Rapidly induced hypothermia with extracorporeal lung and heart assist (ECLHA) improves the neurological outcome after prolonged cardiac arrest in dogs

PURPOSE: We reported previously that therapeutic hypothermia with extracorporeal lung and heart assist (ECLHA) improved neurological outcome after 15 min cardiac arrest (CA) in dogs, although 45 min was needed to achieve hypothermia. We now investigate whether rapidly induced hypothermia with ECLHA (RHE) would result in a better outcome than slowly induced hypothermia with ECLHA (SHE) in dogs. METHODS: Fifteen mongrel female dogs were divided into two groups: an RHE (n = 7) and an SHE (n = 8) group. Normothermic ventricular fibrillation was induced for 15 min and the animals were resuscitated by ECLHA. Rapid hypothermia was induced with a heat exchanger added to the ECLHA circuit in the RHE group, and by immersing the drainage tube of the ECLHA circuit in an ice water bath in the SHE group. Hypothermia (33 degrees C) was maintained for 20 h. The dogs were weaned from ECLHA at 24 h after resuscitation and treated for 96 h; neurological deficit scores (NDS) were measured throughout this period. RESULTS: It took 1.6+/-0.8 min to reach 33 degrees C in the RHE group and 49.5+/-12.1 min to reach 33 degrees C in the SHE group. There was no difference in survival rate between the two groups. The NDS at 96 h in the RHE group was better than that in the SHE group (26% (range: 10-28%) versus 32% (26-37%); p < 0.05) although there was no significant difference in NDS between the two groups until 72 h. CONCLUSION: Rapid hypothermic induction might be an important factor to improve neurological outcomes in prolonged CA models.     

A moderate dose of propofol and rapidly induced mild hypothermia with extracorporeal lung and heart assist (ECLHA) improve the neurological outcome after prolonged cardiac arrest in dogs

BACKGROUND AND PURPOSE: Propofol has been shown to protect against neuronal damage induced by brain ischaemia in small animal models. We reported previously that mild hypothermia (33 degrees C) in combination with extracorporeal lung and heart assist (ECLHA) improved the neurological outcome in dogs with cardiac arrest (CA) of 15 min induced during normothermia. In the present study, we investigated the neuroprotective effect of propofol infusion under mild hypothermia with ECLHA in this model. METHODS: Twenty-one female dogs (15 mongrel dogs and 6 beagles) were divided into three groups: Midazolam 0.1 mg/(kg h) infusion group (M, n=7), Propofol 2 mg/(kg h) infusion group (P2, n=7), Propofol 4 mg/(kg h) infusion group (P4, n=7). Normothermic ventricular fibrillation (VF) was induced in all dogs for 15 min, followed by brief ECLHA and 168 h of intensive care. The drug infusion was initiated at a constant rate after the restoration of spontaneous circulation (ROSC) to 24 h. Mild hypothermia (33 degrees C) was maintained for 20 h. Neurological deficit scores (NDS: 0%=normal, 100%=brain death) were evaluated for neurological function from 33 to 168 h. RESULTS: One dog in the M group died, and the remaining dogs survived for 168 h. The P4 group showed better neurological recovery compared with the M group (48 h, 21+/-16% versus 32+/-15%; 72 h, 7+/-6% versus 25+/-11%; 96 h, 6+/-6% versus 21+/-6%; 120 h, 5+/-5% versus 20+/-6%; 144 h, 4+/-4% versus 20+/-6%; 168 h, 4+/-4% versus 20+/-6%, p<0.05). One dog in the P2 and three dogs in the P4 group achieved full neurological recovery (NDS: 0%). The number of intact pyramidal cells in the hippocampal CA1 was greater in the propofol groups than midazolam group (p<0.05). CONCLUSION: The combination of propofol infusion at a rate of 4 mg/(kg h), 24h and rapidly induced mild hypothermia (33 degrees C) with ECLHA might provide a successful means of cerebral resuscitation from CA.     

The effects of pre-arrest heparin administration dose for cardiac arrest model using extracorporeal lung and a heart assist (ECLHA) in dogs

BACKGROUND AND PURPOSE: Clinical and experimental studies have shown that marked activation of blood coagulation occurs in cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Extracorporeal lung and heart assist (ECLHA) is applied in CA patients who cannot be rescued using conventional therapies. We hypothesized that the dose of heparin administered during the pre-arrest period would influence the outcome in a canine model of CA induced by 15 min of normothermia followed by ECLHA, which consists of heparin coating membrane lung and tubing. We therefore investigated the effects of two dose regimes of the pre-arrest heparin for this model. METHODS: Twelve mongrel female dogs were divided into two groups: a group given 200 U/kg heparin (H200, n=6) and a group given 700 U/kg heparin (H700, n=6), group during pre-arrest period. Normothermic ventricular fibrillation (VF) was induced in all dogs for 15 min, followed by 24h of ECLHA with rapidly induced mild hypothermia (33 degrees C) and 120 h of intensive care. Outcome evaluations included: (1) activated coagulation time (ACT); (2) catecholamine dose; (3) hematocrit (Hct) and platelet count; (4) survival rate; (5) neurological deficit scores (NDS); (6) postmortal macroscopic examination with the exception of the brain. RESULTS: In the H200 group, four dogs died of cardiogenic shock within 28 h. The autopsy revealed extensive patchy hemorrhages in the heart and intestine. In the H700 group, the amount of dopamine was significantly lower (6+/-10mg versus 75+/-41 mg, p<0.05) and the survival rate was significantly higher (100% versus 17%, p<0.05) than in the H200 group. The NDS at 120 h in the H700 group was 18+/-8% and the autopsy revealed an almost normal external appearance of the vital organs. There were no significant differences between groups in either the Hct and platelet count during the 24h of resuscitation, and no bleeding complications were observed. CONCLUSION: The use of ECLHA to resuscitate animals in prolonged CA may require a large dose of systemic heparin during the pre-arrest period even if ECLHA circuit was coated with heparin.     

Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs

BACKGROUND AND METHODS: This study was designed to explore the effect of mild cerebral and systemic hypothermia (34 degrees C) on outcome after prolonged cardiac arrest in dogs. After ventricular fibrillation with no flow of 10 min, and standard external CPR with epinephrine (low flow) from ventricular fibrillation time of 10 to 15 min, defibrillation and restoration of spontaneous normotension were between ventricular fibrillation time of 16 and 20 min. This procedure was followed by controlled ventilation to 20 hr postarrest and intensive care to 72 hr postarrest. In control group 1 (n = 10), core temperature was 37.5 degrees C; in control group 2 (n = 10), cooling was started immediately after restoration of spontaneous normotension; and in group 3 (n = 10), cooling was initiated with start of CPR. Cooling was by clinically feasible methods. RESULTS: Best overall performance categories achieved (1 = normal; 5 = brain death) were better in group 2 (p = .012) and group 3 (p = .005) than in group 1. Best neurologic deficit scores were 36 +/- 14% in group 1, 22 +/- 15% in group 2 (p = .02), and 19 +/- 18% in group 3 (p = .01). Brain histopathologic damage scores were also lower (better) in groups 2 (p = .05) and 3 (p = .03). Myocardial damage was the same in all three groups. CONCLUSION: Mild cerebral hypothermia started during or immediately after external CPR improves neurologic recovery.     

Accidental hypothermia with cardiac arrest: Complete recovery after prolonged resuscitation and rewarming by extracorporeal circulation

A 51-year-old male remained immersed in sea water (6°C) for 40 min. Brought ashore, the ECG showed asystole. Advanced life support was immediately commenced. On arrival in hospital his rectal temperature was 27°C, but continued to fall to 24°C. The ECG remained isoelectric. Cardiopulmonary resuscitation was continued until extracorporeal circulation was established 190 min after rescue. Upon rewarming ventricular fibrillation occurred which was converted to sinus rhythm with a bolus of lignocaine followed by D.C. conversion at 31.5°C. When rewarming was complete after 60 min, signs of severe heart failure became evident. Sternotomy and pericardiotomy were performed to exclude cardiac tamponade. After 60 min of re-perfusion the patient was be weaned from bypass supported by a high-dose vasopressor infusion and nitroglycerine. He was discharged after 13 days with no evidence of any permanent organ damage. Given the advantage of providing circulatory support, extracorporeal circulation may be useful when rewarming hypothermic victims with cardiac arrest.     

Successful extracorporeal lung assist (ECLA) for a patient with severe asthma and cardiac arrest.

A 20-year-old male had a severe asthma attack complicated by a cardiac arrest despite maximal conventional therapy including mechanical ventilation. He was treated successfully with emergency veno-arterial Extra-corporeal Lung Assist started after 30 minutes of cardiopulmonary resuscitation. We believe that ECLA is a life-saving measure for intractable asthma and cardiac arrest.     

Full recovery of an avalanche victim with profound hypothermia and prolonged cardiac arrest treated by extracorporeal re-warming

Survival of hypothermic avalanche victims with cardiac arrest is rare. This report describes full recovery of a 29-year-old backcountry skier completely buried for 100 min at 3.0m (9.8 ft) depth. On extrication he was unconscious, but breathing spontaneously into an air pocket; core body temperature measured 22.0 degrees C (71.6 degrees F). He was intubated and ventilated on site. Ventricular fibrillation commenced during helicopter transportation, whereby chest compression was lacking for 15 min. At the nearest hospital continuous cardiopulmonary resuscitation was initiated, but defibrillation failed. Tympanic core body temperature measurement confirmed life-threatening hypothermia of 21.7 degrees C (71.1 degrees F) and serum K(+) was 4.3 mmol/l, necessitating transferral to a hospital with cardiopulmonary bypass facilities. Defibrillation finally succeeded following re-warming, by femoral veno-arterial bypass, to 34.5 degrees C (94.1 degrees F). Total duration of cardiac arrest was 150 min. The patient developed pulmonary oedema, treated by extracorporeal membrane oxygenation, but progressed well and was discharged from hospital on day 17, fit to resume professional and social activities. Follow-up cerebral magnetic resonance imaging 2 years after avalanche burial demonstrated only minimal changes attributable to unrelated, prior cranial trauma. Extensive neurological and psychological investigations gave excellent results. This report confirms previous literature that an air pocket with patent airways is essential for survival of a completely buried avalanche victim after 35 min and endorses the recommended management strategies of the International Commission for Mountain Emergency Medicine ICAR MEDCOM. In particular, all hypothermic victims extricated with an air pocket and free airways must be treated optimistically, even despite prolonged cardiac arrest. This remarkable case documents the fastest drop in core temperature ever recorded during snow burial, namely 9.0 degrees C (16.2 degrees F)/h, and the second-lowest reversible core temperature in avalanche literature.     

Outcome from severe accidental hypothermia with cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation

Purpose

This study aimed to identify factors of neurologic prognosis in severe accidental hypothermic patients with cardiac arrest.

Basic procedures

This retrospective observational study was performed in a tertiary care university hospital in Sapporo, Japan (January 1994 to December 2012). We investigated 26 patients with accidental hypothermic cardiac arrest resuscitated with extracorporeal cardiopulmonary resuscitation (ECPR). We evaluated the neurologic outcome in patients who were resuscitated with ECPR at discharge from hospital.

Main findings

In those 26 patients, their median age was 50.5 years; and 69.2% were male. The cause of hypothermia was exposure to cold air in 46.1%, submersion in 46.1%, and avalanche in 7.8%. Ten (38.5%) of these patients survived to favorable neurological outcome at discharge. Factors associated with favorable neurological outcome were a cardiac rhythm other than asystole (P = .009), nonasphyxial hypothermia (P = .006), higher pH (P = .01), and lower serum lactate (P = .01). In subgroup analyses, the patients with hypothermic cardiac arrest due to submersion or avalanche (asphyxia group) showed no factors associated with good neurological outcome, whereas the nonasphyxia group showed a significantly lower core temperature (P = .02) and a trend towards a lower serum lactate (P = .09).

Principal conclusions

Patients with hypothermic cardiac arrest due to nonasphyxial hypothermia have improved neurologic outcomes when treated with ECPR compared to patients with asphyxial hypothermic cardiac arrest. Further investigation is needed to develop a prediction rule for patients with nonasphyxial hypothermic cardiac arrest to determine which patients would benefit from treatment with ECPR.     

Sodium bicarbonate improves outcome in prolonged prehospital cardiac arrest

OBJECTIVE: This study evaluates the effect of early administration of an empirical (1 mEq/kg) sodium bicarbonate dose on survival from prehospital cardiac arrest within brief (<5 minutes), moderate (5-15 minutes), and prolonged (>15 minutes) down time. METHODS: Prospective randomized, double-blinded clinical intervention trial that enrolled 874 prehospital cardiopulmonary arrest patients managed by prehospital, suburban, and rural regional emergency medical services. Over a 4-year period, the randomized experimental group received an empirical dose of bicarbonate (1 mEq/kg) after standard advanced cardiac life support interventions. Outcome was measured as survival to emergency department, as this was a prehospital study. RESULTS: The overall survival rate was 13.9% (110/792) for prehospital arrest patients. There was no difference in the amount of sodium bicarbonate administered to nonsurvivors (0.859 +/- 0.284 mEq/kg) and survivors (0.8683 +/- 0.284 mEq/kg) (P = .199). Overall, there was no difference in survival in those who received bicarbonate (7.4% [58/420]), compared with those who received placebo (6.7% [52/372]) (P = .88; risk ratio, 1.0236; 0.142-0.1387). There was, however, a trend toward improved outcome with bicarbonate in prolonged (>15 minute) arrest with a 2-fold increase in survival (32.8% vs 15.4%; P = .007). CONCLUSION: The empirical early administration of sodium bicarbonate (1 mEq/kg) has no effect on the overall outcome in prehospital cardiac arrest. However, a trend toward improvement in prolonged (>15 minutes) arrest outcome was noted.     

Long-term neurological outcome after cardiac arrest and therapeutic hypothermia

Aim of the studyTo analyse the neurological status of survivors after cardiac arrest (CA) treated with hypothermia.MethodsWe prospectively included all patients with CA treated with hypothermia at intensive care units (ICU) in two university hospitals and one regional hospital. All adult survivors at 6 months after CA, n = 48, were invited for neurological follow-up and 43 accepted. History, clinical status, ability testing and questionnaires were administered to screen for difficulties, including Assessment of Motor and Process Skills, Neurobehavioral Cognitive Status Examination, Frontal Lobe Assessment Battery, EQ-VAS quality of life scale, Skåne Sleep Index, Hospital Anxiety and Depression Rating Scale, Self-reported Montgomery and Åstrand Depression Rating Scale, Global Deterioration Scale, Rivermead Behavioural Memory Test, and the Cerebral Performance Categories (CPC).ResultsNo patient was found to be in a chronic vegetative state and all patients were living at home, one with extensive help. Thirty-six patients were in CPC1 at follow-up, and some degree of neurological sequelae was found in 40 patients, but was mild in all but 3. Three patients had no subjective complaints, nor could any deficits be detected. Initial defects improved over-time. Short-term memory loss, executive frontal lobe dysfunction along with mild depression and sleep rhythm disturbances were the most common findings.ConclusionsMild cognitive impairment is common following hypothermia-treated cardiac arrest but has little effect on activities of daily living or quality of life.     

Advanced cardiac life support training improves long-term survival from in-hospital cardiac arrest

CONTEXT: Advanced cardiac life support (ACLS) training was introduced to bring order and a systematic approach to the treatment of cardiac arrest by professional responders. In spite of the wide dissemination of ACLS training, it has been difficult to demonstrate improved outcome following such training. OBJECTIVE: To determine the value of formal ACLS training in improving survival from in-hospital cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: A multi-center, prospective cohort study examined patient outcomes after resuscitation efforts by in-hospital rescue teams with and without ACLS-trained personnel. A total of 156 patients, experiencing 172 in-hospital cardiopulmonary arrest events over a 38-month period (January 1998 to March 2001) were studied. MAIN OUTCOME MEASURES: Primary endpoints included return of spontaneous circulation (ROSC), survival to hospital discharge, 30-day survival, and 1-year survival. RESULTS: The immediate success of resuscitation efforts for all patients was 39.7% (62/156). There was a significant increase in ROSC with ACLS-trained personnel (49/113; 43.4%) versus no ALCS-trained personnel (16/59; 27.1%; p=0.04). Likewise, patients treated by ACLS-trained personnel had increased survival to hospital discharge (26/82; 31.7% versus 7/34; 20.6%; p=0.23), significantly better 30-day survival (22/82; 26.8% versus 2/34; 5.9%; p<0.02), and significantly improved 1-year survival (18/82; 21.9% versus 0/34; 0%; p<0.002). CONCLUSION: The presence of at least one ACLS-trained team member at in-hospital resuscitation efforts increases both short and long-term survival following cardiac arrest.     

Hemodynamic directed CPR improves short-term survival from asphyxia-associated cardiac arrest

Aim

Adequate coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) is essential for establishing return of spontaneous circulation. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus an absolute depth-guided approach in a porcine model of asphyxia-associated cardiac arrest. We hypothesized that a hemodynamic directed approach would improve short-term survival compared to depth-guided care.

Methods

After 7 min of asphyxia, followed by induction of ventricular fibrillation, 19 female 3-month old swine (31 ± 0.4 kg) were randomized to receive one of three resuscitation strategies: (1) hemodynamic directed care (CPP-20): chest compressions (CCs) with depth titrated to a target systolic blood pressure of 100 mmHg and titration of vasopressors to maintain CPP > 20 mmHg; (2) depth 33 mm (D33): target CC depth of 33 mm with standard American Heart Association (AHA) epinephrine dosing; or (3) depth 51 mm (D51): target CC depth of 51 mm with standard AHA epinephrine dosing. All animals received manual CPR guided by audiovisual feedback for 10 min before first shock.

Results

45-Min survival was higher in the CPP-20 group (6/6) compared to D33 (1/7) or D51 (1/6) groups; p = 0.002. Coronary perfusion pressures were higher in the CPP-20 group compared to D33 (p = 0.011) and D51 (p = 0.04), and in survivors compared to non-survivors (p < 0.01). Total number of vasopressor doses administered and defibrillation attempts were not different.

Conclusions

Hemodynamic directed care targeting CPPs > 20 mmHg improves short-term survival in an intensive care unit porcine model of asphyxia-associated cardiac arrest.     

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.

Ibuprofen improves survival and neurologic outcome after resuscitation from cardiac arrest

Post-ischemic inflammatory changes in the central nervous system (CNS) following cardiac arrest and resuscitation are potentially responsible for ultimate survival and much of the neurologic damage, producing greater morbidity and mortality in successfully resuscitated patients. This study was undertaken to assess the non-steroidal anti-inflammatory agent, ibuprofen, in a controlled and monitored experimental model of canine cardiac arrest and resuscitation. With the investigator blinded as to the intervention, eight of 21 dogs were randomly assigned to receive ibuprofen as an i.v. bolus (10 mg/kg) and a 6-h i.v. infusion (5 mg/kg per h). The other 13 dogs received an equivalent volume of 0.9% NaCl to serve as controls. No statistically significant differences between the two groups were detected in any pre-arrest variables. All 21 dogs were successfully resuscitated. At 24 h, dogs receiving ibuprofen exhibited 100% survival, while control dogs exhibited only 54% survival (P = 0.03). The majority of deaths for the control group occurred within the first 6 h. Neurologic deficit scores were assigned at 1, 2, 6 and 24 h after resuscitation. A general trend occurred such that dogs treated with ibuprofen improved over time, while the control dogs remained severely impaired. A significant difference in neurologic deficit score was detected at 6 h (P = 0.01). At 24 h the ibuprofen group exhibited minimal neurologic deficit (5.9 +/- 3.2), and the control group exhibited significantly more severe neurologic impairment (52.2 +/- 13.0, P = 0.01). These results suggest that ibuprofen may be helpful in the pharmacologic management of cardiac arrest as a means of increasing survival and decreasing neurologic impairment.