Prolonged infusion of sedatives and analgesics in adult intensive care patients: A systematic review of pharmacokinetic data reporting and quality of evidence

Abstract

Although pharmacokinetic (PK) data for prolonged sedative and analgesic agents in intensive care unit (ICU) has been described, the number of publications in this important area appear relatively few, and PK data presented is not comprehensive. Known pathophysiological changes in critically ill patients result in altered drug PK when compared with non-critically ill patients. ClinPK Statement was recently developed to promote consistent reporting in PK studies, however, its applicability to ICU specific PK studies is unclear. In this systematic review, we assessed the overall ClinPK Statement compliance rate, determined the factors affecting compliance rate, graded the level of PK evidence and assessed the applicability of the ClinPK Statement to future ICU PK studies. Of the 33 included studies (n=2016), 22 (67%) were low evidence quality descriptive studies (Level 4). Included studies had a median compliance rate of 80% (IQR 66% to 86%) against the ClinPK Statement. Overall pooled compliance rate (78%, 95% CI 73% to 83%) was stable across time (P=0.38), with higher compliance rates found in studies fitting three compartments models (88%, P<0.01), two compartments models (83%, P<0.01) and one compartment models (77%, P=0.17) than studies fitting noncompartmental or unspecified models (69%) (P<0.01). Data unique to the interpretation of PK data in critically ill patients, such as illness severity (48%), organ dysfunction (36%) and renal replacement therapy use (32%), were infrequently reported. Discrepancy between the general compliance rate with ClinPK Statement and the under-reporting of ICU specific parameters suggests that the applicability of the ClinPK Statement to ICU PK studies may be limited in its current form.