Background and objectiveQuantitative measures extracted from ventricular fibrillation (VF) waveform reflect the metabolic state of the myocardium and are associated with survival outcome. The quality of delivered chest compressions during cardiopulmonary resuscitation are also linked with survival. The aim of this research is to explore the viability and effectiveness of a thoracic impedance (TI) based chest compression (CC) guidance system to control CC depth within individual subjects and influence VF waveform properties. MethodsThis porcine investigation includes an analysis of two protocols. CC were delivered in 2 min episodes at a constant rate of 110 CC min−1. Subject-specific CC depth was controlled using a TI-thresholding system where CC were performed according to the amplitude (ZRMS, 0.125 to 1.250 Ω) of a band-passed TI signal (ZCC). Protocol A was a retrospective analysis of a 12-porcine study to characterise the response of two VF waveform metrics: amplitude spectrum area (AMSA) and mean slope (MS), to varying CC quality. Protocol B was a prospective 12-porcine study to determine if changes in VF waveform metrics, due to CC quality, were associated with defibrillation outcome. ResultsProtocol A: A directly proportional relationship was observed between ZRMS and CC depth applied within each subject (r = 0.90; p <0.001). A positive relationship was observed between ZRMS and both AMSA (p <0.001) and MS (p <0.001), where greater TI thresholds were associated with greater waveform metrics. Protocol B: MS was associated with return of circulation following defibrillation (odds ratio = 2.657; p = 0.043). ConclusionTI-thresholding was an effective way to control CC depth within-subjects. Compressions applied according to higher TI thresholds evoked an increase in AMSA and MS. The response in MS due to deeper CC resulted in a greater incidence of ROSC compared to shallow chest compressions.