Postintubation Sedation Practices Within Multiple Emergency Departments Across a Large Pediatric Health Care Organization.

OBJECTIVE: Children requiring rapid or standard sequence intubation are at risk of experiencing paralysis without adequate sedation when the duration of neuromuscular blockade exceeds the duration of sedation provided by the induction agent. The objective of this study was to evaluate the rate of appropriately timed postintubation sedation (PIS; defined as the administration of PIS before the clinical effects of the induction agent have dissipated) in patients requiring intubation across multiple emergency department/urgent care sites within a large pediatric health care organization. METHODS: This retrospective cohort study included patients admitted to 1 of 6 affiliated pediatric emergency department or urgent care sites who were intubated with an induction agent and neuromuscular blocker between January 2016 and December 2021. Patients were excluded if they were intubated in the setting of status epilepticus or cardiac arrest. Stepwise logistic regression identified factors associated with appropriately timed PIS. RESULTS: A total of 283 patients met the inclusion criteria (mean age, 8 ± 7.6 years; 56% male). Two hundred thirty-eight patients (83%) received some form of PIS (105 [37%] received appropriately timed PIS and 133 [47%] received delayed PIS), and 45 patients (16%) received no PIS. The median time to receive PIS following administration of the induction agent was 21 minutes (interquartile range, 11-40 minutes). Patients induced with fentanyl were the least likely to receive PIS, whereas patients induced with etomidate were the most likely. However, because of the short duration of etomidate, most patients induced with etomidate failed to receive PIS in a timely manner. CONCLUSIONS: Delayed PIS is common and may result in periods of ongoing paralysis without adequate sedation. Emergency department providers and pharmacists must recognize the brevity of some induction agents and provide more timely PIS.

Peripheral Vasoactive Administration in Critically Ill Children With Shock: A Single-Center Retrospective Cohort Study.

OBJECTIVES: Management of fluid refractory pediatric shock requires prompt administration of vasoactive agents. Although delivery of vasoactive therapy is generally provided via a central venous catheter, their placement can delay drug administration and is associated with complications. We characterize peripheral vasoactive administration in a cohort of critically ill children with shock, evaluate progression to central venous catheter placement, and describe complications associated with extravasation. DESIGN: Retrospective cohort study. SETTING: Single-center, quaternary PICU (January 2010 to December 2015). PATIENTS: Children (31 d to 18 yr) who received epinephrine, norepinephrine, or dopamine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared patients based on the initial site of vasoactive infusion: peripheral venous access (PVA) or central venous access (CVA) and, within the PVA group, compared patients based on subsequent placement of a central catheter for vasoactive infusion. We also characterized peripheral extravasations. We evaluated 756 patients: 231 (30.6%) PVA and 525 (69.4%) CVA patients. PVA patients were older, had lower illness severity, and more frequently had vasoactive therapy initiated at night compared with CVA patients. In PVA patients, 124 (53.7%) had a central catheter placed after a median of 140 minutes (interquartile range, 65-247 min) of peripheral treatment. Patients who avoided central catheter placement had lower illness severity. Of the 93 patients with septic shock, 44 (47.3%) did not have a central catheter placed. Extravasations occurred in four of 231 (1.7% [95% CI, 0.03-3.4]) PVA patients, exclusively in the hand. Three patients received pharmacologic intervention, and none had long-term disabilities. CONCLUSIONS: In our experience, peripheral venous catheters can be used for vasoactive administration. In our series, the upper limit of the 95% CI for extravasation is approximately 1-in-30, meaning that this route may be an appropriate option while evaluating the need for central access, particularly in patients with low illness severity.

Decreases in Nephrotoxic Pain Medications Are Not Associated With Increased Opioid Utilization in Critically Ill Children.

OBJECTIVES: Quality improvement initiatives to decrease rates of nephrotoxic medication exposure have reduced rates of acute kidney injury (AKI) in noncritically ill children. The objective of our study was to analyze the implementation of a similar program in critically ill children and to measure important balancing measures including opioid and benzodiazepine exposure. DESIGN: Prospective quality improvement study. SETTING: PICU at Children's Hospital Colorado between 2018 and 2020. PATIENTS: All children admitted to PICU. INTERVENTIONS: Quality improvement initiative called Nephrotoxic Injury Negated by Just-In-Time Action (NINJA). MEASUREMENT AND MAIN RESULTS: Eight thousand eight hundred thirty-three PICU patient admissions were included. Mean rates of nephrotoxic medication exposure/1,000 PICU patient days decreased from 46 to 26, whereas rates of nephrotoxic AKI/1,000 PICU patient days did not change. Nonsteroidal anti-inflammatory drug dispenses per 1,000 patient days were reduced from 521 to 456. Similarly, opioid and benzodiazepine exposures per 1,000 patient days were reduced from 812 to 524 and 441 to 227, respectively, during the study observation period. CONCLUSIONS: The NINJA intervention was efficaciously implemented in our single-center PICU. Nephrotoxic exposure is a modifiable factor that did not inadvertently increase exposure to opioids and benzodiazepines.

Increased Testing and Health Care Costs for Pediatric Cannabis Exposures.

OBJECTIVES: This study aimed to evaluate the process of identifying marijuana exposure in a children's hospital emergency department and compare the cost of diagnostic testing and procedures. METHODS: A retrospective chart review was performed on patients 31 days to 20 years old with a positive marijuana toxicology screen result between November 2009 and December 2014. Primary outcomes included time to provider recognition of marijuana exposure, number of diagnostic tests and procedures performed, and length of hospital stay. Patients were analyzed based on time of exposure recognition (forthcoming compared with not forthcoming of marijuana exposure) and age (children <12 years compared with adolescents >12 years). RESULTS: There were 37 children and 38 adolescents included. Mean time to exposure recognition was 2.3 ± 4.3 hours in children compared with 0.4 ± 0.9 hours in adolescents (P = 0.02). Patients who were not forthcoming of marijuana exposure experienced more than twice as many diagnostic tests or procedures compared with children who were forthcoming of marijuana exposure (mean, 8.91 vs 4 tests, P < 0.0001) and more than a 4-fold higher cost of potentially avoidable diagnostic tests/procedures. Length of hospital stay was significantly longer in children (18.34 ± 2.39 hours) compared with adolescents (4.22 ± 0.52 hours; P ≤ 0.0001). Few parents or guardians were able to disclose characteristics of the marijuana product. CONCLUSION: Delay in recognition of marijuana exposure is associated with high resource utilization, unnecessary medical costs, and prolonged length of stay.

Concentrated hypertonic saline in severe pediatric traumatic brain injury.

OBJECTIVE: Describe outcomes associated with bolus and continuous infusions of hypertonic saline (HTS) in children with severe traumatic brain injury (TBI). METHODS: IRB-approved, single-center, retrospective review of children admitted between January 1, 2012 to August 30, 2018 with a diagnosis of severe TBI who received HTS. RESULTS: Forty-five children (age 9.3 ± 5.8 yr; 60% male) met inclusion criteria. One-hundred eighty-nine equiosmolar bolus doses of HTS were administered to 43 patients (3% HTS, n = 84 doses; 6% HTS, n = 38 doses; 12% HTS, n = 67 doses) for episodes of acute intracranial hypertension (pressure above 20 mmHg). Significant reductions in ICP were observed at 30, 60, and 120 min following HTS boluses with the greatest decrease observed in patients receiving 12%. Thirty-four patients received a continuous infusion of HTS. Higher concentrations of HTS were associated with a more favorable fluid balance (p < .001), fewer episodes of pulmonary edema (p = .003), and higher intake of protein and energy (p < .001). CONCLUSIONS: Equiosmolar bolus doses of concentrated HTS were associated with significant reductions in ICP. Benefits of higher concentrations of continuous HTS may include improved fluid balance, less pulmonary edema, and greater amounts of protein and energy intake.

Nalbuphine Reduces Opioid-Associated Urinary Retention in Pediatric Patients.

OBJECTIVES: To evaluate the effect of nalbuphine administration on urine output in critically ill children with opioid-associated urinary retention. DESIGN: Institutional review board approved, single center, retrospective medical chart review. SETTING: Large medical-surgical PICU within a free-standing, tertiary care children's hospital. PATIENTS: Patients admitted to the PICU between October 1, 2014, and February 29, 2016, who received IV nalbuphine after meeting criteria for opioid-associated oliguria (defined as urine output below 1 mL/kg/hr and received at least one dose of opioid therapy within the preceding 12 hr). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Seventeen patients who received 21 doses of nalbuphine were analyzed. The median age and weight of patients were 6 years (interquartile range, 3-11.5 yr) and 18 kg (interquartile range, 12-35 kg), respectively. Two distinct dosing strategies became evident, specifically 0.05 mg/kg (n = 11 doses) and 0.1 mg/kg (n = 10 doses). Urine output increased significantly from baseline (median, 0 mL/kg/hr; interquartile range, 0-0.53 mL/kg/hr) to 6 hours post nalbuphine administration (median, 1.48 mL/kg/hr; interquartile range, 0-2 mL/kg/hr; p = 0.0002). Patients who received 0.1 mg/kg/dose had a greater urine output response compared with those who received 0.05 mg/kg/dose. Five patients (29%) had a catheter inserted into their bladder after administration of nalbuphine. Pain scores (grouped 6 hr before and after nalbuphine administration and single pain scores documented immediately before and after nalbuphine administration) were unchanged. CONCLUSIONS: Nalbuphine administration, at a dose of 0.1 mg/kg, improved urine output in a cohort of children with opioid-associated urinary retention. Pain control did not appear influenced by the provision of nalbuphine. Additional studies are needed to determine the influence of nalbuphine on urinary catheter insertion rates and catheter-associated urinary tract infections.

Low-Dose Epinephrine Boluses for Acute Hypotension in the PICU.

OBJECTIVES: To describe the use of low-dose bolus epinephrine in critically ill children during an acute hypotensive episode or prearrest condition. DESIGN: Institutional Review Board approved, single-center, retrospective medical chart review. SETTING: Large medical-surgical PICU within a freestanding, tertiary care children's hospital. PATIENTS: Patients admitted to the PICU between June 1, 2015, and June 1, 2016, who received low-dose (≤ 5 µg/kg) IV bolus epinephrine. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Twenty-four resuscitation episodes (63 doses; 19 patients) were analyzed. Median age and weight of patients were 9 years (interquartile range, 1-15 yr) and 38.5 kg (interquartile range, 12-54.8 kg). Median Pediatric Risk of Mortality III score was 17 (interquartile range, 10-27). Mean epinephrine dose was 1.3 ± 1.1 µg/kg. Median number of doses per patient was two. If more than one dose was provided, median dosing interval was 6.5 minutes. Heart rate and mean arterial blood pressure were compared at the time of epinephrine administration and 1-4 minutes (median = 1 min) following administration. Heart rate changed from 130 ± 41 to 150 ± 33 beats/min (p < 0.05), and mean arterial blood pressure changed from 51 ± 17 to 75 ± 27 mm Hg (p < 0.001). Variability in mean arterial blood pressure response was observed; nonresponders required extracorporeal membrane oxygenation; 66% of doses resulted in up to 100% mean arterial blood pressure increase, and 21% of doses resulted in greater than 100% mean arterial blood pressure increase. Doses below 1 µg/kg were associated with a lower mean arterial blood pressure increase than doses between 1 and 5 µg/kg (mean percent change in mean arterial blood pressure = 6.6% vs 60%, respectively). Children less than or equal to 2 years old had the greatest percentage increase in heart rate and mean arterial blood pressure. CONCLUSIONS: Provision of low-dose bolus epinephrine during periods of acute hypotension can result in a significant increase in mean arterial blood pressure and heart rate. This dosing strategy may provide temporary stabilization while other therapies are added or adjusted, but further research is needed.

Marijuana Misadventures in Children: Exploration of a Dose-Response Relationship and Summary of Clinical Effects and Outcomes.

OBJECTIVES: This study aimed to explore a dose-response relationship of delta-9-tetrahydrocannabinol (THC) in THC-naïve children after unintentional acute exposure and compare clinical outcomes with non-naïve children. METHODS: A retrospective review was performed on children aged 31 days to 20 years who presented to Children's Hospital Colorado for care related to acute THC toxicity. The children were divided into groups based on exposure: group 1 (THC naïve) and group 2 (THC non-naïve). RESULTS: A total of 38 children (age, 3.5 [3] years) met inclusion for group 1 and an equal number of children (age, 15.1 [3.9] years) met the criteria for comparison in group 2. Eight naïve patients had documentation of estimated THC dose ingested (mean [SD], 7.13 [5.8] mg/kg; range, 2.9-19.5 mg/kg). A direct relationship between estimated oral THC dose, level of medical intervention required, and hospital disposition was observed. Lethargy/somnolence was more common in the naïve group (84% vs. 26%, P < 0.0001) whereas problems in cognition, perception, and behavior were more common in the non-naïve group (4% vs 11%, P = 0.01). The duration of clinical effect and length of hospital stay were longer in the naïve group (19.3 vs 5.0 hours, P < 0.0001) and (0.73 vs 0.19 days, P < 0.0001) respectively. CONCLUSIONS: There seems to be a direct relationship between the estimated oral THC dose (mg/kg), hospital disposition, and level of medical intervention required. Symptoms and duration of effects after THC exposure varied based on the route of exposure, age of patient, and history of previous THC experience.

Supra-therapeutic tacrolimus concentrations associated with concomitant nicardipine in pediatric liver transplant recipients.

Tacrolimus is prescribed to prevent allograft rejection in pediatric liver transplant recipients; however, its metabolism through the cytochrome P-450 enzyme system presents a multitude of challenges in regard to drug interactions. Here, we describe four children (ages 1.4-8.7 yr) who acutely developed supra-therapeutic serum tacrolimus trough concentrations, despite standard dosing, while on concomitant nicardipine therapy following liver transplantation. Even though tacrolimus regimens were altered (dosage reductions and held doses), serum tacrolimus concentrations remained elevated. Resolution of high tacrolimus concentrations was achieved only after the discontinuation of nicardipine. Following the termination of nicardipine, all children eventually required dosage increases in their tacrolimus regimens to re-achieve target serum concentrations. We conclude that concomitant use of tacrolimus and nicardipine can result in high tacrolimus concentrations due to the inhibition of cytochrome p450 enzymes responsible for the metabolism of tacrolimus. We encourage clinicians to consider alternative antihypertensive options in children on tacrolimus therapy. If nicardipine therapy is necessary, we recommend a 50% reduction in tacrolimus dose and daily serum concentration monitoring.

Hyponatremia in children with bronchiolitis admitted to the pediatric intensive care unit is associated with worse outcomes.

OBJECTIVE: To characterize the relationship between hyponatremia (serum sodium <135 mEq/L) and clinical outcomes in children ages 1 month to 2 years admitted to the pediatric intensive care unit (PICU) with bronchiolitis. STUDY DESIGN: Single-center retrospective cohort study comprising children who were admitted to the PICU between January 2009 and April 2011. Serum sodium concentrations, collected within the first 2 hours after admission to the PICU, were recorded and associations with clinical outcomes were calculated. Quantitative data are presented as mean ± SD or percentage. Student t-test, Fisher exact test, and χ(2) analyses were performed as appropriate. Subjects were excluded if they were previously diagnosed with chronic disease that would affect initial serum sodium concentration. RESULTS: Children with bronchiolitis were enrolled (n = 102; age = 10.7 ± 6.7 months). Twenty-three patients (22%) were diagnosed with hyponatremia within 2 hours of admission. Mortality (13% vs 0%; P = .011), ventilator time (8.41 ± 2 days vs 4.11 ± 2 days; P = .001), duration of stay in the PICU (10.63 ± 2.5 days vs 5.82 ± 2.09 days; P = .007), and noninvasive ventilator support (65% vs 24%; P = .007) were significantly different between subjects with hyponatremia vs those without. There were no differences in the number of patients with seizures, bronchodilator use, steroid use, intubation requirement, oxygen use at discharge, or hospital readmission. CONCLUSIONS: Pediatric patients diagnosed with bronchiolitis who present with a serum sodium concentration less than 135 mEq/L within 2 hours of admission to the PICU fare worse than their cohorts with normonatremia. A prospective study to evaluate the effects of hyponatremia appears justified.

Thrombosis risk factor assessment and implications for prevention in critically ill children.

OBJECTIVES: To describe nursing compliance with a computer-based pediatric thrombosis risk assessment tool; to generate an estimate of risk factors present in our population; and to explore relationships between risk factors and confirmed thrombotic events. DESIGN: Institutional review board-approved prospective, observational cohort study. SETTING: Pediatric intensive care unit within a tertiary care children's hospital. PATIENTS: All infants and children admitted to the pediatric intensive care unit during a 6-month study period (January 1, 2010-June 30, 2010). MEASUREMENTS AND MAIN RESULTS: Eight hundred admissions were enrolled, representing 742 patients. Thrombosis risk assessment scores were recorded for 707 admissions (88% of total). Mean age = 6.95 ± 6 yrs, mean weight = 28 ± 23 kg, 45% female. A total of 32 thrombi (14 prehospital and 18 in-hospital) were present in the study group. This translated to an overall occurrence rate of 4.3% (1.9% for prehospital and 2.4% for in-hospital). Logistic regression identified that for every 1-point increase in total thrombosis score, the risk of developing a symptomatic thrombus increased by 1.57-fold (95% confidence interval 0.192-5.5) to 2.12-fold (95% confidence interval 0.175-18.34), for prehospital and in-hospital thrombi, respectively (p < .05). The most important risk factors identified for development of any thrombus were thrombophilia (acquired or inherited) (p < .001), presence of a central catheter (p = .01), and age <1 or >14 yrs (p = .052). CONCLUSIONS: Incorporation of a scoring system into the bedside nursing assessment flow sheet was successful and identified children at risk for in-hospital thrombosis. The overall score appears to be most indicative of thrombus risk. These data may serve as a platform for future development of routine screening and possible interventional trials in critically ill children.

Adherence to a Pediatric Continuous Infusion Propofol Policy for Sedation in Mechanically Ventilated Patients: Opportunities for Change and Improvement.

OBJECTIVE: To evaluate adherence to an institutional continuous infusion propofol policy for sedation in mechanically ventilated patients, investigate the rate of propofol-related infusion syndrome (PRIS), and explore areas of improvement to enhance policy compliance and safety. METHODS: This was a single center, retrospective chart review of patients admitted to a pediatric or cardiac intensive care unit within a large free-standing quaternary care pediatric hospital who received continuous propofol for non-procedural continuous sedation for at least 6 hours between 2014 and 2019. Propofol exposure (dose and duration), laboratory data, and hemodynamic outcomes of patients were evaluated. RESULTS: A total of 104 patients (108 admissions and 133 treatment courses) met inclusion criteria. Policy adherence to propofol dosing and duration limitations were 70% (93/133 courses) and 68% (91/133 courses), respectively. Adherence to all elements of laboratory and hemodynamic monitoring was 23%. Hypotension and bradycardia were common among patients during propofol treatment courses. Except for hypertriglyceridemia, no significant difference in specific laboratory values were detected between patients exposed to greater than 66 mcg/kg/min (4 mg/kg/hr), compared with those exposed to less than 66 mcg/kg/min of propofol. Patients receiving therapy for longer than 48 hours had the highest rates of laboratory values associated with PRIS. No patient in the study cohort met full criteria for PRIS. CONCLUSIONS: Adherence to elements of an institutional propofol policy was variable. Improvements in policy adherence may be enhanced by updating policy features, leveraging the electronic medical record order-set, and gaining consensus among key stakeholders.

Methylnaltrexone in the Management of Opioid-Associated Urinary Retention in Children.

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.

Persistent hiccups associated with epidural ropivacaine in a newborn.

OBJECTIVE: To report a case of persistent hiccups associated with epidural ropivacaine in a newborn infant. CASE SUMMARY: A term female infant (3.05 kg) received epidural ropivacaine for pain control during and after an operative procedure to correct a tracheoesophageal fistula. Three intermittent doses of ropivacaine were administered during the operative period (total dose 2.29 mg/kg) followed by a continuous epidural (caudal) infusion (0.1% ropivacaine; initial dose 0.23 mg/kg/h plus fentanyl 0.46 µg/kg/h). The infant was extubated in the recovery area and transferred to the intensive care unit. Within hours of transfer, she developed persistent hiccups. The epidural infusion was titrated for pain control, up to 0.32 mg/kg/h (ropivacaine). The hiccup frequency increased to every 10-30 seconds, with the patient appearing hypotonic with lip trembling and intermittent tongue fasciculation. An electroencephalogram did not show any epileptiform activity or focal features consistent with seizure activity. The epidural infusion was reduced to 0.26 mg/kg/h (ropivacaine), with dramatic improvement in hiccups and tone. The infusion was discontinued and complete resolution of hiccups was observed. DISCUSSION: Ropivacaine is commonly used for infiltration anesthesia and peripheral and epidural block anesthesia. Use of the Naranjo probability scale determined that our patient's hiccups were probably caused by ropivacaine. To our knowledge, this is the first report of persistent hiccups associated with epidural ropivacaine. CONCLUSIONS: Clinicians should consider the potential of neurotoxicity, manifested as persistent hiccups, when epidural ropivacaine is administered to young infants.

Pediatric empyemas - Has the pendulum swung too far?

BACKGROUND: The management of childhood empyemas has transformed over the past decade, with current trends favoring chest tube placement and intrapleural fibrinolytic therapy. Although this strategy often avoids the need for video-assisted thoracoscopic surgery (VATS), hospital length of stay can be long. METHODS: To characterize national trends and outcomes associated with empyema management, the Pediatric Health Information System (PHIS) database was queried to identify children (2 months-18 years) treated for an empyema between January 2010 and December 2017. The cohort was divided into those treated with primary VATS and those treated with chest tube and intrapleural fibrinolysis. Number of chest radiographic studies obtained, frequency of pediatric intensive care unit (PICU) admission, mechanical ventilation requirements, and length of hospitalization were compared between groups. RESULTS: A total of 3,365 otherwise healthy children met inclusion criteria. Among them, 523 (16%) were managed with primary VATS and 2,842 (84%) were managed with chest tube and fibrinolytic therapy. Of those who were treated with chest tube and fibrinolysis, 193 (6.8%) subsequently underwent VATS. The percentage of children treated with chest tube and fibrinolysis increased from 65% in 2010 to 95% in 2017 (p<0.001). After adjusting for age, race, ethnicity, payer, and region, children who underwent primary VATS received fewer chest radiographic studies, were less likely to be admitted to the PICU or require mechanical ventilation and had a shorter PICU and hospital length of stay compared to those who were treated with chest tube and fibrinolytic therapy (p<0.001 for all analyses). DISCUSSION: Although national trends favor chest tube and fibrinolysis, primary VATS are associated with a shorter hospital and PICU length of stay and a lower requirement for mechanical ventilation. Future studies should aim to risk stratify children who may suffer from a protracted course with the goal to offer primary VATS to this subset of children and return them to normal life more expeditiously. LEVEL OF EVIDENCE: III.

Evaluation of off-label recombinant activated factor VII for multiple indications in children.

Despite a paucity of safety and efficacy data, the use of recombinant activated factor VII in children for off-label indications has now surpassed its use in hemophilia. A retrospective chart review was conducted of 46 subjects (age, 6.7 +/- 6 years; weight, 26 +/- 20 kg) who received recombinant activated factor VII for nonhemophiliac indications between January 1, 2004, and September 1, 2005. Indications for use included prevention (n = 6) or treatment (n = 40) of bleeding due to general surgery, hepatic failure, gastrointestinal bleeding, severe traumatic brain injury, bone marrow transplant, cardiac, acetaminophen overdose, and multiorgan system failure. Decreases in prothrombin time, partial thromboplastin time, and international normalized ratio were observed. No inappropriate thrombotic events were noted. Administration of recombinant activated factor VII was associated with a reduction in coagulation markers without obvious adverse thrombotic events at cost of $4189 per dose. These findings should be confirmed in a prospective trial.

Vancomycin disposition and penetration into ventricular fluid of the central nervous system following intravenous therapy in patients with cerebrospinal devices.

OBJECTIVE/AIMS: To determine the cerebrospinal fluid concentrations and percent CNS penetration of intravenous vancomycin in patients with cerebrospinal devices at a pediatric institution. METHODS: We performed a prospective evaluation of intravenous (IV) vancomycin in patients who received a single prophylactic dose of vancomycin (15-20 mg/, maximum dose 1 g) prior to insertion of a CNS shunt (group I) or a therapeutic regimen (a dose of 10-20 mg/kg every 6-12 h) for a documented/suspected shunt infection (group II). Ventricular cerebrospinal fluid (VCSF) samples were taken during the procedure in group I and multiple serum and VCSF samples were collected in group II. Pharmacokinetic parameters were calculated using a one-compartment model, and percent CNS penetration was estimated using area-under-the-curve methodology. RESULTS: Group I: 21 VCSF samples were analyzed from 19 patients (mean age 7.2 +/- 6.4 years). Over 40% of samples failed to have detectable vancomycin concentrations (range 0-2 microg/ml). Group II: 6 patients (mean age 11 +/- 8.7 years) had VCSF concentrations ranging from nondetectable to 6.59 microg/ml (mean 2.48 +/- 0.52 microg/ml). Percent penetration ranged from 0.77 to 18%. CONCLUSIONS: Single-dose, pre-operative vancomycin results in low VCSF vancomycin concentrations and repeated dosing in patients with documented/presumed device infections yields variable CNS penetration.