Phosphatase alkaline levels are not associated with poor outcomes in subarachnoid hemorrhage patients.

INTRODUCTION: Alkaline phosphatase (ALP) levels are often elevated in cerebrovascular and cardiovascular disease. Their prognostic role after subarachnoid hemorrhage (SAH) remains to be elucidated. METHODS: We performed a retrospective single center study of patients with non-traumatic SAH admitted to the intensive care unit (ICU) of Erasme Hospital (Brussels, Belgium) from 2006 to 2019. Exclusion criteria were previous history of liver cirrhosis or malignancies and early death (i.e. within 24 h from ICU admission). Baseline information, clinical data, radiologic data were collected, the occurrence of DCI as well as serum ALP levels during the first 12 days of ICU stay. Unfavorable neurological outcome (UO) at 3 months was defined as a Glasgow Outcome Scale of 1-3. RESULTS: Six hundred and fifty patients were included; ALP levels increased from baseline after day 6 from admission, in particular among patients with an initial poor clinical status. There was no difference in the ALP levels between patients with or without DCI over time. Patients with UO had higher ALP levels over time than others; however, in the multivariable analysis, nor ALP levels on admission or the highest ALP value during the ICU stay were independently associated with UO. CONCLUSIONS: The results of this study suggested that ALP levels had no prognostic role in SAH patients. Other possible prognostic biomarkers should be evaluated in this setting.

ß-lactam antibiotic concentrations during continuous renal replacement therapy.

INTRODUCTION: The use of standard doses of ß-lactam antibiotics during continuous renal replacement therapy (CRRT) may result in inadequate serum concentrations. The aim of this study was to evaluate the adequacy of unadjusted drug regimens (i.e., similar to those used in patients with normal renal function) in patients treated with CRRT and the influence of CRRT intensity on drug clearance. METHODS: We reviewed data from 50 consecutive adult patients admitted to our Department of Intensive Care in whom routine therapeutic drug monitoring (TDM) of broad-spectrum ß-lactam antibiotics (ceftazidime or cefepime, CEF; piperacillin/tazobactam; TZP; meropenem, MEM) was performed using unadjusted ß-lactam antibiotics regimens (CEF = 2 g q8h; TZP = 4 g q6h; MEM = 1 g q8h). Serum drug concentrations were measured twice during the elimination phase by high-performance liquid chromatography (HPLC-UV). We considered therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory concentration (MIC) of Pseudomonas aeruginosa during optimal periods of time for each drug (≥70% for CEF; ≥ 50% for TZP; ≥ 40% for MEM). Therapy was considered as early (ET) or late (LT) phase if TDM was performed within 48 hours of antibiotic initiation or later on, respectively. RESULTS: We collected 73 serum samples from 50 patients (age 58 ± 13 years; Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission 21 (17-25)), 35 during ET and 38 during LT. Drug concentrations were above 4 times the MIC in 63 (90%), but above 8 times the MIC in 39 (53%) samples. The proportions of patients with adequate drug concentrations during ET and LT were quite similar. We found a weak but significant correlation between ß-lactam antibiotics clearance and CRRT intensity. CONCLUSIONS: In septic patients undergoing CRRT, doses of ß-lactam antibiotics similar to those given to patients with normal renal function achieved drug levels above the target threshold in 90% of samples. Nevertheless, 53% of samples were associated with very high drug levels and daily drug regimens may need to be adapted accordingly.

Can changes in renal function predict variations in ß-lactam concentrations in septic patients?

This study investigated whether variations in creatinine clearance (CLCr) are correlated with changes in ß-lactam concentrations or pharmacokinetics in septic patients. Data for 56 adult patients admitted to the ICU in whom routine therapeutic drug monitoring (TDM) of broad-spectrum ß-lactams (ceftazidime, cefepime, piperacillin or meropenem) was performed were reviewed. Patients were included if they had at least two TDM during their ICU stay for the same antibiotic and were not concomitantly treated with any extracorporeal replacement therapy. Serum drug concentrations were measured by HPLC-UV. Antibiotic pharmacokinetics were calculated using a one-compartment model and the percentage of time spent above four times the MIC (%T>4×MIC) for Pseudomonas aeruginosa and the antibiotic clearance (ATB-CL) were obtained. CLCr was measured on the same day as the TDM using 24-h urine collection. The %T>4×MIC and ATB-CL were significantly correlated with CLCr at the first (r=-0.41, P=0.002; r=0.56, P<0.001, respectively) and second (r=-0.61, P<0.001; r=0.63, P<0.001, respectively) TDM. However, changes in ATB-CL were only weakly correlated with changes in CLCr (r=0.34, P=0.01). The proportion of patients with insufficient ß-lactam concentrations at the first and second TDM were 39% and 30%, respectively, and increased proportionally to CLCr. Although CLCr was significantly correlated with concentrations and clearance of broad-spectrum ß-lactams, changes in CLCr did not reliably predict variations in drug pharmacokinetics/pharmacodynamics. Routine TDM should be considered to adapt ß-lactam doses in this setting.