Search

Objective: To evaluate the association between methylnaltrexone and urine output (UOP) in critically ill children with opioid-associated urinary retention., Methods: This retrospective study included patients admitted to the pediatric intensive care unit between December 1, 2019, and November 30, 2020, who received methylnaltrexone for opioid-associated oliguria (spontaneous UOP below 1 mL/kg/hr and at least 1 dose of an opioid within the preceding 6 hours)., Results: Twenty-five patients (median age = 5.5 years, IQR 1.7-16.4; median weight = 19 kg, IQR 9-45) were included. Mean methylnaltrexone dose was 0.15 ± 0.006 mg/kg. A statistically significant increase in UOP from baseline to 6 hours following methylnaltrexone was observed (p = 0.001), but not all patients responded. Fourteen patients (56%) had no UOP following methylnaltrexone administration, while 11 (44%) demonstrated a robust increase (median = 0 mL/kg/hr at baseline [IQR 0-0] to 1.96 mL/kg/hr [IQR 1.08-2.22; p = 0.001]) within 6 hours following methylnaltrexone administration. Younger patients responded better than older patients (responder age = 2.5 years [IQR 0.8-7]) versus 11.4 years [IQR 1.75-17.5] for non-responders) (p = 0.04). Both intravenous (IV) and subcutaneous (SQ) routes were associated with an increase in UOP (IV, p = 0.04; SQ, p = 0.02). The effect persisted for up to 24 hours after administration. Sixty-four percent of patients required urinary catheter placement. Pain scores (averaged 6 hours before and after methylnaltrexone) remained unchanged (p = 0.44)., Conclusions: Methylnaltrexone may increase spontaneous UOP in some children with opioid-associated urinary retention, but urinary catheterization rates remain high., Competing Interests: Disclosures. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2022.)

Objective: Our objective was to determine the incidence and risk factors for intravenous acetazolamide-associated acute kidney injury (AKI)., Methods: We utilized a retrospective cohort study including patients <19 years of age initiated on intravenous acetazolamide while admitted to an ICU. Data collection included patient demographics, clinical variables, acetazolamide dosing, and serum creatinine (SCr) values. Incidence of AKI was assessed per Kidney Disease Improving Global Outcomes criteria. Descriptive statistical analysis and ordinal logistic regression analysis were performed to determine the incidence of AKI and variables associated with AKI., Results: A total of 868 patients met study criteria (male 55.8%, median age 0.66 years [IQR 0.19, 3.0 years]). Intravenous acetazolamide was administered at 5.1 ± 2.8 mg/kg/dose for a median of 4 doses (IQR 2, 6). Median baseline SCr was 0.28 mg/dL (IQR 0.22, 0.37), corresponding to a creatinine clearance of 115 ± 55 mL/min/1.73 m 2 . Acute kidney injury occurred in 26.8% (n = 233) of patients (stage I = 20.1%, stage II = 3.7%, stage III 3.1%), and no patients received renal replacement therapy. An ordinal logistic regression model identified an increased odds of AKI with cyclosporine, ethacrynic acid, and piperacillin-tazobactam administration., Conclusions: Acute kidney injury occurs frequently in critically ill pediatric patients receiving intravenous acetazolamide., Competing Interests: Disclosures. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. BSM had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2021.)

Renal toxicity has been described with tramadol overdoses; however, it is typically associated with rhabdomyolysis, multiorgan failure and/or mortality. Our patient was a 16-year-old female who was evaluated following an intentional tramadol ingestion, estimated 27.8 to 37 mg/kg, and had a seizure prior to arriving at our health care facility. Her symptoms were consistent with a tramadol ingestion; however, she developed transient acute renal impairment (peak serum creatinine, 4.04 mg/dL), which improved over 6 days with minimal intervention. No other causes were identified to explain her acute renal impairment thus it was attributed to the tramadol overdose. Providers should be aware that transient acute renal impairment could occur with an intentional tramadol ingestion and may not require aggressive intervention., Competing Interests: Disclosure. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all patient information in this report and take responsibility for the integrity and accuracy of the report., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2021.)

Local anesthetic agents play a key role in the treatment and prevention of pain in children. Although generally safe and effective, as with any pharmacologic agent, adverse effects may occur with the administration of these medications. Systemic absorption or inadvertent systemic injection during bolus dosing or continuous infusion can result in local anesthetic systemic toxicity with life-threatening neurological and cardiac complications. The following article reviews the pharmacology of local anesthetic agents, outlines previous reports of systemic toxicity during regional anesthesia, and discusses prevention and treatment algorithms., Competing Interests: Disclosure. The authors declare no conflicts or financial interests in any products or services mentioned in the manuscript including grants, equipment, medications, employment, gifts, and honoraria., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2021.)

Toxicity related to acetaminophen is most encountered with the acute ingestion of large doses. However, toxicity may also result from chronic ingestion, even when recommended doses are administered over a prolonged period of time. We present the case of a 20-month-old female toddler who received therapeutic recommended doses of acetaminophen (oral or intravenous) following multiple surgical interventions for treatment of a tracheo-esophageal fistula following ingestion of a button battery. The potential role of chronic acetaminophen administration in the etiology of hepatoxicity is discussed and prevention strategies are presented., Competing Interests: Disclosures. The authors declare no conflicts or financial interest. The authors had full access to all patient information in this report and take responsibility for the integrity and accuracy of the report., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2021.)

Objective: Metronidazole is recommended as a first-line treatment of necrotizing enterocolitis (NEC) in neonates. Metronidazole-associated neurotoxicity has been reported, but long-term neurodevelopmental effects in neonates have not been explored. The primary objective was to evaluate the relationship of cumulative metronidazole dose with each Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) composite score in neonates with NEC. Secondary objectives included comparison of seizure rates, mean Bayley-III scores, and neurodevelopmental impairment defined as 2 of 3 Bayley-III composite scores ≤ 79 or 1 score ≤ 70 between the metronidazole exposed and non-exposed groups., Methods: This multisite, retrospective cohort study compared infants with a birth weight < 1500 grams between January 1, 2011, and December 31, 2016, who developed stage 2 or greater NEC or spontaneous intestinal perforation and were followed up at a developmental clinic visit at approximately 1 year of age. Patients were excluded if admitted >72 hours of life, had congenital neurodevelopmental anomalies, hypoxic ischemic encephalopathy, grade III or IV intraventricular hemorrhage, or seizures prior to treatment of NEC. Included patients were stratified into 2 groups based on metronidazole exposure versus no metronidazole. Data were assessed using descriptive and inferential statistical techniques, using SAS 9.4., Results: Forty-one patients were included. Seven patients received metronidazole and 34 patients were in the non-metronidazole group. The only statistical difference noted between groups was for gestational age, with the non-exposed group being more premature. There was no statistical difference in Bayley-III scores, seizure rates, or neurodevelopmental impairment between groups., Conclusion: No differences in neurodevelopmental outcomes were found between those with and without metronidazole exposure. Further studies are needed to validate our results., Competing Interests: Disclosure. The only financial disclosure to provide is that Dr. Chaaban has obtained research funding from the National Institutes of Health (5K08GM127308). The other authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2021.)

Toxic epidermal necrolysis is a rare, life-threatening skin disease with no consensus on adjunctive treatment, particularly in pediatric patients. We present the case of a 13-year-old previously healthy patient with drug-associated toxic epidermal necrolysis who experienced significantly shortened length of hospital stay and duration of symptoms compared with published literature when treated with 2 doses of etanercept 50 mg during 5 days., Competing Interests: Disclosures. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all patient information in this report and take responsibility for the integrity and accuracy of the report., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2021.)

Objective: The objective of this survey was to assess the current use of continuous infusion propofol in PICUs across the United States and Canada., Methods: A list of institutions with PICU beds/units was identified through the residency directories available on the American Society of Health-Systems Pharmacists (ASHP) and Canadian Society of Hospital Pharmacists (CHSP) Web sites. A REDCap questionnaire was sent to each identified institution's program director via email. An initial reminder email was sent out 2 weeks later and a second reminder email was sent 4 weeks after the initial request. The survey was closed at 6 weeks., Results: A total of 514 emails were sent to residency program directors, and 50 pharmacists responded to the survey. Of the pharmacists that did respond, 27 (54%) reported using propofol while 23 (46%) did not. Of those that did not, 43.5% reported the FDA boxed warning as the primary reason. Thirty-seven percent of respondents using propofol felt comfortable using a maximum infusion rate of 200 mcg/kg/min. Twenty-nine percent, 25%, and 33% of those who responded as using propofol felt comfortable using this agent for a maximum duration of 24, 48, and 72 hours, respectively. The majority of respondents using propofol did not have a case of propofol-related infusion syndrome., Conclusions: Despite the FDA warning, propofol is used as a continuous infusion (with variable limitations) by a majority of pharmacists in North America. Self-reported incidence of propofol-related infusion syndrome (PRIS) remains low., Competing Interests: Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria., (Copyright Published by the Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2019.)

Objectives: In 2011, approximately 1.7 million pediatric patients had a codeine-containing prescription filled at a US retail pharmacy. Numerous cases involving serious adverse effects or fatalities have been reported in children who have been prescribed codeine. In 2013, the US Food and Drug Administration added a boxed warning to avoid codeine in children after a tonsillectomy. The purpose of this study is to determine pharmacists' and pediatricians' knowledge of the boxed warning for codeine in children., Methods: Two separate surveys were administered to community pharmacists in Maryland, pediatricians, and pediatric residents at a single institution in Maryland. Both surveys consisted of questions regarding knowledge of the boxed warning for codeine in children., Results: There was no difference in the awareness of the boxed warning between pharmacists (48.9%, n = 43) and pediatricians (51.3%, n = 41, p = 0.88). More pharmacists knew that ultrarapid metabolizers have the risk for increased adverse events from codeine (39.5% pharmacists vs. 20% pediatricians, p = 0.01). In addition, 36% of pharmacists and 33% of pediatricians noted that it was never appropriate to use codeine in a child (p = 0.73)., Conclusions: Only half of pharmacists and pediatricians surveyed were aware of the boxed warning for codeine. One third of pharmacists and pediatricians in this study would never use codeine in a child. Therefore, more education is needed for pharmacists and pediatricians regarding the dangers of using codeine in children., Competing Interests: Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Objectives: This study aimed to determine the association between methadone use and corrected Q-T interval (QTc) prolongation in critically ill children., Methods: A retrospective cohort study of critically ill children receiving methadone at a tertiary care pediatric hospital was conducted. Patients younger than 19 years who had been admitted to the intensive care unit between January 1, 2009, and June 21, 2013, who had received methadone while inpatients, and who had had electrocardiograms (ECGs) performed within 30 days before and after methadone initiation were included. The primary outcome was the net change in QTc interval between baseline and postmethadone ECGs. Secondary outcomes included percent change in QTc interval and the proportion of patients whose QTc intervals changed from normal to prolonged following methadone initiation. We also evaluated potential predictors of QTc interval prolongation, including age, sex, admission diagnosis category, exposure to other QTc-prolonging medications, presence of congenital heart disease or known arrhythmias, and methadone daily dose and route of administration., Results: Sixty-four patients met the inclusion criteria. The median (25th, 75th percentiles) change in QTc interval following methadone initiation was -8 msec (-34, 13.5 msec; p = 0.19). Five patients (8%) had a baseline normal QTc interval that became prolonged after methadone initiation. We identified no statistically significant predictors of QTc prolongation after methadone initiation., Conclusions: In this dedicated pediatric safety study, methadone initiation did not result in prolongation of the QTc interval. Although these findings suggest methadone initiation may not have a substantial effect of QTc prolongation in critically ill children, a controlled, prospective evaluation in this population remains warranted., Competing Interests: Disclosures The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. Dr Greenberg was supported by National Institutes of Health (NIH) T32 training grants 5T32HD43728-10 and 5T32HD043029-13. Dr Hornik receives salary support for research from the National Center for Advancing Translational Sciences of the NIH (UL1TR001117). Dr Zimmerman is funded by KL2TR001115-03 from the Duke Clinical and Translational Science Awards. The authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

OBJECTIVES: To determine if the incidence of nephrotoxicity is higher in pediatric patients treated with the combination of vancomycin and piperacillin-tazobactam, compared to patients treated with vancomycin alone. Secondary objectives were to determine if admission to an intensive care unit (ICU), higher serum vancomycin trough concentrations (>15 mg/L), or receipt of other nephrotoxic agents were related to the development of nephrotoxicity. METHODS: This was a retrospective, single-center, cohort study of 79 patients treated with vancomycin and 106 patients treated with vancomycin and pipracillin/tazobacatam (TZP). Serum creatinine was trended to determine if patients had nephrotoxicity, which was defined as at least a 100% increase in serum creatinine or an increase of ≥0.5 mg/dL from the baseline value. Fisher's exact test was used to compare the incidence of nephrotoxicity in the vancomycin group to the combination group. Secondary objectives were evaluated by using relative risk (RR). RESULTS: Nephrotoxicity developed in 3 of 79 patients (3.8%) in the vancomycin group and in 25 of 106 patients (23.6%) on combination therapy (p = 0.0001). In patients receiving only vancomycin, there was no statistically significant increase in nephrotoxicity for patients in the ICU (RR 1.85, 95% confidence interval [CI] 0.175-19.62, p = 0.61), those with higher vancomycin troughs (RR 2.32, CI 0.226-23.86, p = 0.48), or those receiving other nephrotoxic medications (RR 2.94, CI 0.2779-31.05, p = 0.37). In the combination group, having higher serum vancomycin trough concentrations increased the risk of nephrotoxicity (RR 5.22, CI 2.407-11.306, p < 0.0001). CONCLUSIONS: Combination therapy with vancomycin and TZP is potentially more nephrotoxic than vancomycin alone. ICU admissions, high vancomycin troughs (>15 mg/L), and concomitant nephrotoxic medications cannot be excluded as risk factors for the observed increase in nephrotoxicity in patients receiving vancomycin and TZP.

As a pharmacist, being asked to give advice about medication use during pregnancy or lactation can be daunting. This article reviews the principles of drug transfer across the placenta, into breast milk, and reviews the rating scales and different resources available. The Food and Drug Administration classification scale is reviewed and the upcoming changes are explained, along with recent labeling changes for specific medications or drug classes when appropriate. This article provides the pharmacist with a practical set of tools to review the information available and assess the risks of treating or withholding a medication for mother and infant.