Alexandra Schratter

Emergency preservation and resuscitation improve survival after 15 minutes of normovolemic cardiac arrest in pigs

Objective: Outcome after prolonged normovolemic cardiac arrest is poor, and new resuscitation strategies have to be found. We hypothesized that the induction of deep hypothermia for emergency preservation and resuscitation (EPR) during prolonged cardiac arrest, before the start of reperfusion, will mitigate the deleterious cascades leading to neuronal death and will thus improve outcome. Design: Prospective experimental study. Setting: University research laboratory. Subjects: Thirteen pigs, Large White breed (27–37 kg). Interventions: After 15 mins of ventricular fibrillation, pigs were subjected to 1) EPR (n = 6), 20 mins of hypothermic stasis induced with a cold saline aortic flush; or 2) 20 mins of conventional resuscitation (n = 7). Then cardiopulmonary bypass was initiated in both groups, followed by defibrillation. Controlled ventilation and mild hypothermia were continued for 20 hrs; survival was for 9 days. For neurologic evaluation, neurologic deficit score (100% = brain dead, 0–10% = normal), overall performance category (1 = normal, 5 = dead or brain dead), and brain histologic damage score were used. Measurements and Main Results: In the EPR group, brain temperature decreased from 38.5°C ± 0.2°C to 16.7°C ± 2.5°C within 235 ± 27 secs. Five animals achieved restoration of spontaneous circulation and survived to 9 days: two pigs with overall performance category 2 and three pigs with overall performance category 3. Their neurologic deficit score was 45% (interquartile range 35, 50) and histologic damage score was 142 (interquartile range 109, 159). In the control group, four pigs achieved restoration of spontaneous circulation: one survived to 9 days with overall performance category 3, neurologic deficit score 45%, and histologic damage score 226 (restoration of spontaneous circulation, p = .6; survival, p = .03; overall performance category, p = .02). Conclusions: EPR is feasible in an experimental pig model and improves survival after prolonged cardiac arrest in pigs. Further experimental studies are needed before this concept can be brought into clinical practice.

Cold aortic flush and chest compressions enable good neurologic outcome after 15 mins of ventricular fibrillation in cardiac arrest in pigs.

Objective:The induction of deep cerebral hypothermia via ice-cold saline aortic flush during prolonged ventricular fibrillation cardiac arrest, followed by hypothermic stasis and delayed resuscitation (emergency preservation and resuscitation), improved neurologic outcome after cardiac arrest in pigs, as compared to conventional resuscitation. We hypothesized that emergency preservation and resuscitation with chest compressions would further improve outcome in the same model. Design:Prospective experimental study. Setting:University research laboratory. Subjects:Twenty-four female, large, white breed pigs (27–37 kg). Interventions:Fifteen minutes of ventricular fibrillation cardiac arrest were followed by 20 mins of resuscitation with chest compressions (control, n = 8), deep cerebral hypothermia via 200 mL/kg 4°C saline aortic flush and hypothermic stasis (emergency preservation and resuscitation, n = 8), and emergency preservation and resuscitation combined with chest compressions (emergency preservation and resuscitation plus chest compressions, n = 8). At 35 mins after cardiac arrest, cardiopulmonary bypass was initiated, followed by defibrillation. Mild hypothermia was continued for 20 hrs. Pigs were evaluated after 9 days using a neurologic deficit (neurologic deficit score: 100% = brain dead; 0%–10% = normal) and an overall performance category score (overall performance category score: 1 = normal; 2 = slightly handicapped; 3 = severely handicapped; 4 = comatose; 5 = dead/brain dead). Measurements and Main Results:Brain temperature decreased from 38.5°C to 15.3°C ± 3.3°C in the emergency preservation and resuscitation group, and to 11.3°C ± 1.2°C in the emergency preservation and resuscitation plus chest compressions group. In the control group, restoration of spontaneous circulation was achieved in four out of eight pigs, and one survived to 9 days. In the emergency preservation and resuscitation group, restoration of spontaneous circulation was achieved in seven out of eight pigs and five survived; in the emergency preservation and resuscitation plus chest compressions group, all had restoration of spontaneous circulation and seven survived (restoration of spontaneous circulation, p = .08). Neurologic outcome for (median and interquartile range) the control group included overall performance category score of 3, neurologic deficit score of 45%; for the emergency preservation and resuscitation group, overall performance category score was 3 (2–5) and neurologic deficit score was 45% (36; 50) and in the emergency preservation and resuscitation plus chest compressions group, overall performance category score was 2 (1–3) and neurologic deficit score was 13% (5; 21) (overall performance category score, p = .04; neurologic deficit score emergency preservation and resuscitation vs. emergency preservation and resuscitation plus chest compressions, p = .003). Conclusions:Emergency preservation and resuscitation by deep cerebral hypothermia combined with chest compressions during prolonged cardiac arrest in pigs are feasible and improve neurologic outcome.

Distribution of neuropathological lesions in pig brains after different durations of cardiac arrest

AIM OF THE STUDY To evaluate all brain regions reported to be selectively vulnerable to global ischaemia in a pig cardiac arrest model with different durations of no-flow by establishing a semi-quantitative brain histopathologic scoring system and to compare histological damage with neurological deficits. METHODS In a prospective randomised laboratory investigation, 35 female Large White pigs weighing 35-45 kg underwent ventricular fibrillation cardiac arrest for 0, 7, 10 or 13 min. In the brains of all animals that survived until the final endpoint (72 h post-arrest), 22 distinct regions were evaluated on paraffin-embedded sections in terms of type and extent of lesions. The results of the histological examination were compared to the results of a neurological outcome evaluation after 72 h. RESULTS Significant differences were found in all cortex regions, the caudate nucleus and putamen, the hippocampal formation, the cerebellar cortex, and the thalamus between the ischaemic groups (7- and 10-min groups) and the control group (0-min group). No 13-min group animal survived. The main findings were neuronal necrosis and oedema. In animals from the 10-min group, many neurons were reabsorbed in the cerebral cortex, caudate nucleus and cerebellar granule cell layer. There was a highly significant correlation between histological damage and neurological deficits. CONCLUSIONS The pattern of neuronal lesions in this pig model bear good resemblance to the pattern known in humans and other animal models. The amount of histological lesions in selectively vulnerable brain regions correlates to neurological outcome.

Surface vs. aortic flush cooling during cardiac arrest in pigs

Background: To investigate the feasibility and efficacy of earlier induction of hypothermia already during the ‘no‐flow’ period of cardiac arrest with non‐invasive surface cooling or invasive aortic flush cooling.