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(1) Background: Cardiopulmonary resuscitation (CPR), as a form of basic life support, is critical for maintaining cardiac and cerebral perfusion during cardiac arrest, a medical condition with high expected mortality. Current guidelines emphasize the importance of rapid recognition and prompt initiation of high-quality CPR, including appropriate cardiac compression depth and rate. As space agencies plan missions to the Moon or even to explore Mars, the duration of missions will increase and with it the chance of life-threatening conditions requiring CPR. The objective of this review was to examine the effectiveness and feasibility of chest compressions as part of CPR following current terrestrial guidelines under hypogravity conditions such as those encountered on planetary or lunar surfaces; (2) Methods: A systematic literature search was conducted by two independent reviewers (PubMed, Cochrane Register of Controlled Trials, ResearchGate, National Aeronautics and Space Administration (NASA)). Only controlled trials conducting CPR following guidelines from 2010 and after with advised compression depths of 50 mm and above were included; (3) Results: Four different publications were identified. All studies examined CPR feasibility in 0.38 G simulating the gravitational force on Mars. Two studies also simulated hypogravity on the Moon with a force of 0.17 G/0,16 G. All CPR protocols consisted of chest compressions only without ventilation. A compression rate above 100/s could be maintained in all studies and hypogravity conditions. Two studies showed a significant reduction of compression depth in 0.38 G (−7.2 mm/−8.71 mm) and 0.17 G (−12.6 mm/−9.85 mm), respectively, with nearly similar heart rates, compared to 1 G conditions. In the other two studies, participants with higher body weight could maintain a nearly adequate mean depth while effort measured by heart rate (+23/+13.85 bpm) and VO2max (+5.4 mL·kg−1·min−1) increased significantly; (4) Conclusions: Adequate CPR quality in hypogravity can only be achieved under increased physical stress to compensate for functional weight loss. Without this extra effort, the depth of compression quickly falls below the guideline level, especially for light-weight rescuers. This means faster fatigue during resuscitation and the need for more frequent changes of the resuscitator than advised in terrestrial guidelines. Alternative techniques in the straddling position should be further investigated in hypogravity.

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