Effectiveness of combinations of active compression-decompression cardiopulmonary resuscitation, impedance threshold devices and head-up cardiopulmonary resuscitation in adult out-of-hospital cardiac arrest: A systematic review.

Objective: This review summarises the current evidence base for combinations of neuroprotective CPR adjuncts (active compression-decompression chest compressions, impedance threshold devices, and head-up positioning) during out-of-hospital cardiac arrest. Methods: A systematic search (PROSPERO registration CRD42023432302) was performed in English on MEDLINE, EMBASE, and the Cochrane Library in August 2023, and repeated in February 2024. All randomised and observational studies (not abstracts) reporting on any combination of the aforementioned CPR adjuncts were included. Papers were screened independently by two researchers, with a third reviewer acting as tiebreaker. Out-of-hospital, non-traumatic, cardiac arrests in patients >18 years were eligible for inclusion. Risk of bias was assessed using the Risk of Bias 2 tool and the Newcastle-Ottawa scale. Results: Eight of 1172 unique articles identified in the initial searches were included, with five randomised controlled trials and three observational studies. No randomised trial investigated a bundle of all three interventions. All randomised controlled trials were at intermediate or high risk of bias. Neurologically favourable survival was greater in patients treated with an impedance threshold device and active compression-decompression CPR when compared to standard CPR (8.9% vs 5.8%, p = 0.019) in the largest existing randomised trial. Conflicting results were found in observational studies comparing the complete neuroprotective bundle to standard CPR. Conclusions: This review was limited by small study numbers and overlapping samples, which precluded a meta-analysis. Limited data suggests that combinations of adjuncts to improve cerebral perfusion during CPR may improve survival with favourable neurological outcome. A randomised controlled trial is required to establish whether combining all three together results in improved outcomes.

Thromboelastometry and Platelet Function during Acclimatization to High Altitude.

Interaction between hypoxia and coagulation is important given the increased risk of thrombotic diseases in chronically hypoxic patients who reside at sea level and in residents at high altitude. Hypoxia alters the proteome of platelets favouring a prothrombotic phenotype, but studies of activation and consumption of specific coagulation factors in hypoxic humans have yielded conflicting results. We tested blood from 63 healthy lowland volunteers acclimatizing to high altitude (5,200 m) using thromboelastometry and assays of platelet function to examine the effects of hypoxia on haemostasis. Using data from two separate cohorts of patients following identical ascent profiles, we detected a significant delay in clot formation, but increased clot strength by day 7 at 5,200 m. The latter finding may be accounted for by the significant rise in platelet count and fibrinogen concentration that occurred during acclimatization. Platelet function assays revealed evidence of platelet hyper-reactivity, with shortened PFA-100 closure times and increased platelet aggregation in response to adenosine diphosphate. Post-expedition results were consistent with the normalization of coagulation following descent to sea level. These robust findings indicate that hypoxia increases platelet reactivity and, with the exception of the paradoxical delay in thromboelastometry clotting time, suggest a prothrombotic phenotype at altitude. Further work to elucidate the mechanism of platelet activation in hypoxia will be important and could impact upon the management of patients with acute or chronic hypoxic respiratory diseases who are at risk of thrombotic events.