Yield of intermittent versus continuous EEG in comatose survivors of cardiac arrest treated with hypothermia

Introduction

Electroencephalography (EEG) has a central role in the outcome prognostication in subjects with anoxic/hypoxic encephalopathy following a cardiac arrest (CA). Continuous EEG monitoring (cEEG) has been consistently developed and studied; however, its yield as compared to repeated standard EEG (sEEG) is unknown.

Methods

We studied a prospective cohort of comatose adults treated with therapeutic hypothermia (TH) after a CA. cEEG data regarding background activity and epileptiform components were compared to two 20-minute sEEGs extracted from the cEEG recording (one during TH, and one in early normothermia).

Results

Thirty-four recordings were studied. During TH, the agreement between cEEG and sEEG was 97.1% (95% CI: 84.6 to 99.9%) for background discontinuity and reactivity evaluation, while it was 94.1% (95% CI 80.3 to 99.2%) regarding epileptiform activity. In early normothermia, we did not find any discrepancies. Thus, concordance results were very good during TH (kappa 0.83), and optimal during normothermia (kappa = 1). The median delay between CA and the first EEG reactivity testing was 18 hours (range: 4.75 to 25) for patients with perfect agreement and 10 hours (range: 5.75 to 10.5) for the three patients with discordant findings (P = 0.02, Wilcoxon).

Conclusions

Standard intermittent EEG has comparable performance with continuous EEG both for variables important for outcome prognostication (EEG reactivity) and identification of epileptiform transients in this relatively small sample of comatose survivors of CA. This finding has an important practical implication, especially for centers where EEG resources are limited.     

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.     

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 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.     

Prevalence and effect of fever on outcome following resuscitation from cardiac arrest

Objective

Evaluate the prevalence of fever in the first 48 h after cardiac arrest and its effect on outcomes.

Methods

Review of patients treated between 1/1/2005 and 6/30/2010. Fever was defined as T ≥ 38.0 °C. We classified categories of post-cardiac arrest illness severity as (I) awake, (II) coma + mild cardiopulmonary dysfunction (SOFA cardiac + respiratory score <4), (III) coma + moderate-severe cardiopulmonary dysfunction, and (IV) deep coma. Associations between fever and survival or good neurologic outcome were examined between hypothermia (TH) and non-TH groups.

Results

In 336 patients, mean age was 60 years (SD 16), 63% experienced out-of-hospital cardiac arrest and 65% received TH. A shockable rhythm was present in 40%. Post arrest illness severity was category II in 38%, category III in 20%, and category IV in 42%. Fever was present in 42% of subjects, with a post-arrest median onset of 15 h in the non-TH cohort and 36 h in TH cohort. Fever was not associated with survival within the whole cohort (OR 0.32, CI 0.15, 0.68) or TH cohort (OR 1.21, CI 0.69, 2.14), but was associated with survival in non-TH cohort (OR 0.47, CI 0.20, 1.10). Fever was not associated with good outcomes in the whole cohort (OR 0.83, CI 0.49, 1.40), TH cohort (OR 1.09, CI 0.56, 2.12) or non-TH cohort (OR 0.34, CI 0.11, 1.06).

Conclusions

The development of fever within the first 48 h after ROSC is common. Fever is associated with death in non-TH patients. TH treatment appears to mitigate this effect, perhaps by delaying fever onset.     

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.     

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.     

Duplex sonography of cerebral blood flow after cardiac arrest—A prospective observational study

Aim

Despite successful resuscitation, cardiac arrest (CA) often has a poor clinical prognosis. Different diagnostic tools have been established to predict patients’ outcome. However, their sensitivity remains low. Assessment of cerebral perfusion by duplex ultrasound might provide additional information regarding the extent of neuronal damage. The aim of the present study was to analyse the changes of global cerebral blood flow (CBF) and intracranial blood flow parameters in the acute stage after CA and its correlation with patients’ outcome.

Methods

We investigated 54 patients (17–85 years, mean age: 63 ± 17 years) after CA with return of spontaneous circulation on an intensive care unit. All patients received therapeutic hypothermia (TH) for 24 h after CA and reanimation. Serial measurements of CBF as well as intracranial blood flow velocities and pulsatility indices of the middle cerebral artery and the basal vein of Rosenthal were performed within the first 10 days using duplex ultrasound. Clinical outcome was measured using the Cerebral Performance Category.

Results

Measurements were successful in 53 patients. CBF values differed between 210 and 1100 ml/min. 24 patients (45%) attained a good outcome. No correlation between CBF or intracranial blood flow characteristics and outcome was found. Neither cerebral hypo- nor hyperperfusion was associated with a fatal outcome.

Conclusion

Cerebral perfusion varies widely after CA. Neither hypo- nor hyperperfusion seems to be an independent risk factor for poor outcome. Duplex ultrasound of cerebral haemodynamics after CA is suitable but probably of limited prognostic value.     

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.     

Effect of moderate hyperventilation and induced hypertension on cerebral tissue oxygenation after cardiac arrest and therapeutic hypothermia

Aim

Improving cerebral perfusion is an essential component of post-resuscitation care after cardiac arrest (CA), however precise recommendations in this setting are limited. We aimed to examine the effect of moderate hyperventilation (HV) and induced hypertension (IH) on non-invasive cerebral tissue oxygenation (SctO₂) in patients with coma after CA monitored with near-infrared spectroscopy (NIRS) during therapeutic hypothermia (TH).

Methods

Prospective pilot study including comatose patients successfully resuscitated from out-of-hospital CA treated with TH, monitored with NIRS. Dynamic changes of SctO₂ upon HV and IH were analyzed during the stable TH maintenance phase. HV was induced by decreasing PaCO₂ from ∼40 to ∼30 mmHg, at stable mean arterial blood pressure (MAP ∼ 70 mmHg). IH was obtained by increasing MAP from ∼70 to ∼90 mmHg with noradrenaline.

Results

Ten patients (mean age 69 years; mean time to ROSC 19 min) were studied. Following HV, a significant reduction of SctO₂ was observed (baseline 74.7 ± 4.3% vs. 69.0 ± 4.2% at the end of HV test, p < 0.001, paired t-test). In contrast, IH was not associated with changes in SctO₂ (baseline 73.6 ± 3.5% vs. 74.1 ± 3.8% at the end of IH test, p = 0.24).

Conclusions

Moderate hyperventilation was associated with a significant reduction in SctO₂, while increasing MAP to supra-normal levels with vasopressors had no effect on cerebral tissue oxygenation. Our study suggests that maintenance of strictly normal PaCO₂ levels and MAP targets of 70 mmHg may provide optimal cerebral perfusion during TH in comatose CA patients.     

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.     

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.     

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.     

Neuromuscular blockade during therapeutic hypothermia after cardiac arrest: Observational study of neurological and infectious outcomes

Introduction

Neuromuscular blockade (NMB) is widely used during therapeutic hypothermia (TH) after cardiac arrest but its effect on patient outcomes is unclear. We compared the effects of NMB on neurological outcomes and frequency of early-onset pneumonia in cardiac-arrest survivors managed with TH.

Methods

We retrospectively studied consecutive adult cardiac-arrest survivors managed with TH in a tertiary-level intensive care unit between January 2008 and July 2013. Patients given continuous NMB for persistent shivering were compared to those managed without NMB. Cases of early-onset pneumonia and vital status at ICU discharge were recorded. To avoid bias due to between-group baseline differences, we adjusted the analysis on a propensity score.

Results

Of 311 cardiac-arrest survivors, 144 received TH, including 117 with continuous NMB and 27 without NMBs. ICU mortality was lower with NMB (hazard ratio [HR], 0.54 [0.32; 0.89], p = 0.016) but the difference was not significant after adjustment on the propensity score (HR, 0.70 [0.39; 1.25], p = 0.22). The proportion of patients with good neurological outcomes was not significantly different (36% with and 22% without NMB, p = 0.16). Early-onset pneumonia was more common with NMB (HR, 2.36 [1.24; 4.50], p = 0.009) but the difference was not significant after adjustment on the propensity score (HR, 1.68 [0.90; 3.16], p = 0.10).

Conclusions

Continuous intravenous NMB during TH after cardiac arrest has potential owns effects on ICU survival with a trend increase in the frequency of early-onset pneumonia. Randomised controlled trials are needed to define the role for NMB among treatments for TH-induced shivering.     

Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest

Introduction  

Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome.     

Prognostic value of electroencephalography (EEG) after out-of-hospital cardiac arrest in successfully resuscitated patients used in daily clinical practice

Background

Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and predicting outcome is complex with neurophysiological testing and repeated clinical neurological examinations as key components of the assessment. In this study we examine the association between different electroencephalography (EEG) patterns and mortality in a clinical cohort of OHCA-patients.

Methods

From 2002 to 2011 consecutive patients were admitted to an intensive-care-unit after resuscitation from OHCA. Utstein-criteria for pre-hospital data and review of individual patients’ charts for post-resuscitation care were used. EEG reports were analysed according to the 2012 American Clinical Neurophysiology Society's guidelines.

Results

A total of 1076 patients were included, and EEG was performed in 20% (n = 219) with a median of 3(IQR 2–4) days after OHCA. Rhythmic Delta Activity (RDA) was found in 71 patients (36%) and Periodic Discharges (PD) in 100 patients (45%). Background EEG frequency of Alpha+ or Theta was noted in 107 patients (49%), and change in cerebral EEG activity to stimulation (reactivity) was found in 38 patients (17%). Suppression (all activity <10 μV) was found in 26 (12%) and burst-suppression in 17 (8%) patients. A favourable EEG pattern (reactivity, favourable background frequency and RDA) was independently associated with reduced mortality with hazard ratio (HR) 0.43 (95%CI: 0.24–0.76), p = 0.004 (false positive rate: 31%) and a non-favourable EEG pattern (no reactivity, unfavourable background frequency, and PD, suppressed voltage or burst-suppression) was associated with higher mortality (HR = 1.62(1.09–2.41), p = 0.02) after adjustment for known prognostic factors (false positive rate: 9%).

Conclusion

EEG may be useful in work-up in prognostication of patients with OHCA. Findings such as Rhythmic Delta Activity (RDA) seem to be associated with a better prognosis, whereas suppressed voltage and burst-suppression patterns were associated with poor prognosis.     

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.     

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.     

Prognostic value of electrographic postanoxic status epilepticus in comatose cardiac-arrest survivors in the therapeutic hypothermia era

Background

The independent prognostic significance of postanoxic status epilepticus (PSE) has not been evaluated prospectively since the introduction of therapeutic hypothermia. We studied 1-year functional outcomes and their determinants in comatose survivors of cardiac arrest (CA), with special attention to PSE.

Methods

106 comatose CA survivors admitted to the intensive care unit in 2005–2010 were included in a prospective observational study. The main outcome measure was a Cerebral Performance Category scale (CPC) of 1 or 2 (favorable outcome) 1 year after CA.

Results

CA occurred out-of-hospital in 89 (84%) patients and was witnessed from onset in 94 (89%). Median times were 6 min (IQR, 0–11) from CA to first-responder arrival and 23 min (14–40) from collapse to return of spontaneous circulation. PSE was diagnosed in 33 (31%) patients at a median of 39 h (4–49) after CA. PSE was refractory in 24 (22%) cases and malignant in 19 (20%). After 1 year, 31 (29.3%) patients had favorable outcomes including 2 (6.44%) with PSE. Factors independently associated with poor outcome (CPC ≥ 3) were PSE (odds ratio [OR], 14.28; 95% confidence interval [95% CI], 2.77–50.0; P = 0.001), time to restoration of spontaneous circulation (OR, 1.04/min; 95% CI, 1–1.07; P = 0.035), and LOD score on day 1 (OR, 1.28/point; 95% CI, 1.08–1.54; P = 0.003).

Conclusion

PSE strongly and independently predicts a poor outcome in comatose CA survivors receiving therapeutic hypothermia, but some patients with PSE survive with good functional outcomes. PSE alone is not sufficient to predict failure to awaken after CA in the era of therapeutic hypothermia.     

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.