The association between intra-arrest therapeutic hypothermia and return of spontaneous circulation among individuals experiencing out of hospital cardiac arrest

Introduction

Therapeutic hypothermia has been shown to improve both mortality and neurologic outcomes following pulseless ventricular tachycardia and fibrillation. Animal data suggest intra-arrest induction of therapeutic hypothermia (IATH) improves frequency of return of spontaneous circulation (ROSC). Our objective was to evaluate the association between IATH and ROSC.

Methods

This was a retrospective analysis of individuals experiencing non-traumatic cardiac arrest in a large metropolitan area during a 12-month period. Six months into the study a prehospital IATH protocol was instituted whereby patients received 2000 ml of 4 °C normal saline directly after obtaining IV/IO access. The main outcome variables were prehospital ROSC, survival to admission, and to discharge. A secondary analysis was conducted to assess the relationship between the quantity of cold saline infused and the likelihood of prehospital ROSC.

Results

551 patients met inclusion criteria with all the elements available for data analysis. Rates of prehospital ROSC were 36.5% versus 26.9% (OR 1.83; 95% CI 1.19-2.81) in patients who received IATH versus normothermic resuscitation respectively. While the frequency of survival to hospital admission and discharge were increased among those receiving IATH, the differences did not reach statistical significance. The secondary analysis found a linear association between the amount of cold saline infused and the likelihood of prehospital ROSC.

Conclusion

The infusion of 4 °C normal saline during the intra-arrest period may improve rate of ROSC even at low fluid volumes. Further study is required to determine if intra-arrest cooling has a beneficial effect on rates of ROSC, mortality, and neurologic function.     

Cardiac arrest survivors with moderate elevated body mass index may have a better neurological outcome: a cohort study

Aim

Body mass index (BMI) may influence the quality of cardiopulmonary resuscitation and may influence prognosis after cardiac arrest. To review the direct effect of obesity on outcome after cardiac arrest, the following cohort study was conducted.

Methods

This study based on a cardiac arrest registry comprising all adult patients with cardiac arrest of non-traumatic origin and restoration of spontaneous circulation (ROSC) admitted to the department of emergency medicine of a tertiary-care facility. Data were collected between January 1992 and December 2007 according to the Utstein criteria. We assessed the association between BMI according to the WHO classification (underweight, BMI < 18.5; normal weight, 18.5-24.9; overweight, 25.0-29.9; obese ≥ 30), six-month survival and neurological recovery.

Results

Analysis was carried out on a total of 1915 adult patients (32% female). Patients had a median age of 59 years (interquartile range [IQR] 49-70) and a median BMI of 26.0 (IQR 23.9-29.1). Survival to six months was 50%. There was no significant difference in survival between the BMI groups (underweight 46%, normal weight 47%, overweight 52%, obese 51%). In a multivariate analysis neurological outcome was better in overweight patients as compared to subjects with normal BMI (odds ratio 1.35; 95% confidence interval 1.02-1.79).

Conclusion

Body mass index may have no direct influence on six-month survival after cardiac arrest, but patients with moderately elevated BMI may have a better neurological prognosis.     

Comparing the survival between extracorporeal rescue and conventional resuscitation in adult in-hospital cardiac arrests: Propensity analysis of three-year data

Aim

Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to have survival benefit over conventional CPR (CCPR) in patients with in-hospital cardiac arrest of cardiac origin. We compared the survival of patients who had return of spontaneous beating (ROSB) after ECPR with the survival of those who had return of spontaneous circulation (ROSC) after conventional CPR.

Methods

Propensity score-matched cohort of adults with in-hospital prolonged CPR (>10 min) of cardiac origin in a university-affiliated tertiary extracorporeal resuscitation center were included in this study. Fifty-nine patients with ROSB after ECPR and 63 patients with sustained ROSC by CCPR were analyzed. Main outcome measures were survival at hospital discharge, 30 days, 6 months, and one year, and neurological outcome.

Results

There was no statistical difference in survival to discharge (29.1% of ECPR responders vs. 22.2% of CCPR responders, p = 0.394) and neurological outcome at discharge and one year later. In the propensity score-matched groups, 9 out of 27 ECPR patients survived to one month (33.3%) and 7 out of 27 CCPR patients survived (25.9%). Survival analysis showed no survival difference (HR: 0.856, p = 0.634, 95% CI: 0.453-1.620) between the groups, either at 30 days or at the end of one year (HR: 0.602, p = 0.093, 95% CI: 0.333-1.088).

Conclusions

This study failed to demonstrate a survival difference between patients who had ROSB after institution of ECMO and those who had ROSC after conventional CPR. Further studies evaluating the role of ECMO in conventional CPR rescued patients are warranted.     

Serum matrix metalloproteinases in patients resuscitated from cardiac arrest. The association with therapeutic hypothermia

Aim

To study the systemic levels of matrix metalloproteinases (MMP) -7, -8 and -9 and their inhibitor TIMP-1 in cardiac arrest patients and the association with mild therapeutic hypothermia treatment on the serum concentration of these enzymes.

Methods

MMP-7, -8 and -9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) were analysed in blood samples obtained from 51 patients resuscitated from cardiac arrest. The samples were taken at 24 and 48 h from restoration of spontaneous circulation (ROSC). The biomarker levels were compared between patients (N = 51) and healthy controls (N = 10) and between patients who did (N = 30) and patients who did not (N = 21) receive mild therapeutic hypothermia.

Results

MMP-7 (median 0.47 ng/ml), MMP-8 (median 31.16 ng/ml) and MMP-9 (median 253.00 ng/ml) levels were elevated and TIMP-1 levels suppressed (median 78.50 ng/ml) in cardiac arrest patients as compared with healthy controls at 24 h from ROSC. Hypothermia treatment associated with attenuated elevation of MMP-9 (p = 0.001) but not MMP-8 (p = 0.02) or MMP-7 (p = 0.69). Concentrations of MMPs -7, -8 and -9 correlated with the leukocyte count but not with C-reactive protein (CRP) or neurone-specific enolase (NSE) levels.

Conclusion

We demonstrated that the systemic levels of MMP-7, -8 and -9 but not TIMP-1 are elevated in cardiac arrest patients in the 48 h post-resuscitation period relative to the healthy controls. Patients who received therapeutic hypothermia had lower MMP-9 levels compared to non-hypothermia treated patients, which generates hypothesis about attenuation of inflammatory response by hypothermia treatment.     

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.     

Repeated magnetic resonance imaging and cerebral performance after cardiac arrest--a pilot study

Aim of the study

Prognostication may be difficult in comatose cardiac arrest survivors. Magnetic resonance imaging (MRI) is potentially useful in the prediction of neurological outcome, and it may detect acute ischemia at an early stage. In a pilot setting we determined the prevalence and development of cerebral ischemia using serial MRI examinations and neurological assessment.

Methods

Ten witnessed out-of-hospital cardiac arrest patients were included. MRI was carried out approximately 2 h after admission to the hospital, repeated after 24 h of therapeutic hypothermia and 96 h after the arrest. The images were assessed for development of acute ischemic lesions. Neurophysiological and cognitive tests as well as a self-reported quality-of-life questionnaire, Short Form-36 (SF-36), were administered minimum 12 months after discharge.

Results

None of the patients had acute cerebral ischemia on MRI at admission. Three patients developed ischemic lesions after therapeutic hypothermia. There was a change in the apparent diffusion coefficient, which significantly correlated with the temperature (p < 0.001). The neurophysiological tests appeared normal. The patients scored significantly better on SF 36 than the controls as regards both bodily pain (p = 0.023) and mental health (p = 0.016).

Conclusions

MRI performed in an early phase after cardiac arrest has limitations, as MRI performed after 24 and 96 h revealed ischemic lesions not detectable on admission. ADC was related to the core temperature, and not to the volume distributed intravenously. Follow-up neurophysiologic tests and self-reported quality of life were good.     

Genetic deletion of NOS3 increases lethal cardiac dysfunction following mouse cardiac arrest

Study aims

Cardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival. We studied the role of NO signaling on cardiovascular outcomes following cardiac arrest and resuscitation using endothelial NO synthase knockout (NOS3^−/−) mice.

Methods

Adult female wild-type (WT) and NOS3^−/− mice were anesthetized, intubated, and instrumented with left-ventricular pressure-volume catheters. Cardiac arrest was induced with intravenous potassium chloride. CPR was performed after 8 min of untreated arrest. ROSC rate, cardiac function, whole-blood nitrosylhemoglobin (HbNO) concentrations, heart NOS3 content and phosphorylation (p-NOS3), cyclic guanosine monophosphate (cGMP), and phospho-troponin I (p-TnI) were measured.

Results

Despite equal quality CPR, NOS3^−/− mice displayed lower rates of ROSC compared to WT (47.6% [10/21] vs. 82.4% [14/17], p < 0.005). Among ROSC animals, NOS3^−/− vs. WT mice exhibited increased left-ventricular dysfunction and 120 min mortality. Prior to ROSC, myocardial effectors of NO signaling including cGMP and p-TnI were decreased in NOS3^−/− vs. WT mice (p < 0.05). Following ROSC in WT mice, significant NOS3-dependent increases in circulating HbNO were seen by 120 min. Significant increases in cardiac p-NOS3 occurred between end-arrest and 15 min post-ROSC, while total NOS3 content was increased by 120 min post-ROSC (p < 0.05).

Conclusions

Genetic deletion of NOS3 decreases ROSC rate and worsens post-ROSC left-ventricular function. Poor cardiovascular outcomes are associated with differences in NOS3-dependent myocardial cGMP signaling and circulating NO metabolites.     

Effectiveness of each target body temperature during therapeutic hypothermia after cardiac arrest

Purpose

According to the 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation, unconscious adult patients with a return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest should be cooled to 32°C to 34°C for 12 to 24 hours. However, it is unclear which target temperature is more adequate. In this study, we prospectively evaluated the outcome and adverse effects following 3 target temperatures (32°C, 33°C, and 34°C) during therapeutic hypothermia with ROSC after out-of-hospital cardiac arrest.

Methods

This is a prospective study of patients with ROSC (>24 hours) after out-of-hospital cardiac arrest who were admitted to the intensive care unit in a tertiary hospital and underwent therapeutic hypothermia during a 22-month period between March 2007 and December 2008.

Results

Sixty-two patients were included. The number of male patients was 44. The mean (SD) ages of the patients was 54.61 (2.002) years. There were 13, 22, and 28 patients who were enrolled in the target temperatures (32°C, 33°C, and 34°C, respectively). There were no significant differences after each target temperature with respect to mortality and neurologic outcomes. Regarding adverse effects, hypotension during the maintenance of therapeutic hypothermia significantly increased when the target temperature was 32°C (P = .023). Based on multivariate analysis, hypotension during the maintenance of therapeutic hypothermia was increased more than 6 times at 32°C compared with 33°C (odds ratio, 6.800; 95% confidence interval, 1.428-32.373).

Conclusion

When performing therapeutic hypothermia in patients with ROSC after an out-of-hospital cardiac arrest, the target temperature would be set to 33°C or 34°C, rather than 32°C. Further multicenter randomized controlled studies may be needed in the future.     

Therapeutic hypothermia after cardiac arrest: A retrospective comparison of surface and endovascular cooling techniques

Objectives

Therapeutic hypothermia (32-34 °C) is recommended for comatose survivors of cardiac arrest; however, the optimal technique for cooling is unknown. We aimed to compare therapeutic hypothermia using either surface or endovascular techniques in terms of efficacy, complications and outcome.

Design

Retrospective cohort study.

Setting

Thirty-bed teaching hospital intensive care unit (ICU).

Patients

All patients (n = 83) undergoing therapeutic hypothermia following cardiac arrest over a 2.5-year period. The mean age was 61 ± 16 years; 88% of arrests occurred out of hospital, and 64% were ventricular fibrillation/tachycardia.

Interventions

Therapeutic hypothermia was initiated in the ICU using iced Hartmann's solution, followed by either surface (n = 41) or endovascular (n = 42) cooling; choice of technique was based upon endovascular device availability. The target temperature was 32-34 °C for 12-24 h, followed by rewarming at a rate of 0.25 °C h⁻¹.

Measurements and main results

Endovascular cooling provided a longer time within the target temperature range (p = 0.02), less temperature fluctuation (p = 0.003), better control during rewarming (0.04), and a lower 48-h temperature load (p = 0.008). Endovascular cooling also produced less cooling-associated complications in terms of both overcooling (p = 0.05) and failure to reach the target temperature (p = 0.04). After adjustment for known confounders, there were no differences in outcome between the groups in terms of ICU or hospital mortality, ventilator free days and neurological outcome.

Conclusion

Endovascular cooling provides better temperature management than surface cooling, as well as a more favorable complication profile. The equivalence in outcome suggested by this small study requires confirmation in a randomized trial.     

New conventional long-term survival normovolemic cardiac arrest pig model

Aim of the study

A reproducible long-term intensive care and outcome cardiac arrest model for exploring new cerebral preservation strategies is needed. We tried to determine effects and limitations of current therapies after different ‘no-flow’ times.

Methods

Thirty-five female Large White Breed pigs (26-37 kg) were included in the study. Three pigs served as sham animals without cardiac arrest (CA). Ventricular fibrillation (VF) CA was induced in 32 animals for 0, 7, 10 and 13 min (each group consisting of 8 animals), followed by 8 min of chest compressions, mechanical ventilation and vasopressors. Thereafter, up to 3 defibrillations were delivered. After restoration of spontaneous circulation (ROSC), the animals underwent intensive care for 20 h. Neurologic examination was performed at designated time points using a neurologic deficit (ND) and an overall performance category (OPC) score.

Results

Restoration of spontaneous circulation was achieved in 8 of 8 animals in the 0 min-group, 6 of 8 in the 7 min-group, 7 of 8 in the 10 min-group and 0 of 8 in the 13 min-group. All animals of the sham-group and 0 min-group were neurologically intact survivors; the 7 and 10 min-groups showed a median ND of 55%(26;94) and 73%(58;78), respectively. There were no significant differences between the 7 and 10 min-groups regarding OPC and NDS. Coronary perfusion pressure during CPR decreased concordantly with ‘no-flow’ times with a tendency towards significance.

Conclusion

This study established a reproducible cardiac arrest and resuscitation model in pigs which will be used to test novel resuscitation strategies to improve neurologic outcome 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.     

Perfluorocarbon induced intra-arrest hypothermia does not improve survival in a swine model of asphyxial cardiac arrest

Background

Pulseless electrical activity is an important cause of cardiac arrest. Our purpose was to determine if induction of hypothermia with a cold perfluorocarbon-based total liquid ventilation (TLV) system would improve resuscitation success in a swine model of asphyxial cardiac arrest/PEA.

Methods

Twenty swine were randomly assigned to control (C, no ventilation, n = 11) or TLV with pre-cooled PFC (n = 9) groups. Asphyxia was induced by insertion of a stopper into the endotracheal tube, and continued in both groups until loss of aortic pulsations (LOAP) was reached, defined as a pulse pressure less than 2 mmHg. The TLV animals underwent asphyxial arrest for an additional 2 min after LOAP, followed by 3 min of hypothermia, prior to starting CPR. The C animals underwent 5 min of asphyxia beyond LOAP. Both groups then underwent CPR for at least 10 min. The endpoint was the resumption of spontaneous circulation maintained for 10 min.

Results

Seven of 9 animals achieved resumption of spontaneous circulation (ROSC) in the TLV group vs. 5 of 11 in the C group (p = 0.2). The mean pulmonary arterial temperature was lower in total liquid ventilation animals starting 4 min after induction of hypothermia (TLV 36.3 ± 0.2 °C vs. C 38.1 ± 0.2 °C, p < 0.0001). Arterial pO₂ was higher in total liquid ventilation animals at 2.5 min of CPR (TLV 76 ± 12 mmHg vs. C 44 ± 2 mmHg; p = 0.03).

Conclusion

Induction of moderate hypothermia using perfluorocarbon-based total liquid ventilation did not improve ROSC success in this model of asphyxial cardiac arrest.     

Correlations between hemodynamic, oxygenation and tissue perfusion parameters during asphyxial cardiac arrest and resuscitation in a pediatric animal model

Aim

To analyze the correlations between hemodynamic, oxygenation and tissue perfusion values in an infant animal model of asphyctic cardiac arrest (ACA).

Methods

A prospective observational animal study was performed in seventy one, two month-old piglets. CA was induced by removal of mechanical ventilation and was followed by advanced life support after at least 10 min. Correlations between hemodynamic [heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), stroke volume index (SVI) and intrathoracic blood index (ITBI) measured by PiCCO method], blood gas values (arterial and central venous saturation), and tissue perfusion values [intramucosal gastric pH (pHi), and tissue oxygenation (cerebral and renal saturation)] were analyzed during asphyxia, resuscitation and after return of spontaneous circulation (ROSC).

Results

Among global hemodynamic parameters, the only moderate significant correlation observed was between CI and ITBI (r = .551). Among tissue oxygenation/perfusion values, a moderate to good significant correlation (r = .460-.763) between arterial oxygen saturation, central venous, renal and cerebral oxygen saturation was observed. Lactic acid, potassium (K) and pHi were correlated (r = .561-.639), but no correlation was found between them and tissue oxygenation parameters. Global hemodynamic parameters (CI, HR, MAP) did not correlate with renal and cerebral saturations and tissue perfusion parameters.

Conclusions

During ACA and after ROSC global hemodynamic parameters do not correlate with oxygenation and tissue perfusion values. Additional studies which assess the potential usefulness of tissue oxygenation/perfusion parameters during cardiac arrest and ROSC are needed.     

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.     

Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial

Background

There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest.

Methods

We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC).

Results

A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR = 3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR = 2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2.

Conclusion

Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC.     

Therapeutic hypothermia is associated with improved neurologic outcome and survival in cardiac arrest survivors of non-shockable rhythms

Background

Therapeutic hypothermia improves neurologic outcomes in patients resuscitated from cardiac arrest due to ventricular fibrillation. However, its role in patients with cardiac arrest due to non-shockable rhythms (pulseless electrical activity (PEA) and asystole) is unclear. We hypothesized that therapeutic hypothermia favorably impacts neurologic outcome and survival in patients resuscitated from cardiac arrest due to non-shockable rhythms.

Methods

Retrospectively collected data on consecutive adult patients admitted to Hartford Hospital from 1/1/2004 to 11/1/2010 who survived a cardiac arrest due to PEA or asystole were analyzed. Patients who underwent therapeutic hypothermia (1/1/2007-11/1/2010) formed the hypothermia group while patients admitted prior to the institution of therapeutic hypothermia (1/1/2004-1/1/2007) at Hartford Hospital formed the control group. The primary end-point was measured using the Pittsburgh cerebral performance category (CPC) scale and patients were assessed for a good (CPC 1 and 2) or poor (CPC 3-5) neurological outcome prior to discharge from hospital. A secondary end-point was measured as survival at discharge from hospital.

Results

Of 100 post-cardiac arrest patients included in the study, 15/52 (29%) patients in the hypothermia group had a good neurologic outcome as compared to 5/43 (10%) patients in the control group (P = 0.021). On multivariate analysis, the odds ratio for good neurologic outcome and survival at discharge from the hospital with therapeutic hypothermia as compared to control were 4.35 (95% CI 1.10-17.24, P = 0.04) and 5.65 (CI 1.66-19.23, P = 0.006) respectively.

Conclusion

Therapeutic hypothermia is associated with favorable neurologic outcome and survival in patients resuscitated after cardiac arrest due to non-shockable rhythms.     

Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest

Objective

To compare the efficacy of nifekalant and amiodarone in the treatment of cardiac arrest in a porcine model.

Methods

After 4 min of untreated ventricular fibrillation, animals were randomly treated with nifekalant (2 mg kg⁻¹), amiodarone (5 mg kg⁻¹) or saline placebo (n = 12 pigs per group). Precordial compression and ventilation were initiated after drug administration and defibrillation was attempted 2 min later. Hemodynamics were continuously measured for 6 h after successful resuscitation.

Results

Compared with saline, nifekalant and amiodarone equally decreased the number of electric shocks, defibrillation energy, epinephrine dose, and duration of cardiopulmonary resuscitation required for successful resuscitation (P < 0.01). The incidence of restoration of spontaneous circulation (ROSC) and the 24-h survival rate were higher in both antiarrhythmic drug groups (P < 0.05) vs. the saline group. Furthermore, post-resuscitation myocardial dysfunction at 4-6 h after successful resuscitation was improved in animals given antiarrhythmic drugs as compared with the saline group (P < 0.05). There were no differences between nifekalant and amiodarone for any of these parameters.

Conclusion

The effect of nifekalant was similar to that of amiodarone for improving defibrillation efficacy and for the treatment of cardiac arrest. Administration of either nifekalant or amiodarone before defibrillation increased the ROSC and 24-h survival rates and improved post-resuscitation cardiac function in this porcine model.     

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.     

Prognostic indicators and outcome prediction model for patients with return of spontaneous circulation from cardiopulmonary arrest: the Utstein Osaka Project

Objective

To determine the most important indicators of prognosis in patients with return of spontaneous circulation (ROSC) following out-of-hospital cardiopulmonary arrest (OHCA) and to develop a best outcome prediction model.

Design and patients

All patients were prospectively recorded based on the Utstein Style in Osaka over a period of 3 years (2005-2007). Criteria for inclusion were a witnessed cardiac arrest, age greater than 17 years, presumed cardiac origin of the arrest, and successful ROSC. Multivariate logistic regression (MLR) analysis was used to develop the best prediction model. The dependent variables were favourable outcome (cerebral-performance category [CPC]: 1-2) and poor outcome (CPC: 3-5) at 1 month after the event. Eight explanatory pre-hospital variables were used concerning patient characteristics and resuscitation. External validation was performed on an independent set of Utstein data in 2007.

Results

Subjects comprised 285 patients in VF and 577 patients with pulseless electrical activity (PEA)/asystole. The percentage of favourable outcomes was 31.9% (91/285) in VF and 5.7% (33/577) in PEA/asystole. The most important prognostic indicators of favourable outcome found by MLR were age (p = 0.10), time from collapse to ROSC (TROSC) (p < 0.01), and presence of pre-hospital ROSC (PROSC) (p = 0.15) for VF and age (p = 0.03), TROSC (p < 0.01), PROSC (p < 0.01), and conversion to VF (p = 0.01) for PEA/asystole. For external validation data, areas under the receiver-operating characteristic curve were 0.867 for VF and 0.873 for PEA/asystole.

Conclusions

A model based on four selected indicators showed a high predictive value for favourable outcome in OHCA patients with ROSC.