Publications

info:eu-repo/semantics/published

SCOPUS: no.j

Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum β-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam), resulting in inappropriate serum concentrations. Obesity may further modify the pharmacokinetics of these agents. We reviewed our data on critically ill obese patients (body mass index of ≥ 30 kg/m(2)) treated with a broad-spectrum β-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically nonobese patients (body mass index of <25 kg/m(2)) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. Sixty-eight serum levels were obtained from 49 obese patients. There was considerable variability in β-lactam serum concentrations (coefficient of variation of 50% to 92% for the three drugs). Standard drug regimens of β-lactams resulted in insufficient serum concentrations in 32% of the patients and overdosed concentrations in 25%. Continuous renal replacement therapy was identified by multivariable analysis as a risk factor for overdosage and a protective factor for insufficient β-lactam serum concentrations. The serum drug levels from the obese cohort were well matched for age, gender, renal function, and sequential organ failure assessment (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only difference observed between the two cohorts was in the subgroup of patients treated with meropenem and who were not receiving continuous renal replacement therapy: serum concentrations were lower in the obese cohort. No differences were observed in pharmacokinetic variables between the two groups. Routine therapeutic drug monitoring of β-lactams should be continued in obese critically ill patients.

Introduction: Brain damage after cardiac arrest (CA) remains a major cause of death and morbidity worldwide. Prognostication of outcome is of importance to help clinicians in the management of CA patients. Scarce data exist on the prognosis value of C-Reactive Protein (CRP) in this setting. Hypothesis: The aim of the study was to assess the prognostic values of daily blood CRP measurements after CA. Methods: We reviewed the data of all patients admitted to our ICU after CA from January 2008 and December 2011 and who survived for at least 24 hours. We collected demographic data, cardiac arrest characteristics (initial rhythm, location of arrest, time to return of spontaneous circulation (ROSC), cardiac or non-cardiac cause), occurrence of infection, ICU mortality and neurological outcome (good = Cerebral Performance Category (CPC) 1-2; poor = CPC 3-5). CRP levels were collected from admission to day 5. Results: CRP measurements were obtained in 130 patients on admission and day 1, 102 on day 2, 75 on day 3, 67 on day 4 and 59 on day 5. 76 patients (58%) developed an infection; overall mortality was 56%. CRP levels significantly increased from admission to day 5 with a peak on days 2 and 3 (0.6 [0.1-4.3] mg/dl on admission, 3.8 [1.7-7.3] mg/dl on day 1, 14.0 [7.9-17.0] mg/dl on day 2, 16.0 [10.0-21.0] mg/dl on day 3, 16.0 [7.3-20.0] mg/dl on day 4 and 14.0 [6.0-20.0] mg/dl on day 5). CRP levels were higher in in-hospital CA (n=41) than out-of-hospital CA (n=89) and in non-shockable (n=74) than shockable (n=56) rhythms, especially on admission and day 1. CRP levels were not correlated to the time to ROSC, neither to the development of an infection (p=0.12). CRP levels were not related to ICU mortality (p=0.5) or neurological outcome (CPC of 1-2, n=54) (p=0.47). Conclusions: CRP levels increase in the following days after resuscitated CA, reflecting an inflammatory response. Higher CRP levels in in-hospital CA and non-shockable rhythms, likely represented differences in patient populations. As their increase is the rule, CRP levels are not very useful to identify infection or to predict outcome in this setting.