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 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.     

Time to awakening and neurologic outcome in therapeutic hypothermia-treated cardiac arrest patients

Introduction

Therapeutic hypothermia (TH) has been shown to improve outcomes in comatose Post-Cardiac Arrest Syndrome (PCAS) patients. It is unclear how long it takes these patients to regain neurologic responsiveness post-arrest. We sought to determine the duration to post-arrest awakening and factors associated with times to such responsiveness.

Methods

We performed a retrospective chart review of consecutive TH-treated PCAS patients at three hospitals participating in a US cardiac arrest registry from 2005 to 2011. We measured the time from arrest until first documentation of “awakening”, defined as following commands purposefully.

Results

We included 194 consecutive TH-treated PCAS patients; mean age was 57 ± 16 years; 59% were male; 40% had an initial shockable rhythm. Mean cooling duration was 24 ± 8 h and mean rewarming time was 14 ± 13 h. Survival to discharge was 44%, with 78% of these discharged with a good neurologic outcome. Of the 85 patients who awakened, median time to awakening was 3.2 days (IQR 2.2, 4.5) post-cardiac arrest. Median time to awakening for a patient discharged in good neurological condition was 2.8 days (IQR 2.0, 4.5) vs. 4.0 days (IQR 3.5, 7.6) for those who survived to discharge without a good neurological outcome (p = 0.035). There was no significant association between initial rhythm, renal insufficiency, paralytic use, post-arrest seizure, or location of arrest and time to awakening.

Conclusion

In TH-treated PCAS patients, time to awakening after resuscitation was highly variable and often longer than three days. Earlier awakening was associated with better neurologic status at hospital discharge.     

Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest

Objective

Therapeutic hypothermia, also known as targeted temperature management (TTM), improves clinical outcomes in patients resuscitated from cardiac arrest. Hyperthermia after discontinuation of active temperature management (“rebound pyrexia”) has been observed, but its incidence and association with clinical outcomes is poorly described. We hypothesized that rebound pyrexia is common after rewarming in post-arrest patients and is associated with poor neurologic outcomes.

Methods

Retrospective multicenter US clinical registry study of post-cardiac arrest patients treated with TTM at 11 hospitals between 5/2005 and 10/2011. We assessed the incidence of rebound pyrexia (defined as temperature >38 °C) in post-arrest patients treated with TTM and subsequent clinical outcomes of survival to discharge and “good” neurologic outcome at discharge, defined as cerebral performance category (CPC) 1–2.

Results

In this cohort of 236 post-arrest patients treated with TTM, mean age was 58.1 ± 15.7 y and 106/236 (45%) were female. Of patients who survived at least 24 h after TTM discontinuation (n = 167), post-rewarming pyrexia occurred in 69/167 (41%), with a median maximum temperature of 38.7 (IQR 38.3–38.9). There were no significant differences between patients experiencing any pyrexia and those without pyrexia regarding either survival to discharge (37/69 (54%) v 51/98 (52%), p = 0.88) or good neurologic outcomes (26/37 (70%) v 42/51 (82%), p = 0.21). We compared patients with marked pyrexia (greater than the median pyrexia of 38.7 °C) versus those who experienced no pyrexia or milder pyrexia (below the median) and found that survival to discharge was not statistically significant (40% v 56% p = 0.16). However, marked pyrexia was associated with a significantly lower proportion of CPC 1–2 survivors (58% v 80% p = 0.04).

Conclusions

Rebound pyrexia occurred in 41% of TTM-treated post-arrest patients, and was not associated with lower survival to discharge or worsened neurologic outcomes. However, among patients with pyrexia, higher maximum temperature (>38.7 °C) was associated with worse neurologic outcomes among survivors to hospital discharge.     

Neurologic prognostication and bispectral index monitoring after resuscitation from cardiac arrest

Objective

While the use of therapeutic hypothermia (TH) has improved outcomes after resuscitation from cardiac arrest, prognostication of survival and neurologic function remains difficult during the post-arrest time period. Bispectral index (BIS) monitoring, a non-invasive measurement of simplified electroencephalographic data, is increasingly being considered for post-arrest neurologic assessment and outcomes prediction, although data supporting the technique are limited. We hypothesized that BIS values within 24 h after resuscitation would correlate with neurologic outcomes at discharge.

Methods

We prospectively collected BIS data in consecutive patients initially resuscitated from cardiac arrest and treated with TH in one academic medical center. We assessed BIS values in context of cerebral performance category (CPC) assessment on the day of discharge.

Results

Data were collected in 62 post-arrest patients, of whom 26/62 (42%) survived to hospital discharge. Mean BIS values at 24 h post-resuscitation were significantly different in the survivors with CPC 1-2 (“good” outcome) vs those with CPC 3-5 (“poor” outcome) or death during hospitalization (49 ± 13 vs 30 ± 20; p < 0.001). Receiver operator characteristic analysis suggested that 24 h BIS was most predictive of CPC 1-2 outcome compared to the other timepoints; a BIS cutpoint of 45 exhibited a sensitivity of 63% and a specificity of 86%, with a positive likelihood ratio of 4.67. Sixteen patients exhibited a BIS of zero during at least one timepoint; all of these patients died during hospitalization.

Conclusions

BIS monitoring values at 24 h post-resuscitation are correlated with neurologic outcomes in patients undergoing TH treatment. In 16/62 patients, a BIS of zero at any timepoint was observed, which was uniformly correlated with poor outcome after resuscitation from cardiac arrest; however, a non-zero BIS is insufficient as a sole predictor of good neurologic survival.     

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.     

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 kynurenine pathway activation following cardiac arrest in rats,pigs, and humans

Aim of the study

Kynurenine pathway (KP) is a major route of the tryptophan (TRP) catabolism. In the present study, TRP and KP metabolites concentrations were measured in plasma from rats, pigs and humans after cardiac arrest (CA) in order to assess KP activation and its potential role in post-resuscitation outcome.

Methods

Plasma was obtained from: (A) 24 rats, subjected to 6 min CA and 6 min of cardiopulmonary resuscitation (CPR); (B) 10 pigs, subjected to 10 min CA and 5 min CPR; and (C) 3 healthy human volunteers and 5 patients resuscitated from CA. KP metabolites were quantified by liquid chromatography multiple reaction monitoring mass spectrometry. Assessments were available at baseline, and 1–4 h, and 3–5 days post-CA.

Results

KP was activated after CA in rats, pigs, and humans. Decreases in TRP occurred during the post-resuscitation period and were accompanied by significant increases in its major metabolites, 3-hydroxyanthranilic acid (3-HAA) and kynurenic acid in each species, that persisted up to 3–5 days post-CA (p < 0.01). In rats, changes in KP metabolites reflected changes in post-resuscitation myocardial function. In pigs, changes in TRP and increases in 3-HAA were significanlty related to the severity of cerebral histopathogical injuries. In humans, KP activation was observed, together with systemic inflammation. Post-CA increases in 3-HAA were greater in patients that did not survive.

Conclusion

In this fully translational investigation, the KP was activated early following resuscitation from CA in rats, pigs, and humans, and might have contributed to post-resuscitation outcome.     

Predictors of long-term survival after out-of-hospital cardiac arrest: The impact of Activities of Daily Living and Cerebral Performance Category scores

Background

Current focus on immediate survival from out-of-hospital cardiac arrest (OHCA) has diverted attention away from the variables potentially affecting long-term survival.

Aim

To determine the relationship between neurological and functional status at hospital discharge and long-term survival after OHCA.

Methods

Prospective data collection for all OHCA patients aged >18 years in the Jerusalem district (n = 1043, 2008–2009). Primary outcome measure: Length of survival after OHCA. Potential predictors: Activities of Daily Living (ADL) and Cerebral Performance Category (CPC) scores at hospital discharge, age and sex.

Results

There were 52/279 (18.6%) survivors to hospital discharge. Fourteen were discharged on mechanical ventilation (27%). Interviews with survivors and/or their legal guardians were sought 2.8 ± 0.6 years post-arrest. Eighteen died before long-term follow-up (median survival 126 days, IQR 94–740). Six improved their ADL and CPC scores between discharge and follow-up. Long-term survival was positively related with lower CPC scores (p = 0.002) and less deterioration in ADL from before the arrest to hospital discharge (p = 0.001). For each point increment in ADL at hospital discharge, the hazard ratio of death was 1.31 (95%CI 1.12, 1.53, p = 0.001); this remained unchanged after adjustment for age and sex (HR 1.26, 95%CI 0.07, 1.48, p = 0.005).

Conclusions

One-third of the patients discharged from hospital after OHCA died within 30 months of the event. Long-term survival was associated both with better neurological and functional level at hospital discharge and a smaller decrease in functional limitation from before to after the arrest, yet some patients with a poor neurological outcome survived prolonged periods after hospital discharge.     

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.     

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.     

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.     

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.     

Increased survival with hypotensive resuscitation in a rabbit model of uncontrolled hemorrhagic shock in pregnancy

Aim

We sought to compare the effects of conservative hypotensive and aggressive normotensive resuscitation strategies on blood loss, fluid requirements, blood lactate and survival rate in a clinically relevant model of uncontrolled hemorrhagic shock in pregnancy.

Method

60 anesthetized New Zealand white rabbits at late gestation underwent uncontrolled hemorrhagic shock by transecting a small artery in the mesometrium, followed by blood withdrawal via the carotid artery, to a mean arterial pressure (MAP) of 40–45 mmHg. They were randomly divided into six groups (n = 10 per group): sham shock (group SS); shock without resuscitation (group SH); hypotensive resuscitation in the simulated prehospital phase with Ringer's solution to MAP of 50, 60, or 70 mmHg, respectively (groups RE50, RE60, RE70); and aggressive resuscitation in the prehospital phase with Ringer's solution to MAP of 80 mmHg (group RE80). Finally, in the simulated hospital phase, animals in the resuscitated groups underwent surgical control of bleeding and were fully resuscitated with half of the heparinized shed blood and Ringer's solution to MAP of 80 mmHg.

Results

Hypotensive resuscitation significantly decreased blood loss and subsequent volume infusion, leading to higher hematocrit, lower lactate concentration, and shorter prothrombin time and activated partial thromboplastin time. Median survival time in group RE60 (4.3 ± 0.6 days) was significantly longer than that in groups RE50 (2.7 ± 0.4 days), RE70 (2.3 ± 0.3 days), and RE80 (1.7 ± 0.3 days) (P < 0.05).

Conclusions

We conclude that in this rabbit model of uncontrolled hemorrhage in pregnancy, hypotensive resuscitation to MAP of 60 mmHg may be an optimal target MAP before hemorrhage can be controlled by surgical intervention.     

Heparin dosing in critically ill patients undergoing therapeutic hypothermia following cardiac arrest

Purpose

To determine the effects of anticoagulation with intravenous unfractionated heparin (IVUH) during therapeutic hypothermia (TH) post-cardiac arrest.

Methods

Single-center, retrospective, observational trial in the intensive care units of two hospitals within the Detroit Medical Center. Unresponsive survivors of cardiac arrest, receiving treatment doses of IVUH during TH were included. Patients were required to have at least 1 measured activated partial thromboplastin time (aPTT) during TH. Coagulation parameters were collected at 3 distinct temperature phases: baseline, TH, and post-re-warming (±37 °C) target aPTT defined as 1.5–2 times baseline.

Results

Forty-six patients received IVUH during TH, with 211 aPTTs. Heparin starting rate was 13 ± 4 units/kg/h. Average baseline, TH and post-TH aPTT were 34 ± 12, 142 ± 48, and 56 ± 17 s, respectively. Using standard dosing strategies, initial aPTT was above the target range in 89% of patients. After re-warming, aPTT significantly decreased (142 ± 48 s vs 56 ± 17 s, p = 0.005), and heparin dose significantly increased (7.9 ± 3 vs 9 ± 4 units/kg/h, p < 0.001). There was a significant difference between aPTT among all three groups, and heparin dose between TH and post-TH even after correcting for age, sex, body mass index, heparin rate, and APACHE II score (p < 0.001). Three patients experienced a major bleeding event.

Conclusions

Current dosing protocols for IVUH should not be utilized during TH. Heparin requirements are drastically reduced during TH and prolonged interruptions may be required to allow for adequate clearance of UH.     

Health-related quality of life improves during the first six months after cardiac arrest and hypothermia treatment

Aim of the study

To investigate whether there were any changes in and correlations between anxiety, depression and health-related quality of life (HRQoL) over time, between hospital discharge and one and six months after cardiac arrest (CA), in patients treated with therapeutic hypothermia (TH).

Method

During a 4-year period at three hospitals in Sweden, 26 patients were prospectively included after CA treated with TH. All patients completed the questionnaires Hospital Anxiety and Depression Scale (HADS), Euroqol (EQ5D), Euroqol visual analogue scale (EQ-VAS) and Short Form 12 (SF12) at three occasions, at hospital discharge, and at one and 6 months after CA.

Result

There was improvement over time in HRQoL, the EQ5D index (p = 0.002) and the SF12 physical component score (PCS) (p = 0.005). Changes over time in anxiety and depression were not found. Seventy-three percent of patients had an EQ-VAS score below 70 (scale 0–100) on overall health status at discharge from hospital; at 6 months the corresponding figure was 41%. Physical problems were the most common complaint affecting HRQoL. A correlation was found between depression and HRQoL, and this was strongest at six months (rs = −0.44 to −0.71, p ≤ 0.001).

Conclusion

HRQoL improves over the first 6 months after a CA. Patients reported lower levels of HRQoL on the physical as compared to mental component. The results indicate that the less anxiety and depression patients perceive, the better HRQoL they have and that time can be an important factor in recovery after CA.     

Value analysis of continuous EEG in patients during therapeutic hypothermia after cardiac arrest

Introduction

Therapeutic hypothermia (TH) is standard of care after ventricular fibrillation cardiac arrest (CA). Continuous EEG monitoring (cEEG) is increasingly used during TH. Analysis regarding value of cEEG utilization in this population in the context of cost and outcome has not been performed. We compared outcome and EEG charges in CA patients with selective versus routine cEEG.

Methods

A protocol for TH after CA without routine cEEG was implemented in December 2005, comprising our TH-pre-cEEG cohort. In November 2009, this protocol was changed to include cEEG in all CA–TH patients, comprising our TH-cEEG cohort. Clinical outcome using the Cerebral Performance Category (CPC) at discharge and estimated EEG charges were calculated retrospectively for both cohorts, based on National Charge Data 50th percentile charges expressed in USD per the CMS 2010 Standard Analytical File as reported in Code Correct by MedAssets, Inc.

Results

Our TH-pre-cEEG cohort comprised 91 patients, our TH-cEEG cohort 62. In the TH-pre-cEEG cohort, 19 patients (21%) had rEEGs, 4 (4%) underwent cEEG. The mean estimated EEG charges for the TH-pre-cEEG cohort was $1571.59/patient, and TH-cEEG cohort was $4214.93/patient (p < 0.0001). Two patients (2.1%) in the TH-pre-cEEG cohort had seizures, compared to five (8.1%) in the TH-cEEG cohort (p = 0.088). There was no difference in mortality or clinical outcome in these cohorts.

Conclusions

Routine use of cEEG during TH after CA improved seizure detection, but not outcomes. There was a three-fold increase in EEG estimated charges with routine use of cEEG.     

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.     

Cerebellar Purkinje cell neurodegeneration after cardiac arrest: Effect of therapeutic hypothermia

Aims

The cerebellum is among the brain regions most vulnerable to damage caused by cardiac arrest, and cerebellar Purkinje cell loss may contribute to neurologic dysfunction, including post-hypoxic myoclonus. However, it remains unknown whether cerebellar Purkinje cells are protected by post-cardiac arrest therapeutic hypothermia (TH). Therefore, we examined the effect of post-cardiac arrest TH onset and duration on cerebellar Purkinje cell loss.

Methods

Samples from a previously published study of post-cardiac arrest TH were utilized for the present analysis. Adult male rats subjected to asphyxial cardiac arrest and cardiopulmonary resuscitation were block randomized to normothermia (37.0 °C) or TH (33.0 °C) initiated 0, 1, 4, or 8 h after return of spontaneous circulation (ROSC) and maintained for 24 or 48 h. Cerebella from rats surviving 7 days after ROSC were processed for histology and immunohistochemistry. Purkinje cell density was quantified in Nissl-stained sections of the primary fissure of the cerebellar vermis.

Results

With post-cardiac arrest normothermia, Purkinje cell density in the primary fissure was severely reduced compared to sham-injured controls (3.8 ± 1.8 cells mm⁻¹ vs. 35.9 ± 2.4 cells mm⁻¹, p < 0.001). TH moderately improved Purkinje cell survival in all groups combined (14.0 ± 5.6 cells mm⁻¹, p < 0.001 compared to normothermia). There was no statistical difference in Purkinje cell protection based on TH onset time or duration.

Conclusion

These results indicate that post-cardiac arrest TH protects selectively vulnerable cerebellar Purkinje cells within a broad therapeutic window. The potential clinical implications for improving Purkinje cell survival require further investigation.