Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: A systematic review and meta-analysis. Part 1: Patients not 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 survivors from cardiac arrest not treated using therapeutic hypothermia (TH). PubMed, Scopus and the Cochrane Database of Systematic reviews were searched for eligible studies. Sensitivity, specificity, false positive rates (FPR) for each predictor were calculated and results of predictors with similar time points and outcome definitions were pooled. Quality of evidence (QOE) was evaluated according to the GRADE guidelines.

Results

50 studies (2828 patients) were included in final analysis. Presence of myoclonus at 24–48 h, bilateral absence of short-latency somatosensory evoked potential (SSEP) N20 wave at 24–72 h, absence of electroencephalographic activity >20–21 μV ≤72 h and absence of pupillary reflex at 72 h predicted CPC 4–5 with 0% FPR and narrow (<10%) 95% confidence intervals. Absence of SSEP N20 wave at 24 h predicted CPC 3–5 with 0% [0–8] FPR. Serum thresholds for 0% FPR of biomarkers neuron specific enolase (NSE) and S-100B were highly inconsistent among studies. Most of the studies had a low or very low QOE and did not report blinding of the treating team from the results of the investigated predictor.

Conclusions

In comatose resuscitated patients not treated with TH presence of myoclonus, absence of pupillary reflex, bilateral absence of N20 SSEP wave and low EEG voltage each predicted poor outcome early and accurately, but with a relevant risk of bias.     

心搏骤停后昏迷患者神经功能预后评估的研究进展

心肺复苏后昏迷患者早期神经功能预后评估作为心搏骤停(CA)后管理的重要组成部分,具有显著的临床意义.本文从神经系统检查、脑电图、诱发电位、神经影像学及血清生物标志物等方面,结合亚低温治疗对神经功能评估的影响,综述了CA后昏迷患者神经功能预后评估的研究进展.     

Neurologic outcome in comatose patients resuscitated from out-of-hospital cardiac arrest with prolonged downtime and treated with therapeutic hypothermia

Background

Previous reports have shown that prolonged duration of resuscitation efforts in out-of-hospital cardiac arrest (OHCA) is associated with poor neurologic outcome. This concept has recently been questioned with advancements in post-cardiac arrest care including the use of therapeutic hypothermia (TH). The aim of this study was to determine the rate of good neurologic outcome based on the duration of resuscitation efforts in OHCA patients treated with TH.

Methods

This prospective, observational, study was conducted between January 2008 and September 2012. Inclusion criteria consisted of adult non-traumatic OHCA patients who were comatose after return of spontaneous circulation (ROSC) and received TH. The primary endpoint was good neurologic outcome defined as a cerebral performance category score of 1 or 2. Downtime was calculated as the length of time between the patient being recognized as pulseless and ROSC.

Results

105 patients were treated with TH and 19 were excluded due to unknown downtime, leaving 86 patients for analysis. The median downtime was 18.5 (10.0–32.3) min and 33 patients (38.0%) had a good neurologic outcome. When downtime was divided into four groups (≤10 min, 11–20 min, 21–30 min, >30 min), good neurologic outcomes were 62.5%, 37%, 25%, and 21.7%, respectively (p = 0.02). However, even with downtime >20 min, 22.9% had a good neurologic outcome, and this percentage increased to 37.5% in patients with an initial shockable rhythm.

Conclusions

Although longer downtime is associated with worse outcome in OHCA patients, we found that comatose patients who have been successfully resuscitated and treated with TH have neurologically intact survival rates of 23% even with downtime >20 min.     

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.     

The efficacy and safety of prehospital therapeutic hypothermia in patients with out-of-hospital cardiac arrest: A systematic review and meta-analysis

BackgroundThe benefit of therapeutic hypothermia (TH) to patients suffering out-of-hospital cardiac arrest (OHCA) has been well established. However, the effect of prehospital cooling remains unclear. We aimed to investigate the efficacy and safety of prehospital TH for OHCA patients by conducting a systematic review of randomised controlled trials (RCTs).MethodsThe MEDLINE, EMbase and CENTRAL databases were searched for publications from inception to April 2015. RCTs that compared cooling with no cooling in a prehospital setting among adults with OHCA were eligible for inclusion. Random- and fixed-effect models were used depending on inter-study heterogeneity.ResultsEight trials that recruited 2379 participants met the inclusion criteria. Prehospital TH was significantly associated with a lower temperature at admission (mean difference (MD) −0.94; 95% confidence interval (CI) −1.06 to −0.82). However, survival upon admission (Risk ratio (RR) 1.01, 95%CI 0.98–1.04), survival at discharge (RR 1.02, 95%CI 0.91–1.14), in-hospital survival (RR 1.05, 95%CI 0.92–1.19) and good neurological function recovery (RR 1.06, 95% CI 0.91–1.23) did not differ between the TH-treated and non-treated groups. Prehospital cooling increased the incidence of recurrent arrest (RR 1.23, 95%CI 1.02–1.48) and decreased the PH at admission (MD −0.04, 95%CI −0.07 to −0.02). Pulmonary oedema did not differ between the arms (RR 1.02, 95%CI 0.67–1.57). None of the potentially controversial issues (cooling methods, time of inducing TH, the proportion of continuing cooling in hospital, actual prehospital infusion volume and primary cardiac rhythms) affected the efficacy.ConclusionEvidence does not support the administration of prehospital TH to patients with OHCA.     

Efficacy of diffusion-weighted magnetic resonance imaging performed before therapeutic hypothermia in predicting clinical outcome in comatose cardiopulmonary arrest survivors

Aim of the studyTo develop a clinically relevant and qualitative brain magnetic resonance imaging (MRI) scoring system for acute stage comatose cardiac arrest patients.MethodsConsecutive comatose post-cardiopulmonary arrest patients were prospectively enrolled. Routine brain MRI sequences were scored by two independent and blinded experts. Predefined brain regions were qualitatively scored on diffusion-weighted imaging (DWI) sequences according to the severity of the abnormality on a scale from 0 to 4. The mean score provided by the raters determined poor outcome defined under the Cerebral Performance Categories 3, 4, or 5. DWI scans were repeated after therapeutic hypothermia (TH). The same qualitative scoring system was applied and results were compared to the initial scores.ResultsOut of 24 recruited patients, 19 with brain MRI scans were included. Of the 19 included patients, seven showed a good outcome at hospital discharge and 12 patients showed poor neurologic outcome. Median time from the arrest to the initial DWI was 166 min (IQR 114–240 min). At 100% specificity, the overall, cortex, and cortex plus deep grey nuclei scores predicted poor patient outcome with a sensitivity of 91.7–100% (95% CI). Follow-up DWI scans after TH showed worse results than initial scans.ConclusionA qualitative MRI scoring system effectively assessed the severity of hypoxic-ischaemic brain injury following cardiopulmonary arrest. The scoring system may provide useful prognostic information in comatose cardiopulmonary arrest patients.     

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.     

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.     

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.     

Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI

Aim

To determine if early cardiac catheterization (CC) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infarction (STEMI) is absent.

Methods

We conducted a retrospective observational study of a prospective cohort of 754 consecutive comatose patients treated with therapeutic hypothermia (TH) following cardiac arrest.

Results

A total of 269 (35.7%) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH. Of these, 122 (45.4%) received CC while comatose (early CC). Acute coronary occlusion was discovered in 26.6% of patients treated with early CC compared to 29.3% of patients treated with late CC (p = 0.381). Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC (65.6% vs. 48.6%; p = 0.017). In a multivariate regression model that included study site, age, bystander CPR, shock on admission, comorbid medical conditions, witnessed arrest, and time to return of spontaneous circulation, early CC was independently associated with a significant reduction in the risk of death (OR 0.35, 95% CI 0.18–0.70, p = 0.003).

Conclusions

In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality. The incidence of acute coronary occlusion is high, even when STEMI is not present on the postresuscitation electrocardiogram.     

Outcomes of hanging-induced cardiac arrest patients who underwent therapeutic hypothermia: A multicenter retrospective cohort study

Objectives

The aim of this study was to analyze the outcomes of patients with hanging-induced cardiac arrest who underwent therapeutic hypothermia (TH).

Method

In this multicenter, retrospective registry-based study, discharged patients after out-of-hospital cardiac arrest and treatment with TH were enrolled between June 2007 and March 2013. Several prehospital and hospital variables were examined for an outcome analysis with multivariable logistic regression.

Results

A total of 964 patients who had cardiac arrest were enrolled in this study. All patients underwent TH during post-cardiac arrest care after return of spontaneous circulation (ROSC). Of all patients, 105 were assigned to the hanging group and 859 to the non-hanging group. Six patients (6%) with good neurologic outcomes (Cerebral Performance Category 1 or 2) in the hanging group at the time of discharge were found. A shorter time interval between witnessed arrest and ROSC and a Glasgow Coma Scale over 4 after ROSC are statistically significant variables of good neurologic outcomes after hanging-induced cardiac arrest treated with TH.

Conclusion

A small number of patients who underwent TH after a hanging-induced cardiac arrest provided good neurologic outcomes, and some variables influenced these outcomes.     

An observational study of patient selection criteria for post-cardiac arrest therapeutic hypothermia

Background

To date, there is no comprehensive assessment of how therapeutic hypothermia and post-arrest care are being implemented clinically. At this stage in the translation of post-arrest science to clinical practice, this analysis is overdue. This study examines the first step of post-arrest care – the selection of patients for TH and post-arrest care.

Methods

We conducted a systematic review to search for all publicly available TH and post-arrest protocols. Observational data was reported and no statistical inferences were made.

Results

Notable variation was observed in the following selection criteria: total ischemic time and hemodynamic requirements. Additionally, only some of the criteria were evidence based.

Conclusion

This study demonstrates the wide range and variety of patient selection criteria that are being used for implementation of post-cardiac arrest care. The consequences of this selection criteria variability are currently unmeasured and likely underestimated. Variability is likely to breed inefficiency. Some patients who could benefit do not get treated. Other patients get cooled, yet will never regain consciousness. This variability may be important when considering inter-hospital variation in post-arrest care and outcomes.     

Clinical predictors of survival in patients treated with therapeutic hypothermia following cardiac arrest

Introduction

Therapeutic hypothermia has been shown to provide neuroprotection and improved survival in patients suffering a cardiac arrest. We report outcomes of consecutive patients receiving therapeutic hypothermia for cardiac arrest and describe predictors of short and long-term survival.

Methods

Eighty patients receiving therapeutic hypothermia between January 2005 and December 2008 were identified and categorized as those who survived and died. Outcomes and predictors of survival were determined.

Results

Forty-five patients (56%) survived to hospital discharge and were alive at 30 days and among survivors 41 (91%) were alive 1 year after discharge. Survivors were younger, were more likely to present with VF, required less epinephrine during resuscitation, were more likely to have preserved renal function, and were less likely to be taking beta-blockers and ACE inhibitors. Predictors of survival included VF on presentation (OR 14.9, CI 2.7-83.2, p = 0.002), pre-cardiac arrest aspirin use (OR 9.7, CI 1.6-61.1, p = 0.02), return of spontaneous circulation <20 min (OR 9.4, CI 2.2-41.1, p = 0.003), absence of coronary artery disease (OR 5.3, CI 1.1-24.7, p = 0.002) and preserved renal function.

Conclusion

Therapeutic hypothermia is useful in the treatment of patients suffering a cardiac arrest. Several clinical factors may aid in predicting patients who are likely to survive after a cardiac arrest.     

Outcomes of asphyxial cardiac arrest patients who were treated with therapeutic hypothermia: A multicentre retrospective cohort study

IntroductionWhile therapeutic hypothermia (TH) is in clinical use, its efficacy in certain patient groups is unclear. This study was designed to describe the characteristics and outcomes of patients with out-of-hospital cardiac-arrest (OHCA) caused by asphyxia, who were treated with TH.Patients and methodsA multicentre, retrospective, registry-based study was performed using data from the period 2007–2012. Comatose patients who were treated with TH after asphyxial cardiac arrest were included, while those who with cardiac arrest attributed to hanging, drowning or gas intoxication were excluded.ResultsOf a total of 932 OHCA patients in the registry, 111 were enrolled in this study. The mean age was 65.8 ± 16.3 years with individuals who were ≥65 years of age accounted for 61.3% of the cohort. Foreign-body airway obstruction was the most common cause (70.3%) of the cardiac arrest. Eighty patients (72.1%) presented with an initial non-shockable rhythm. In all institutions target TH temperatures were 32–34 °C, but TH maintenance times varied. A total of 52 patients (46.8%) survived, of whom six patients (5.4%) showed a good neurologic outcome (cerebral performance category scale 1–2). The pupil light reflex, corneal reflex and time to return of spontaneous circulation (p = 0.012, 0.015 and 0.032, respectively) were associated with survival. Witnessed arrest, age, previous lung disease, bystander basic life support and time factors were not associated with survival.ConclusionAbout half of patients who underwent TH after asphyxial cardiac arrest survived, but a very small number showed a good neurologic outcome. The TH maintenance times were not uniform in these patients. Additional research regarding both the appropriate TH guidelines for patients with asphyxial cardiac arrest and improvement of their neurologic outcome is needed.     

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.     

Early microcirculatory impairment during therapeutic hypothermia is associated with poor outcome in post-cardiac arrest children: A prospective observational cohort study

Aims of the study

This study aimed to evaluate if the microcirculation is impaired during and after therapeutic hypothermia (TH) in children with return of spontaneous circulation after cardiac arrest (CA) and to assess if microcirculatory impairment predicts mortality. This has been reported for post-CA adults, but results might be different for children because etiology, pathophysiology, and mortality rate differ.

Methods

This prospective observational cohort study included consecutive, non-neonatal post-CA children receiving TH upon intensive care admission between June 2008 and June 2012. Also included were gender-matched and age-matched normothermic, control children without cardiorespiratory disease. The buccal microcirculation was non-invasively assessed with Sidestream Dark Field Imaging at the start of TH, halfway during TH, at the start of re-warming, and at normothermia. Macrocirculatory, respiratory, and biochemical parameters were also collected.

Results

Twenty post-CA children were included of whom 9 died. During hypothermia, the microcirculation was impaired in the post-CA patients and did not change over time. At normothermia, the core body temperature and the microcirculation had increased and no longer differed from the controls. Microcirculatory deterioration was associated with mortality in the post-CA patients. In particular, the microcirculation was more severely impaired at TH start in the non-survivors than in the survivors – positive predictive value: 73–83, negative predictive value: 75–100, sensitivity: 63–100%, and specificity: 70–90%.

Conclusions

The microcirculation is impaired in post-CA children during TH and more severe impairment at TH start was associated with mortality. After the stop of TH, the microcirculation improves rapidly irrespective of outcome.     

Repeated diffusion weighted imaging in comatose cardiac arrest patients with therapeutic hypothermia

BackgroundThe aim of this study was to evaluate the changing pattern and prognostic values of diffusion-weighted imaging (DWI) at two time points in cardiac arrest patients treated with therapeutic hypothermia.MethodsTwenty two patients with cardiac arrest who underwent two DWI studies were enrolled in the retrospective study. The first DWI was performed after the induction of therapeutic hypothermia (median 6.0 h) and was repeated between 48 h and 168 h (second DWI, median 74 h). Apparent diffusion coefficient (ADC) values were measured in the predefined brain regions, and qualitative analysis was also performed. Good neurologic outcomes were defined as Cerebral Performance Category (CPC) scores of 1 and 2.ResultsThe ADC value tended to increase over time except the cortical regions of the poor outcome group (N = 10). In the comparisons of receiver operating characteristic (ROC) curve to predict poor outcome using ADC value, postcentral cortex in the second DWI has a better association with neurological outcome (p = 0.001, area under the curve (AUC) = 0.996 for second DWI, AUC = 0.571 for first DWI). In the same analysis using qualitative score, precentral cortex, postcentral cortex, parietal lobe, occipital lobe, caudate and putamen in the second DWI have a better association with neurological outcome.ConclusionsThe changing pattern of ADC values after cardiac arrest is different according to anatomic region and neurologic status. The DWI after 48 h has a better association with neurological outcome of cardiac arrest patients in both quantitative and qualitative analysis.     

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.     

The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia

Aim

The incidence and timing of electrographic seizures and epileptiform activity in comatose, adult, post-cardiac arrest syndrome (PCAS) patients treated with therapeutic hypothermia (TH) have not been extensively investigated. We hypothesized that onset most frequently occurs within the first 24 h post-arrest and is associated with poor neurologic outcome.

Methods

Single-center, retrospective analysis of a cohort of 38 comatose PCAS patients treated with TH and continuous-EEG-monitoring (cEEG), initiated as soon as possible after ICU admission. All raw cEEG waveform records were cleared of annotations and clinical information and classified by two fellowship-trained electroencephalographers.

Results

Twenty-three percent (9/38) of patients had electrographic seizures (median onset 19 h post-arrest); 5/9 (56%) had seizure-onset prior to rewarming; 7/9 (78%) had status epilepticus. Forty-five percent (17/38) had evidence of epileptiform activity (electrographic seizures or interictal epileptiform discharges), typically occurring during first 24 h post-arrest. Interictal epileptiform activity was highly associated with later detection of electrographic seizures (6/14, 43%, p = 0.001). Ninety-four percent (16/17) of patients with epileptiform activity had poor neurologic outcome or death at discharge (Cerebral Performance Category scale 3–5; p = 0.002) as did all (9/9) patients with electrographic seizures (p = 0.034).

Conclusions

Electrographic seizures and epileptiform activity are common cEEG findings in comatose, PCAS patients treated with TH. In this preliminary study, most seizures were status epilepticus, had onset prior to rewarming, evolved from prior interictal epileptiform activity, and were associated with short-term mortality and poor neurologic outcome. Larger, prospective studies are needed to further characterize seizure activity in comatose post-arrest patients.