The association between opioid dose and kidney function and clinical outcome in critically ill patients, a retrospective cohort study

Background: Critically ill patients are prone to develop acute kidney injury. Apart from the nervous system, opioid receptor expression is highest in the kidneys, although their function in the kidney is unclear. In view of the frequent use of opioids, high expression of its receptors in the kidney and high incidence of AKI in critically ill patients, these may be interconnected. Aim: To determine the association between opioid dose and kidney function and outcome in critically ill patients. Methods: In this retrospective cohort study adult patients admitted to ICU (2013-2020), were eligible. The association between opioid administration and kidney function and mortality were determined using total cumulative dose and quartiles. Demographics, disease severity, and sedatives dose were covariates. Results: 2824 patients (median [IQR] age 64 [53-71] years, ICU-LOS of 8 [4-15] days, 64 % male) were included. Cumulative opioid dose (day 1-3 of ICU-admission), corrected for covariates, was not associated with change in plasma creatinine concentrations: (unstandardized-B for every mg/hour opioids given these days (Confidence Interval): -0.15 (- 0.36-0.06) mu mol/L, p = 0.15), or urine output: -0.42 (- 1.41-0.56) mL for (p = 0.40). Mortality increased from 3.5 % in Quartile 1 of cumulative opioid dose to 10.3 % in Q4. Covariate-corrected mortality hazard ratios compared with Q1 were: Q2: 1.12 (0.85-1.48), p = 0.41, Q3: 1.58 (1.19-2.09), p = 0.001 and Q4: 1.50 (1.06-2.12), p = 0.021. Conclusions: In critically ill patients, opioid dose was not associated with a change in kidney function. However, opioid dose was associated with an increased ICU-LOS and mortality risk.