Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial
Open Access
- 11 March 2012
- Vol. 2 (2), e000635
- https://doi.org/10.1136/bmjopen-2011-000635
Abstract
Objectives To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients. Design Secondary analysis from a randomised antibiotic strategy trial (the Procalcitonin And Survival Study). The randomised arms were conserved from the primary trial for the main analysis. Setting Nine mixed surgical/medical intensive care units across Denmark. Participants 1200 adult intensive care patients, 18+ years, expected to stay +24 h. Exclusion criteria: bilirubin >40 mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling, pregnant/breast feeding and psychiatric patients. Interventions Patients were randomised to guideline-based therapy (‘standard-exposure’ arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements (‘high-exposure’ arm). Main outcome measures Primary end point: estimated glomerular filtration rate (eGFR) 2. Secondary end points: (1) delta eGFR after starting/stopping a drug and (2) RIFLE criterion Risk ‘R’, Injury ‘I’ and Failure ‘F’. Analysis was by intention to treat. Results 28-day mortality was 31.8% and comparable (Jensen et al, Crit Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the high-exposure versus 3016/6949 (43.4%) in the ‘standard-exposure arm were spent with eGFR 2, p2/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m2/24 h) vs meropenem: 2.9 ml/min/1.73 m2/24 h (2.5 to 3.3 ml/min/1.73 m2/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m2/24 h (2.3 to 3.1 ml/min/1.73 m2 /24 h)). eGFR 2 in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively. Conclusions Piperacillin/tazobactam was identified as a cause of delayed renal recovery in critically ill patients. This nephrotoxicity was not observed when using other beta-lactam antibiotics. Trial registration ClinicalTrials.gov identifier: NCT00271752.Keywords
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