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Background and Purpose— Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. Methods— Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion–diffusion mismatch not progressing to infarction after 1 month. Results— Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent ( P =0.006), and National Institutes of Health Stroke Scale score on admission was lower ( P =0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction ( P =0.0003). Conclusions— Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00975962.

SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Pre-hospital electrocardiographic (ECG) diagnosis and direct referral for primary PCI enables STEMI patients living far from a PCI centre to achieve a system delay comparable with patients living in close vicinity of a PCI centre.

IntroductionWe report data from the first Utstein-style study of physician-provided pre-hospital advanced airway management.Materials and methodsAnaesthesiologists from eight pre-hospital critical care teams in the Central Denmark Region (a mixed rural and urban region with 1.27 million inhabitants) prospectively registered data according to the template for reporting data from pre-hospital advanced airway management. Data collection took place from February 1st 2011 to October 31st 2012. Included were patients of all ages on whom pre-hospital advanced airway management was performed. The objective was to estimate the incidences of failed and difficult pre-hospital endotracheal intubation, and complications related to pre-hospital advanced airway management.ResultsThe overall incidence of successful pre-hospital endotracheal intubation among 636 intubation attempts was 99.7%, even though 22.4% of pre-hospital endotracheal intubations required more than one intubation attempt. The overall incidence of complications related to pre-hospital advanced airway management was 7.9%. Following rapid sequence intubation, the incidence of first pass success was 85.8%, the overall incidence of complications was 22.0%, the incidence of hypotension 7.3% and that of hypoxia 5.3%. Multiple endotracheal intubation attempts were associated with an increased overall incidence of complications. No airway management related deaths occurred.DiscussionThe overall incidence of successful pre-hospital endotracheal intubations compares to those found in other physician-staffed pre-hospital systems. The incidence of pre-hospital endotracheal intubations requiring more than one attempt is higher than suspected. The incidence of hypotension or hypoxia after pre-hospital rapid sequence intubation compares to those found in UK emergency departments.ConclusionPre-hospital advanced airway management including pre-hospital endotracheal intubation performed by experienced anaesthesiologists is associated with high success rates and relatively low incidences of complications. An increased first pass success rate following pre-hospital endotracheal intubation may further reduce the incidence of complications and enhance patient safety in our system.