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We had previously experienced a case involving prolonged cardiopulmonary resuscitation (CPR) on Mt. Fuji (3776 m), demanding strenuous work by the rescuers. The objective of this study was to compare the effect of compression-only and conventional CPR on oxygen saturation of rescuers in a hypoxemic environment.Changes in percutaneous arterial oxygen saturation (SpO2) and heart rate during CPR action were measured in a hypobaric chamber with barometric pressure adjusted to be equivalent to 3700 m above sea level (630–640 hPa). Thirty-three volunteers performed CPR with or without breaths using a CPR mannequin.In a 3700-m-equivalent environment, SpO2 was reduced only when CPR was performed without breaths (P < .05, one-way analysis of variance (ANOVA) post hoc Tukey test). Heart rate increased during CPR regardless of the presence or absence of breaths. Mean scores on the Borg scale, a subjective measure of fatigue, after CPR action in the 3700-m-equivalent environment were significantly higher (15 ± 2) than scores after CPR performed at sea level (11 ± 2, P < .01, paired t-test). No lethal dysrhythmia was found in subjects with a wearable electrode shirt.Prolonged CPR at high altitude exerts a significant physical effect upon the condition of rescuers. Compression-only CPR at high altitude may deteriorate rescuer oxygenation, whereas CPR with breaths might ameliorate such deterioration.