Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: A systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia

Aims and methods

To systematically review the accuracy of early (≤7 days) predictors of poor outcome, defined as death or vegetative state (Cerebral Performance Categories [CPC] 4–5) or death, vegetative state or severe disability (CPC 3–5), in comatose adult survivors from cardiac arrest (CA) treated using therapeutic hypothermia (TH). Electronic databases were searched for eligible studies. Sensitivity, specificity, and false positive rates (FPR) for each predictor were calculated. Quality of evidence (QOE) was evaluated according to the GRADE guidelines.

Results

37 studies (2403 patients) were included. A bilaterally absent N20 SSEP wave during TH (4 studies; QOE: Moderate) or after rewarming (5 studies; QOE: Low), a nonreactive EEG background (3 studies; QOE: Low) after rewarming, a combination of absent pupillary light and corneal reflexes plus a motor response no better than extension (M ≤ 2) (1 study; QOE: Very low) after rewarming predicted CPC 3–5 with 0% FPR and narrow (<10%) 95% confidence intervals. No consistent threshold for 0% FPR could be identified for blood levels of biomarkers. In 6/8 studies on SSEP, in 1/3 studies on EEG reactivity and in the single study on clinical examination the investigated predictor was used for decisions to withdraw treatment, causing the risk of a self-fulfilling prophecy.

Conclusions

in the first 7 days after CA, a bilaterally absent N20 SSEP wave anytime, a nonreactive EEG after rewarming or a combination of absent ocular reflexes and M ≤ 2 after rewarming predicted CPC 3–5 with 0% FPR and narrow 95% CIs, but with a high risk of bias.     

Heparin-binding protein: An early indicator of critical illness and predictor of outcome in cardiac arrest

Aim

To investigate plasma levels of the neutrophil-borne heparin-binding protein (HBP) in patients with induced hypothermia after cardiac arrest (CA), and to study any association to severity of organ failure, incidence of infection and neurological outcome.

Methods

This study included 84 patients with CA of mixed origin who were treated with hypothermia. Plasma samples from 7 time points during the first 72 h after return of spontaneous circulation (ROSC) were collected and analyzed for HBP with an ELISA. Outcomes were dichotomized: a cerebral performance category scale (CPC) of 1–2 at 6 months follow-up was considered a good outcome, a CPC of 3–5, a poor outcome. Patient data, including APACHE II and SOFA-scores were retrieved from the computerized system for quality assurance for intensive care.

Results

At 6 h and 12 h after CA, plasma levels of HBP were significantly higher among patients with a poor outcome. A receiver operated characteristics (ROC)-analysis yielded respective areas under curve (AUC) values of 0.68 and 0.70. This was similar to APACHE II and SOFA-score AUC values. There was a significant correlation between early elevated HBP-values and time to ROSC. HBP-levels were not higher in patients with infections at any time.

Conclusions

Elevated HBP is an early indicator of organ failure and poor neurological outcome after CA, independent of microbial infection, and should be further evaluated in prospective trials. The temporal profile of HBP is suggestive of a role in the pathogenesis of critical illness after CA.     

Serotonin syndrome after therapeutic hypothermia for cardiac arrest: A case series

Aim

To describe causes, manifestations, and diagnosis of serotonin syndrome following therapeutic hypothermia (TH) after cardiac arrest.

Methods

Retrospective case series from a tertiary academic medical center.

Results

Three male patients suffered witnessed out-of-hospital cardiac arrests and were treated with induced TH. Initial cardiac rhythms included asystole in two and ventricular fibrillation in one. Following completion of rewarming, all three developed neurological signs unexpected for their clinical condition. These included rigidity, hyperreflexia, diffuse tremors, ankle clonus, and marked agitated delirium. Patients also were febrile, hypertensive, and tachycardic. A diagnosis of serotonin syndrome was made in all cases and serotonergic medications were discontinued. All three patients recovered consciousness and two made a full neurological recovery. One patient remained dependent on others for activities of daily living at the time of hospital discharge because of short-term memory impairment.

Conclusions

Unexpected neurologic findings and prolonged high fever following recovery from TH can be manifestations of serotonin syndrome rather than post-cardiac arrest anoxic brain injury.     

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.     

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.     

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%.     

The Glasgow coma score is a predictor of good outcome in cardiac arrest patients treated with therapeutic hypothermia

Background

With the recent introduction of therapeutic hypothermia the application of sedation becomes necessary in cardiac arrest patients. We therefore analysed the usefulness of the Glasgow coma score (GCS) for outcome prediction in survivors of cardiac arrest treated with therapeutic hypothermia.

Patients and methods

In a prospective observational study we identified 72 comatose patients admitted to our intensive care unit after cardiac arrest. All patients were treated with therapeutic hypothermia. After sedation stop the Glasgow coma scale (GCS) was recorded until day 4. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score.

Results

Forty-four of 72 patients (61%) were discharged with a favourable neurological outcome (CPC 1 + 2). GCS was significantly higher in patients with good outcome compared to patients with unfavourable outcome at every point in time after sedation stop (p < 0.001). The value for prediction of good outcome with the highest accuracy was a GCS > 4 at the first day after sedation stop (sensitivity 61%, PPV 90% and AUC 0.808) and GCS > 6 in the following days (sensitivity 84%, PPV 92.5% and AUC 0.921 at day 4). In particular a score of >3 on the motor component of the GCS predicted good outcome with a specificity of 100% (sensitivity 43%) at the first day.

Conclusions

Our results indicate that monitoring of the GCS is a simple and reliable method for clinical outcome assessment in patients treated with therapeutic hypothermia. Thus, GCS monitoring remains a powerful tool to predict outcome of patients treated with therapeutic hypothermia.     

Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest: Results of a pilot study

Objective

To conduct a pilot study to evaluate the prognostic potential of serum tau protein measurements to predict neurological outcome 6 months following resuscitation from cardiac arrest.

Methods

In this retrospective observational study, we employed a new ultra sensitive digital immunoassay technology to examine serial serum samples from 25 cardiac arrest patients to examine tau release into serum as a result of brain hypoxia, and probe for its significance predicting six-month neurological outcome. Serial blood samples were obtained from resuscitated cardiac arrest survivors during their first five days in an intensive care unit, and serum total tau was measured. Cerebral function assessments were made using Cerebral Performance Categorization (CPC) at discharge from the ICU and six months later. Tau data were analyzed in the context of 6-month CPC scores.

Results

Tau elevations ranged from modest (<10 pg/mL) to very high (hundreds of pg/mL), and exhibited unexpected bi-modal kinetics in some patients. Early tau elevations appeared within 24 h of cardiac arrest, and delayed elevations appeared after 24–48 h. In patients with delayed elevations, areas under the curves of tau concentration vs. hours since cardiac arrest were highly predictive of 6-month outcome (P < 0.0005).

Conclusion

High-sensitivity serum tau measurements combined with an understanding of tau release kinetics could have utility for hypoxic brain injury assessment and prediction of cerebral function outcome.     

Serum procalcitonin as a marker of post-cardiac arrest syndrome and long-term neurological recovery,but not of early-onset infections,in comatose post-anoxic patients treated with therapeutic hypothermia

Objective

To examine the relationship of early serum procalcitonin (PCT) levels with the severity of post-cardiac arrest syndrome (PCAS), long-term neurological recovery and the risk of early-onset infections in patients with coma after cardiac arrest (CA) treated with therapeutic hypothermia (TH).

Methods

A prospective cohort of adult comatose CA patients treated with TH (33 °C, for 24 h) admitted to the medical/surgical intensive care unit, Lausanne University Hospital, was studied. Serum PCT was measured early after CA, at two time-points (days 1 and 2). The SOFA score was used to quantify the severity of PCAS. Diagnosis of early-onset infections (within the first 7 days of ICU stay) was made after review of clinical, radiological and microbiological data. Neurological recovery at 3 months was assessed with Cerebral Performance Categories (CPC), and was dichotomized as favorable (CPC 1–2) vs. unfavorable (CPC 3–5).

Results

From December 2009 to April 2012, 100 patients (median age 64 [interquartile range 55–73] years, median time from collapse to ROSC 20 [11–30] min) were studied. Peak PCT correlated with SOFA score at day 1 (Spearman's R = 0.44, p < 0.0001) and was associated with neurological recovery at 3 months (peak PCT 1.08 [0.35–4.45] ng/ml in patients with CPC 1–2 vs. 3.07 [0.89–9.99] ng/ml in those with CPC 3–5, p = 0.01). Peak PCT did not differ significantly between patients with early-onset vs. no infections (2.14 [0.49–6.74] vs. 1.53 [0.46–5.38] ng/ml, p = 0.49).

Conclusions

Early elevations of serum PCT levels correlate with the severity of PCAS and are associated with worse neurological recovery after CA and TH. In contrast, elevated serum PCT did not correlate with early-onset infections in this setting.     

Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II)

Aim of the study

Hypothermia exerts profound protection from neurological damage and death after resuscitation from circulatory arrest. Its application during concomitant cardiogenic shock has been discussed controversially, and still hypothermia is used with reserve when haemodynamic parameters are impaired. On the other hand hypothermia improves force development in isolated human myocardium. Thus, we hypothesized that hypothermia could beneficially affect cardiac function in patients during cardiogenic shock.

Methods

14 Patients, admitted to Intensive Care Unit for cardiogenic shock under inotropic support, were enrolled and moderate hypothermia (33 °C) was induced for either one (n = 5, short-term) or twenty-four (n = 9, mid-term) hours.

Results

12 patients suffered from ischaemic cardiomyopathy, 2 were female, and 6 were included after cardiac arrest and resuscitation. Body temperature was controlled by an intravascular cooling device. Short-term hypothermia consistently decreased heart rate, and increased stroke volume, cardiac index and cardiac power output. Metabolic and electrocardiographic parameters remained constant during cooling. Improved cardiac function persisted during mid-term hypothermia, but was reversed during re-warming. No severe or persistent adverse effects of hypothermia were observed.

Conclusion

Moderate Hypothermia is safe and feasable in patients during cardiogenic shock. Moreover, hypothermia improved parameters of cardiac function, suggesting that hypothermia might be considered as a positive inotropic intervention rather than a risk for patients during cardiogenic shock.     

Bispectral Index to Predict Neurological Outcome Early After Cardiac Arrest

Aim of the study

To address the value of continuous monitoring of bispectral index (BIS) to predict neurological outcome after cardiac arrest.

Methods

In this prospective observational study in adult comatose patients treated by therapeutic hypothermia after cardiac arrest we measured bispectral index (BIS) during the first 24 hours of intensive care unit stay. A blinded neurological outcome assessment by cerebral performance category (CPC) was done 6 months after cardiac arrest.

Results

Forty-six patients (48%) had a good neurological outcome at 6-month, as defined by a cerebral performance category (CPC) 1-2, and 50 patients (52%) had a poor neurological outcome (CPC 3-5). Over the 24 h of monitoring, mean BIS values over time were higher in the good outcome group (38 ± 9) compared to the poor outcome group (17 ± 12) (p < 0.001). Analysis of BIS recorded every 30 minutes provided an optimal prediction after 12.5 h, with an area under the receiver operating characteristic curve (AUC) of 0.89, a specificity of 89% and a sensitivity of 86% using a cut-off value of 23. With a specificity fixed at 100% (sensitivity 26%) the cut-off BIS value was 2.4 over the first 271 minutes. In multivariable analyses including clinical characteristics, mean BIS value over the first 12.5 h was a predictor of neurological outcome (p = 6E-6) and provided a continuous net reclassification index of 1.28% (p = 4E-10) and an integrated discrimination improvement of 0.31 (p = 1E-10).

Conclusions

Mean BIS value calculated over the first 12.5 h after ICU admission potentially predicts 6-months neurological outcome after cardiac arrest.     

Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome

Aim of the study

To investigate serum levels of glial fibrillary acidic protein (GFAP) for evaluation of neurological outcome in cardiac arrest (CA) patients and compare GFAP sensitivity and specificity to that of more studied biomarkers neuron-specific enolas (NSE) and S100B.

Method

A prospective observational study was performed in three hospitals in Sweden during 2008-2012. The participants were 125 CA patients treated with therapeutic hypothermia (TH) to 32-34 °C for 24 hours. Samples were collected from peripheral blood (n = 125) and the jugular bulb (n = 47) up to 108 hours post-CA. GFAP serum levels were quantified using a novel, fully automated immunochemical method. Other biomarkers investigated were NSE and S100B. Neurological outcome was assessed using the Cerebral Performance Categories scale (CPC) and dichotomized into good and poor outcome.

Results

GFAP predicted poor neurological outcome with 100% specificity and 14-23% sensitivity at 24, 48 and 72 hours post-CA. The corresponding values for NSE were 27-50% sensitivity and for S100B 21-30% sensitivity when specificity was set to 100%. A logistic regression with stepwise combination of the investigated biomarkers, GFAP, did not increase the ability to predict neurological outcome. No differences were found in GFAP, NSE and S100B levels when peripheral and jugular bulb blood samples were compared.

Conclusion

Serum GFAP increase in patients with poor outcome but did not show sufficient sensitivity to predict neurological outcome after CA. Both NSE and S100B were shown to be better predictors. The ability to predict neurological outcome did not increased when combining the three biomarkers.     

Feasibility of bispectral index monitoring to guide early post-resuscitation cardiac arrest triage

Introduction

Triage after resuscitation from cardiac arrest is hindered by reliable early estimation of brain injury. We evaluated the performance of a triage model based on early bispectral index (BIS) findings and cardiac risk classes.

Methods

Retrospective evaluation of serial patients resuscitated from cardiac arrest, unable to follow commands, and undergoing hypothermia. Patients were assigned to a cardiac risk group: STEMI, VT/VF shock, VT/VF no shock, or PEA/asystole, and to a neurological dysfunction group, based on the BIS score following first neuromuscular blockade (BISi), and classified as BISi > 20, BISi 10–20, or BISi < 10. Cause of death was described as neurological or circulatory.

Results

BISi in 171 patients was measured at 267(±177) min after resuscitation and 35(±1.7)°C. BISi < 10 suffered 82% neurological-cause and 91% overall mortality, BISi 10–20 35% neurological and 55% overall mortality, and BISi > 20 12% neurological and 36% overall mortality. 33 patients presented with STEMI, 15 VT/VF-shock, 41 VT/VF-no shock, and 80 PEA/asystole. Among BISi > 20 patients, 75% with STEMI underwent urgent cardiac catheterization (cath) and 94% had good outcome. When BISi > 20 with VT/VF and shock, urgent cath was infrequent (33%), and 4 deaths (44%) were uniformly of circulatory etiology. Of 56 VT/VF patients without STEMI, 24 were BISi > 20 but did not undergo urgent cath – 5(20.8%) of these had circulatory-etiology death. Circulatory-etiology death also occurred in 26.5% BIS > 20 patients with PEA/asystole. When BISi < 10, a neurological etiology death dominated independent of cardiac risk group.

Conclusions

Neurocardiac triage based on very early processed EEG (BIS) is feasible, and may identify patients appropriate for individualized post-resuscitation care. This and other triage models warrant further study.     

Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest: Prognostic implications

Aim

Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level of vasopressor support and mortality.

Methods

In a 6-year period, 310 comatose OHCA patients treated with TH were included. Temperature, hemodynamic parameters and level of vasopressors were registered from admission to 24 h after rewarming. Level of vasopressor support was assessed by the cardiovascular sub-score of Sequential Organ Failure Assessment (SOFA). The population was stratified by use of dopamine as first line intervention (D-group) or use of dopamine + norepinephrine/epinephrine (DA-group). Primary endpoint was 30-day mortality and secondary endpoint was in-hospital cause of death.

Results

Patients in the DA-group carried a 49% all-cause 30-day mortality rate compared to 23% in the D-group, p_log-rank < 0.0001, corresponding to an adjusted hazard ratio (HR) of 2.0 (95% CI: 1.3–3.0), p = 0.001). The DA-group had an increased 30-day mortality due to neurological injury (HR = 1.7 (95% CI: 1.1–2.7), p = 0.02). Cause of death was anoxic brain injury in 78%, cardiovascular failure in 18% and multi-organ failure in 4%. The hemodynamic changes of TH reversed at normothermia, although the requirement for vasopressor support (cardiovascular SOFA ≥ 3) persisted in 80% of patients.

Conclusions

In survivors after OHCA treated with TH the induced hemodynamic changes reversed after normothermia, while the need for vasopressor support persisted. Patients requiring addition of norepinephrine/epinephrine on top of dopamine had an increased 30-day all-cause mortality, as well as death from neurological injury.     

The impact of severe acidemia on neurologic outcome of cardiac arrest survivors undergoing therapeutic hypothermia

Introduction

Therapeutic Hypothermia (TH) has become a standard of care in improving neurological outcomes in cardiac arrest (CA) survivors. Previous studies have defined severe acidemia as plasma pH < 7.20. We investigated the influence of severe acidemia at the time of initiation of TH on neurological outcome in CA survivors.

Methods

A retrospective analysis was performed on 196 consecutive CA survivors (out-of-hospital CA and in-hospital CA) who underwent TH with endovascular cooling between January 2007 and October 2012. Arterial blood gas drawn prior to initiation of TH was utilized to measure pH in all patients. Shockable and non-shockable CA patients were divided into two sub-groups based on pH (pH < 7.2 and pH ≥ 7.2). The primary end-point was measured using the Pittsburgh Cerebral Performance Category (CPC) scale prior to discharge from the hospital: good (CPC 1 and 2) and poor (CPC 3 to 5) neurologic outcome.

Results

Sixty-two percent of shockable CA patients with pH ≥ 7.20 had good neurological outcome as compared to 34% patients with pH < 7.20. Shockable CA patients with pH ≥ 7.20 were 3.3 times more likely to have better neurological outcome when compared to those with pH <7.20 [p = 0.013, OR 3.3, 95% CI (1.28–8.45)]. In comparison, non-shockable CA patients with p ≥ 7.20 did not have a significantly different neurological outcome as compared to those with pH < 7.20 [p = 0.97, OR 1.02, 95% CI (0.31–3.3)].

Conclusion

Presence of severe acidemia at initiation of TH in shockable CA survivors is significantly associated with poor neurological outcomes. This effect was not observed in the non-shockable CA survivors.     

Blood pH is a Useful Indicator for Initiation of Therapeutic Hypothermia in the Early Phase of Resuscitation after Comatose Cardiac Arrest: A Retrospective Study

Background

Therapeutic hypothermia (TH) is one of the key treatments after cardiac arrest (CA). Selection of post-CA patients for TH remains problematic, as there are no clinically validated tools to determine who might benefit from the therapy.

Objective

The aim of this study was to investigate retrospectively whether laboratory findings or other patient data obtained during the early phase of hospital admission could be correlated with neurological outcome after TH in comatose survivors of CA.

Methods

Medical charts of witnessed CA patients admitted between June 2003 and July 2009 who were treated with TH were reviewed retrospectively. The subjects were grouped based on their cerebral performance category (CPC) 6 months after CA, as either good recovery (GR) for CPC 1–2 or non-good recovery (non-GR) for CPC 3–5. The following well-known determinants of outcome obtained during the early phase of hospital admission were evaluated: age, gender, body mass index, cardiac origin, presence of ventricular fibrillation (VF), time from collapse to cardiopulmonary resuscitation, time from collapse to return of spontaneous circulation, body temperature, arterial blood gases, and blood test results.

Results

We analyzed a total of 50 (25 GR and 25 non-GR) patients. Multivariate logistic analysis showed that initial heart rhythm and pH levels were significantly higher in the GR group than in the non-GR group (ventricular tachycardia/VF rate: p = 0.055, 95% confidence interval [CI] 0.768–84.272, odds ratio [OR] 8.047; pH: 7.155 ± 0.139 vs. 6.895 ± 0.100, respectively, p < 0.001, 95% CI 1.838–25.827; OR 6.89).

Conclusion

These results imply that in addition to initial heart rhythm, pH level may be a good candidate for neurological outcome predictor even though previous research has found no correlation between initial pH value and neurological outcome.     

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.     

Is enteral feeding tolerated during therapeutic hypothermia?

Objective

To determine whether patients undergoing therapeutic hypothermia following cardiac arrest tolerate early enteral nutrition.

Methods

We undertook a single-centre longitudinal cohort analysis of the tolerance of enteral feeding by 55 patients treated with therapeutic hypothermia following resuscitation from cardiac arrest. The observation period was divided into three phases: (1) 24 h at target temperature (32–34 °C); (2) 24 h rewarming to 36.5 °C; and (3) 24 h maintained at a core temperature below 37.5 °C.

Results

During period 1, patients tolerated a median of 72% (interquartile range (IQR) 68.7%; range 31.3–100%) of administered feed. During period 2 (rewarming phase), a median of 95% (IQR 66.2%; range 33.77–100%) of administered feed was tolerated. During period 3 (normothermia) a median of 100% (IQR 4.75%; range 95.25–100%) of administered feed was tolerated. The highest incidence of vomiting or regurgitation of feed (19% of patients) occurred between 24 and 48 h of therapy.

Conclusions

Patients undergoing therapeutic hypothermia following cardiac arrest may be able to tolerate a substantial proportion of their daily nutritional requirements. It is possible that routine use of prokinetic drugs during this period may increase the success of feed delivery enterally and this could usefully be explored.     

C-reactive protein levels after cardiac arrest in patients treated with therapeutic hypothermia

Aim

Prognostication of outcome after cardiac arrest (CA) is challenging. We assessed the prognostic value of daily blood levels of C-reactive protein (CRP), a cheap and widely available inflammatory biomarker, after CA.

Methods

We reviewed the data of all patients admitted to our intensive care unit (ICU) after CA between January 2009 and December 2011 and who survived for at least 24 h. We collected demographic data, CA characteristics (initial rhythm; location of arrest; time to return of spontaneous circulation [ROSC]), occurrence of infection, ICU survival and neurological outcome at three months (good = cerebral performance category [CPC] 1–2; poor = CPC 3–5). CRP levels were measured daily from admission to day 3.

Results

A total of 130 patients were admitted after successful resuscitation from CA and survived more than 24 h; 76 patients (58%) developed an infection and overall mortality was 56%. CRP levels increased from admission to day 3. CRP levels were higher in in-hospital than in out-of-hospital CA, especially on admission and day 1 (44.1 vs. 2.1 mg L⁻¹ and 74.5 vs. 29.5 mg L⁻¹, respectively; p < 0.001), and in patients with non-shockable than in those with shockable rhythms. In a logistic regression model, high CRP levels on admission were independently associated with poor neurological outcome at 3 months.

Conclusion

CRP levels increase in the days following successful resuscitation of CA. Higher CRP levels in patients with in-hospital CA, non-shockable rhythms and infection, suggest a greater inflammatory response in these patients. High CRP levels on admission may identify patients at high-risk of poor outcome and could be a target for future therapies.     

Effect of cardiac compressions and hypothermia treatment on cardiac troponin I in newborns with perinatal asphyxia

Background

The American Heart Association, the European Resuscitation and the International Liaison Committee issued new neonatal resuscitation guidelines (2010) where therapeutic hypothermia is introduced after hypoxic-ischaemic encephalopathy (HIE) in term infants to prevent brain injury. Our study aimed to investigate whether hypothermia can reduce the release of a cardiac cellular marker, cardiac troponin I (cTnI), in HIE infants compared to normothermia care, if cTnI can be used as a prognostic marker for long term neuro-developmental outcome and if cardiac compression at birth affects the level of cTnI.

Methods

We retrospectively collected resuscitation data at birth and cTnI levels for the first 3 days in HIE infants who fulfilled cooling entry criteria. These infants received either normothermia care or induced hypothermia treatment in the neonatal period and were then followed up and tested by standard cognitive and motor assessments. The outcome is defined as death, disability or good.

Results

We confirmed an increase in cTnI after cardiac compressions (p = 0.003, Mann–Whitney test). We found that hypothermia significantly reduced the release of cTnI (peak level and area under the curve within 24 h of age), p = 0.002, linear regression. Receiver operating characteristic curves showed a level of cTnI at 24 h of age <0.22 ng/ml for normothermic and <0.15 ng/ml for hypothermic infants predicts a good outcome.

Conclusions

Our results suggest that hypothermia is cardio protective after HIE. The level of cTnI at 24 h of age is a good prognostic marker for neuro-developmental outcome at 18–22 months in both normothermia and hypothermia infants.