Use of heart rate variability in prediction of clinical deterioration in critically ill hospitalised adults: a systematic review protocol.

INTRODUCTION: Heart rate variability (HRV) is a measurement derived from the beat-to-beat variation in heart rate and reflects the complex interaction of physiological systems, including autonomic, endocrine, immune and cardiorespiratory. Reduced HRV has been shown to be associated with adverse outcomes in several disease states. In critical illness, commonly used prognostic tools such as the Acute Physiology and Chronic Health Evaluation II score rely on intermittently collected or rapidly obsolete data and may fail to detect acute deterioration. Continuous, non-invasive HRV monitoring may be able to predict physiological deterioration effectively in critically ill adults. However, its clinical utility remains uncertain due to methodological heterogeneity and a multitude of confounding factors. This systematic review aims to evaluate the prognostic value of HRV and HRV-derived measures for mortality and other clinically significant outcomes in critically ill adults. Furthermore, it will appraise the methods used to measure HRV in this population. METHODS AND ANALYSIS: This systematic review protocol is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomised and non-randomised studies involving hospitalised, non-pregnant adults who are critically ill (as defined by author) will be included. Studies must use HRV or HRV-derived measures to predict mortality or other predefined clinically significant outcomes to be included. Searches will be conducted in Embase, MEDLINE, Scopus, Web of Science, American Psychological Association (APA) PsycINFO and the Cochrane Central Register of Controlled Trials, with no date restrictions. Two reviewers will independently perform screening, data extraction and risk of bias assessment-with a third reviewer to resolve conflicts. The primary outcome is all-cause mortality. Secondary outcomes include Intensive Care Unit (ICU) and hospital length of stay, mechanical ventilation and renal replacement therapy requirement and arrhythmia burden. Results will be synthesised narratively, with random-effects meta-analysis undertaken if the data permit. Prognostic effect measures (eg, ORs, HRs and risk ratios) will be extracted according to reported mortality time point, with adjusted estimates prioritised over unadjusted estimates where both are available. Methodological quality and adherence to international HRV measurement standards will be assessed. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool and the Newcastle-Ottawa Scale for randomised and non-randomised studies, respectively. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval is not required, as this review will use only published data. This review will appraise the current literature on HRV as a prognostic marker in the critically ill and audit the data collection methods employed against international standards to give insight into its clinical utility and inform future research. Findings will be disseminated through a peer-reviewed journal publication as well as presentation in the relevant settings. REGISTRATION: PROSPERO CRD420251175808.