Drug-drug interactions in neonatal intensive care: A prospective cohort study.

BACKGROUND: To characterize the prevalence and profile of drug-drug interactions (DDIs), the drugs most related to major DDIs and risk factors of their prescription in a neonatal intensive care unit (NICU). METHODS: Neonates admitted to a NICU who had at least one medication prescribed and a hospital stay >24 h were included in a prospective cohort study (August 2017 to July 2018). All medications prescribed during the hospitalization were collected from all neonates (n = 220), with the screening for DDIs. Prevalence and type of DDIs was identified. Network analysis was used to identify the drugs more implicated with DDIs. Logistic regression was used for the analysis of risk factors (p < 0.05). RESULTS: Over 70% of neonates were exposed to DDIs and 29% were exposed to major DDIs. The network analysis identified furosemide, fentanyl, aminophylline and fluconazole as most implicated with DDI, fentanyl was especially associated with major DDIs. The number of drugs (OR 1.60, p < 0.01), caesarean delivery (OR 2.68, p < 0.05), gestational age (OR 1.03, p < 0.01) and APGAR score (OR 0.78, p < 0.01) were identified as risk factors for exposure to DDI. CONCLUSION: Neonates in intensive care have a high exposure to DDIs and the occurrence of major DDIs is related specifically to the prescription of fentanyl. The number of prescribed drugs, gestational age, cesarean delivery and low APGAR score in the first minute were identified as risk factors for DDIs in NICU.

Population Pharmacokinetics of Magnesium Sulfate in Preeclampsia and Associated Factors.

BACKGROUND AND OBJECTIVE: The pharmacokinetic basis of magnesium sulphate (MgSO4) dosing regimens for preeclampsia (PE) prophylaxis and treatment is not clearly established. The aim of study is to develop a population pharmacokinetic (PK) model of MgSO4 in PE, and to determine key covariates having an effect in MgSO4 pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect in MgSO4 PK. METHODS: A prospective cohort study was conducted from June 2016 to February 2018 in patients with PE administered MgSO4 as a 4-g bolus followed by continuous infusion at a rate of 1 g/h. Serum magnesium concentrations were obtained before treatment administration and 2, 6, 12, and 18 h after the initial dose. The software Monolix was used to estimate population PK parameters of MgSO4 [clearance (CL), volume of distribution (V), half-life] and to develop a PK model with baseline patient demographic, clinical, and laboratory covariates. RESULTS: The study population consisted of 109 patients. The PK profile of MgSO4 was adequately described by a one-compartment PK model. The model estimate of the population CL was 1.38 L/h; for V, it was 13.3 L; and the baseline magnesium concentration was 0.77 mmol/L (1.87 mg/dL). The baseline body weight and serum creatinine statistically influenced MgSO4 CL and V, respectively. The model was parameterized as CL and V. CONCLUSION: The PK of MgSO4 in pregnant women with PE is significantly affected by creatinine and body weight. Pregnant women with PE and higher body weight have a higher V and, consequently, a lower elimination rate of MgSO4. Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO4 elimination rate.

Incidence of Adverse Drug Reactions in High-Risk Pregnancy: A Prospective Cohort Study in Obstetric Intensive Care.

PURPOSE: To estimate the cumulative incidence of adverse drug reactions (ADRs) in women with high-risk pregnancy hospitalized in an obstetric intensive care unit, then to describe the medicines involved and to identify major risk factors. METHODS: From June 2016 to December 2017, patients admitted to the ICU with high-risk pregnancy were considered eligible in this observational, longitudinal, prospective study. Patients were investigated daily for the occurrence of ADRs through pharmaceutical anamnesis, active search in medical records and questioning of the health team. Suspected ADRs were classified according to Naranjo's algorithm. Written informed consent was obtained from all patients. Univariate and multivariate logistic regression were used to identify risk factors of ADR. RESULTS: The study population consisted of 607 high-risk pregnancies from 851 women admitted to the ICU, of whom 244 admitted for non-obstetric conditions, with an ICU stay less than 24 h or readmitted to the ICU were excluded. The mean age was 27.0 ± 7.5 years-old, mean gestational age was 33.8 ± 6.3 weeks. ADR were observed in 165 women (27.2%). No severe ADR was observed and 29.7% were of moderate severity. The most often implicated medicine was magnesium sulphate (25.2%) with 44.5% of patients administered that substance experiencing ADRs consisting of somnolence (68.6%), absent patellar reflex (21.6%) and hypotension (9.8%). Risk factors of ADR were blood pressure (adjusted odds-ratio (aOR) 1.02), haemoglobin level (aOR 1.21) and body temperature (aOR 0.71). CONCLUSIONS: ADRs affect about one third of high-risk pregnancies, mainly due to magnesium sulphate administrations. High blood pressure, lower body temperature, and high haemoglobin concentration on admission were associated with an increased risk of ADR.