Purpose: As the global population ages, Post-Intensive Care Syndrome (PICS) has emerged as a critical public health concern. However, in sepsis survivors aged 90 years or older, the etiology of cognitive and mental decline remains obscured by the natural aging process. A pivotal unresolved debate in critical care is distinguishing whether this neuro-psychiatric decline is driven by “mechanical ventilation” (associated with sedation and immobilization) or “general anesthesia” (representing surgical stress and systemic inflammation). This study aimed to evaluate the association of the National Database (NDB) codes for general anesthesia and mechanical ventilation with the new-onset neuro-psychiatric medication use in sepsis survivors aged ≥ 90 years. Patients and Methods: In this retrospective cohort study using the National Database of Japan, we identified a previously independent cohort of sepsis survivors aged ≥ 90 years without prior psychotropic use or home care. The primary outcome was new CNS-active medication initiation within 6 months. We performed multivariate logistic regression, utilizing Variance Inflation Factor (VIF) analysis to mathematically rule out multicollinearity between anesthesia and ventilation. Results: Among 269 strictly selected independent survivors, 83 (30.9%) initiated new CNS-active medications. VIF analysis confirmed the complete statistical independence of the two factors (VIF < 1.02). General anesthesia independently predicted the outcome (Odds Ratio OR 1.85; 95% CI 1.05– 3.25; P = 0.032), whereas mechanical ventilation did not (OR 0.82; P = 0.502). Phenotypic analysis revealed general anesthesia shifted risks toward sleep-wake (50.0%) and sensory dysregulation (43.8%) rather than frank dementia (27.3%). Furthermore, general anesthesia was associated with a significant concurrent loss of physical and mental autonomy (P = 0.036). Conclusion: Supported by VIF analysis, the general anesthesia code was independently associated with systemic neuro-vulnerability in nonagenarians. Surgical stress is specifically associated with a phenotypic shift toward sleep and sensory dysregulation and concurrent loss of autonomy, necessitating a paradigm shift in surgical decision-making. Plain Language Summary: Sepsis is a severe, life-threatening condition. In very old patients (aged 90 or older), surviving sepsis often comes with a decline in mental health or cognitive function. It has been unclear whether this decline is caused by the surgical stress of “general anesthesia” or the “mechanical ventilation” used during intensive care. In this study, we looked at a nationwide database in Japan to examine 269 sepsis survivors aged 90 or older who were completely independent before their illness. We found that receiving general anesthesia significantly increased the risk of needing new psychiatric medications—specifically for sleep and sensory issues like pain—after recovery. Mechanical ventilation did not show this effect. Our findings suggest that surgery itself is a significant physiological stressor associated with a devastating loss of autonomy in extremely old patients, highlighting the need for careful decision-making before surgery. Keywords: post-intensive care syndrome, PICS, nonagenarians, sepsis, general anesthesia, sleep disorders
Shimoyama et al. (Fri,) studied this question.