Alterations in Respiratory Heart Rate Variability in Brain-Injured Neuro-ICU Patients Compared With Healthy Humans

BackgroundRespiratory heart rate variability (RespHRV), the physiological variation in heart rate in phase with breathing, is mainly generated by central brainstem mechanisms. Its characteristics and determinants in brain-injured patients in the neuro-intensive care unit (neuro-ICU) are poorly understood. ObjectiveTo characterize RespHRV amplitude and phase in brain-injured patients compared to healthy participants, and to explore clinical variables influencing RespHRV in the neuro-ICU. MethodsWe analyzed 55 brain-injured patients (traumatic brain injury, aneurysmal subarachnoid hemorrhage, or other causes) and 31 healthy controls. ECG and respiratory signals were recorded and processed to extract cycle-by-cycle RespHRV amplitude and phase. Group differences were assessed using Mann-Whitney and Watson-Williams tests. In an additional analysis, 55 patients RespHRV amplitude and phase were modeled using generalized linear mixed-effects models to evaluate the impact of sedation, mechanical ventilation mode, vasoactive and analgesic drugs, and time, including random intercepts and slopes for subjects. ResultsCompared to controls, brain-injured patients exhibited a significantly lower RespHRV amplitude (1.04 [0.45, 1.96] vs. 6.21 [4.08, 9.34] bpm; p < 0.001) and an inverted RespHRV phase, with peak heart rate occurring during expiration rather than inspiration. Mixed-effects modeling revealed that machine-triggered ventilation and high level of sedation induced a significant reduction in RespHRV amplitude. ConclusionsBrain-injured patients demonstrate markedly impaired central generation of RespHRV, with peripheral contributors likely accounting for the remaining variability. Ventilation mode and pharmacological interventions strongly alter RespHRV. Restoration of normal RespHRV patterns may serve as a physiological marker of autonomic and brainstem recovery, warranting further investigation in longitudinal studies.