Phosphodiesterase 3 inhibitors do not influence lactate kinetics and clinical outcomes in patients with septic shock: A multicentre cohort study

Abstract

Purpose: We investigated the association between the administration of phosphodiesterase 3 inhibitors (PDE3i) and lactate kinetics, resolution of organ failure, ICU and hospital length of stay (LOS) and hospital mortality in a retrospective cohort of patients with septic shock and persistently elevated lactate concentrations.

Material and methods: Patients with septic shock and two arterial lactate concentrations ≥4 mmol/L with at least 4 h between measurements were eligible. Clinical data of the first four days of admission were collected in an online database. For each patient, the area between the actual lactate concentrations and 2.2 mmol/L (AUC_lact2.2), was calculated for three days.

Results: Data on 229 patients from 10 hospitals were collected, of whom 123 received PDE3i (54%). First, a linear multivariate model was developed to predict AUC_lact2.2 (R² = 0.57). Adding PDE3i as a cofactor did not affect R². Second, 60 patients receiving PDE3i at any time between days 0 and 2 were compared to 60 propensity matched no-PDE3i patients. Third, 30 patients who received PDE3i from ICU admission to day 3 were compared to 30 propensity-matched no-PDE3i patients. These analyses showed no differences in AUC_lact2.2, SOFA scores, ICU or hospital LOS or hospital mortality between treatment groups.

Conclusions: No association was found between the administration of PDE3i and lactate kinetics, resolution of organ failure, ICU or hospital LOS or hospital mortality.

Keywords: Lactate; Organ failure; Phosphodiesterase 3 inhibitors; Sepsis; Septic shock; Treatment.