Ototoxic drugs and sensorineural hearing loss following severe neonatal respiratory failure.

AIM: To determine relationships between ototoxic drugs and 4-y sensorineural hearing loss (SNHL) in near-term and term survivors of severe neonatal respiratory failure. METHODS: All 81 survivors of the Canadian arm of the Neonatal Inhaled Nitric Oxide Study (mortality 32, loss to follow-up 9) received loop diuretics, aminoglycosides, and neuromuscular blockers (NMB), and 50 received vancomycin as neonates. Prospective, longitudinal secondary outcome using audiological tests diagnosed late-onset, progressive SNHL in 43 (53%); not flat (sloping) in 29, flat (severe to profound) in 14. Risk for SNHL was determined. RESULTS: A combination of duration of diuretic use of >14 d and average NMB dose of >0.96 mg/kg/d contributed to SNHL among survivors (odds ratio 5.2; 95% CI 1.6, 16.7). Markers of illness severity did not contribute. Dosage or duration of aminoglycosides use did not relate to SNHL. Cumulative dosages and duration of use of diuretics; NMB; use of vancomycin; and overlap of diuretics with NMB, aminoglycosides, and vancomycin individually linked to SNHL (p<0.001). CONCLUSION: Overuse of loop diuretics and/or NMB contributes to SNHL after neonatal respiratory failure; markers of illness severity or the appropriate administration of aminoglycosides do not.

Use of plasma lactate to predict early mortality and adverse outcome after neonatal extracorporeal membrane oxygenation: a prospective cohort in early childhood.

OBJECTIVE: To examine the use of plasma lactate levels to predict mortality and neurodevelopmental outcome of neonates treated with extracorporeal membrane oxygenation. DESIGN: Prospective cohort study. SETTING: Two level III neonatal intensive care units in Canada and the United States. PATIENTS: Seventy-four neonates requiring extracorporeal membrane oxygenation in two neonatal intensive care units from 1994 to 1996. INTERVENTIONS: Differences in clinical and biochemical measurements, including serial lactate levels between three outcome groups (early deaths, adverse survivors, and normal survivors) were compared using analysis of variance. We also examined the predictive relationship between plasma lactate levels and the outcome at neonatal intensive care unit discharge and at 18-24 months postnatal age by backward, stepwise regression and Fisher's exact test. MEASUREMENTS AND MAIN RESULTS: Fifteen (20%) neonates died before neonatal intensive care unit discharge (early deaths), with seven additional deaths before follow-up, which are included in the adverse survivors group. Among 49 early childhood survivors (22 +/- 7 months), 27 were disabled or delayed with Mental and Performance Developmental Indices of 70 +/- 21 and 72 +/- 22, respectively. Early deaths had higher plasma lactate levels and were more acidemic than adverse and normal survivors, who were not different from each other (p <.05). Plasma lactate and the lowest arterial pH independently predicted 42% of the variance of the outcome ( p<.001). A peak lactate level of >or=25 mM predicted early mortality (sensitivity, 47%; specificity, 100%; positive and negative predictive values, 100% and 88%, respectively; p<.001), whereas a level of >or=15 mM predicted adverse outcome (sensitivity, 35%; specificity, 91%; positive and negative predictive values, 89% and 38%, respectively; p<.05). The predictability of plasma lactate was significantly improved in 45 neonates without congenital diaphragmatic hernia or lethal anomalies (sensitivity of 100% for early mortality, negative predictive value of 63% for adverse outcome). CONCLUSIONS In addition to assessing tissue oxygenation, plasma lactate may facilitate the decision-making process by providing early predictive information about the outcome of neonates treated with extracorporeal membrane oxygenation.

Late-onset, progressive sensorineural hearing loss after severe neonatal respiratory failure.

OBJECTIVES: To determine the prevalence of sensorineural hearing loss (SNHL) at the age of 4 years among survivors of severe neonatal respiratory failure with and without congenital diaphragmatic hernia and to document the occurrence of late-onset or progressive SNHL among the survivors. DESIGN: Prospective, longitudinal secondary outcome study. SETTING: Multicenter Canadian study in 9 tertiary referral centers. PATIENTS: Eighty-one (89%) of ninety 4-year-old survivors born from 1994 to 1996 of > or =34 weeks gestation at birth with severe neonatal respiratory failure (2 oxygenation indices > or =25 at least 15 minutes apart). MAIN OUTCOME MEASURES: Repeated audiologic measurements from birth to the age of 4 years with documentation of the entire cohort at 2 and 4 years of age. RESULTS: Forty-three (53%) of 81 tested 4-year-old survivors had SNHL; 28 (42%) of 66 without congenital diaphragmatic hernia and 15 (100%) of 15 with congenital diaphragmatic hernia. High-frequency SNHL occurred in 65% of the patients. Of the 43 children with SNHL at 4 years, 30 (70%) had loss at 2 years, and 18 (60%) of these 30 had progressive loss between 2 and 4 years of age. For 13 children with SNHL onset after 2 years of age, the loss was less severe with lesser involvement of the lower frequencies. CONCLUSION: Survivors of severe neonatal respiratory failure frequently develop late-onset SNHL that may be progressive. Urgent investigation is required to enable further understanding and prevention of this problem. Severe neonatal respiratory failure should be an indication for long-term audiologic surveillance.