Presented at the Neonatal Society 2009 Spring Meeting.
Liu X1, Borooah M1, Chakkarapani E1, Stone J2, Thoresen M1
1 Child Health, St Michaels Hospital and Clinical Sciences at South Bristol, University of Bristol, UK
2 Biochemsity department, Bristol Royal infirmary, UK
Background: Hypothermia (HT) has been introduced as neuroprotective treatment for newborn infants with moderate or severe neonatal encephalopathy treated in neonatal intensive care units (1-3). Gentamicin is given to all infants at risk for gram-negative infections. It is routinely prescribed to babies with severe perinatal asphyxia and is ototoxic and nephrotoxic in high serum concentrations. We question whether its metabolism is reduced during HT resulting in higher and potentially toxic serum concentrations. Since 1998 we have enrolled 95% of infants that presented with moderate or severe encephalopathy into open or randomised HT trials using the same entry criteria. All infants received our standard gentamicin regime and serum concentrations and plasma creatinine levels were monitored regularly.
Objective: To define whether 72 hours therapeutic HT results in high serum gentamicin concentrations in infants as compared to those receiving normothermic (NT) care.
Methods: The audit was approved and data was collected retrospectively. Fifty-five infants were in randomised trials of HT or NT after perinatal asphyxia. Eligible infants were those with grade 2 or 3 encephalopathy after birth and eligibility for hypothermia therapy. Babies who received HT treatment had rectal temperature at 33.5-34.5°C for 72 hours. Those received NT care had rectal temperature at 37°C ± 0.5°C. Gentamicin was prescribed 4-5mg/kg once daily for all babies. Trough serum concentrations were monitored before the second dose or the third dose. Trough high gentamicin concentration is >2mg/l.
Results: No differences in serum gentamicin concentrations (gentamicin[HT]=2.19±1.7mg/l and gentamicin[NT]=2.30±2.0mg/l) were found. Only data for those babies with pre-2nd dose gentamicin concentrations are shown in Figure 1 (n=40). HT and NT groups had similar distribution of plasma creatinine levels (creatinine[HT]=115.6±42.8mmol/l and creatinine[NT]=121.0±45.1mmol/l).
Conclusion: Serum gentamicin levels are not affected by 72 hours of hypothermia after perinatal asphyxia. This is consistent with our previous findings of similar plasma gentamicin levels after normothermia or hypothermia recovery in a survival model of global hypoxic-ischaemic injury in newborn piglets. Our data also confirm that gentamicin clearance is strongly associated with creatinine clearance (r2=0.36).
References
1. Eicher DJ, Wagner CL, Katikaneni LP, et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005;32(1):11-7.
2. Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. The Lancet 2005;365(9460):663-670.
3. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353(15):1574-84.