Abstract
This is a pilot retrospective study to assess the effect of glomerular hyper-filtration (GHF) related to sickle cell disease (SCD) on vancomycin clearance and ultimately on therapeutic drug levels in children admitted to the pediatric intensive care unit (PICU) with acute chest syndrome (ACS).
The patients’ steady-state vancomycin trough levels (VTL) and the area under the curve (AUC) were compared with those of age- and gender-matched control group; matching was made at a 1:3 ratio.
Twelve SCD patients with ACS and treated with vancomycin were compared with 36 non-SCD patients (control group). Compared with the control patients, the ACS patients had significantly lower initial serum VTL (median = 6.00 mcg/mL vs. 9.75 mcg/mL) (p = 0.007), and their average VTL were still lower (median = 6.65 mcg/mL vs. 10.00 mcg/mL) post vancomycin dose adjustment (p = 0.039). The time to achieve the therapeutic vancomycin level was significantly longer for the ACS patients (median = 4.75 days) than for the control group (median = 1 day) (p = 0.009). The AUC was also significantly lower in the ACS patients (median = 293 mg*h/L) than in the control group (median = 405.5 mg*h/L) (p = 0.007). The AUC was negatively associated with creatinine clearance (Beta Coefficient = −0.366, p-value=<0.001) even when adjusted for receiving loading dose, standard dose per weight, and severity of critical illness.
These findings support the attributed role of the GHF associated with SCD leading to lower vancomycin level in ACS cases. Therefore, the standard dosing approach for vancomycin in ACS patients may be ineffective. We thus advocate for individualized dosing with careful monitoring of drug levels to account for GHF.