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Title: Temperature post out-of-hospital cardiac arrest : the TOPCAT study
Author: Lyon, Richard Mark
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
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Introduction: Out-of-hospital cardiac arrest (OHCA) is a significant cause of death and severe neurological disability in Scotland. Optimal pre-hospital resuscitation is required for the patient to achieve return of spontaneous circulation (ROSC). The only post-ROSC therapy shown to increase survival is mild therapeutic hypothermia (MTH), but its mechanism of action and optimal application are still unknown. The quality of pre-hospital resuscitation in Scotland is unmeasured. The relationship between body temperature post-OHCA, systemic inflammation, markers of brain injury and outcome are still poorly defined. This study examines two aspects of OHCA; firstly, the clinical practice of resuscitation in the prehospital and Emergency Department (ED) setting and, secondly, the post-ROSC physiological changes of body temperature, systemic inflammation and serum markers of brain injury. Methods: Prospective observational study of all OHCA patients admitted to a single centre for a 14- month period (1/08/2008 to 1/02/2010). Oesophageal temperature was measured, blood samples assayed for markers of systemic inflammation (TNF-a, IL-ip, 1L-6, IL-8, IL-10, 1L- 12, elastase, cell surface markers of neutrophil activation) and markers of brain injury (neuron-specific enolase [NSE], SI00b, glial fibrillary acidic protein [GFAP]) in the ED and Intensive Care Unit (ICU). Selected patients had pre-hospital temperature monitoring and blood sampling. Routine physiological variables were recorded. Patients who survived to ICU had repeat blood samples taken at 24-,48-,72- and 120-hours post-ROSC. Patients were followed up for 6-months. We conducted qualitative analysis of the effect of having a doctor on-scene at an OHCA and performed a Scottish national survey on the ED management of post-OHCA patients. Results: 236 OHCA patients were included in the study. 161 (68%) were pronounced dead at the scene or in the ED. 75 (32%) were admitted to ICU for cooling; 49 (21%) died in ICU and 27 (11%) survived to hospital discharge. We have characterised the natural progression of core body temperature post-OHCA. Patients who achieved ROSC and had oesophageal temperature measured pre-hospital all had temperatures below normal. Quality of prehospital resuscitation performed by ambulance crews was observed to be highly variable. Standard ED care of post-OHCA patients varied across Scotland. All patients arriving in the ED post-OHCA had a relatively low temperature (34.3°C, 95% CI 34.1-34.5). Patients surviving to hospital discharge were warmer on admission to ICU than patients who died in hospital (35.6°C vs. 34.4°C, p < 0.01). Patients surviving to hospital discharge also took longer to reach target therapeutic hypothermia level than non-survivors (222 vs. 313 min, p < 0.05). Cell surface markers of neutrophil activation, IL-6, IL-8, IL-10 and elastase were all significantly raised in the early post-ROSC period. The degree of cytokinaemia at 24- hours was related to survival outcome. In the context of MTH, SI00b at 24-hours was superior to NSE and GFAP at predicting in-hospital death following OHCA, with an AUCROC of 0.90 (95% CI 0.82-0.98). Conclusions: The quality of pre-hospital and in-hospital resuscitation in Scotland is variable. Both prehospital and ED management of OHCA patients varied on a local and national scale. Following OHCA all patients have oesophageal temperatures below normal in the prehospital phase and on arrival in the ED. 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. A systemic inflammatory response occurs earlier in the post-ROSC phase than previously anticipated. SI00b is a more reliable predictor of outcome following OHCA than NSE or GFAP. The mechanisms of action underlying changes in oesophageal temperature and survival from OHCA remain unclear. This study adds to the information around oesophageal temperature post-OHCA and MTH further studies are warranted to clarify the mechanism of action of MTH post-OHCA and the role of inflammatory response in determining survival.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available