Association of severe mental illness and septic shock case fatality rate in patients admitted to the intensive care unit: A national population-based cohort study

BackgroundPatients with severe mental illness (SMI) (i.e., schizophrenia, bipolar disorder, or major depressive disorder) have been reported to have excess mortality rates from infection compared to patients without SMI, but whether SMI is associated with higher or lower case fatality rates (CFRs) among infected patients remains unclear. The primary objective was to compare the 90-day CFR in septic shock patients with and without SMI admitted to the intensive care unit (ICU), after adjusting for social disadvantage and physical health comorbidity. Methods and findingsWe conducted a nationwide, population-based cohort study of all adult patients with septic shock admitted to the ICU in France between January 1, 2014, and December 31, 2018, using the French national hospital database. We matched (within hospitals) in a ratio of 1:up to 4 patients with and without SMI (matched-controls) for age (5 years range), sex, degree of social deprivation, and year of hospitalization. Cox regression models were conducted with adjustment for smoking, alcohol and other substance addiction, overweight or obesity, Charlson comorbidity index, presence of trauma, surgical intervention, Simplified Acute Physiology Score II score, organ failures, source of hospital admission (home, transfer from other hospital ward), and the length of time between hospital admission and ICU admission. The primary outcome was 90-day CFR. Secondary outcomes were 30- and 365-day CFRs, and clinical profiles of patients.A total of 187,587 adult patients with septic shock admitted to the ICU were identified, including 3,812 with schizophrenia, 2,258 with bipolar disorder, and 5,246 with major depressive disorder. Compared to matched controls, the 90-day CFR was significantly lower in patients with schizophrenia (1,052/3,269 = 32.2% versus 5,000/10,894 = 45.5%; adjusted hazard ratio (aHR) = 0.70, 95% confidence interval (CI) 0.65,0.75, p < 0.001), bipolar disorder (632/1,923 = 32.9% versus 2,854/6,303 = 45.3%; aHR = 0.70, 95% CI = 0.63,0.76, p < 0.001), and major depressive disorder (1,834/4,432 = 41.4% versus 6,798/14,452 = 47.1%; aHR = 0.85, 95% CI = 0.81,0.90, p < 0.001). Study limitations include inability to capture deaths occurring outside hospital, lack of data on processes of care, and problems associated with missing data and miscoding in medico-administrative databases. ConclusionsOur findings suggest that, after adjusting for social disadvantage and physical health comorbidity, there are improved septic shock outcome in patients with SMI compared to patients without. This finding may be the result of different immunological profiles and exposures to psychotropic medications, which should be further explored Author summary Why was this study done? Patients with severe mental illness (SMI) have been reported to have excess mortality from sepsis (number of deaths due to sepsis in the whole population).Whether SMI is associated with higher or lower sepsis-associated case fatality remains unclear (number of deaths due to sepsis in the population with sepsis).No study has determined whether SMI is associated with excess case fatality in patients with septic shock, the most severe form of sepsis when accounting for the most relevant confounding variables. What did the researchers do and find? In this nationwide, population-based cohort study, we compared 30-, 90-, and 365-day case fatality rates (CFRs) in septic shock patients with and without SMI admitted to the intensive care unit (ICU).We identified 187,587 adult patients with septic shock admitted to the ICU, including 3,812 with schizophrenia, 2,258 with bipolar disorder, and 5,246 with major depressive disorder.The 30-, 90-, and 365-day CFRs were lower in patients with SMI than in patients without SMI after controlling for multiple potential confounding factors (using intrahospital matching and adjustments for multiple comorbidities and illness severity) and addressing potential biases not considered in previous studies. What do these findings mean? Our findings suggest improved septic shock outcomes in patients with SMI compared to patients without.Our findings also suggest that the excess mortality from sepsis is due to an increased risk of sepsis/infection among patients with SMI, but not due to increase case fatality among septic patients.This finding may be the result of different immunological profiles and exposures to psychotropic medications, a hypothesis that needs to be confirmed in future studies.