New antipsychotic prescription and recurrent infections among adult sepsis survivors: a population-based cohort study

Purpose — Antipsychotic agents, which may increase the risk of infection through dopaminergic dysregulation, are prescribed to a fraction of patients following critical illness. We compared the rate of recurrent sepsis among patients who filled a prescription for antipsychotics with high- or low-D₂ affinity.

Methods — Population-based cohort with active comparator design. We included sepsis survivors older than 65 years with intensive care unit admission and new prescription of antipsychotics in Ontario 2008–2019. The primary outcome were recurrent sepsis episodes within 1 year of follow-up. Patients who filled a prescription within 30 days of hospital discharge for high-D₂ affinity antipsychotics (e.g., haloperidol) were compared with patients who filled a prescription within 30 days of hospital discharge for low-D₂ affinity antipsychotics (e.g., quetiapine). Multivariable zero-inflated Poisson regression models with robust standard errors adjusting for confounding at baseline were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI).

Results — Overall, 1879 patients filled a prescription for a high-D₂, and 1446 patients filled a prescription for a low-D₂ affinity antipsychotic. Patients who filled a prescription for a high-D₂ affinity antipsychotic did not present a higher rate of recurrent sepsis during 1 year of follow-up, compared with patients who filled a prescription for a low-D₂ affinity antipsychotic (IRR: 1.12; 95% CI: 0.94, 1.35).

Conclusions — We did not find conclusive evidence of a higher rate of recurrent sepsis associated with the prescription of high-D₂ affinity antipsychotics (compared with low-D2 affinity antipsychotics) by 1 year of follow-up in adult sepsis survivors with intensive care unit admission.