Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms

Aim

Mild therapeutic hypothermia (32-34 °C) improves neurological recovery and reduces the risk of death in comatose survivors of cardiac arrest when the initial rhythm is ventricular fibrillation or pulseless ventricular tachycardia. The aim of the presented study was to investigate the effect of mild therapeutic hypothermia (32-34 °C for 24 h) on neurological outcome and mortality in patients who had been successfully resuscitated from non-ventricular fibrillation cardiac arrest.

Methods

In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest with asystole or pulseless electric activity as the first documented rhythm. Data were collected from 1992 to 2009. Main outcome measures were neurological outcome within six month and mortality after six months.

Results

Three hundred and seventy-four patients were analysed. Hypothermia was induced in 135 patients. Patients who were treated with mild therapeutic hypothermia were more likely to have good neurological outcomes in comparison to patients who were not treated with hypothermia with an odds ratio of 1.84 (95% confidence interval: 1.08-3.13). In addition, the rate of mortality was significantly lower in the hypothermia group (odds ratio: 0.56; 95% confidence interval: 0.34-0.93).

Conclusion

Treatment with mild therapeutic hypothermia at a temperature of 32-34 °C for 24 h is associated with improved neurological outcome and a reduced risk of death following out-of-hospital cardiac arrest with non-shockable rhythms.     

Cold saline infusion and ice packs alone are effective in inducing and maintaining therapeutic hypothermia after cardiac arrest

Aim of the study

Hypothermia treatment with cold intravenous infusion and ice packs after cardiac arrest has been described and used in clinical practice. We hypothesised that with this method a target temperature of 32-34 °C could be achieved and maintained during treatment and that rewarming could be controlled.

Materials and methods

Thirty-eight patients treated with hypothermia after cardiac arrest were included in this prospective observational study. The patients were cooled with 4 °C intravenous saline infusion combined with ice packs applied in the groins, axillae, and along the neck. Hypothermia treatment was maintained for 26 h after cardiac arrest. It was estimated that passive rewarming would occur over a period of 8 h. Body temperature was monitored continuously and recorded every 15 min up to 44 h after cardiac arrest.

Results

All patients reached the target temperature interval of 32-34 °C within 279 ± 185 min from cardiac arrest and 216 ± 177 min from induction of cooling. In nine patients the temperature dropped to below 32 °C during a period of 15 min up to 2.5 h, with the lowest (nadir) temperature of 31.3 °C in one of the patients. The target temperature was maintained by periodically applying ice packs on the patients. Passive rewarming started 26 h after cardiac arrest and continued for 8 ± 3 h. Rebound hyperthermia (>38 °C) occurred in eight patients 44 h after cardiac arrest.

Conclusions

Intravenous cold saline infusion combined with ice packs is effective in inducing and maintaining therapeutic hypothermia, with good temperature control even during rewarming.     

A rapid, safe, and low-cost technique for the induction of mild therapeutic hypothermia in post-cardiac arrest patients

Aim of study

The benefits of inducing mild therapeutic hypothermia (MTH) in cardiac arrest patients are well established. Timing and speed of induction have been related to improved outcomes in several animal trials and one human study. We report the results of an easily implemented, rapid, safe, and low-cost protocol for the induction of MTH.

Methods

All in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA) patients admitted to an intensive care unit meeting inclusion criteria were cooled using a combination modality of rapid, cold saline infusion (CSI), evaporative surface cooling, and ice water gastric lavage. Cooling tasks were performed with a primary emphasis on speed. The main endpoints were the time intervals between return of spontaneous circulation (ROSC), initiation of hypothermia (IH), and achievement of target temperature (TT).

Results

65 patients underwent MTH during a 3-year period. All patients reached target temperature. Median ROSC-TT was 134 min. Median ROSC-IH was 68 min. Median IH-TT was 60 min. IH-TT cooling rate was 2.6 °C/h. Complications were similar to that of other large trials. 31% of this mixed population of IHCA and OHCA patients recovered to a Pittsburgh cerebral performance score (CPC) of 1 or 2.

Conclusion

A protocol using a combination of core and surface cooling modalities was rapid, safe, and low cost in achieving MTH. The cooling rate of 2.6 °C/h was superior to most published protocols. This method uses readily available equipment and reduces the need for costly commercial devices.     

Esophageal temperature after out-of-hospital cardiac arrest: An observational study

Introduction

Out-of-hospital cardiac arrest (OHCA) is a significant cause of death and severe neurological disability. The only post-return of spontaneous circulation (ROSC) therapy shown to increase survival is mild therapeutic hypothermia (MTH). The relationship between esophageal temperature post OHCA and outcome is still poorly defined.

Methods

Prospective observational study of all OHCA patients admitted to a single centre for a 14-month period (1/08/2008 to 31/09/2009). Esophageal temperature was measured in the Emergency Department and Intensive Care Unit (ICU). Selected patients had pre-hospital temperature monitoring. Time taken to reach target temperature after ROSC was recorded, together with time to admission to the Emergency Department and ICU.

Results

164 OHCA patients were included in the study. 105 (64.0%) were pronounced dead in the Emergency Department. 59 (36.0%) were admitted to ICU for cooling; 40 (24.4%) died in ICU and 19 (11.6%) survived to hospital discharge. Patients who achieved ROSC and had esophageal temperature measured pre-hospital (n = 29) had a mean pre-hospital temperature of 33.9 °C (95% CI 33.2-34.5). All patients arriving in the ED post OHCA had a relatively low esophageal temperature (34.3 °C, 95% CI 34.1-34.6). Patients surviving to hospital discharge were warmer on admission to ICU than patients who died in hospital (35.7 °C vs 34.3 °C, p < 0.05). Patients surviving to hospital discharge also took longer to reach T_targ than non-survivors (2 h 48 min vs 1 h 32 min, p < 0.05).

Conclusions

Following OHCA all patients have esophageal temperatures below normal in the pre-hospital phase and on arrival in the Emergency Department. Patients who achieve ROSC following OHCA and survive to hospital discharge are warmer on arrival in ICU and take longer to reach target MTH temperatures compared to patients who die in hospital. The mechanisms of action underlying esophageal temperature and survival from OHCA remain unclear and further research is warranted to clarify this relationship.     

Facilitation of hypothermia by quinpirole and 8-OH-DPAT in a rat model of cardiac arrest

Aim of the study

Therapeutic hypothermia improves outcome after cardiac arrest. Dopamine D₂ agonists and serotonin 5-HT_1A agonists lower body temperature by decreasing the set-point. We investigated the effect of these drugs on temperature and cerebral recovery of rats after cardiac arrest.

Methods

Male Wistar-Han rats were subjected to 6 min of cardiac arrest due to ventricular fibrillation. Following restoration of circulation, 1 mg quinpirole, 1 mg 8-OH-DPAT or vehicle were injected subcutaneously. Body temperature was monitored for 48 h. One additional group was kept normothermic. Animals were neurologically tested by a tape removal test. After 7 days, histology of hippocampal CA-1 sector was analysed with Nissl and TUNEL staining.

Results

Rats became spontaneously hypothermic after cardiac arrest. Induction of hypothermia was facilitated by both quinpirole (−0.033 ± 0.008 °C/min) and 8-OH-DPAT (−0.029 ± 0.010 °C/min) when compared to vehicle (−0.020 ± 0.005 °C/min). Total ‘dose’ of hypothermia (area under the curve) was not different. All animals showed a neurological deficit, which improved with time; after 7 days, test results of the normothermic group (30 [11-88] s) still tended to be worse than those of the hypothermic groups (vehicle 8 [6-14] s, quinpirole 9 [4-17] s, 8-OH-DPAT 10 [8-22] s). There were no clear differences in Nissl or TUNEL histology after 7 days.

Conclusion

Both quinpirole and 8-OH-DPAT led to faster induction of hypothermia. However, the outcome was not different from spontaneous hypothermia, probably because the total ‘dose’ of hypothermia was not influenced.     

Examining the contextual effects of neighborhood on out-of-hospital cardiac arrest and the provision of bystander cardiopulmonary resuscitation

Objective

To understand the association between neighborhood and individual characteristics in determining whether or not bystanders perform cardiopulmonary resuscitation (CPR) in cases of out-of-hospital cardiac arrest (OHCA).

Methods

Between October 1, 2005 to November 30, 2008, 1108 OHCA cases from Fulton County (Atlanta), GA, were eligible for bystander CPR. We conducted multi-level non-linear regression analysis and derived Empirical Bayes estimates for bystander CPR by census tract.

Results

279 (25%) cardiac arrest victims received bystander CPR. Provision of bystander CPR was significantly more common in witnessed events (odds ratio [OR] 1.64; 95% confidence interval [CI] 1.21-2.22, p < 0.001) and those that occurred in public locations (OR 1.67; 95% CI 1.16-2.40, p < 0.001). Other individual-level characteristics were not significantly associated with bystander CPR. Cardiac arrests in the census tracts that rank in the highest income quintile, as compared to the lowest income quintile were much more likely (OR 4.98; 95% CI 1.65-15.04) to receive bystander CPR.

Conclusion

Cardiac arrest victims in the highest income census tracts were much more likely to receive bystander CPR than in the lowest income census tracts, even after controlling for individual and arrest characteristics. Low-income neighborhoods may be particularly appropriate targets for community-based CPR training and awareness efforts.     

Epidemiology and outcomes from non-traumatic out-of-hospital cardiac arrest in Korea: A nationwide observational study

Objectives

We aimed to describe the epidemiological features and to determine the predictors for survival to discharge of non-traumatic out-of-hospital cardiac arrest (OHCA) in Korea.

Subjects and methods

A nationwide Utstein style OHCA database (2006-2007) was constructed from ambulance records and hospital medical record review. Cases were enrolled when they were non-traumatic OHCA with presumed cardiac aetiology. Using the population census (2005), we calculated age-gender standardized incidence rates (SIR) and mortality (SMR). We modelled a multivariate logistic regression analysis to determine the effect of risk factors on hospital outcomes.

Results

The total number of EMS-assessed non-traumatic OHCA patients was 19 045. The SIR was 20.9 (2006) and 22.2 (2007) per 100 000 and survival-to-discharge rate was 2.3% for EMS-assessed non-traumatic OHCA, and was 3.5% for the resuscitation-attempted group. From a multivariate logistic regression analysis, witnessed arrest, and shorter basic life support (BLS) and EMS intervals turned out to be significant predictors of good outcome in the resuscitation-attempted group.

Conclusion

From a nationwide OHCA cohort, the incidence of EMS-assessed non-traumatic OHCA was found to be low. Survival-to-discharge rate in the resuscitation-attempted group was 3.5%, which was significantly associated with witnessed arrest, and shorter BLS and EMS intervals.     

Non-invasive continuous cerebral temperature monitoring in patients treated with mild therapeutic hypothermia: An observational pilot study

Aim of the study

To investigate if body temperature as measured with a prototype of a non-invasive continuous cerebral temperature sensor using the zero-heat-flow method to reflect the oesophageal temperature (core temperature) during mild therapeutic hypothermia after cardiac arrest.

Methods

In patients over 18 years old with restoration of spontaneous circulation after cardiac arrest, a temperature sensor that uses the zero-heat-flow principle was placed on the forehead during the periods of cooling and re-warming. This temperature was compared to oesophageal temperature as the primary temperature-monitoring site. To assess agreement, we used the Bland-Altman approach and Lin's concordance correlation coefficient.

Results

From September 2008 to April 2009, data from 19 patients were analysed. The median time from restoration of spontaneous circulation until temperature sensor application was 53 min (interquartile range, 31; 96). All sensors were removed when a core temperature of 36 °C was reached. These measurements were in agreement with oesophageal temperature measurements. No allergic reaction, rash or other irritation occurred on the skin around or under the probes. Bland-Altman results showed a bias of −0.12 °C and 95% limits of agreement of −0.59 and +0.36 °C. Lin's concordance correlation coefficient was 0.98.

Conclusions

Body temperature measurements using a non-invasive continuous cerebral temperature sensor prototype that uses the zero-heat-flow method accurately reflected oesophageal temperature measurements during mild therapeutic hypothermia in patients with restoration of spontaneous circulation after cardiac arrest.     

Impact of transport to critical care medical centers on outcomes after out-of-hospital cardiac arrest

Background

Post-resuscitation care has emerged as an important predictor of survival from out-of-hospital cardiac arrest (OHCA). In Japan, selected hospitals are certified as Critical Care Medical Centers (CCMCs) based on their ability and expertise.

Hypothesis

Outcome after OHCA is better in patients transported to a CCMC compared a non-critical care hospital (NCCH).

Materials and methods

Adults with OHCA of presumed cardiac etiology, treated by emergency medical services systems, and transported in Osaka from January 1, 2005 to December 31, 2007 were registered using a prospective Utstein style population cohort database. Primary outcome measure was 1 month neurologically favorable survival (CPC ≤ 2). Outcomes of patients transported to CCMC were compared with patients transported to NCCH using multiple logistic regressions and stratified on the basis of stratified field ROSC.

Results

10,383 cases were transported. Of these, 2881 were transported to CCMC and 7502 to NCCH. Neurologically favorable 1-month survival was greater in the CCMC group [6.7% versus 2.8%, P < 0.001]. Among patients who were transported to hospital without field ROSC, neurologically favorable outcome was greater in the CCMC group than the NCCH group [1.7% versus 0.5%; adjusted odds ratio (OR), 3.39; 95% confidence interval (CI), 2.17-5.29; P < 0.001]. In the presence of field ROSC, survival was similar between the groups [43% versus 41%; adjusted OR, 1.09; 95% CI, 0.82-1.45; P = 0.554].

Conclusions

Survival after OHCA of presumed cardiac etiology transported to CCMCs was better than those transported to NCCHs. For OHCA patients without field ROSC, transport to a CCMC was an independent predictor for a good neurological outcome.     

Outcome after resuscitation using controlled rapid extracorporeal cooling to a brain temperature of 30 °C, 24 °C and 18 °C during cardiac arrest in pigs

Aim of the study

To identify the optimal level of hypothermia during cardiac arrest, just prior to resuscitation with an extracorporeal cooling system and without fluid overload, for neurological outcome at day 9 in pigs.

Methods

In a prospective randomised laboratory investigation, 24 female Large White pigs (31-38 kg) underwent ventricular-fibrillation cardiac arrest for 15 min, followed by 1 min, 3 min or 5 min (n = 8 per group) of 4 °C cooling with an extracorporeal cooling system via an aortic balloon catheter and resuscitation with cardiopulmonary bypass. Sixty minutes following induction of cardiac arrest, defibrillation attempts were started. Mild hypothermia (34.5 °C) and intensive care were continued for 20 h and final outcome was evaluated after 9 days.

Results

Brain temperature decreased from 38.5 °C to 30.4 ± 1.6 °C within 221 ± 81 s in the 1-min group; to 24.2 ± 4.6 °C within 375 ± 127 s in the 3-min group; and to 18.8 ± 4.0 °C within 450 ± 121 s in the 5-min group. Restoration of spontaneous circulation was achieved in seven (1-min group), six (3-min group) and six (5-min group) animals (p = 0.78), whereas survival to 9 days was only achieved in six, three and three animals in each group (p = 0.22), respectively.

Conclusions

An extracorporeal cooling system rapidly induced brain hypothermia following prolonged normovolaemic cardiac arrest in pigs. Difference in outcome was not statistically significant amongst the three groups with various levels of hypothermia (30 °C, 24 °C and 18 °C) during cardiac arrest prior to resuscitation; however, the animals with the least temperature reduction showed a trend to better survival at 9 days. Further studies are necessary to investigate optimised methods for induction, as well as level, of cerebral hypothermia.     

Association between deprivation status at community level and outcomes from out-of-hospital cardiac arrest: a nationwide observational study

Study objectives

We sought to examine the association between area deprivation and outcomes of out-of-hospital cardiac arrest in Korea.

Methods

Data were obtained from the emergency medical service (EMS) system. A nationwide OHCA cohort database from January2006 to December 2007 was constructed via hospital chart review and ambulance run sheet data. We enrolled all EMS-assessed OHCA victims and excluded cases without available hospital outcome data or residential address. The Carstairs index was used to categorize districts according to level of deprivation into five quintiles, from (Q1, the least deprived) to (Q5, the most deprived). Main outcomes were survival to hospital discharge, survival to admission, and return of spontaneous circulation (ROSC).

Results

34,227 patients were included. Initial rhythm, witnessed status, attempted bystander cardiopulmonary resuscitation (CPR), CPR by EMS, CPR in the emergency department (ED), and elapsed time interval significantly varied according to area deprivation level (p < 0.001). OHCA outcomes were consistently worse in the most deprived areas. The adjusted OR (95% CI) for survival to hospital discharge was 0.58 (0.45-0.77) in the most deprived areas compared to the least deprived areas.

Conclusion

Community deprivation was strongly associated with survival among out-of-hospital cardiac arrest patients in Korea.     

Relationship between blood, nasopharyngeal and urinary bladder temperature during intravascular cooling for therapeutic hypothermia after cardiac arrest

Objectives

Therapeutic hypothermia improves survival and neurological outcome in patients successfully resuscitated after cardiac arrest. Accurate temperature control during cooling is essential to prevent cooling-related side effects.

Methods

Prospective observational study of 12 patients assessed during therapeutic hypothermia (32-34 °C) achieved by intravascular cooling following cardiac arrest. Simultaneous temperature measurements were taken using a Swan-Ganz catheter (blood temperature BLT), nasopharyngeal probe (nasopharyngeal temperature NPT) and the urinary bladder catheter (urinary bladder temperature UBT). A total of 1728 measurements (144 measurements per patient) were recorded over a 48-h period and analyzed. Blood temperature was considered as the reference measurement.

Results

Temperature profiles obtained from BLT, NPT and UBT compared with the use of analysis of variance did not differ significantly. Pearson correlation revealed that the correlation between BLT and NPT as well as BLT and UBT was statistically significant (r = 0.96, p < 0.001 and r = 0.95, p < 0.001, respectively). Bland-Altman analysis proved that the agreement between all measurements was satisfactory and the differences were not clinically important.

Conclusions

In 12 post-cardiac arrest patients undergoing intravascular cooling, both nasopharyngeal and urinary bladder temperature measurements were similar to blood temperatures measured using a pulmonary artery catheter.     

S-100B is superior to NSE, BDNF and GFAP in predicting outcome of resuscitation from cardiac arrest with hypothermia treatment

Objective

To conduct a pilot study to evaluate the blood levels of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) and S-100B as prognostic markers for neurological outcome 6 months after hypothermia treatment following resuscitation from cardiac arrest.

Design

Prospective observational study.

Setting

One intensive care unit at Uppsala University Hospital.

Patients

Thirty-one unconscious patients resuscitated after cardiac arrest.

Interventions

None.

Measurements and main results

Unconscious patients after cardiac arrest with restoration of spontaneous circulation (ROSC) were treated with mild hypothermia to 32-34 °C for 26 h. Time from cardiac arrest to target temperature was measured. Blood samples were collected at intervals of 1-108 h after ROSC. Neurological outcome was assessed with Glasgow-Pittsburgh cerebral performance category (CPC) scale at discharge from intensive care and again 6 months later, when 15/31 patients were alive, of whom 14 had a good outcome (CPC 1-2). Among the predictive biomarkers, S-100B at 24 h after ROSC was the best, predicting poor outcome (CPC 3-5) with a sensitivity of 87% and a specificity of 100%. NSE at 96 h after ROSC predicted poor outcome, with sensitivity of 57% and specificity of 93%. BDNF and GFAP levels did not predict outcome. The time from cardiac arrest to target temperature was shorter for those with poor outcome.

Conclusions

The blood concentration of S-100B at 24 h after ROSC is highly predictive of outcome in patients treated with mild hypothermia after cardiac arrest.     

Out-of-hospital cardiac arrests in young adults in Melbourne, Australia

Background

Characteristics and outcomes of out-of-hospital cardiac arrest (OHCA) in young adults are not well described in Australia.

Methods

A 10-year retrospective case review of all OHCA in young adults (aged 16-39) and not witnessed by EMS, was performed using data from the Victorian Ambulance Cardiac Arrest Registry (VACAR).

Results

Between 2000 and 2009 there were 30,006 adult cardiac arrests of which 3912 (13%) were in this age group. The median (IQR) age was 30 (25-35) years for both sexes with a 3:1 male to female ratio. Overdose was the most common precipitant (33.5%) followed by presumed cardiac (20%). Bystander CPR occurred in 21.2%, EMS median response time was 7 min and resuscitation was attempted in 36% of OHCAs. The presenting rhythm was asystole in 84.6%, PEA in 8.8% and VF/VT in 6.6%. Survival to hospital discharge, for all cause OHCA where resuscitation was attempted, was similar for young adult and older adults (8.8% vs 8.4%, p = 0.2). However, for presumed cardiac aetiology OHCA, young adults had a greater proportion of survivors (14.8% vs 9.0%, p < 0.001). Cardiac arrest with shockable rhythm (VF/pulseless VT) had a survival rate of 31.2% for young adults compared to 18.5% for older adults (p < 0.001).

Conclusion

Survival to hospital discharge rates from OHCA due to a ‘presumed cardiac’ precipitant in young adults is much better than older adults, however, all cause OHCA survival is similar. Multi agency novel upstream preventive strategies aimed at tackling drug overdose may reduce this aetiology of OHCA and save lives.     

Global incidences of out-of-hospital cardiac arrest and survival rates: Systematic review of 67 prospective studies

Aim

The aim of this investigation was to estimate and contrast the global incidence and outcome of out-of-hospital cardiac arrest (OHCA) to provide a better understanding of the variability in risk and survival of OHCA.

Methods

We conducted a review of published English-language articles about incidence of OHCA, available through MEDLINE and EmBase. For studies including adult patients and both adult and paediatric patients, we used Utstein data reporting guidelines to calculate, summarize and compare incidences per 100,000 person-years of attended OHCAs, treated OHCAs, treated OHCAs with a cardiac cause, treated OHCA with ventricular fibrillation (VF), and survival-to-hospital discharge rates following OHCA.

Results

Sixty-seven studies from Europe, North America, Asia or Australia met inclusion criteria. The weighted incidence estimate was significantly higher in studies including adults than in those including adults and paediatrics for treated OHCAs (62.3 vs 34.7; P < 0.001); and for treated OHCAs with a cardiac cause (54.6 vs 40.8; P = 0.004). Neither survival to discharge rates nor VF survival to discharge rates differed statistically significant among studies. The incidence of treated OHCAs was higher in North America (54.6) than in Europe (35.0), Asia (28.3), and Australia (44.0) (P < 0.001). In Asia, the percentage of VF and survival to discharge rates were lower (11% and 2%, respectively) than those in Europe (35% and 9%, respectively), North America (28% and 6%, respectively), or Australia (40% and 11%, respectively) (P < 0.001, P < 0.001).

Conclusions

OHCA incidence and outcome varies greatly around the globe. A better understanding of the variability is fundamental to improving OHCA prevention and resuscitation.     

Assessment of outcomes and differences between in- and out-of-hospital cardiac arrest patients treated with cardiopulmonary resuscitation using extracorporeal life support

Aim

Cardiopulmonary resuscitation (CPR) using extracorporeal life support (ECLS) for in-hospital cardiac arrest (IHCA) patients has been assigned a low-grade recommendation in current resuscitation guidelines. This study compared the outcomes of IHCA and out-of-hospital cardiac arrest (OHCA) patients treated with ECLS.

Methods

A total of 77 patients were treated with ECLS. Baselines characteristics and outcomes were compared for 38 IHCA and 39 OCHA patients.

Results

The time interval between collapse and starting ECLS was significantly shorter after IHCA than after OHCA (25 (21-43) min versus 59 (45-65) min, p < 0.001). The weaning rate from ECLS (61% versus 36%, p = 0.03) and 30-day survival (34% versus 13%, p = 0.03) were higher for IHCA compared with OHCA patients. IHCA patients had a higher rate of favourable neurological outcome compared to OHCA patients, but the difference was not statistically significant (26% versus 10%, p = 0.07). Kaplan-Meier analysis showed improved 30-day and 1-year survival for IHCA patients treated with ECLS compared to OHCA patients who had ECLS. However, multivariate stepwise Cox regression model analysis indicated no difference in 30-day (odds ratio 0.94 (95% confidence interval 0.68-1.27), p = 0.67) and 1-year survival (0.99 (0.73-1.33), p = 0.95).

Conclusion

CPR with ECLS led to more favourable patient outcomes after IHCA compared with OHCA in our patient group. The difference in outcomes for ECLS after IHCA and OHCA disappeared after adjusting for patient factors and the time delay in starting ECLS.     

Hypothermia and neuroprotection by sulfide after cardiac arrest and cardiopulmonary resuscitation

Background

Poor neurological outcome remains a major problem in patients suffering cardiac arrest. Recent data have demonstrated potent neuroprotective effects of the administration of sulfide donor compounds after ischaemia/reperfusion injury following cardiac arrest and resuscitation. Therefore, we sought to evaluate the impact of sodium sulfide (Na₂S), a liquid hydrogen sulfide donor on core body temperature and neurological outcome after cardiac arrest in rats.

Methods

Fifty male Wistar rats were randomized into two groups (sulfide vs. placebo, n = 25 per group). Cardiac arrest was induced by transoesophageal ventricular fibrillation during general anaesthesia. After 6 min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. An investigator blinded bolus of either Na₂S (0.5 mg/kg body weight) or placebo 1 min before the beginning of CPR, followed by a continuous infusion of Na₂S (1 mg/kg body weight/h) or placebo for 6 h, was administered intravenously. 1 day, 3 days, and 7 days after restoration of spontaneous circulation, neurological outcome was evaluated by a tape removal test. After 7 days of reperfusion, coronal brain sections were analyzed by TUNEL- and Nissl-staining. A caspase activity assay was used to determine antiapoptotic properties of Na₂S.

Results

Temperature course was similar in both groups (mean minimal temperature in the sulfide group 31.3 ± 1.2 °C vs. 30.8 ± 1.9 °C in the placebo group; p = 0.29). Despite significant neuroprotection demonstrated by the tape removal test after 3 days of reperfusion in the sulfide treated group, there was no significant difference in neuronal survival at day 7. Likewise results from TUNEL-staining revealed no differences in the amount of apoptotic cell death between the groups after 7 days of reperfusion.

Conclusion

In our rat model of cardiac arrest, sulfide therapy was associated with only a short term beneficial effect on neurological outcome.