Mild induced hypothermia and survival after out-of-hospital cardiac arrest

Background

Mild induced hypothermia (MIH) was introduced for post cardiac arrest care in Sweden in 2003, based on two clinical trials. This retrospective study evaluated its association with 30-day survival after out-of-hospital cardiac arrest (OHCA) in a Swedish community from 2003 to 2015.

Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation

AIM OF THE STUDY: We investigated implementation and efficacy of mild therapeutic hypothermia in the treatment of out-of-hospital cardiac arrest due to ventricular fibrillation. MATERIALS AND METHODS: Two periods were compared, an historical one (36 patients) between 2000 and 2002 where therapeutic hypothermia was never used, and a recent period (32 patients) between 2003 and 2005 where therapeutic hypothermia (32-34 degrees C) was implemented prospectively in our unit. Cooling was obtained by simply using wet cloths and ice packs. Survival in the two groups and factors associated with survival were analysed, together with the neurological prognosis in discharged patients. RESULTS: Survival was significantly higher in the hypothermia group (56% versus 36%), whereas no significant difference was observed in severity between the two periods. Only age, time from return to spontaneous circulation <20min, and therapeutic hypothermia were independently associated with survival. Therapeutic hypothermia was well tolerated and was associated with a significant improvement in neurological outcome. Whereas only 23% of patients actually reached the target temperature in 2003, 100% did in 2005. CONCLUSION: Therapeutic hypothermia is efficient in significantly improving survival and neurological outcome of out-of-hospital cardiac arrest with ventricular fibrillation. By using a simple method, it can be implemented easily and quickly, without side effects.     

Therapeutic hypothermia after out-of-hospital cardiac arrest in Finnish intensive care units: the FINNRESUSCI study

Purpose

We aimed to evaluate post-resuscitation care, implementation of therapeutic hypothermia (TH) and outcomes of intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients in Finland.

Methods

We included all adult OHCA patients admitted to 21 ICUs in Finland from March 1, 2010 to February 28, 2011 in this prospective observational study. Patients were followed (mortality and neurological outcome evaluated by Cerebral Performance Categories, CPC) within 1 year after cardiac arrest.

Results

This study included 548 patients treated after OHCA. Of those, 311 patients (56.8 %) had a shockable initial rhythm (incidence of 7.4/100,000/year) and 237 patients (43.2 %) had a non-shockable rhythm (incidence of 5.6/100,000/year). At ICU admission, 504 (92 %) patients were unconscious. TH was given to 241/281 (85.8 %) unconscious patients resuscitated from shockable rhythms, with unfavourable 1-year neurological outcome (CPC 3–4–5) in 42.0 % with TH versus 77.5 % without TH (p < 0.001). TH was given to 70/223 (31.4 %) unconscious patients resuscitated from non-shockable rhythms, with 1-year CPC of 3–4–5 in 80.6 % (54/70) with TH versus 84.0 % (126/153) without TH (p = 0.56). This lack of difference remained after adjustment for propensity to receive TH in patients with non-shockable rhythms.

Conclusions

One-year unfavourable neurological outcome of patients with shockable rhythms after TH was lower than in previous randomized controlled trials. However, our results do not support use of TH in patients with non-shockable rhythms.     

Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest

BackgroundComatose survivors of out-of-hospital cardiac arrest (OHCA) have high in-hospital mortality due to a complex pathophysiology that includes cardiovascular dysfunction, inflammation, coagulopathy, brain injury and persistence of the precipitating pathology. Therapeutic hypothermia (TH) is the only intervention that has been shown to improve outcomes in this patient population. Due to the similarities between the post-cardiac arrest state and severe sepsis, it has been postulated that early goal-directed hemodyamic optimization (EGDHO) combined with TH would improve outcome of comatose cardiac arrest survivors.ObjectiveWe examined the feasibility of establishing an integrated post-cardiac arrest resuscitation (PCAR) algorithm combining TH and EGDHO within 6 h of emergency department (ED) presentation.MethodsIn May, 2005 we began prospectively identifying comatose (Glasgow Motor Score < 6) survivors of OHCA treated with our PCAR protocol. The PCAR patients were compared to matched historic controls from a cardiac arrest database maintained at our institution.ResultsBetween May, 2005 and January, 2008, 18/20 (90%) eligible patients were enrolled in the PCAR protocol. They were compared to historic controls from 2001 to 2005, during which time 18 patients met inclusion criteria for the PCAR protocol. Mean time from initiation of TH to target temperature (33 °C) was 2.8 h (range 0.8–23.2; SD = h); 78% (14/18) had interventions based upon EGDHO parameters; 72% (13/18) of patients achieved their EGDHO goals within 6 h of return of spontaneous circulation (ROSC). Mortality for historic controls who qualified for the PCAR protocol was 78% (14/18); mortality for those treated with the PCAR protocol was 50% (9/18) (p = 0.15).ConclusionsIn patients with ROSC after OHCA, EGDHO and TH can be implemented simultaneously.     

Immediate prehospital hypothermia protocol in comatose survivors of out-of-hospital cardiac arrest

Therapeutic hypothermia (TH) improves the outcomes of cardiac arrest (CA) survivors. The aim of this study was to evaluate retrospectively the efficacy and safety of an immediate prehospital cooling procedure implemented just after the return of spontaneous circulation with a prehospital setting. During 30 months, the case records of comatose survivors of out-of-hospital CA presumably due to a cardiac disease were studied. A routine protocol of immediate postresuscitation cooling had been tested by an emergency team, which consisted of an infusion of large-volume, ice-cold intravenous saline. We decided to assess the efficacy and tolerance of this procedure. A total of 99 patients were studied; 22 were treated with prehospital TH, and 77 consecutive patients treated with prehospital standard resuscitation served as controls. For all patients, TH was maintained for 12 to 24 hours. The demographic, clinical, and biological characteristics of the patients were similar in the 2 groups. The rate of patients with a body temperature of less than 35°C upon admission was 41% in the cooling group and 18% in the control group. Rapid infusion of fluid was not associated with pulmonary edema. After 1 year of follow-up, 6 (27%) of 22 patients in the cooling group and 30 (39%) of 77 patients in the control group had a good outcome. Our preliminary observation suggests that in comatose survivors of CA, prehospital TH with infusion of large-volume, ice-cold intravenous saline is feasible and can be used safely by mobile emergency and intensive care units.     

Therapeutic hypothermia after out-of-hospital cardiac arrest due to Brugada syndrome

A 56-year-old man was admitted to our hospital after successful resuscitation for out-of-hospital cardiac arrest. Electrocardiogram on admission showed right bundle branch block and ST segment elevation in leads V1-3. Subsequent intravenous infusion of isoproterenol rapidly resolved ST segment elevation, suggesting Brugada syndrome. Therapeutic hypothermia, that was performed with a target temperature of 34.0 degrees C did not induce ST segment elevation in leads V1-3. The J-ST segment elevation rather became much more normal, suggesting a beneficial effect of mild therapeutic hypothermia. Serial ECG showed the temporal variation of ST segment elevation, and pilsicainide challenge test showed the occurrence of ST segment elevation, confirming the diagnosis of Brugada syndrome. Clinical observation suggested that mild therapeutic hypothermia reversed the Brugada phenotype through the prevention of fever as well as being indicated for cerebral protection after cardiac arrest. In conclusion, therapeutic hypothermia with a temperature of 34.0 degrees C can be used safely in Brugada syndrome.     

Better lactate clearance associated with good neurologic outcome in survivors who treated with therapeutic hypothermia after out-of-hospital cardiac arrest

Introduction

Several methods have been proposed to evaluate neurological outcome in out-of-hospital cardiac arrest (OHCA) patients. Blood lactate has been recognized as a reliable prognostic marker for trauma, sepsis, or cardiac arrest. The objective of this study was to examine the association between initial lactate level or lactate clearance and neurologic outcome in OHCA survivors who were treated with therapeutic hypothermia.

Methods

This retrospective cohort study included patients who underwent protocol-based 24-hour therapeutic hypothermia after OHCA between January 2010 and March 2012. Serum lactate levels were measured at the start of therapy (0 hours), and after 6 hours, 12 hours, 24 hours, 48 hours and 72 hours. The 6 hour and 12 hour lactate clearance were calculated afterwards. Patients’ neurologic outcome was assessed at one month after cardiac arrest; good neurological outcome was defined as Cerebral Performance Category one or two. The primary outcome was an association between initial lactate level and good neurologic outcome. The secondary outcome was an association between lactate clearance and good neurologic outcome in patients with initial lactate level >2.5 mmol/l.

Results

Out of the 76 patients enrolled, 34 (44.7%) had a good neurologic outcome. The initial lactate level showed no significant difference between good and poor neurologic outcome groups (6.07 ±4 .09 mmol/L vs 7.13 ± 3.99 mmol/L, P = 0.42), However, lactate levels at 6 hours, 12 hours, 24 hours, and 48 hours in the good neurologic outcome group were lower than in the poor neurologic outcome group (3.81 ± 2.81 vs 6.00 ± 3.22 P <0.01, 2.95 ± 2.07 vs 5.00 ± 3.49 P <0.01, 2.17 ± 1.24 vs 3.86 ± 3.92 P <0.01, 1.57 ± 1.02 vs 2.21 ± 1.35 P = 0.03, respectively). The secondary analysis showed that the 6-hour and 12-hour lactate clearance was higher for good neurologic outcome patients (35.3 ± 34.6% vs 6.89 ± 47.4% P = 0.01, 54.5 ± 23.7% vs 25.6 ± 43.7% P <0.01, respectively). After adjusting for potential confounding variables, the 12-hour lactate clearance still showed a statistically significant difference (P = 0.02).

Conclusion

The lactate clearance rate, and not the initial lactate level, was associated with neurological outcome in OHCA patients after therapeutic hypothermia.     

Infectious complications in survivors of cardiac arrest admitted to the medical intensive care unit

PURPOSE: To describe the incidence, associated factors and outcome of infectious complications in patients admitted to the medical intensive care unit (MICU) after cardiopulmonary resuscitation (CPR). MATERIALS AND METHODS: We identified a retrospective cohort of 56 patients consecutively admitted to MICU after CPR. We collected data on demographics, the first MICU day APACHE III score, mode and location of cardiac arrest, CPR duration, witnessed aspiration, prior antibiotics, the lowest first MICU day Glasgow coma score (GCS), new infections, duration of mechanical ventilation and mortality. RESULTS: Seventy-nine percent of the arrests occurred in the hospital. Pulseless electrical activity was the most common rhythm (52%). New infections developed in 46%. The most common infection was pneumonia (65%) and the most common pathogen Staphylococcus aureus (31%). Blood cultures were obtained in 40 patients during the first 48 h and pathogens were isolated in five (12.5%). Patients with infection were younger (53.7 vs. 70.4 years, P<0.001). Median first day GCS was eight in-patients with infection compared with ten in those without (P=0.032). Patients with infection had longer duration of mechanical ventilation (median 9 vs. 2 days, P=0.001) and MICU length of stay (median 8 vs. 3 days, P<0.001). Hospital mortality was 54% in-patients with infection versus 37% without (P=0.197). CONCLUSIONS: Infectious complications are common in survivors of cardiac arrest and are associated with increased morbidity.     

Mild therapeutic hypothermia after cardiac arrest - a nationwide survey on the implementation of the ILCOR guidelines in German intensive care units

AIM: To investigate the implementation of mild therapeutic hypothermia (MTH) after cardiac arrest into clinical practice. METHODS AND RESULTS: A structured evaluation questionnaire was sent to all German hospitals registered to have ICUs; 58% completed the survey. A total of 93 ICUs (24%) reported to use MTH. Of those, 93% started MTH in patients after out-of-hospital resuscitation with observed ventricular fibrillation and 72% when other initial rhythms were observed. Only a minority of ICUs initiate MTH in patients after cardiac arrest with cardiogenic shock (28%), whereas 48% regarded cardiogenic shock as a contra-indication for MTH. On average, target temperature was 33.1+/-0.6 degrees C and duration of cooling 22.9+/-4.9 h. Many centres used economically priced cold packs (82%) and cold infusions (80%) for cooling. The majority of the ICUs considered infection, hypotension and bleeding as relevant complications of hypothermia which was of therapeutic relevance in less than 25% of the cases. CONCLUSIONS: MTH is underused in German ICUs. Centres which use MTH widely follow the recommendations of ILCOR with respect to the indication and timing of cooling. In hospitals that use MTH the technique is considered to be safe and inexpensive. More efforts are needed to promote this therapeutic option and hypothermia since MTH has now been included into European advanced cardiovascular life support protocols.     

Blood levels of copeptin on admission predict outcomes in out-of-hospital cardiac arrest survivors treated with therapeutic hypothermia

Introduction

Prognostic stratification of cardiac arrest survivors is essential for the selection of the most appropriate therapeutic strategy. However, accurate early outcome predictions for this patient population remain challenging. At present, there is a lack of data examining the prognostic value of C-terminal provasopressin (copeptin) in cardiac arrest survivors.

Methods

A group of 40 out-of-hospital cardiac arrest survivors who were treated with endovascular hypothermia was analyzed. Copeptin levels were measured in blood samples taken at admission using a commercially available immunoassay. Neurological outcome was assessed at 30 days post admission according to the Cerebral Performance Category (CPC): CPC 1, no neurological deficit; CPC 2, mild to moderate dysfunction; CPC 3, severe dysfunction; CPC 4, coma; and CPC 5, death.

Results

Copeptin levels were significantly lower in patients with CPC 1 compared with CPC 2 or CPC 3 to CPC 5 (74.3 ± 14.4 pmol/l, 219.8 ± 33.9 pmol/l and 302.7 ± 52.1 pmol/l, respectively; P < 0.0001). Using an optimal cutoff value ≤ 217.9 pmol/l calculated from the receiver operating characteristic curve (area under curve = 0.801, 95% confidence interval = 0.644 to 0.910; P = 0.0001), the sensitivity of predicting survival with good neurological outcome was 78.6% and the specificity was 75.0%. Multiple logistic regression analysis revealed that a copeptin level > 217.9 pmol/l was an independent predictor of severe neurological dysfunction or death, with an adjusted odds ratio of 27.00 (95% confidence interval = 2.27 to 321.68; P = 0.009).

Conclusion

The present study found that copeptin levels have a significant prognostic value at the time of hospital admission, and are a promising diagnostic tool for predicting outcomes in out-of-hospital cardiac arrest survivors.     

Incidence of iatrogenic dyscarbia during mild therapeutic hypothermia after successful resuscitation from out-of-hospital cardiac arrest

To investigate the incidence of iatrogenic dyscarbia in survivors of out-of-hospital cardiac arrest treated with induced mild hypothermia.We performed a retrospective cohort study of the ventilatory management based on blood gas analyses of patients resuscitated from prehospital cardiac arrest. In the pilot phase, we assessed the ventilatory management in the patients treated in one university hospital during a 4-year study period. Subsequently, a more recent (1-year) retrospective cohort of resuscitated patients from all five Finnish university hospitals concerning the first 48 h after hospital admission was analyzed. Core temperatures and temperature corrected (or non-corrected) blood gas analysis results with focus on carbon dioxide tension were analyzed. In addition, a survey was performed to investigate the ventilatory strategies in all Finnish hospitals providing mild hypothermia for cardiac arrest victims.The pilot cohort suggested a high incidence of hypo- or hyper-carbia during hypothermia treatment. In the multicenter patient population of 122 patients contributing a total of 1627 measurements, the PaCO₂ distribution was as follows: less than 4 kPa in 148 samples out of 1627 (9%), 4–4.6 kPa in 404 (25%), 4.7–6 kPa in 887 (55%) and more than 6 kPa in 188 samples (12%). There was a significant difference in the incidence of hypercarbia between the hospitals (p < 0.05).We conclude that normocarbia was achieved/maintained only in approximately 55% of the samples. The incidence of hypo- or hyper-carbia (dyscarbia) was high (45%). This may predispose for serious derangements in the cerebral perfusion of the resuscitated patient. These results call for vigilance in adjustment of the ventilatory management to meet the needs of the patients treated with mild hypothermia.     

Copeptin levels are associated with organ dysfunction and death in the intensive care unit after out-of-hospital cardiac arrest

IntroductionWe studied associations of the stress hormones copeptin and cortisol with outcome and organ dysfunction after out-of-hospital cardiac arrest (OHCA).MethodsPlasma was obtained after consent from next of kin in the FINNRESUSCI study conducted in 21 Finnish intensive care units (ICUs) between 2010 and 2011. We measured plasma copeptin (pmol/L) and free cortisol (nmol/L) on ICU admission (245 patients) and at 48 hours (additional 33 patients). Organ dysfunction was categorised with 24-hour Sequential Organ Failure Assessment (SOFA) scores. Twelve-month neurological outcome (available in 276 patients) was classified with cerebral performance categories (CPC) and dichotomised into good (CPC 1 or 2) or poor (CPC 3 to 5). Data are presented as medians and interquartile ranges (IQRs). A Mann–Whitney U test, multiple linear and logistic regression tests with odds ratios (ORs) 95% confidence intervals (CIs) and beta (B) values, repeated measure analysis of variance, and receiver operating characteristic curves with area under the curve (AUC) were performed.ResultsPatients with a poor 12-month outcome had higher levels of admission copeptin (89, IQR 41 to 193 versus 51, IQR 29 to 111 pmol/L, P = 0.0014) and cortisol (728, IQR 522 to 1,017 versus 576, IQR 355 to 850 nmol/L, P = 0.0013). Copeptin levels fell between admission and 48 hours (P <0.001), independently of outcome (P = 0.847). Cortisol levels did not change between admission and 48 hours (P = 0.313), independently of outcome (P = 0.221). The AUC for predicting long-term outcome was weak for copeptin (0.62, 95% CI 0.55 to 0.69) and cortisol (0.62, 95% CI 0.54 to 0.69). With logistic regression, admission copeptin (standard deviation (SD) increase OR 1.4, 95% CI 1.03 to 1.98) and cortisol (SD increase OR 1.5, 95% CI 1.1 to 2.0) predicted ICU mortality but not 12-month outcome. Admission factors correlating with SOFA were shockable rhythm (B −1.3, 95% CI −2.2 to −0.5), adrenaline use (B 1.1, 95% CI 0.2 to 2.0), therapeutic hypothermia (B 1.3 95% CI 0.4-2.2), and copeptin (B 0.04, 95% CI 0.02 to 0.07).ConclusionsAdmission copeptin and free cortisol were not of prognostic value regarding 12-month neurological outcome after OHCA. Higher admission copeptin and cortisol were associated with ICU death, and copeptin predicted subsequent organ dysfunction.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0831-y) contains supplementary material, which is available to authorized users.     

Sex differences in cardiac arrest survivors who receive therapeutic hypothermia

Objective

Sex differences have not been well defined for patients undergoing therapeutic hypothermia (TH). We aimed to determine sex differences in mortality and Cerebral Performance Category (CPC) scores at discharge among those receiving TH.

Methods

This retrospective cohort study used data abstracted from an “ICE alert” database, an institutional protocol expediting mild TH for postarrest patients. Quality assurance variables (such as age, time to TH, CPC scores, and mortality) were reviewed and compared by sex. χ² Test and Wilcoxon rank sum test were used. Stepwise logistic regression was used to assess the association between mortality and sex, while controlling for patient characteristics and clinical presentation of cardiac arrest.

Results

Three hundred thirty subjects were analyzed, 198 males and 132 females. Subjects' mean age (SD) was 61.7 years (15.0); there was no significant sex difference in age. There were no statistically significant sex differences in history of coronary artery disease, congestive heart failure, arrhythmia, hypertension, chronic obstructive pulmonary disease, renal disease, type 1 and/or type 2 diabetes mellitus, or those previously healthy. Obesity (body mass index > 35 kg/m²) was more likely in females (37, 28.0%) than males (35, 17.7%); P = .03. Females (64, 49.6%) were more likely than males (71, 36.8%) to have shock; P = .02. There was no difference in arrest to initiating hypothermia, but there was a significant difference in time to target temperature (in median minutes, interquartile range): male (440, 270) vs female (310, 270), P = .003. There was no statistical difference in CPC at discharge. Crude mortality was not different between sexes: male, 67.7%; female, 70.5%; P = .594. However, after controlling for differences in age, obesity, shock, and other variables, females were less likely to die (odds ratio, 0.46; 95% confidence interval, 0.23-0.92; P = .03) than males.

Conclusion

There is no statistically significant difference in CPC or crude mortality outcomes between sexes. After adjusting for confounders, females were 54% less likely to die than males.     

Mode of death after admission to an intensive care unit following cardiac arrest

Objective To determine the mode of death in patients admitted to an intensive care unit (ICU) after cardiac arrest who died before hospital discharge.Design Prospectively defined retrospective review of a database and individual patient medical records and ICU charts.Setting Eleven-bed multidisciplinary intensive care unit in a general hospital in the United Kingdom.Patients and participants All patients admitted to ICU between February 1998 and July 2003 after a cardiac arrest in the previous 24 h.Measurements and results The outcome at hospital discharge and mode of death in non-survivors were recorded. Based on the mode of death, non-survivors were placed in one of three groups: multiple organ failure death, neurological death or cardiovascular death. Two hundred and five patients were admitted to ICU after a cardiac arrest; 113 (55.1%) after out-of-hospital cardiac arrest and 92 (44.9%) after in-hospital cardiac arrest. One hundred and twenty-six (61.5%) patients died before hospital discharge and of these 58 (46.0%) died due to neurological injury. After cardiac arrest, 22.9% of the in-hospital patients and 67.7% of the out-of-hospital patients died due to neurological injury, irrespective of the primary cardiac arrest arrhythmia.Conclusions Two-thirds of the patients dying after out-of-hospital cardiac arrest died due to neurological injury and this proportion was approximately the same for ventricular fibrillation/ventricular tachycardia and pulseless electrical activity/asystole. Approximately a quarter of the patients dying after in-hospital cardiac arrest died due to neurological injury.