Long-Term Postoperative Pain Prediction Using Higher-Order Singular Value Decomposition of Intraoperative Physiological Responses: Prospective Cohort Study

BACKGROUND: Long-term postoperative pain (POP) and patient responses to pain relief medications are not yet fully understood. Although recent studies have developed an index for the nociception level of patients under general anesthesia based on multiple physiological parameters, it remains unclear whether these parameters correlate with long-term POP outcomes. OBJECTIVE: This study aims to extract unbiased and interpretable descriptions of how the dynamics of physiological parameters change over time and across patients in response to surgical procedures and intraoperative medications using a multivariate-temporal analysis. We demonstrated that there is an association (correlation) between the main features of intraoperative physiological responses and long-term POP, which has a predictive value, even without claiming causality. METHODS: We proposed a complex higher-order singular value decomposition method to accurately decompose patients’ physiological responses into multivariate structures evolving over time. We used intraoperative vital signs of 175 patients from a mixed surgical cohort to extract three interconnected, low-dimensional, complex-valued descriptions of patients’ physiological responses: multivariate factors, reflecting subphysiological parameters; temporal factors, reflecting common intrasurgery temporal dynamics; and patients’ factors, describing interpatient changes in physiological responses. RESULTS: Adoption of the complex higher-order singular value decomposition method allowed us to clarify the dynamic correlation structure included in the intraoperative physiological responses. Instantaneous phases of the complex-valued physiological responses of 242 patients within the subspace of principal descriptors enabled us to discriminate between mild and not-mild (moderate-severe) levels of pain at postoperative days 30 and 90. Following rotation of physiological responses before projection to align with the common multivariate-temporal dynamic, the method achieved an area under curve for postoperative day 30 and 90 outcomes of 0.81 and 0.89 for thoracic surgery, 0.87 and 0.83 for orthopedic surgery, 0.87 and 0.88 for urological surgery, 0.86 and 1 for colorectal surgery, 1 and 1 for transplant surgery, and 0.83 and 0.92 for pancreatic surgery, respectively. CONCLUSIONS: By categorizing patients into different surgical groups, we identified significant surgery-related principal descriptors. Each of them potentially encodes different surgical stimulation. The dynamics of patients’ physiological responses to these surgical events were linked to long-term POP development.