Kim W. Benner

Pediatric off-label use of recombinant factor VIIa.

OBJECTIVE. Our goal was to report our institutional experience with recombinant factor VIIa for the treatment and/or prevention of bleeding in nonhemophiliac children. METHODS. This was a retrospective case series in a tertiary pediatric referral hospital. RESULTS. During 1999–2006, 135 patients received recombinant factor VIIa for off-label use. The median number of doses was 2; the median dose was 88 μg/kg. The most common diagnoses among patients receiving recombinant factor VIIa were disseminated intravascular coagulation/sepsis (28), surgical bleeding (19), procedural prophylaxis (16), and trauma (15). The median volume of blood products administered 24 hours before recombinant factor VIIa treatment was 29.7 vs 11.7 mL/kg 24 hours after treatment. Only 1 high-risk patient had significant bleeding after receiving prophylactic recombinant factor VIIa before an invasive procedure. Nonsurvivors had significantly increased incidence of multiple organ dysfunction syndrome (75%) compared with survivors (23%). The largest group of patients (n = 28) received recombinant factor VIIa for bleeding and/or coagulopathy because of disseminated intravascular coagulation; the mortality in this group was 26 (93%) of 28. Eleven patients received multiple doses of recombinant factor VIIa to treat bleeding complications after hematopoietic stem cell transplant, without improvement in blood use. Mortality in medical patients was 58% vs 16% in surgical patients. Three patients had significant thrombotic adverse events after receiving recombinant factor VIIa, resulting in 2 deaths and 1 leg amputation. CONCLUSIONS. Off-label use of recombinant factor VIIa significantly decreases blood-product administration; surgical patients had control of life-threatening bleeding with low associated mortality. Prophylactic recombinant factor VIIa may be effective in preventing bleeding if given before invasive procedures in children at high risk. Prolonged use of recombinant factor VIIa for bleeding complications after hematopoietic stem cell transplant is not effective in preventing packed red blood cell transfusion. Presence of disseminated intravascular coagulation and mulitorgan dysfunction syndrome may help predict futility of recombinant factor VIIa treatment. Off-label use of recombinant factor VIIa is associated with thromboembolic events in children.

Severe invasive community-associated methicillin-resistant Staphylococcus aureus infections in previously healthy children.

Objective: An increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections has been reported in the literature. Most severe, life-threatening infections were previously thought to be associated with chronically ill or frail patients. Our pediatric intensive care unit (PICU) has seen a recent dramatic increase in primary, severe invasive CA-MRSA infections in healthy children. Design/Setting: A retrospective chart review of all previously healthy patients admitted to our 19-bed combined medical-surgical PICU with a primary diagnosis of severe invasive, culture-proven CA-MRSA disease during the past 6 years. Results: Eleven previously healthy patients were admitted to our PICU with severe, primary, invasive CA-MRSA infections from March 2006 through September 2007, in contrast to no patients meeting these criteria in the preceding 5 years. The mortality rate was 27%, compared with an overall PICU mortality rate during the study period of <7%. The mean PICU length of stay of these patients was 14.9 days, compared with an average PICU length of stay of 2.4 days. Despite initiation of treatment with vancomycin at admission to the PICU in all but one case, patients took a mean of 5.7 days to convert to negative blood cultures. Eight patients had bacteremia longer than 4 days. Six of the patients developed bilateral necrotizing pneumonia requiring prolonged mechanical ventilation. Conclusions: Severe CA-MRSA infections in healthy children are increasing at an alarming rate in our institution. This acute rise in incidence, coupled with an alarmingly high associated mortality rate, raises important questions about the initial empirical antibiotic therapy we use in caring for patients presenting with suspected life-threatening CA-MRSA disease. Vancomycin monotherapy may not be adequate treatment for severe CA-MRSA infections.

The use of enteral naloxone to treat opioid-induced constipation in a pediatric intensive care unit.

Objective: To describe the effects of enteral naloxone used to treat opioid-induced constipation in pediatric intensive care patients. Design: Retrospective chart review. Setting: Pediatric intensive care unit. Patients: Twenty-three patients who received opioid therapy and enteral naloxone in our institution from January 2003 to February 2004 were compared with a randomly sampled control group matched for age, weight, sex, and length of stay who received opioids but had not received enteral naloxone. Interventions: None. Measurements: Daily stool output, daily opiate usage, nutrition, adjuvant laxative use, and side effects were assessed. Results: Patients stayed an average of 5 days (range, 0–13 days) in the pediatric intensive care unit before enteral administration of naloxone was instituted and received it for an average of 9 consecutive days (range, 3–30 days). Mean stool output for study patients before administration of enteral naloxone was 0.14 ± 0.38 stools per day, whereas after its initiation it was 1.60 ± 1.14 stools per day (p < .001). However, two patients developed significant opiate withdrawal symptoms after receiving enteral naloxone. The average stool output for control patients was 0.53 ± 1.21 stools per day. Conclusions: Enteral naloxone may be effective in increasing stool output in opioid-induced constipation but carries the risk of introducing withdrawal symptoms. Further studies are needed to evaluate this agent for opioid-induced constipation in the intensive care unit.

Correlation of vancomycin dosing to serum concentrations in pediatric patients: a retrospective database review.

OBJECTIVES Appropriate antimicrobial dosing maximizes therapeutic benefit while minimizing development of antimicrobial resistance. Common pediatric references recommend vancomycin dosing of 40 mg/kg/day divided every 6 to 8 hours for non-central nervous system infections, while some clinicians report utilizing higher initial doses to optimize efficacy. This study compares vancomycin serum concentrations following traditional dosing of 10 mg/kg/dose every 6 to 8 hours versus 15 to 20 mg/kg/dose every 6 to 8 hours. STUDY DESIGN Retrospective database review of vancomycin serum concentrations in pediatric patients. RESULTS Three hundred fifty-seven patients were analyzed. The mean peak concentration of the 10 mg/kg groups every 6 and every 8 hours were below 25 mg/L, whereas the mean peak concentrations of the 15 mg/ kg groups every 6 and 8 hours were within the 25-40 mg/L range (p < 0.001). The mean trough concentration of the 10 mg/kg group every 6 hours was within the 5-15 mg/L range while the 10 mg/kg group dosed every 8 hours was below target. However, the mean trough concentrations of the 15 mg/kg group dosed every 6 and 8 hours were both within the 5-15 mg/L range (p < 0.001). CONCLUSIONS Vancomycin doses of 15 mg/kg every 6 to 8 hours produce peak and trough serum concentrations within target range more often than 10 mg/kg every 6 to 8 hours.

Fatal Hypermagnesemia Caused by an Epsom Salt Enema: A Case Illustration

The authors describe a case of fatal hypermagnesemia caused by an Epsom salt enema. A 7-year-old male presented with cardiac arrest and was found to have a serum magnesium level of 41.2 mg/dL (33.9 mEq/L) after having received an Epsom salt enema earlier that day. The medical history of Epsom salt, the common causes and symptoms of hypermagnesemia, and the treatment of hypermagnesemia are reviewed. The easy availability of magnesium, the subtle initial symptoms of hypermagnesemia, and the need for education about the toxicity of magnesium should be of interest to physicians.

Epidemiology of Infections Due to Extended-Spectrum Beta-Lactamase-Producing Bacteria in a Pediatric Intensive Care Unit

OBJECTIVES To determine the proportion of infections caused by extended-spectrum ß-lactamase (ESBL)-producing Klebsiella or Escherichia coli Gram-negative organisms in the pediatric intensive care unit (PICU), and to identify risk factors for these infections. METHODS A retrospective, single-center chart review of patients admitted to a PICU in a 5-year period with infections caused by Klebsiella species or E coli was completed. Data collected include demographics, length of stay, outcome, and relevant risk factors previously defined in the literature. RESULTS A total of 110 isolates were cultured from 94 patients. A total of 53% of the isolates were E coli, and the remainder were Klebsiella subspecies. Of the 110 isolates, 13 isolates (11.8%) in 7 patients were ESBL positive. The ESBL-producing isolates were equally distributed amongE coli and Klebsiella and were primarily cultured from tracheal aspirates. Most of the ESBL-positive isolates (9 of 13; 69%) were cultured from patients who received ceftazidime and/or cefotaxime in the preceding 30 days. Patients infected with E coli had higher PRISM 1 scores and were more likely to have a Foley catheter, whereas infections with Klebsiella were more common in mechanically ventilated males. Although not statistically significant, 80% of patients who were infected with non-ESBL-producing organisms survived to hospital discharge versus 57% of those infected with ESBL-producing E coli and Klebsiella. CONCLUSIONS Almost 12% of E coli and Klebsiella isolates in this patient population tested positive for ESBL production. ESBL production was equally distributed between E coli and Klebsiella species. These organisms were cultured from 7% of the study patients. As reported in previous studies, patients infected with ESBL-producing organisms most often had received prior cephalosporins and had a longer length of stay in the PICU.

ASHP therapeutic position statement on the institutional use of 0.9% sodium chloride injection to maintain patency of peripheral indwelling intermittent infusion devices.

0.9% Sodium chloride injection is a safe and effective indwelling solution for maintaining catheter patency of peripheral indwelling intermittent infusion devices (PIIIDs) in adults and children age one year or older. ASHP supports the use of 0.9% sodium chloride injection in preference to heparin-

Meperidine restriction in a pediatric hospital.

BACKGROUND Much has been published revealing concerns surrounding the use of meperidine due to associated toxicities, drug interactions, and lack of proven efficacy. Thus, many adult institutions have chosen to remove or limit the use of this agent, while little has been published about the restriction of meperidine in pediatrics. Many clinicians feel there are still clinical situations in which this agent may be useful. OBJECTIVE To describe methods taken in a pediatric hospital to restrict the use of meperidine and review literature describing uses of meperidine as a second-line agent. METHODS In our pediatric institution, a policy to restrict the use of meperidine was developed, approved, and implemented. An assessment of meperidines use 6 months prior to policy implementation was done, along with a postinitiation review of use. RESULTS Data revealed that the use of meperidine dropped from 646 doses in 84 patients to 226 doses in 27 patients after restriction, as anticipated. Previous to implementation of these restrictions, orthopedics physicians ordered the majority of meperidine prescriptions, while the gastroenterology service ordered the majority of meperidine prescriptions after implementation of the restriction policy. However, the use of the required form was not widely adopted, with only 30% of practitioners utilizing it postrestriction. Widespread restriction of meperidine and education about use of the form at this institution are still under way. CONCLUSION Not only are there limited reasons for using meperidine, there are acceptable alternatives for every known indication. Limiting meperidines use via a restriction policy and/or removal from the institution formulary can help limit the use of this potentially toxic agent in the pediatric patient.

Knowledge Gain of Pharmacy Students and Pharmacists Comparing Simulation Versus Traditional Learning Methodology

OBJECTIVES: The purpose of this study was to evaluate the difference between education via written materials alone and written materials enhanced with hands-on simulation. METHODS: A simulation case, educational module, and assessment regarding torsades de pointes (TdP) in an adolescent patient were designed. The written educational module was given to all study participants. A total of 92 third-year pharmacy students and 26 pharmacists participated in the study. RESULTS: When approximately half of the participants had been to simulation, an anonymous assessment was given. Responses from those who had been to simulation and those who had not, and whether they had read, skimmed or not read the educational material were compared. A non-paired Student t-test compared the percentage correct and responses of individual questions between groups. Mean participant scores of those who went to simulation (70% ± 16%) were statistically significantly higher than mean scores of those who had not attended simulation (54% ± 21%; p<0.0001). Furthermore, those who attended simulation and read the module (72% ± 3%), skimmed (68% ± 13%), or did not read the module (66% ± 16%) had higher scores than those who did not attend simulation and read the module (62% ± 26%), skimmed the module (54 ± 17%) or did not read the module (51% ± 20%). CONCLUSIONS: Hands-on simulation significantly improved assessment scores. Overall, reading the educational module and participating in simulation yielded the best scores. Participants who attended the simulation and did not read the module had higher average scores than participants who read the educational module and did not go to simulation.

Board #115 - Research Abstract Evaluating the Education of Pharmacy Students and Pharmacists at a Pediatric Hospital Using an Educational Module and Simulation Training Versus Educational Module Alone (Submission #10181)

Hypothesis Simulation training provides hands on experience in a safe environment, where students and clinicians are able to practice without any risk of harming a patient. Pharmacists and pharmacy students are often educated with print-based or online reading materials and lectures; simulation training, however, provides a unique opportunity for advancing clinical competence and education by presenting a realistic patient case in a low-risk environment. This project aimed to evaluate the difference between pharmacy education via written materials alone and pharmacy education via written materials plus hands-on simulation. Methods A simulation case, educational module, and assessment regarding torsades de pointes (TdP) in an adolescent patient were designed for this study. Third-year pharmacy students attending simulation and pharmacists employed by Children’s of Alabama were included. The written educational module was given to all participants at least 10 days prior to attending simulation. The anonymous assessment was given to all third-year pharmacy students and pharmacists at a time when approximately half of the participants had been to simulation. The assessment included demographic information; whether or not the participant had been to simulation regarding TdP within the last thirty days; whether or not the participant had read, skimmed, or not read the module; and assessed clinical concepts addressed in the module and in simulation. The aNew South Walesers from those who had been to simulation and those who had not, and whether they had read, skimmed or not read the educational material were compared. Results Ninety-two students and 26 pharmacists took the assessment. At the time of the assessment, 48 of the students and 13 of the pharmacists had been to simulation. 41.5% reported reading, 37.3% reported skimming, and 21.2% reported not reading the module. A non-paired t-test was used to compare the percentage of total correct aNew South Walesers and aNew South Walesers of individual questions between groups. The mean score of all participants was 62 ± 20, and there was no statistically significant difference between raw scores of students and pharmacists (p=0.245). Mean scores of participants who went to simulation (70 ± 16) were statistically significantly higher than scores of those who had not attended simulation (54 ± 21) (p<0.0001). Further, those who attended simulation and read the module (72 ± 3), skimmed (68 ± 13), or did not read the module (66 ± 16) had higher mean scores than those who did not attend simulation and read the module (62 ± 26), skimmed the module (54 ± 17), or did not read the module (51 ± 20). Conclusion Hands-on simulation education has a statistically significant positive effect on assessment scores. Overall, reading the educational module and participating in simulation yielded the best scores. Participants who attended the simulation and did not read the module had higher average scores than participants who read the educational module and those who did not go to simulation. The data from this study imply that simulation training is beneficial and has an important role in the education of healthcare professionals and students. Disclosures None