Pharmacologic Management of Sialorrhea in Neonatal and Pediatric Patients.

Sialorrhea, defined as an excess flow of saliva or excessive secretions, is common in patients with cerebral palsy and other neurologic disorders and is associated with clinical complications such as increased risk of local skin reactions, infections, aspiration, pneumonia, and dehydration. Upon failure of non-pharmacologic measures, clinicians have several noninvasive pharmacologic options available to manage sialorrhea. This review of the literature provides detailed descriptions of medications used, efficacy, safety, and practical considerations for use of non-injectable pharmacologic agents. The literature search included published -human studies in the English language in PubMed and Google Scholar from 1997 to 2022. Relevant citations within articles were also screened. A total of 15 studies representing 719 pediatric patients were included. Glycopyrrolate, atropine, scopolamine, and trihexyphenidyl all have a potential role for sialorrhea management in children; however, glycopyrrolate remains the most studied option with 374 (n = 52.0%) of the 719 patients included in the systematic review receiving this medication. Overall, glycopyrrolate showed similar efficacy but higher tolerability than its comparators in 2 comparative studies and is often considered the first-line agent. Patient-specific (age, route of administration) and medication-specific (dosage formulation, medication strength) considerations must be weighed when initiating a new therapy or switching to another medication upon treatment failure. Owing to the high propensity of adverse events with all agents, clinicians should consider initiating doses at the lower end of the dosage range, as previous studies have noted a dose-dependent relationship.

Variability in opioid conversion calculators in critically ill children transitioned from fentanyl to hydromorphone.

PURPOSE: Opioid conversion calculators (OCCs) are used to convert between opioids. The purpose of this study was to describe the variability in OCC results in critically ill children transitioned from fentanyl to hydromorphone infusions. METHODS: This was a descriptive, retrospective study. Seventeen OCCs were identified and grouped into 6 groups (groups 1-6) based on the equianalgesic conversions. The OCCs were used to calculate the hydromorphone rate in critically ill children (<18 years) converted from fentanyl to hydromorphone. Information from a previous study on children stabilized on hydromorphone (defined as the first 24-hour period with no change in the hydromorphone rates, <3 hydromorphone boluses administered, and 80% of State Behavior Scale scores between 0 and -1) were utilized. The primary objective was to compare the median hydromorphone rates calculated using the 17 OCCs. The secondary objective was to compare the percent variability of the OCC-calculated hydromorphone rates to the stabilization rate. RESULTS: Seventeen OCCs were applied to data on 28 children with a median age and hydromorphone rate of 2.4 years and 0.08 mg/kg/h, respectively. The median hydromorphone rate calculated using the 17 OCCs ranged from 0.06 to 0.12 mg/kg/h. Group 3 and group 6 OCCs resulted in a calculated hydromorphone rate that was higher than the stabilization rate in 96% and 75% of patients, respectively. Use of group 4 and group 5 OCCs resulted in a calculated hydromorphone rate that was lower than the stabilization rate in 64% and 75% of patients, respectively. CONCLUSION: Given the considerable variability of OCCs, caution should be used when applying OCCs to critically ill children.

Delirium Assessment Treatment Strategies in Critically Ill Pediatric Patients: A Pediatric Pharmacy Association Practice-Based Research Network Survey Study.

OBJECTIVES: The purpose of this study was to describe overall screening, prevention, and treatments for pediatric delirium at various neonatal intensive care units (NICUs), cardiac intensive care units (CICUs), and pediatric intensive care units (PICUs) from the Pediatric Pharmacy Association (PPA) membership. The primary objective was to identify the number of respondents that had a defined delirium-based protocol. The secondary objectives included identification of delirium assessment tools used, first- and second-line delirium treatment options, and monitoring practices for antipsychotics for delirium management. METHODS: A cross-sectional questionnaire was distributed to PPA members from February 8, 2022, to March, 25, 2022. Comparisons between the NICUs, PICUs, and CICUs were conducted by using chi-square tests, with a priori p value of <0.05. RESULTS: The questionnaire was completed by 84 respondents at 62 institutions; respondents practiced in the PICU or mixed PICU (n = 48; 57.1%), CICU (n = 13; 15.5%), and NICU (n = 23; 27.4%). Sixty-one respondents (72.6%) noted their units routinely screen for delirium, and there was a significant difference between the respondents of different units that use a delirium scoring tool (p < 0.01). Only 33 respondents (39.3%) had a defined delirium protocol, and there was no difference between units (p = 0.31). The most common agents used for delirium treatment were quetiapine and risperidone. There was variability in the monitoring used between respondents, but the majority (n = 74; 88%) monitor electrocardiograms to assess the corrected QT interval, but practice variability existed. CONCLUSIONS: Most respondents did not have a defined delirium protocol. Variations were noted in the treatment options and monitoring for critically ill pediatric patients with delirium.

Effect of Phytonadione on Correction of Coagulopathy in Pediatric Patients With Septic Shock.

OBJECTIVES: The purpose of this study was to evaluate phytonadione in children with septic shock with disseminated intravascular coagulopathy (DIC). The primary objective was to identify the number of patients with an international normalized ratio (INR), defined as ≤1.2, following phytonadione. Secondary objectives were to compare patients who achieved a normalized INR versus those with INR >1.2 and to determine factors associated with a normalized INR. METHODS: A retrospective study of children <18 years of age receiving phytonadione from October 1, 2013, to August 31, 2020, with a diagnosis of septic shock, were included. Data collection included demographics, phytonadione regimen, INR values, Pediatric Index of Mortality 2 (PIM2) and Pediatric Risk of Mortality III (PRISM III) scores, fresh frozen plasma (FFP) and cryoprecipitate use. A logistic regression model and generalized linear model were used to explore factors associated with a normalized INR and evaluate phytonadione dosing. RESULTS: Data for initial phytonadione course for 156 patients were evaluated. Sixty-six (42.3%) patients had a normalized INR. Most patients (n = 145; 92.9%) received ≤3 phytonadione doses, with the largest reduction in INR occurring after the second dose. In the logistic regression model, baseline INR, FFP, cryoprecipitate, vasopressors, PIM2, PRISM III, or cumulative phytonadione dose were not associated with achieving a normalized INR. CONCLUSIONS: Less than half of patients achieved a normalized INR. The median cumulative dose of phytonadione and receipt of FFP or cryoprecipitate was not associated with an increased odds of a normalized INR. Future studies are needed to further explore phytonadione use in children with sepsis-induced coagulopathy.

Melatonin Use in Infants Admitted to Intensive Care Units.

OBJECTIVES: Sleep deprivation is a risk factor for delirium development, which is a frequent complication of intensive care unit admission. Melatonin has been used for both delirium prevention and treatment. Melatonin safety, efficacy, and dosing information in neonates and infants is lacking. The purpose of this study was to describe melatonin use in infants regarding indication, dosing, efficacy, and safety. METHODS: This descriptive, retrospective study included infants <12 months of age admitted to an intensive care unit receiving melatonin. Data collection included demographics, melatonin regimen, sedative and analgesic agents, antipsychotics, and delirium-causing medications. The primary objective was to identify the melatonin indication and median dose. The secondary objectives included change in delirium, pain, and sedation scores; change in dosing of analgesic and sedative agents; and adverse event identification. Wilcoxon signed rank tests and linear mixed models were employed with significance defined at p < 0.05. RESULTS: Fifty-five patients were included, with a median age of 5.5 months (IQR, 3.9-8.2). Most (n = 29; 52.7%) received melatonin for sleep promotion. The median body weight-based dose was 0.31 mg/kg/dose (IQR, 0.20-0.45). There was a statistical reduction in cumulative morphine equivalent dosing 72 hours after melatonin administration versus before, 17.1 versus 21.4 mg/kg (p = 0.049). No adverse events were noted. CONCLUSIONS: Most patients (n = 29; 52.7%) received melatonin for sleep promotion at a median dose was 0.31 mg/kg/dose. Initiation of melatonin was associated with a reduction of opioid exposure; however, there was no reduction in pain/sedation scores.

Ketamine Use in Adult and Pediatric Patients Receiving Extracorporeal Membrane Oxygenation (ECMO): A Systematic Review.

Background: Analgesia and sedation are often critical elements of therapy for patients undergoing extracorporeal membrane oxygenation (ECMO). Aside from potential drug-drug interactions, the PK changes associated with ECMO make appropriate analgosedative selection challenging. Ketamine is less lipophilic and has lower protein binding than alternative agents, and may be less impacted by the PK changes during ECMO. Objective: To systematically identify all instances of ketamine use during ECMO support in the literature to elucidate associated efficacy and safety outcomes and prevalence of use, as well as commonly used dosing strategies and pharmacokinetic data. Methods: Web of Science, Cochrane Library, Scopus, Ovid MEDLINE, PubMed, and OVID Embase were searched through 02/2023 using keywords ketamine and ECMO or extracorporal life support (ECLS). Case reports, case series, and studies were included that had (1) original data, (2) included patients that were on ECMO and continuous infusion ketamine, and (3) reported pertinent ketamine related clinical endpoints or prevalence of use. Results: Of the 307 articles screened, 25 were identified as relevant and 11 met our inclusion criteria. Heterogeneity of patient population, ketamine indication, reported outcomes, and reported safety endpoints were identified in the included articles. Commonly reported information includes indications, pharmacokinetics, dosing, adverse effects and use in pediatrics for ketamine, and suspected opioid sparing effect. Conclusion: Our review has found a lack of consistency in reporting and results in adult and pediatric patients. Increased consistency in reporting and larger studies are required to increase our knowledge of ketamine use in both the adult and pediatric patient population.

Sculpting a teaching and learning curriculum to better meet the career needs of postgraduate year 1 and 2 pharmacy residents.

PURPOSE: To describe implementation of the University of Oklahoma College of Pharmacy (OUCOP) teaching and learning curriculum (TLC) for postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) residents, including the required components, evaluation structure, residency graduate outcomes and perceptions captured by a survey following program completion, generalizability to other institutions, and opportunities for future directions. SUMMARY: As part of their residency training, pharmacy residents are required to develop and refine teaching, precepting, and presentation skills. To meet the required and elective competency areas, goals, and objectives on teaching, precepting, and presentation skills, many American Society of Health-System Pharmacists-accredited residency programs have utilized TLC programs. OUCOP offers 2 distinct TLC programs for PGY1 and PGY2 residents, respectively. CONCLUSION: The OUCOP TLC program provided residents with opportunities for development of teaching and presentation skills in a variety of settings. The majority of residency graduates currently practice as a clinical specialist, and the majority lecture, precept, and deliver continuing education presentations. Graduates felt that the mentorship and diversity of teaching activities were the most beneficial qualities of the program. In addition, the majority noted that mentorship in lecture preparation was helpful in creating presentations after graduation. On the basis of the feedback from the survey, several changes have been made to better prepare residents for their postgraduate careers. TLC programs should conduct ongoing assessments to continue to foster the development of precepting and teaching skills for residents' future careers.

Azithromycin for Eradication of Ureaplasma and Prevention of Bronchopulmonary Dysplasia in Preterm Neonates in the Neonatal Intensive Care Unit.

Azithromycin has been explored as a treatment option for eradication of Ureaplasma and prevention of bronchopulmonary dysplasia (BPD) in preterm neonates. However, there is debate about the need for eradication of Ureaplasma and whether azithromycin is safe and efficacious for this indication. This literature review provides an overview of the evidence for use of azithromycin for eradication of Ureaplasma and prevention of BPD, including dosing and duration of azithromycin used in these studies. The literature search included articles published in the English language in Medline and PubMed from 1946 to January 2022. Relevant citations within identified articles were also reviewed. A total of 9 studies representing 388 neonates were included. The percentage of neonates that tested positive for Ureaplasma in these studies ranged from 18.6% to 57.1%. Azithromycin was initiated at <3 days of life in 8 studies (88.9%). Dosing was variable and ranged from 5 to 20 mg/kg/dose administered once daily, and the duration of treatment ranged from 1 to 35 days. Most studies used intravenous azithromycin. Overall, azithromycin was more efficacious than placebo at Ureaplasma eradication; however, most of these studies did not find a difference in the incidence of BPD between patients receiving azithromycin versus placebo. No adverse effects, specifically pyloric stenosis or QT interval prolongation, were noted in these studies.

Characterization of early versus late opioid iatrogenic withdrawal syndrome in critically ill children transitioning from fentanyl -infusions to methadone.

OBJECTIVE: Methadone is used to prevent opioid iatrogenic withdrawal syndrome (IWS) in children, but the optimal dose and overlap time with an opioid infusion have not been elucidated. The purpose was to compare clinical manifestations among patients who developed opioid IWS within 24 hours (early) versus ≥24 hours (late) of fentanyl discontinuation when enteral methadone was initiated. DESIGN: A retrospective, descriptive study. SETTING: Pediatric and cardiovascular intensive care units at a tertiary care health system. PARTICIPANTS: Sixty-seven children received fentanyl infusions for ≥3 days and initiated on methadone prior to fentanyl discontinuation. MAIN OUTCOME MEASURES: The primary objective was to compare clinical characteristics between those with early versus late opioid IWS. Opioid IWS was defined as a Withdrawal Assessment Tool-1 score ≥3 within 5 days of fentanyl discontinuation. Secondary objectives included a comparison of time to IWS, clinical characteristics, and risk factors among patients with and without IWS. RESULTS: Fifty children (74.6 percent) developed opioid IWS within a median time of 3.5 hours. No differences were noted for those with and without IWS. Thirty-seven patients (74.0 percent) with IWS developed early IWS. A higher percentage of males in the late versus early group developed IWS, 100 percent versus 51.4 percent, p = 0.002. The median overlap time with methadone and fentanyl was shorter in the early versus late IWS group without reaching statistical significance, 27.5 versus 64.0 hours, p = 0.127. CONCLUSIONS: The majority developed opioid IWS, with most developing early IWS, despite methadone initiation. Future studies should evaluate the optimal methadone dosing and overlap time to prevent opioid IWS.

Vasopressin-Induced Hyponatremia in Infants Following Cardiovascular Surgery.

BACKGROUND: Vasopressin is increasingly used in infants following cardiac surgery. Hyponatremia is a noted adverse event, but incidence and risk factors remain undefined. OBJECTIVE: The primary objective was to identify the incidence of vasopressin-induced hyponatremia. Secondary objectives included comparing baseline and change in serum sodium concentrations between infants receiving vasopressin with and without hyponatremia, and comparing vasopressin dose, duration, and clinical characteristics in those with and without hyponatremia. METHODS: This Institutional Review Board-approved, retrospective case-control study included infants <6 months following cardiac surgery receiving vasopressin for ≥6 hours at a tertiary care, academic hospital. Patients who developed hyponatremia, cases, were matched to controls in a 1:2 fashion. Demographics and clinical characteristics were collected. Descriptive and inferential statistics were employed. A conditional logistic regression was used to assess odds of hyponatremia. RESULTS: Of the included 142 infants, 20 (14.1%) developed hyponatremia and were matched with 40 controls. There was significant difference in median nadir between controls and cases, 142.0 versus 128.5 mEq/L (<0.001). A significantly higher number of cases received corticosteroids, loop diuretics, and chlorothiazide versus controls. The regression analysis demonstrated that each additional hour of vasopressin increased the odds of developing hyponatremia by 5% (adjusted odds ratio 1.05 [confidence interval 1-1.1]). CONCLUSIONS AND RELEVANCE: Vasopressin-induced hyponatremia incidence was <15%. Vasopressin duration was independently associated with hyponatremia development.

Caffeine dosing in premature neonates: impact of birth weight on a pharmacokinetic simulation study.

BACKGROUND: The optimal caffeine dosing in extremely premature neonates remains elusive. This study aimed to evaluate the impact of birth weight on caffeine pharmacokinetics and various dosing regimens. METHODS: In this pharmacokinetic simulation study, we generated the body weights (0-49 days of postnatal age [PNA]) of neonates <28 weeks gestational age with different birth weights (550, 750, and 1050 g). Their pharmacokinetic parameters were determined based on published pharmacokinetic models. Then, we simulated and compared the caffeine base concentration-time profiles of standard versus off-label caffeine citrate dose regimens. RESULTS: The half-life decreased and the weight-adjusted clearance increased more significantly in neonates with lower birth weights, resulting in lower caffeine plasma concentrations. The neonate with the lowest birth weight did not achieve a threshold trough concentration of 15 mg/L after receiving the standard dose (5 mg/kg/day), while the higher-birth-weights (≥750 g) had trough concentrations below the threshold around the second week of life. Higher caffeine doses (10 mg/kg/day) resulted in peak concentrations of <36 mg/L by 10-14 days of PNA while maintaining trough concentrations above 15 mg/L throughout the 49 days PNA. CONCLUSION: Higher-than-standard caffeine dosing may be needed for extremely premature neonates, especially for those with lower birth weights. IMPACT: Extremely premature neonates with a lower birth weight may require a higher weight-based caffeine dosing due to their higher weight-adjusted clearance and shorter half-lives. Not only do these extremely premature neonates have a higher risk of developing bronchopulmonary dysplasia due to their structurally underdeveloped lungs, but the low birth weight-related underdosing may further contribute to the reduced caffeine effectiveness. Higher-than-standard caffeine citrate dosing (e.g., 10 mg/kg/day maintenance dose) may be needed to further prevent bronchopulmonary dysplasia.

Management of Idiopathic Viral Pericarditis in the Pediatric Population.

Idiopathic (viral) pericarditis (IP) is one of the most common etiologies of acute and recurrent pericarditis in children. IP is associated with significant morbidity, and recurrence rates of IP are high and require treatment to decrease risk of recurrence and pericarditis-related chest pain. Despite significant morbidity, sparse guidance exists to comprehensively address management of IP in children. The purpose of this review is to provide an overview of the pharmacotherapy of IP in children, including clinical pearls for managing pediatric patients. Clinicians should consider using the combination of colchicine and nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy, in order to reduce the risk of recurrence and foster symptom improvement in IP. Colchicine dosing may vary depending on patient age, weight, concomitant pharmacotherapies, and disease states. Choice of NSAID should be based on cost, tolerability, and adverse drug events (ADEs). Children should receive higher NSAID attack dosing for >1 week to ensure a reduction in high sensitivity C-reactive protein concentrations and symptom relief. Corticosteroids should be considered last-line for treatment of IP in children, because they increase the risk of recurrence. Immunotherapies may be considered for children with multiple recurrences related to IP despite the use of NSAIDs, colchicine, and/or corticosteroids. Similar to adults, diligent monitoring should be implemented, to prevent drug-drug interactions, drug-disease interactions, and/or ADEs in children.

Publication rates of pharmacy residents involved in a team-based research program.

PURPOSE: The University of Oklahoma College of Pharmacy (OUCOP) implemented an individualized residency research committee and skill development program to facilitate completion and publication of research projects. The purpose of this study was to evaluate the outcomes the program had on project publication rates and subsequent publications after graduation for postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) residents. METHODS: This study included OUCOP PGY1 and PGY2 residents from classes graduating from 2011 through 2019. Literature searches for all resident projects and subsequent publications were performed. Data collection included residency type (PGY1 vs PGY2), initial position after residency, and project type. The primary objective was to identify the publication rate of research projects. Secondary objectives included a comparison of the number of publications after residency graduation between residents who did and did not publish their residency project and analysis of factors associated with subsequent publications. Zero-inflated Poisson regression was utilized to analyze subsequent publication status controlling for other factors. Statistical analyses were performed using SAS/STAT with an a priori P value of <0.05. RESULTS: Eighty-two projects were completed by 73 residents. Forty-three of 82 projects were published (52.4%) by 39 of 73 residents (52.1%). After residency graduation, 54 residents (74.0%) had a subsequent publication. Factors associated with subsequent publications were initial position in an academic role and completion of additional training after residency. CONCLUSION: After implementation of the program, the majority of residents published their projects and had subsequent publications. Future efforts should be taken to identify opportunities to foster independence in research and scholarship for residents.

Efficacy and Safety of Prolonged Magnesium Sulfate Infusions in Children With Refractory Status Asthmaticus.

Objectives: There is a paucity of data on the use of intravenous magnesium sulfate infusion in children with refractory status asthmaticus. The purpose of this study was to evaluate the efficacy and safety of prolonged magnesium sulfate infusion as an advanced therapy. Methods: This is a single center retrospective study of children admitted to our pediatric intensive care unit (PICU) with status asthmaticus requiring continuous albuterol. Treatment group included patients receiving magnesium for ≥4 h and control group included those on other therapies only. Patients were matched 1:4 based on age, sex, obesity, pediatric index of mortality III and pediatric risk of mortality III scores. Primary outcomes included PICU length of stay (LOS) and mechanical ventilation (MV) requirement. Secondary outcomes included mortality, extracorporeal membrane oxygenation (ECMO) requirement, analyses of factors associated with PICU LOS and MV requirement and safety of magnesium infusion. Logistic and linear regressions were employed to determine factors associated with MV requirement and PICU LOS, respectively. Results: Treatment and control groups included 27 and 108 patients, respectively. Median initial infusion rate was 15 mg/kg/hour, with median duration of 28 h. There was no difference in the MV requirement between the treatment and control groups [7 (25.9%) vs. 20 patients (18.5%), p = 0.39]. Median PICU LOS and ECMO use were significantly higher in treatment vs. control group [(3.63 vs. 1.09 days, p < 0.01) and (11.1 vs. 0%, p < 0.01), respectively]. No mortality difference was noted. On regression analysis, patients receiving ketamine and higher prednisone equivalent dosing had higher odds of MV requirement [OR 19.29 (95% CI 5.40-68.88), p < 0.01 and 1.099 (95% CI 1.03-1.17), p < 0.01, respectively]. Each mg/kg increase in prednisone equivalent dosing corresponded to an increase in PICU LOS by 0.13 days (95% CI 0.096-0.160, p < 0.01). Magnesium infusions were not associated with lower MV requirement or lower PICU LOS after controlling for covariates. Fourteen (51.9%) patients in the treatment group had an adverse event, hypotension being the most common. Conclusion: Magnesium sulfate infusions were not associated with MV requirement, PICU LOS or mortality.

Evaluation of Ceftazidime Use in the Neonatal Intensive Care Unit and Association With Cephalosporin-Resistant Gram-Negative Bacteria.

BACKGROUND: Cefotaxime shortage in 2015 led to increased ceftazidime use in the neonatal intensive care unit (NICU). OBJECTIVE: The purpose was to explore whether ceftazidime increases risk for development of resistant gram-negative organisms. METHODS: Retrospective evaluation of NICU patients with cultures positive for Escherichia coli, Pseudomonas aeruginosa, Klebsiella species, or Stenotrophomonas maltophilia between January1, 2015 and August 31, 2020. Isolates were excluded if obtained from same patient and source within 90 days or if patient ≤7 days of life or admitted from a referring hospital. Data collection included demographics and clinical parameters, and culture/susceptibility data. The primary objective was comparison of pathogens and clinical parameters in those with and without third-generation cephalosporin resistance. The secondary objectives included a comparison between those with and without ceftazidime exposure and identification of factors associated with resistance. Comparisons were made using χ2, Fisher exact tests, or Wilcoxon tests. A logistic regression was used to identify risk factors for resistance. RESULTS: Overall, 349 isolates, representing 215 patients, were included. The most common source was endotracheal (n = 192, 55.0%) and pathogens were E coli (31.8%) and P aeruginosa (29.2%). Overall, 12.3% (n = 43) were resistant and these were obtained after longer parenteral nutrition (PN), central line access, and antibiotic days versus susceptible isolates. Higher resistance was noted after ceftazidime exposure versus no exposure, 19.1% versus 6.6%. Each day of ceftazidime was associated with 13% greater odds of P aeruginosa resistance (adjusted odds ratio: 1.13 [95% confidence interval: 1.03-1.23]). CONCLUSION AND RELEVANCE: Ceftazidime duration was associated with increased risk for P aeruginosa resistance. Additional studies are needed to confirm these findings.

Continuous Magnesium Sulfate Infusions for Status Asthmaticus in Children: A Systematic Review.

Objectives: Magnesium sulfate is a second-tier therapy for asthma exacerbations in children; guidelines recommend a single-dose to improve pulmonary function and decrease the odds of admission to the in-patient setting. However, many clinicians utilize prolonged magnesium sulfate infusions for children with refractory asthma. The purpose of this review is to describe the efficacy and safety of magnesium sulfate infusions administered over ≥ 1 h in children with status asthmaticus. Methods: Medline was searched using the keywords "magnesium sulfate" and "children." Articles evaluating the use of magnesium sulfate infusions for ≥1 h published between 1946 and August 2021 were included. Published abstracts were not included because of lack of essential details. All articles were screened by two reviewers. Results: Eight reports including 447 children were included. The magnesium regimens evaluated included magnesium delivered over 1 h (n = 148; 33.1%), over 4-5 h (n = 105; 23.5%), and over >24 h (n = 194; 43.4%). Majority of patients received a bolus dose of 25-75 mg/kg/dose prior to initiation of a prolonged infusion (n = 299; 66.9%). For the patients receiving magnesium infusions over 4-5 h, the dosing regimen varied between 40 and 50 mg/kg/h. For those receiving magnesium infusions >24 h, the dosing varied between 18.4 and 25 mg/kg/h for a duration between 53.4 and 177.5 h. Only three reports including 186 patients (41.6%) included an evaluation of clinical outcomes including evaluation of lung function parameters, reduction in PICU transfers, and/or decrease in emergency department length of stay. Five reports including 261 patients (58.4%) evaluated magnesium serum concentrations. In most reports, the goal concentrations were between 4 and 6 mg/dL. Only 3 (1.1%) out of the 261 patients had supratherapeutic magnesium concentrations. The only reports finding adverse events attributed to magnesium were noted in those receiving infusions for >24 h. Clinically significant adverse events included hypotension (n = 74; 16.6%), nausea/vomiting (n = 35; 7.8%), mild muscle weakness (n = 22; 4.9%), flushing (n = 10; 2.2%), and sedation (n = 2; 0.4%). Conclusion: Significant variability was noted in magnesium dosing regimens, with most children receiving magnesium infusions over >4 h. Most reports did not assess clinical outcomes. Until future research is conducted, the use of prolonged magnesium sulfate infusions should be reserved for refractory asthma therapy.

Ketamine infusions as an adjunct for sedation in critically ill children.

OBJECTIVE: Limited reports have described ketamine's role as an adjunct sedative. The purpose was to describe ketamine's role as an adjunct to achieve goal sedation in mechanically ventilated children. DESIGN: Retrospective, descriptive study. SETTING: Thirteen-bed pediatric intensive care unit (ICU) and 12-bed pediatric cardiovascular ICU. PARTICIPANTS: Seventy-three ketamine courses were included, representing 62 mechanically ventilated children <18 years receiving ketamine for ≥12 hours. MAIN OUTCOME MEASURE(S): The primary outcome was to determine the median dose and time to achieve goal sedation (80 percent of State Behavioral Scale scores between 0 and -1) based on ketamine's place in therapy as an adjunct in the sedation regimen. Secondary outcomes included a comparison of sedative dosing pre- and post-ketamine initiation between place in therapy groups and paralyzed/nonparalyzed patients, and identification of ketamine-attributed adverse drug event (ADEs) or iatrogenic withdrawal syndrome (IWS). RESULTS: The median age was 1.0 years (interquartile range: 0.4-4.9). Ketamine was initiated as first-line (n = 7; 9.6 percent), second-line (n = 39; 53.4 percent), third-line (n = 26; 35.6 percent), or fourth-line (n = 1; 1.4 percent) sedation. The median initial and peak doses were 0.6 mg/kg/h (0.3-0.6) and 0.9 mg/kg/h (0.9-1.2), respectively. The median dose and time to achieve goal sedation was 0.8 mg/kg/h (0.6-1.1) and 2 hours (1-7), respectively. ADEs were noted during three courses (4.1 percent) and IWS after discontinuation of one course (1.4 percent). CONCLUSIONS: The majority were initiated on ketamine as a second- or third-line adjunct sedative. The median initial dose was 0.6 and dose to achieve goal sedation was 0.8 mg/kg/h. Ketamine-attributed ADEs and IWS episodes were rare.