Intrathecal Methotrexate Containing the Preservative Benzyl Alcohol Erroneously Administered in Pediatric Leukemia Patients: Clinical Course and Preventive Process.

Administration of intrathecal chemotherapy for leukemia is a common procedure in pediatric oncology. The direct delivery of drug into the cerebral spinal fluid requires that no preservative be used. Preserved drugs administered in error can result in significant neurotoxicity. A case series is described where preservative-containing methotrexate was incidentally administered intrathecally. All patients were treated at Children's Hospitals and Clinics of Minnesota. Medical records of the patients affected were reviewed and abstracted for this report. Four children with acute lymphoblastic leukemia received 1 dose of intrathecal methotrexate that contained 0.07% benzyl alcohol in January 2019. Overall, minimal to no symptoms were seen after dosing. The error was traced to a drug shortage in which benzyl alcohol-containing methotrexate was obtained and incorrectly stocked. A novel replacement drug procurement process was developed within our institution. The process includes sequestered queues where a drug awaits evaluation and independent double check of entry accuracy in the electronic health record and pharmacy parenteral dose preparation software prior to release and use. In contrast to IV administration, intrathecal benzyl alcohol at concentrations ≥ 0.9% can cause significant neurotoxicity. Although minimal, if any, neurotoxicity was seen in patients who received a 10-fold lower concentration of benzyl alcohol than previously associated with complications, all institutions should recognize the potential for this error and implement similar safety precautions to ensure that this type of error will not occur.

Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List.

OBJECTIVES: The safe use of medications in pediatric patients requires practitioners to consider the unique pharmacokinetics and pharmacodynamics of drugs prescribed in this age group. In an effort to create a standard of care for the safe use of medications in this population, a list of drugs that are potentially inappropriate for use in pediatric patients has been developed and titled the "KIDs List." METHODS: A panel of 7 pediatric pharmacists from the Pediatric Pharmacy Association were recruited to evaluate primary, secondary, and tertiary literature; FDA Pediatric Safety Communications; the Lexicomp electronic database; and product information for drugs that should be considered potentially inappropriate for use in pediatric patients. Information was rated using predefined criteria. A PubMed search was conducted using the following terms: adverse drug events OR adverse drug reactions. The search was limited to humans; age <18 years; case reports, observational studies, or clinical trials; and English language. No date range was used. Results were used to create an evidence-based list of candidate drugs that was then peer-reviewed and subjected to a 30-day public comment period prior to being finalized. RESULTS: A PubMed search yielded 4049 unique titles, of which 210 were deemed relevant for full review. Practitioner recommendations highlighted an additional 77 drugs. FDA Pediatric Safety Communications and the Lexicomp database yielded 22 and 619 drugs, respectively. After critical analysis, peer review, and public review the final KIDs List contains 67 drugs and/or drug classes and 10 excipients. CONCLUSIONS: This extensive effort led to compilation of the first list of drugs that are potentially inappropriate for prescribing in all or in a select subgroup of pediatric patients. If avoidance is not clinically possible, the drug should be used with caution and accompanied by appropriate monitoring.

Accidental Epidural Injection of Rocuronium in a Pediatric Patient: A Case Report and Literature Review.

Accidental administration of non-epidural drugs into the epidural or subarachnoid spaces may be associated with unexpected pain, morbidity, adverse effects, increased level of care, prolonged hospital stay, and mortality. We describe a 12-month-old admitted for secondary-stage hypospadias reconstruction. General anesthesia was induced with sevofiurane and a peripheral catheter was placed. Instead of ropivacaine, rocuronium (80 mg; 6.3 mg/kg) was injected into the epidural space by the caudal route. Surgery was uneventful and was completed 160 minutes after rocuronium was given. The patient exhibited paralysis with 1 of 4 twitches to the train-of-four with some posttetanic potentiation at the end of surgery. He was transferred to the pediatric intensive care unit for supportive ventilation and recovery. He did not experience oxygen desaturation or hypoventilation between the time of rocuronium administration and intubation. He was hemodynamically stable, without respiratory insufficiency, and his neurologic exam was normal, without motor or sensorial block. The patient was discharged home on the morning of the first postoperative day. Clinical examination 1 week after surgery revealed no lasting sequelae from the error.

Fish Oil Lipid Emulsion-Associated Sea-Blue Histiocyte Syndrome in a Pediatric Patient.

A syndrome of hepatosplenomegaly, thrombocytopenia, and anemia and the presence of sea-blue histiocytes in bone marrow has been associated with parenteral soybean oil administration in patients receiving long-term total parenteral nutrition (TPN). A case is described here where this syndrome was observed in a pediatric patient who received long-term parenteral fish oil nutrition.

Retrospective analysis of large-dose intrapleural alteplase for complicated pediatric parapneumonic effusion and empyema.

OBJECTIVES: Medical treatment of complicated parapneumonic effusion or empyema in pediatric patients includes antibiotics and pleural space drainage. Intrapleural fibrinolysis may facilitate pleural drainage; however, there is a lack of consensus regarding the optimal dosing regimen. The primary purpose of this study was to evaluate the efficacy and safety of a large-dose intrapleural alteplase regimen in pediatric patients. Secondarily, this investigation sought to differentiate the clinical characteristics of responders and non-responders to intrapleural alteplase therapy. METHODS: All patients with parapneumonic effusions treated with intrapleural alteplase between June 2003 and December 2011 were reviewed retrospectively. Efficacy was assessed by comparing chest tube output, in mL/hr and mL/kg/hr, for 24 hours before and after the first dose of alteplase. Additional efficacy outcomes included duration of in situ chest tubes, a need for surgical intervention for pleural effusion, and length of hospital stay. Safety was assessed by frequency and severity of adverse events. Non-responders and responders were compared based on demographic and disease characteristics. Responders were defined as patients who did not require surgical intervention after intrapleural alteplase therapy. RESULTS: Seventy-three patients, aged 0.5 to 22.5 years, received intrapleural alteplase to facilitate pleural drainage. Median alteplase dose was 7 mg (range, 3 to 10 mg; median 0.38 mg/kg). Chest tube output increased from 10.7 to 24.2 mL/hr (p = 0.006), and median length of hospital stay was 9 days. Eighty-four percent of patients were responders. The most common adverse events were pain (20.5%) and oxygen desaturation greater than 10% from baseline (16.4%). High-flow nasal cannula was the most common intervention for oxygen desaturation to 80% to 90%. Nine patients (12%) required a blood transfusion during the study. CONCLUSION: Large-dose intrapleural alteplase is effective in facilitating pleural drainage in pediatric patients with complicated parapneumonic effusion or empyema. Common adverse effects include pain and oxygen desaturation. The potential for bleeding warrants clinical monitoring.

Recommendations for meeting the pediatric patient's need for a clinical pharmacist: a joint opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group.

Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. Although progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this joint opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by elevating the minimum expectations for pharmacists entering pediatric practice, standardizing pediatric pharmacy education, expanding the current number of pediatric clinical pharmacists, and creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, and research initiatives.

Recommendations for Meeting the Pediatric Patient's Need for a Clinical Pharmacist: A Joint Opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group.

Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. While progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this Joint Opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by 1) elevating the minimum expectations for pharmacists entering practice to provide pediatric care; 2) standardizing pediatric pharmacy education; 3) expanding the current number of pediatric clinical pharmacists; and 4) creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, or research initiatives.

Otoacoustic emission screen results in critically ill neonates who received gentamicin in the first week of life.

STUDY OBJECTIVE: To characterize the extent that serum gentamicin concentrations are associated with hearing loss indicated by otoacoustic emission (OAE) screen failure in critically ill neonates receiving gentamicin in accordance with a high-dose, extended-interval dosing protocol. DESIGN: Retrospective medical record review. SETTING: Two neonatal intensive care units in a pediatric tertiary care system. PATIENTS: Sequential sample of 528 critically ill neonates who were admitted between February 2003 and January 2008 and who received a gentamicin pharmacokinetic consultation during the first week of life and an OAE hearing screen before hospital discharge. Neonates were stratified into two groups: very low birth weight (VLBW [≤ 1500 g]) and non-VLBW (> 1500 g). MEASUREMENTS AND MAIN RESULTS: Gentamicin was dosed intravenously to achieve a target calculated gentamicin peak serum concentration (C(max)) of 7-10 µg/ml and a target trough serum concentration (C(min)) of less than 2 µg/ml. The dosage administered was 4 mg/kg/dose every 48 hours if the neonate's birth weight was less than 1250 g or if the neonate was receiving indomethacin. Otherwise, the dosing interval was every 24 hours. Initial OAE screen results were obtained from the medical records, and follow-up results were collected for neonates who failed the initial OAE screen. The overall rate of OAE screen failure was 13.1% (69/528 patients). The rate of OAE screen failure was 34.1% (29/85 patients) in the VLBW neonates, which was significantly higher than the failure rate in non-VLBW neonates (9.0% [40/443 patients], p=0.001). Multivariate analysis of non-VLBW neonates determined that each 1-µg/ml increase in gentamicin C(max) was associated with an increased risk of OAE screen failure (odds ratio [OR] 1.4, 95% confidence interval (CI) 1.1-1.7, p=0.003). Further, the non-VLBW neonate subpopulation had an increased rate of OAE screen failure if the gentamicin C(max) exceeded 10 µg/ml (OR 2.2, 95% CI 1.1-4.2, p=0.022) compared with neonates whose C(max) was 10 µg/ml or lower. No association between serum gentamicin concentration and OAE screen failure could be determined among the VLBW neonates. CONCLUSION: Neonates weighing more than 1500 g at birth and whose gentamicin C(max) exceeded 10 µg/ml were at an increased risk for OAE screen failure. Monitoring and maintaining gentamicin C(max) at or below 10 µg/ml may minimize hearing impairment; however, further studies are necessary.

Pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol in critically ill neonates.

STUDY OBJECTIVE: To determine the pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates. DESIGN: Retrospective medical record review with pharmacokinetic analysis. SETTING: Two neonatal intensive care units in a pediatric tertiary care system. PATIENTS: Sequential sample of 644 critically ill neonates less than 7 days old without evidence of renal dysfunction who received gentamicin, dosed by using a simplified, weight-based, extended-interval dosing protocol, on the first day of life for suspected sepsis between February 2003 and January 2008, and who had subsequent gentamicin plasma concentrations measured during their first week of life. MEASUREMENTS AND MAIN RESULTS: Data were collected on birth weight, gestational age at birth, serum creatinine concentration during the first 10 days of life, medical conditions, and concomitant drugs. Gentamicin dosing and its pharmacokinetic parameters were noted for each patient. A mean dose of 3.96 mg/kg/dose of gentamicin was administered intravenously every 48 hours in neonates weighing less than 1250 g at birth and every 24 hours in those weighing 1250 g or more. If the neonate received concurrent indomethacin, however, gentamicin was given every 48 hours. Protocol success was defined as a peak gentamicin plasma concentration of 7-10 mg/L and a trough concentration less than 2 mg/L. Mean gentamicin peak and trough concentrations were 9.38 mg/L (95% confidence interval [CI] 9.24-9.52 mg/L) and 1.00 mg/L (95% CI 0.96-1.04 mg/L), respectively. With use of the protocol, 361 neonates (56.1%) achieved gentamicin peak plasma concentrations in the range defined as successful and 610 neonates (94.7%) achieved successful trough concentrations. The mean gentamicin apparent volume of distribution and half-life were 0.48 L/kg (95% CI 0.47-0.49 L/kg) and 8.31 hours (95% CI 8.09-8.52 hrs), respectively. CONCLUSION: This simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates was effective in achieving therapeutic peak plasma concentrations of gentamicin in most of the patients and, as a high proportion of patients had acceptable trough concentrations, may minimize the potential for toxicity.

Effects of light exposure on total parenteral nutrition and its implications in the neonatal population.

Total parenteral nutrition (TPN) is a necessary form of nutrition in neonates with functional or anatomical disruption of the digestive tract. However, laboratory and human investigation have shown that exposure of the TPN solution to light causes the formation of peroxides and other degradation products that are quantifiable in experimental TPN solutions, laboratory animals, and neonates. Premature neonates are at a higher risk for the development and progression of peroxide damage due to their relative lack of antioxidant and free radical scavenger reserves. Furthermore, cell damage seen in a number of neonatal disease states is exacerbated by the presence of peroxides that are generated via intrinsic pathologic processes and from exogenous sources such as TPN. Numerous studies show that the formation of TPN photodegradation products can be slowed or prevented by the application of various light protection mechanisms. While it is not yet known if minimizing TPN associated photodegradation byproducts has a significant direct effect on preventing or mitigating the overall clinical course of some neonatal disease states, it is becoming increasingly clear that light protecting TPN can avoid specific metabolic complications in neonatal patients. It is prudent to implement mechanisms that prevent photodegradation of TPN components from the manufacturer source to the point of patient administration.

Dosage and effectiveness of intrapleural doxycycline for pediatric postcardiotomy pleural effusions.

STUDY OBJECTIVE: To determine the effectiveness of intrapleural doxycycline for the treatment of postcardiotomy pleural effusions in pediatric patients. DESIGN: Retrospective case series. SETTING: Intensive care unit in a pediatric tertiary care center. PATIENTS: Sequential sample of 12 pediatric patients who underwent cardiotomy for congenital heart disease and received doxycycline pleurodesis for persistent pleural effusion that lasted more than 7 days between December 21, 2001, and May 23, 2005. MEASUREMENTS AND MAIN RESULTS: Mean age of the patients was 1 year (range 2 wks-2.5 yrs). Eighteen courses of doxycycline were administered among the 12 patients. An average dose of 19.1 mg/kg/dose of parenteral doxycycline was diluted in normal saline to a final syringe concentration of 2-8 mg/ml and injected through a chest tube. The patient was rotated according to a protocol. The doxycycline dose remained in the pleural space for approximately 6 hours before being drained under suction. Treatment success was defined as achievement of 0-ml/hour chest tube output after a doxycycline dose. The overall treatment success rate was 94% (17 of 18 courses). The mean times from dosing to treatment success and chest tube removal were 76 hours (range < 1 to 140 hrs) and 130 hours (range 8-453 hrs), respectively. Seventy-two percent of the courses (13 of 18) achieved treatment success within 96 hours and chest tube removal within 168 hours after dosing. Doxycycline concentration did not appear to be related to treatment success. Chest pain was the most common adverse effect. CONCLUSION: Intrapleural doxycycline infusion is effective for postcardiotomy pleural effusion in pediatric patients with persistent chest tube drainage lasting more than 7 days.

Accidental administration of oxytocin to a premature infant.

Oxytocin has been used for several decades in close proximity to newborns, yet no published information is available regarding complications associated with its accidental administration to a newborn. We describe a case where oxytocin instead of vitamin K was accidentally administered intramuscularly to a premature infant shortly after birth. The patient described remained hemodynamically stable but developed transient hyponatremia as the sole biochemical abnormality.