Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children.

Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence. Design, Setting, and Participants: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry. Exposure: Administration of steroids within 2 days of admission. Main Outcomes and Measures: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. Results: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators. Conclusions and Relevance: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19: A retrospective cohort analysis from 28 U.S. Hospitals.

OBJECTIVES: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19). STUDY DESIGN: This was a retrospective study on 356 hospitalized patients with MIS-C from March 2020 to September 2021 (28 sites in the United States) in the Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry. The effect of IVIG and steroids initiated in the first 2 days of admission, alone or in combination, on LOS was analyzed. Adjustment for confounders was made by multivariable mixed regression with a random intercept for the site. RESULTS: The median age of the study population was 8.8 (Interquartile range (IQR) 4.0, 13) years. 247/356 (69%) patients required intensive care unit (ICU) admission during hospitalization. Overall hospital mortality was 2% (7/356). Of the total patients, 153 (43%) received IVIG and steroids, 33 (9%) received IVIG only, 43 (12%) received steroids only, and 127 (36%) received neither within 2 days of admission. After adjustment of confounders, only combination therapy showed a significant decrease of ICU LOS by 1.6 days compared to no therapy (exponentiated coefficient 0.71 [95% confidence interval 0.51, 0.97, p = 0.03]). No significant difference was observed in hospital LOS or the secondary outcome variable of the normalization of inflammatory mediators by Day 3. CONCLUSIONS: Combination therapy with IVIG and steroids initiated in the first 2 days of admission favorably impacts ICU but not the overall hospital LOS in children with MIS-C.

Response of focal refractory status epilepticus to lacosamide in an infant.

Status epilepticus (SE) is a life-threatening medical emergency which is frequently encountered in the critical care setting and can be refractory to treatment. Refractory status epilepticus (RSE) is defined as SE that has failed to respond to adequately used first-line and second-line antiepileptic medications. Super refractory status epilepticus is defined as SE that persists for 24 hours or more after the use of an anaesthetic agent or recurs after its withdrawal.If SE persists beyond a period of 7 days it is referred to as prolonged, refractory status epilepticus (PRSE). There are limited data guiding treatment of RSE in the paediatric population.Lacosamide (LCM) is licensed as an adjunctive treatment for partial-onset seizures. Evidence for the efficacy of LCM in paediatric SE is scarce. This case report may suggest a synergistic effect of LCM on slow-activation sodium channels in conjunction with medications such as phenytoin that causes fast inactivation of sodium channels. The dual fast and slow inactivation of sodium channels may enhance the effectiveness in treatment of RSE. This is the first case report of PRSE in an infant, successfully treated with LCM. A brief review of literature is also a part of this report.

Calcium Responsive Pediatric Septic Shock Refractory to Isotonic Crystalloids and Inotropic Agents.

Pediatric septic shock is a life-threatening condition with significant rates of morbidity and mortality. Standard management includes fluid resuscitation, timely antimicrobial administration, and epinephrine or norepinephrine if unresolved with initial management. Additional therapies are not well defined and include vasopressin, hydrocortisone, phenylephrine, levosimendan, dopamine, and others. Many of these agents modify cellular effects of calcium in the smooth muscle. The use of a calcium infusion may improve vasoactivity in the smooth muscle without the use of signaling pathways. Children are more susceptible to the effects of calcium, which may predispose them to enhanced vasoconstriction with the administration of intravenous calcium. We present a case in which a patient on chronic calcium channel blocker therapy presented with septic shock. She continued to remain hypotensive after fluid resuscitation, antibiotics, epinephrine, and norepinephrine. Her blood pressure improved with the initiation of a continuous calcium chloride infusion. Norepinephrine and epinephrine doses were decreased after the initiation of the calcium infusion.

Use of Furosemide and Chlorothiazide Combination Continuous Infusion in Furosemide-Refractory Patients in the Pediatric Intensive Care Unit: A Retrospective Cohort Study.

OBJECTIVE: Our objective was to describe the efficacy and safety of furosemide and chlorothiazide combination continuous infusion (FCCCI) in children in a pediatric intensive care unit (ICU), including postoperative cardiac patients. METHODS: This was a retrospective cohort study in a pediatric ICU within a tertiary care teaching hospital. Children aged < 18 years admitted from 1 January 2010 to 31 December 2019 were included if they received a furosemide infusion for at least 6 h and then transitioned to FCCCI. Each patient acted as their own control. RESULTS: A total of 203 patients (107 [53%] postoperative cardiac) met the study inclusion criteria. The study population was 55% male and 74% Caucasian, with a median age of 4.9 months. Of the total patients, 143 (70.4%) required mechanical ventilation and 39 (19.2%) required dialysis. The median duration of furosemide and FCCCI was 24.6 h (interquartile range [IQR] 12.4-54) and 41 h (IQR 15-162), respectively. Urine output increased by 52% with FCCCI (mean increase of 2.2 mL/kg/h [95% confidence interval {CI} 1.8-2.5]; p < 0.01). The change to FCCCI led to a net negative daily fluid balance (mean difference - 301.9 mL/day [95% CI - 390.9 to - 212.9]; p < 0.01). FCCCI resulted in a greater requirement for potassium bolus supplementation (mean increase of 12.8 boluses [95% CI 8.5-17.2]; p < 0.01) and a small but statistically significant increase in serum creatinine (mean difference 0.1 mg/dL [95% CI 0.06-0.14]; p < 0.01) with a resultant decrease in estimated glomerular filtration rate (mean difference - 13.5 [95% CI 9.7-17.4]; p < 0.01). Of the furosemide-refractory patients, 78.9% were responsive to FCCCI. Younger patients and patients who underwent cardiothoracic surgery were more likely to be responsive. Nonresponders to FCCCI had slightly higher mortality (21 vs. 6.6%, p = 0.05). CONCLUSIONS: FCCCI resulted in a significant improvement in diuresis with achievement of negative fluid balance in pediatric ICU patients. FCCCI is a reasonable approach to aggressive diuresis in the pediatric patient, particularly in patients with limited access. Serum potassium should be routinely monitored during such therapy.

Assessment of Phenobarbital Administration to Reduce Opioid and Benzodiazepine Use in the Immediate Postoperative Period Following Stage 2 Single-Ventricle Palliation.

OBJECTIVE: The Glenn procedure may lead to the development of elevated cerebral venous pressures, which is believed to result in "Glenn headaches." This manifests as excessive irritability, often requiring significant use of opioids and benzodiazepines. This study was designed to report our experience with the use of phenobarbital in the postoperative phase after the Glenn procedure. METHODS: We performed a retrospective chart review to compare Glenn patients before and after implementation of a sedation protocol using phenobarbital. The 2 groups were compared for demographics, surgical characteristics, and cumulative sedation usage. Correlation coefficients between the preoperative catheterization variables and sedation usage were also calculated. RESULTS: Groups A (pre-phenobarbital; n = 8) and B (post-phenobarbital; n = 11) were comparable in terms of demographics, cardiac anatomy, preoperative catheterization data, and hemodynamics. Patients in Group B received a median dose of 21.8 mg/kg of phenobarbital during their ICU stay. Although there was a decreased administration of morphine equivalents (2.60 mg/kg vs 2.25 mg/kg, p = 0.38), benzodiazepine (0.1 mg/kg vs 0.074 mg/kg, p = 0.43), and dexmedetomidine (47 mcg/kg vs 37.2 mcg/kg, p = 0.53) in Group B, the differences were not statistically significant. There was also no strong correlation between preoperative hemodynamic variables and the postoperative sedation requirement, and there was no statistically significant difference in overall outcomes between the 2 groups. CONCLUSIONS: While phenobarbital may have mitigated the use of opioids, benzodiazepines, and alpha-agonist agents in some postoperative Glenn patients, the overall findings for all patients were not statistically significant. Further prospective studies are needed to ascertain the role of phenobarbital in these patients.

Effect of IV Acetaminophen Usage on Opioid Requirements, Outcomes and Costs of Care for Postoperative Children in a Pediatric Intensive Care Unit.

OBJECTIVE: Children admitted to the ICU are commonly treated with opioids for postoperative pain. We hypothesized that administration of IV acetaminophen in the immediate postoperative period is effective in lowering cumulative opioid use leading to other benefits. METHODS: This was a retrospective chart review of patients admitted to the PICU between December 2016 and April 2019. For each patient, data including demographics, cumulative opioid usage per kilogram, oral or rectal acetaminophen, x-ray findings, hospital costs, and surgical procedure were collected. Cumulative opioid usage was determined by converting all opioids to morphine equivalents (MEs) per kg. Standard descriptive and comparative analyses were conducted using SAS 9.4 (SAS Institute, Inc, Cary, NC). RESULTS: A total of 200 patients met inclusion and exclusion criteria (N = 92 in IV acetaminophen group and N = 108 in no IV acetaminophen group). There was no significant difference in ME per kilogram between the groups (0.3 ME/kg in IV acetaminophen group, IQR 0.5 ME/kg versus 0.4 ME/kg in no IV acetaminophen group, IQR 0.5 ME/kg, adjusted p = 0.38). Rate of atelectasis was not significant between the groups (47.8% in IV acetaminophen versus 45.4% in no acetaminophen group, p = 0.28). There was a significant difference in median total hospital costs between the groups ($22,456 in IV acetaminophen group, IQR $18,650 versus $18,552 in no IV acetaminophen group, IQR $13,361, adjusted p = 0.04). CONCLUSIONS: IV acetaminophen in the immediate postoperative period did not lead to a decrease in cumulative opioid usage or rate of atelectasis. IV acetaminophen usage was associated with increase in overall hospital costs per patient.

Survey of Pharmacists Regarding the Use of Propofol Infusions in the PICUs in North America.

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.

An Introduction to Pharmacotherapy for Inborn Errors of Metabolism.

Inborn errors of metabolism comprise a wide array of diseases and complications in the pediatric patient. The rarity of these disorders limits the ability to conduct and review robust literature regarding the disease states, mechanisms of dysfunction, treatments, and outcomes. Often, treatment plans will be based on the pathophysiology associated with the disorder and theoretical agents that may be involved in the metabolic process. Medication therapies usually consist of natural or herbal products. Established efficacious pediatric doses for these products are difficult to find in tertiary resources, and adverse effects are routinely limited to single case reports. This review article attempts to summarize some of the more common inborn errors of metabolism in a manner that is applicable to pharmacists who will provide care for these patients.

Evaluation of the Tolerability of Intermittent Intravenous Sildenafil in Pediatric Patients With Pulmonary Hypertension.

OBJECTIVES: The primary purpose of this study was to determine the tolerability of intermittent intravenous (IV) sildenafil for the treatment of pulmonary hypertension in pediatric patients. Secondary objectives were to evaluate parameters related to efficacy. METHODS: This was a retrospective chart review from January 2013 to August 2014 of pediatric patients under age 18 years treated with intermittent doses of IV sildenafil for pulmonary hypertension. Patients were excluded if they were over age 18 years or received sildenafil for other indications. Measures collected to assess tolerability include blood pressure and heart rate before and after the administration of IV sildenafil, as well as adverse events. RESULTS: Thirty-seven patients (21 females and 16 males) were identified meeting inclusion criteria, and 21 (56.8%) were on oral sildenafil prior to the initial IV dose. The mean decrease in blood pressure after the first dose of IV sildenafil was 7.16/2.74 mmHg. The decrease in systolic blood pressure was statistically significant. During the study period, 5 patients experienced medication related adverse events, primarily hypotension. Despite this, none of the patients had the medication discontinued due to these events. For secondary objectives, a statistically significant difference was not found between other clinical measures before and after intermittent IV sildenafil dosing. CONCLUSIONS: Sildenafil, when administered as intermittent IV doses, was tolerated by the majority of patients evaluated in this study. For pediatric patients with pulmonary hypertension in whom enteral or continuous IV sildenafil cannot be administered, intermittent IV sildenafil may be considered as an alternative administration option.

Medication adsorption into contemporary extracorporeal membrane oxygenator circuits.

OBJECTIVE: This study was conducted to evaluate the amount of medication adsorbed into extracorporeal membrane oxygenation (ECMO) circuits with a polymethylpentane membrane oxygenator and heparin-coated polyvinyl chloride tubing. METHODS: An ECMO circuit with the aforementioned components was set up ex vivo and primed with expired blood. Midazolam, lorazepam, morphine, and fentanyl were administered to the circuit. Fifteen minutes after medication administration, 60 mL of blood were removed and stored in a 60-mL syringe to serve as a control. Medication levels were drawn from the ECMO circuit (test) and control syringe (control) 15 minutes, 24 hours, and 48 hours after the medications were administered. ECMO circuit medication levels were compared to their corresponding syringe control medication levels. Descriptive statistics were used to determine the percentage of medication remaining in the blood and compare it to the control value. RESULTS: Except for morphine, there was a large decline in medication levels over the 48-hour period. Compared to control values, 17.2% of midazolam, 41.3% of lorazepam, 32.6% of fentanyl, and 102% of morphine remained in the ECMO circuit. CONCLUSION: Despite the use of newer components in ECMO circuits, a large quantity of medication is adsorbed into the ECMO circuit. Midazolam, lorazepam, and fentanyl all showed reductions in medication levels greater than 50%. Morphine may have advantages for patients on ECMO, as its concentration does not appear to be affected.

Stenotrophomonas infection in a patient with glucose-6-phosphate dehydrogenase deficiency.

The drug of choice for treatment of Stenotrophomonas maltophilia is sulfamethoxazole/trimethoprim, and second-line therapy usually consists of a fluoroquinolone. However, in patients with glucose-6-phosphate dehydrogenase deficiency, neither sulfamethoxazole/trimethoprim nor a fluoroquinolone is a preferred option as it may result in hemolysis. Currently, there is a paucity of data regarding treatment of S maltophilia infection in these patients. This case report presents a patient who was successfully treated with doxycycline and inhaled colistimethate.

Retrospective financial analysis of medication therapy management services from the pharmacy's perspective.

OBJECTIVE: To determine the net financial gain or loss for medication therapy management (MTM) services provided to patients by an independent community pharmacy during 16 months of operation. DESIGN: Retrospective study. SETTING: Independent community pharmacy in Iowa City, IA, from September 1, 2006, to December 31, 2007. PATIENTS: Patients receiving MTM services during the specified period who had proper documentation of reimbursement for the services. INTERVENTION: MTM services were provided to the patient and documented by the pharmacist or student pharmacist. MAIN OUTCOME MEASURE: Net financial gains or losses for providing MTM services. Sensitivity analyses included costs that might be incurred under various conditions of operation. RESULTS: 103 initial and 88 follow-up MTM visits were conducted during a 16-month time period. The total cost for these services to the pharmacy was $11,191.72. Total revenue from these services was $11,195.00; therefore, the pharmacy experienced a net financial gain of $3.28. Sensitivity analyses were conducted, revealing the net gain/loss to the pharmacy if a student pharmacist was used and the net gain/loss if the pharmacist needed extra training to provide the services. Using a student pharmacist resulted in a net gain of $6,308.48, while extra training for the pharmacist resulted in a net loss of $1,602.72. CONCLUSION: The MTM service programs showed a positive financial gain after 16 months of operation, which should encourage pharmacists to incorporate these services into their practice.