Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey

Abstract

Background. Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian NICUs.Methods. A prospective cross-sectional study was conducted in Italian and Spanish NICUs using a webbased survey with 43 questions. A modi ed Delphi method involved experts re ning the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring.Results. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices.Conclusions. The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in NICUs. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe.The Joint Committee on Infant Hearing (JCIH) identi es ototoxic drugs like aminoglycosides and loop diuretics as risk indicators for hearing loss, so hearing screening is recommended [18; 19]. Recently, vancomycin was linked to hearing loss in very low birth weight infants [20].Apart from previously mentioned drugs, potential ototoxic and nephrotoxic agents encompass antibiotics (e.g., piperacillin/tazobactam), nonsteroidal anti-in ammatory drugs (indomethacin, ibuprofen), antivirals (acyclovir), antifungals (amphotericin B), angiotensin-converting enzyme inhibitors (captopril, enalapril), and spironolactone [21][22][23][24][25][26][27][28][29][30].Newborns on these drugs require close kidney function monitoring for acute kidney injury (AKI) and chronic kidney disease (CKD). A single-center study revealed that 70% of children had lasting kidney damage after nephrotoxic medication-induced AKI [31]. However, diagnosing drug-induced AKI (D-AKI) is complex due to varying criteria, hindering accurate identi cation [32][33][34].Considering that the above-mentioned drugs are among the most commonly used in neonatology, we conducted a survey in Spanish and Italian neonatal units on the use and management of drugs with a higher...