

Methods

We performed a prospective observational study in vasopressor-dependent post-cardiac arrest patients. Inclusion criteria were age >17, non-trauma cardiac arrest, comatose after ROSC, and persistent vasopressor dependence. The decision to initiate TH (33–34 °C) was made by the treating physician. We measured cumulative vasopressor index (CVI) and mean arterial pressure (MAP) every 15 min during the first 6 h after ROSC. The outcome measures were change in CVI (primary outcome) and MAP (secondary outcome) over time. We graphed median CVI and MAP over time for the treated and not treated cohorts, and used propensity adjusted repeated measures mixed models to test for an association between TH induction and change in CVI or MAP over time.

Results

Seventy-five post-cardiac arrest patients were included (35 treated; 40 not treated). We observed no major differences in CVI or MAP over time between the treated and not treated cohorts. In the mixed models we found no statistically significant association between TH induction and changes in CVI or MAP.

Conclusion

In patients with vasopressor-dependency after cardiac arrest, the induction of hypothermia was not associated with a decrease in mean arterial pressure or increase in vasopressor requirement.     

Awakening after cardiac arrest and post resuscitation hypothermia: Are we pulling the plug too early?

Background

Time to awakening after out-of-hospital cardiac arrest (OHCA) and post-resuscitation therapeutic hypothermia (TH) varies widely. We examined the time interval from when comatose OHCA patients were rewarmed to 37 °C to when they showed definitive signs of neurological recovery and tried to identify potential predictors of awakening.

Methods

With IRB approval, a retrospective case study was performed in OHCA patients who were comatose upon presentation to a community hospital during 2006–2010. They were treated with TH (target of 33 °C) for 24 h, rewarmed, and discharged alive. Comatose patients were generally treated medically after TH for at least 48 h before any decision to withdraw supportive care was made. Pre-hospital TH was not used. Data are expressed as medians and interquartile range.

Results

The 89 patients treated with TH in this analysis were divided into three groups based upon the time between rewarming to 37 °C and regaining consciousness. The 69 patients that regained consciousness in ≤48 h after rewarming were termed “early-awakeners”. Ten patients regained consciousness 48–72 h after rewarming and were termed “intermediate-awakeners”. Ten patients remained comatose and apneic >72 h after rewarming but eventually regained consciousness; they were termed “late-awakeners”. The ages for the early, intermediate and late awakeners were 56 [49,65], 62 [48,74], and 58 [55,65] years, respectively. Nearly 67% were male. Following rewarming, the time required to regain consciousness for the early, intermediate and late awakeners was 9 [2,18] (range 0–47), 60.5 [56,64.5] (range 49–71), and 126 [104,151] h (range 73–259), respectively. Within 90 days of hospital admission, favorable neurological function based on a Cerebral Performance Category (CPC) score of 1 or 2 was reported in 67/69 early, 10/10 intermediate, and 8/10 late awakeners.

Conclusion

Following OHCA and TH, arbitrary withdrawal of life support <48 h after rewarming may prematurely terminate life in many patients with the potential for full neurological recovery. Additional clinical markers that correlate with late awakening are needed to better determine when withdrawal of support is appropriate in OHCA patients who remain comatose >48 h after rewarming.     

New treatment bundles improve survival in out-of-hospital cardiac arrest patients: A historical comparison

Introduction

Before the introduction of the new international cardiac arrest treatment guidelines in 2005, patients with out-of-hospital cardiac arrest (OHCA) of cardiac origin in Northern Italy had very poor prognosis. Since 2006, a new bundle of care comprising use of automated external defibrillators (AEDs) and therapeutic hypothermia (TH) was started, while extracorporeal CPR program (ECPR) for selected refractory CA and dispatcher-assisted cardio-pulmonary resuscitation (CPR) was started in January 2010.

Objectives

We hypothesized that a program of bundled care might improve outcome of OHCA patients.

Methods

We analyzed data collected in the OHCA registry of the MB area between September 2007 and August 2011 and compared this with data from 2000 to 2003.

Results

Between 2007 and 2011, 1128 OHCAs occurred in the MB area, 745 received CPR and 461 of these had a CA of presumed cardiac origin. Of these, 125 (27%) achieved sustained ROSC, 60 (13%) survived to 1 month, of whom 51 (11%) were discharged from hospital with a good neurological outcome (CPC ≤ 2), and 9 with a poor neurological outcome (CPC > 2).Compared with data from the 2000 to 2003 periods, survival increased from 5.6% to 13.01% (p < 0.0001). In the 2007–2011 group, low-flow time and bystander CPR were independent markers of survival.

Conclusions

OHCA survival has improved in our region. An increased bystander CPR rate associated with dispatcher-assisted CPR was the most significant cause of increased survival, but duration of CA remains critical for patient outcome.     

The clinical significance of a failed initial intubation attempt during emergency department resuscitation of out-of-hospital cardiac arrest patients

Objective

Advanced airway management is one of the fundamental skills of advanced cardiac life support (ACLS). A failed initial intubation attempt (FIIA) is common and has shown to be associated with adverse events. We analysed the association between FIIA and the overall effectiveness of ACLS.

Methods

Using emergency department (ED) out-of-hospital cardiac arrest (OHCA) registry data from 2008 to 2012, non-traumatic ED-resuscitated adult OHCA patients on whom endotracheal intubation was initially tried were identified. Prehospital and demographic factors and patient outcomes were retrieved from the registry. The presence of a FIIA was determined by reviewing nurse-documented CPR records. The primary outcome was achieving a return of spontaneous circulation (ROSC). The secondary outcomes were time to ROSC and the ROSC rate during the first 30 min of ED resuscitation.

Results

The study population (n = 512) was divided into two groups based on the presence of a FIIA (N = 77). Both groups were comparable without significant differences in demographic or prehospital factors. In the FIIA group, the unadjusted and adjusted odds ratios (ORs) for achieving a ROSC were 0.50 (95% confidence interval [CI], 0.31–0.81) and 0.40 (95% CI, 0.23–0.71), respectively. Multivariable median regression analysis revealed that FIIA was associated with an average delay of 3 min in the time to ROSC (3.08; 95% CI, 0.08–5.80). Competing risk regression analysis revealed a significantly slower ROSC rate during the first 15 min (adjusted subhazard ratio, 0.52; 95% CI, 0.35–0.79) in the FIIA group.

Conclusion

FIIA is an independent risk factor for the decreased effectiveness of ACLS.     

The occurrence of shivering in cardiac arrest survivors undergoing therapeutic hypothermia is associated with a good neurologic outcome

Background

The incidence of shivering in cardiac arrest survivors who undergo therapeutic hypothermia (TH) is varied. Its occurrence is dependent on the integrity of multiple peripheral and central neurologic pathways. We hypothesized that cardiac arrest survivors who develop shivering while undergoing TH are more likely to have intact central neurologic pathways and thus have better neurologic outcome as compared to those who do not develop shivering during TH.

Methods

Prospectively collected data on consecutive adult patients admitted to a tertiary center from 1/1/2007 to 11/1/2010 that survived a cardiac arrest and underwent TH were retrospectively analyzed. Patients who developed shivering during the cooling phase of TH formed the “shivering” group and those that did not formed the “non-shivering” group. The primary end-point: Pittsburgh Cerebral Performance Category (CPC) scale; good (CPC 1–2) or poor (CPC 3–5) neurological outcome prior to discharge from hospital.

Results

Of the 129 cardiac arrest survivors who underwent TH, 34/94 (36%) patients in the “non-shivering” group as compared to 21/35 (60%) patients in the “shivering” group had good neurologic outcome (P = 0.02). After adjusting for confounders using binary logistic regression, occurrence of shivering (OR: 2.71, 95% CI 1.099–7.41, P = 0.04), time to return of spontaneous circulation (OR: 0.96, 95% CI 0.93–0.98, P = 0.004) and initial presenting rhythm (OR: 4.0, 95% CI 1.63–10.0, P = 0.002) were independent predictors of neurologic outcome.

Conclusion

The occurrence of shivering in cardiac arrest survivors who undergo TH is associated with an increased likelihood of good neurologic outcome as compared to its absence.     

Methylphenidate and amantadine to stimulate reawakening in comatose patients resuscitated from cardiac arrest

Background

Despite critical-care packages including therapeutic hypothermia (TH), neurologic injury is common after cardiac arrest (CA) resuscitation. Methylphenidate and amantadine have treated coma in traumatically-brain-injured patients with mixed success, but have not been explored in post-arrest patients.

Objective

Compare the outcome of comatose post-arrest patients treated with neurostimulants to a matched cohort.

Methods

Retrospective cohort study from 6/2008 to 12/2011 in a tertiary university hospital. We included adult patients treated with methylphenidate or amantadine after resuscitation from in-hospital or out-of-hospital CA (OHCA) of any rhythm, excluding patients with traumatic/surgical etiology of arrest, terminal re-arrest within 6 h, or withdrawal of care by family within 6 h. Primary outcome was following commands; secondary outcomes included survival to hospital discharge, cerebral performance category (CPC), and modified Rankin scale (mRS). We compared characteristics and outcomes to a control cohort matched on TH and 72 h FOUR score ± 1.

Results

Of 588 patients, 8 received methylphenidate, 6 received amantadine, and 2 both. Most were female suffering OHCA with median age 61 years. All received TH and a multi-modal neurological evaluation. Initial exam revealed median GCS 6 and FOUR 7, which was unchanged at 72 h. Six patients (38%) followed commands prior to discharge at median 2.5 days (range: 1–18 days) after treatment. Patients receiving neurostimulants trended toward improved rate of following commands, survival to hospital discharge, and distribution of CPC and mRS scores.

Conclusions

Neurostimulants may be considered to stimulate wakefulness in selected post-cardiac arrest patients, but a prospective trial is needed to evaluate this therapy.     

Combining brain computed tomography and serum neuron specific enolase improves the prognostic performance compared to either alone in comatose cardiac arrest survivors treated with therapeutic hypothermia

Aim of the study

We determined whether combining the grey-to-white matter ratio (GWR) on brain computed tomography (CT) and serum neuron specific enolase (NSE) improves the prognostic performance when compared to either alone in cardiac arrest patients treated with therapeutic hypothermia (TH).

Methods

We performed a retrospective study of a cohort of cardiac arrest patients treated with TH. The Hounsfield unit was measured in the caudate nucleus (CN), putamen (P), posterior limb of internal capsule (PIC) and corpus callosum (CC); GWR was calculated as CN/PIC and P/CC. The NSE value was obtained at 0, 24, and 48 h after restoration of spontaneous circulation (ROSC). We analysed the prognostic performance of GWR and NSE, singly and in combination, in predicting poor neurologic outcome (cerebral performance category 3–5).

Results

Of the 224 included patients, 82 showed good neurologic outcome at hospital discharge, while 142 showed poor neurologic outcome. The P/CC (area under receiver operating characteristics (AUROC) 0.864, sensitivity/specificity 52.9%/100%) showed better prognostic performance than did the CN/PIC (AUROC 0.721, sensitivity/specificity 19.8%/100%). The NSE value at 48 h after ROSC (AUROC 0.895, sensitivity/specificity 60.2%/100%) showed the highest prognostic value among the three NSE time points. Analysis of 119 patients undergoing both brain CT and NSE at 48 h indicated that combining P/CC and NSE improved the sensitivity (78.6%) compared to either alone (48.6%, 62.9%).

Conclusion

Combining brain CT and serum NSE improves the prognostic performance when compared to either alone in predicting poor neurologic outcome in cardiac arrest patients treated with TH.     

APACHE II scoring to predict outcome in post-cardiac arrest

Introduction

Despite advancements in management of cardiac arrest, mortality remains high and few severity of illness scoring systems have been calibrated in this population. The goal of the current investigation was to assess the Acute Physiology and Chronic Health Evaluation II score in post-cardiac arrest.

Measurements

This is a prospective observational study of adult post-cardiac arrest patients at a tertiary-care center. The primary outcome variable was in-hospital mortality and secondary outcome variable was neurologic outcome. APACHE II scores were used to predict outcomes using logistic modeling.

Main results

A total of 228 subjects were included in the analysis. The median age of the cohort was 70 (IQR: 64–71) and 32% (72/228) of the patients were female. The median downtime was 15 min (IQR: 7–27) and initial lactate 5.9 mmol/L (IQR: 3.5–8.4). 71 (57%) of deaths occurred prior to the 72-h follow-up and overall in-hospital mortality was 55% (125/228). Discrimination of APACHE II score in all cardiac arrest patients increased in stepwise fashion from 0-h to 72-h follow-up (AUC: 0-h: 0.62; 24-h: 0.75; 48-h: 0.82; 72-h: 0.86).

Conclusions

APACHE II score is a poor predictor of outcome at time zero for out-of-hospital cardiac arrest (OHCA) post-arrest patients consistent with the original development of the score in the critically ill. For in-hospital cardiac arrest (IHCA) at time zero and for both IHCA and OHCA at 24 h and beyond, the APACHE II score was a modest indicator of illness severity and predictor of mortality/neurologic morbidity.     

Extracorporeal life support associated with hypothermia and normoxemia in refractory cardiac arrest

Aim

We describe a 1-year experience with extracorporeal cardiopulmonary resuscitation (ECPR) for in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) associated with intra-arrest hypothermia and normoxemia.

Methods

Since January 1st 2012, ECPR has been applied in our hospital to all patients less than 65 years of age and without major co-morbidities who develop refractory cardiac arrest (CA) with bystander CPR. Over a 1-year period of observation, we recorded 28-day survival with intact neurological outcome and the rate of organ donation.

Results

During the observational period, 24 patients were treated with ECPR, with a median age of 48 years. Ten patients had IHCA. Acute coronary syndrome and/or major arrhythmias were the main cause of arrest. Intra-arrest cooling was used in 17 patients; temperature on ECMO initiation in these patients was 32.9 °C [32–34]. The time from collapse to ECPR was 58 min [45–70] and was shorter in survivors than in non-survivors (41 min [39–58] vs. 60 min [55–77], p = 0.059). Non-survivors were more likely to have coagulopathy and received more blood transfusions. Six patients (25%) survived with good neurological outcome at day 28. Four patients with irreversible brain damage had organ function suitable for donation.

Conclusion

ECPR provided satisfactory survival rates with good neurologic recovery in refractory CA for both IHCA and OHCA. ECMO may help rapidly stabilise systemic haemodynamic status and restore organ function.     

Prophylactic lidocaine for post resuscitation care of patients with out-of-hospital ventricular fibrillation cardiac arrest

Background

Antiarrhythmic drugs like lidocaine are usually given to promote return of spontaneous circulation (ROSC) during ongoing out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation/tachycardia (VF/VT). Whether administering such drugs prophylactically for post-resuscitation care after ROSC prevents re-arrest and improves outcome is unstudied.

Methods

We evaluated a cohort of 1721 patients with witnessed VF/VT OHCA who did (1296) or did not receive prophylactic lidocaine (425) at first ROSC. Study endpoints included re-arrest, hospital admission and survival.

Results

Prophylacic lidocaine recipients and non-recipients were comparable, except for shorter time to first ROSC and higher systolic blood pressure at ROSC in those receiving lidocaine. After initial ROSC, arrest from VF/VT recurred in 16.7% and from non-shockable arrhythmias in 3.2% of prophylactic lidocaine recipients, 93.5% of whom were admitted to hospital and 62.4% discharged alive, as compared with 37.4%, 7.8%, 84.9% and 44.5%, of corresponding non-recipients (all p < 0.0001). Adjusted for pertinent covariates, prophylactic lidocaine was independently associated with reduced odds of re-arrest from VF/VT, odds ratio, (95% confidence interval) 0.34 (0.26–0.44) and from nonshockable arrhythmias (0.47 (0.29–0.78)); a higher hospital admission rate (1.88, (1.28–2.76)) and improved survival to discharge (1.49 (1.15–1.95)). However in a propensity score-matched sensitivity analysis, lidocaine's only beneficial association with outcome was in a lower incidence of recurrent VF/VT arrest.

Conclusions

Administration of prophylactic lidocaine upon ROSC after OHCA was consistently associated with less recurrent VF/VT arrest, and therapeutic equipoise for other measures. The prospect of a promising association between lidocaine prophylaxis and outcome, without evidence of harm, warrants further investigation.     

Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest

Objective

Post-cardiac arrest fever has been associated with adverse outcome before implementation of therapeutic hypothermia (TH), however the prognostic implications of post-hypothermia fever (PHF) in the era of modern post-resuscitation care including TH has not been thoroughly investigated.The aim of the study was to assess the prognostic implication of PHF in a large consecutive cohort of comatose survivors after out-of-hospital cardiac arrest (OHCA) treated with TH.

Methods

In the period 2004–2010, a total of 270 patients resuscitated after OHCA and surviving a 24-h protocol of TH with a target temperature of 32–34 °C were included. The population was stratified in two groups by median peak temperature (≥38.5 °C) within 36 h after rewarming: PHF and no-PHF. Primary endpoint was 30-days mortality and secondary endpoint was neurological outcome assessed by Cerebral Performance Category (CPC) at hospital discharge.

Results

PHF (≥38.5 °C) was associated with a 36% 30-days mortality rate compared to 22% in patients without PHF, p_log-rank = 0.02, corresponding to an adjusted hazard rate (HR) of 1.8 (95% CI: 1.1–2.7), p = 0.02). The maximum temperature (HR = 2.0 per °C above 36.5 °C (95% CI: 1.4–3.0), p = 0.0005) and the duration of PHF (HR = 1.6 per 8 h (95% CI: 1.3–2.0), p < 0.0001) were also independent predictors of 30-days mortality in multivariable models. Good neurological outcome (CPC1-2) versus unfavourable outcome (CPC3-5) at hospital discharge was found in 61% vs. 39% in the PHF group compared to 75% vs. 25% in the No PHF group, p = 0.02.

Conclusions

Post-hypothermia fever ≥38.5 °C is associated with increased 30-days mortality, even after controlling for potential confounding factors. Avoidance of PHF as a therapeutic target should be evaluated in prospective randomized trials.     

Lack of improved outcomes with increased use of targeted temperature management following out-of-hospital cardiac arrest: A multicenter retrospective cohort study

Study aims

To assess whether increased use of targeted temperature management (TTM) within an integrated healthcare delivery system resulted in improved rates of good neurologic outcome at hospital discharge (Cerebral Performance Category score of 1 or 2).

Methods

Retrospective cohort study of patients with OHCA admitted to 21 medical centers between January 2007 and December 2012. A standardized TTM protocol and educational program were introduced throughout the system in early 2009. Comatose patients eligible for treatment with TTM were included. Adjusted odds of good neurologic outcome at hospital discharge and survival to hospital discharge were assessed using multivariate logistic regression.

Results

A total of 1119 patients were admitted post-OHCA with coma, 59.1% (661 of 1119) of which were eligible for TTM. The percentage of patients treated with TTM markedly increased during the study period: 10.5% in the years preceding (2007–2008) vs. 85.1% in the years following (2011–2012) implementation of the practice improvement initiative. However, unadjusted in-hospital survival (37.3% vs. 39.0%, p = 0.77) and good neurologic outcome at hospital discharge (26.3% vs. 26.6%, p = 1.0) did not change. The adjusted odds of survival to hospital discharge (AOR 1.0, 95% CI 0.85–1.17) or a good neurologic outcome (AOR 0.94, 95% CI 0.79–1.11) were likewise non-significant.

Interpretation

Despite a marked increase in TTM rates across hospitals in an integrated delivery system, there was no appreciable change in the crude or adjusted odds of in-hospital survival or good neurologic outcomes at hospital discharge among eligible post-arrest patients.     

Haemodynamic variables and functional outcome in hypothermic patients following out-of-hospital cardiac arrest

Aim of the study

To evaluate the association between haemodynamic variables during the first 24 h after intensive care unit (ICU) admission and neurological outcome in out-of-hospital cardiac arrest (OHCA) victims undergoing therapeutic hypothermia.

Methods

In a multi-disciplinary ICU, records were reviewed for comatose OHCA patients undergoing therapeutic hypothermia. The hourly variable time integral of haemodynamic variables during the first 24 h after admission was calculated. Neurologic outcome was assessed at day 28 and graded as favourable or adverse based on the Cerebral Performance Category of 1–2 and 3–5. Bi- and multivariate regression models adjusted for confounding variables were used to evaluate the association between haemodynamic variables and functional outcome.

Results

67/134 patients (50%) were classified as having favourable outcome. Patients with adverse outcome had a higher mean heart rate (73 [62–86] vs. 66 [60–78] bpm; p = 0.04) and received noradrenaline more frequently (n = 17 [25.4%] vs. n = 9 [6%]; p = 0.02) and at a higher dosage (128 [56–1004] vs. 13 [2–162] μg h⁻¹; p = 0.03) than patients with favourable outcome. The mean perfusion pressure (mean arterial blood pressure minus central venous blood pressure) (OR = 1.001, 95% CI  = 1–1.003; p = 0.04) and cardiac index time integral (OR = 1.055, 95% CI = 1.003–1.109; p = 0.04) were independently associated with adverse outcome at day 28.

Conclusion

Mean perfusion pressure and cardiac index during the first 24 h after ICU admission were weakly associated with neurological outcome in an OHCA population undergoing therapeutic hypothermia. Further studies need to elucidate whether norepinephrine-induced increases in perfusion pressure and cardiac index may contribute to adverse neurologic outcome following OHCA.     

Serum glial fibrillary acidic protein as a predictive biomarker of neurological outcome after cardiac arrest

Aim of the study

Serum glial fibrillary acidic protein (GFAP) has recently been identified as a specific predictor of brain damage and neurological outcome in patients with head trauma. In this study, serum GFAP was assessed as a predictor of neurological outcome in post-cardiac-arrest (PCA) patients.

Methods

This study was a retrospective, single-medical-center analysis, conducted in the intensive care unit of a university hospital. Forty-four sequential PCA patients with cardiogenic or non-cardiogenic arrest were included. The patients were treated with or without therapeutic hypothermia (TH). Serum samples were collected from the patients at 12, 24, and 48 h after the return of spontaneous circulation (ROSC). Serum GFAP concentrations were measured by enzyme-linked immunosorbent assay and compared in patients with good and poor neurological outcomes, evaluated over a period of 6 months using Glasgow Outcome Scale.

Results

Serum GFAP was significantly higher in patients with a poor outcome at 12 and 24 h without TH and at 48 h with TH (P < 0.05). GFAP (>0.1 ng dL⁻¹) was a specific predictor of poor neurological outcome at 6 months with or without TH treatment.

Conclusions

Although this study is preliminary, serum GFAP after ROSC reflected a poor neurological outcome in PCA patients.     

A 5-year experience with cardiopulmonary resuscitation using extracorporeal life support in non-postcardiotomy patients with cardiac arrest

Background

Cardiopulmonary resuscitation (CPR) using extracorporeal life support (ECLS) system has been successfully used to support patients with in- and out-of-hospital cardiac arrest (IHCA, OHCA) when conventional measures have failed. The purpose of the current study is to report on our experience with extracorporeal CPR in non-postcardiotomy patients.

Methods

We retrospectively analysed a total of 85 consecutive adult patients, who have been treated with ECLS between January 2007 and January 2012.

Results

The mean CPR duration was 40 min (20–70 min). The mean ECLS support duration was 49 h (12–92 h). Twenty-eight patients (33%) had ECLS related complications. Forty patients (47%) were successfully weaned and 29 patients (34%) survived to hospital discharge. Among survivors, 93% were without severe neurologic deficit. Duration of CPR was shorter for survivors than for non-survivors [(25: 20–50 min) vs. (50: 25–86 min); p = 0.003]. Immediately after ECLS start, the mean blood lactate level was lower (p = 0.003), and the mean pH value was higher in the survivors’ group (p < 0.0001) compared to the non-survivors’ group. The CPR duration for the IHCA group (25: 20–50 min) was shorter compared to the OHCA group (70: 55–110 min; p < 0.0001). The survival rate in this group was higher compared to the OHCA group (42% vs. 15%; p < 0.02).

Conclusions

CPR using modern miniaturized ECLS systems should be established in the treatment of prolonged cardiac arrest and unsuccessful conventional CPR in selected patients. CPR with ECLS for OHCA has worse outcomes compared to IHCA. Duration of CPR was independent risk factor for mortality after extracorporeal CPR.     

Prognostic implication of initial coagulopathy in out-of-hospital cardiac arrest

Objective

We sought to investigate the prognostic implication of early coagulopathy represented by initial DIC score in out-of-hospital cardiac arrest (OHCA).

Methods

OHCA registry was analyzed to identify patients with ROSC without recent use of anticoagulant between 2008 and 2011. Patients were assessed for prehosptial factors, initial laboratory results and therapeutic hypothermia. Outcome variables were survival discharge, 6-month CPC and survival duration within the first week after ROSC. Logistic regression and Cox proportional hazards models were used for both univariable and multivariable analysis.

Results

Among 273 eligible patients, initial DIC score was available in 252 (92.3%). Higher DIC score was associated with increased inhospital death (odds ratio [OR], 1.89 per unit; 95% confidence interval [CI], 1.48–2.41) and unfavorable long-term outcome (6-month CPC 3–5; OR, 2.21 per unit; 95% CI, 1.60–3.05). The adjusted ORs for both outcomes were 1.61 (95% CI, 1.17–2.22) and 1.84 (95% CI, 1.26–2.67), respectively. We categorized DIC score in five groups as <3, 3, 4, 5 and >5 and analyzed differential mortality risk using Cox proportional hazards model. Compared with reference group (DIC score < 3), the adjusted HR for early mortality in each remaining group was 1.96 (95% CI, 1.13–3.40), 2.26 (95% CI, 1.27–4.02), 2.77 (95% CI, 1.58–4.85) and 4.29 (95% CI, 2.22–8.30), respectively (p-trend < 0.001). The area under the receiver operating characteristic of DIC score for prediction of unfavorable long-term outcome was 0.79 (95% CI, 0.69–0.88).

Conclusion

Increased initial DIC score in OHCA was an independent predictor for poor outcomes and early mortality risk.