A Pilot Study to Determine the Drug Levels of Vancomycin and Amikacin in Critically Ill Children with Early Acute Kidney Injury

Abstract Introduction: Vancomycin and Amikacin are drugs with renal excretion primarily and are used widely in critically ill children. Fall in urine output is one of the first events in case of kidney injury in PICU setting. It is not clear how early AKI (eAKI),defined as only fall in urine output by KDIGO 2012 AKI definition before rise in serum creatinine, impacts levels of these drugs.We conducted pilot study to determine drug levels of Vancomycin and Amikacin in critically children with eAKI and 48 hours after modification. Methods: Children on Vancomycin or Amikacin were monitored for hourly urine output . Serum creatinine and Amikacin or Vancomycin levels were measured at 24 hours and again at diagnosis of eAKI.Serum Vancomycin and Amikacin levels were estimated in-house as a research tool by high performance liquid chromatography (HPLC) done on Agilent Infinity II system. Results: Incidence of eAKI was 15.7% in children on Vancomycin and these children also had AKI by serum creatinine criterion. Among children on Amikacin, incidence of eAKI was 12.5% and none developed AKI by serum creatinine criterion. In children on Vancomycin, mean drug levels when eAKI was diagnosed was 22.8 ±4.36 mg/L and creatinine was 1.03 ±0.31 mg/dl, both significantly higher than baseline ( P < 0.0001).Post drug-dose modification trough level was 15.48 ±1.64 mg/L still significantly high ( P < 0.0001) but mean serum creatinine reduced to 0.66 ±0.10 mg/dl. Drug levels and creatinine at D7 were comparable.Mean Amikacin levels in children with eAKI were 59.9 ±13.79mg/L, significantly higher than baseline ( P < 0.0001). 48 h after dose reduction, trough Amikacin levels remained significantly elevated but there was no significant difference in serum creatinine from baseline levels in these children with eAKI.Amikacin level at day 7 also significantly higher despite dose modification. Conclusion: Children on Vancomycin with eAKI had simultaneous rise in serum creatinine. Drug levels remained 48h after drug dose modification and became comparable only at day 7. In children on Amikacin,with eAKI, serum creatinine showed no significant rise but drug levels in these children remained significantly high compared to baseline at 48h after dose modification as well at day 7.