Mark G. Roback

Risk factors for cerebral edema in children with diabetic ketoacidosis

BACKGROUND Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined. METHODS In this multicenter study, we identified 61 children who had been hospitalized for diabetic ketoacidosis within a 15-year period and in whom cerebral edema had developed. Two additional groups of children with diabetic ketoacidosis but without cerebral edema were also identified: 181 randomly selected children and 174 children matched to those in the cerebral-edema group with respect to age at presentation, onset of diabetes (established vs. newly diagnosed disease), initial serum glucose concentration, and initial venous pH. Using logistic regression we compared the three groups with respect to demographic characteristics and biochemical variables at presentation and compared the matched groups with respect to therapeutic interventions and changes in biochemical values during treatment. RESULTS A comparison of the children in the cerebral-edema group with those in the random control group showed that cerebral edema was significantly associated with lower initial partial pressures of arterial carbon dioxide (relative risk of cerebral edema for each decrease of 7.8 mm Hg [representing 1 SD], 3.4; 95 percent confidence interval, 1.9 to 6.3; P<0.001) and higher initial serum urea nitrogen concentrations (relative risk of cerebral edema for each increase of 9 mg per deciliter [3.2 mmol per liter] [representing 1 SD], 1.7; 95 percent confidence interval, 1.2 to 2.5; P=0.003). A comparison of the children with cerebral edema with those in the matched control group also showed that cerebral edema was associated with lower partial pressures of arterial carbon dioxide and higher serum urea nitrogen concentrations. Of the therapeutic variables, only treatment with bicarbonate was associated with cerebral edema, after adjustment for other covariates (relative risk, 4.2; 95 percent confidence interval, 1.5 to 12.1; P=0.008). CONCLUSIONS Children with diabetic ketoacidosis who have low partial pressures of arterial carbon dioxide and high serum urea nitrogen concentrations at presentation and who are treated with bicarbonate are at increased risk for cerebral edema.

Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update.

We update an evidence-based clinical practice guideline for the administration of the dissociative agent ketamine for emergency department procedural sedation and analgesia. Substantial new research warrants revision of the widely disseminated 2004 guideline, particularly with respect to contraindications, age recommendations, potential neurotoxicity, and the role of coadministered anticholinergics and benzodiazepines. We critically discuss indications, contraindications, personnel requirements, monitoring, dosing, coadministered medications, recovery issues, and future research questions for ketamine dissociative sedation.

Predictors of Airway and Respiratory Adverse Events With Ketamine Sedation in the Emergency Department: An Individual-Patient Data Meta-analysis of 8,282 Children

STUDY OBJECTIVE Although ketamine is one of the most commonly used sedatives to facilitate painful procedures for children in the emergency department (ED), existing studies have not been large enough to identify clinical factors that are predictive of uncommon airway and respiratory adverse events. METHODS We pooled individual-patient data from 32 ED studies and performed multiple logistic regressions to determine which clinical variables would predict airway and respiratory adverse events. RESULTS In 8,282 pediatric ketamine sedations, the overall incidence of airway and respiratory adverse events was 3.9%, with the following significant independent predictors: younger than 2 years (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.47 to 2.72), aged 13 years or older (OR 2.72; 95% CI 1.97 to 3.75), high intravenous dosing (initial dose > or =2.5 mg/kg or total dose > or =5.0 mg/kg; OR 2.18; 95% CI 1.59 to 2.99), coadministered anticholinergic (OR 1.82; 95% CI 1.36 to 2.42), and coadministered benzodiazepine (OR 1.39; 95% CI 1.08 to 1.78). Variables without independent association included oropharyngeal procedures, underlying physical illness (American Society of Anesthesiologists class >or = 3), and the choice of intravenous versus intramuscular route. CONCLUSION Risk factors that predict ketamine-associated airway and respiratory adverse events are high intravenous doses, administration to children younger than 2 years or aged 13 years or older, and the use of coadministered anticholinergics or benzodiazepines.

Consensus-Based Recommendations for Standardizing Terminology and Reporting Adverse Events for Emergency Department Procedural Sedation and Analgesia in Children

Children commonly require sedation and analgesia for procedures in the emergency department. Establishing accurate adverse event and complications rates from the available literature has been difficult because of the difficulty in aggregating results from previous studies that have used varied terminology to describe the same adverse events and outcomes. Further, serious adverse events occur infrequently, necessitating the study of large numbers of children to assess safety. These limitations prevent the establishment of a sufficiently large database on which evidence-based practice guidelines may be based. We assembled a panel of pediatric sedation researchers and experts to develop consensus-based recommendations for standardizing procedural sedation and analgesia terminology and reporting of adverse events. Our goal was to create a uniform reporting mechanism for future studies to facilitate the aggregation and comparison of results.

Predictors of Emesis and Recovery Agitation With Emergency Department Ketamine Sedation: An Individual-Patient Data Meta-Analysis of 8,282 Children

STUDY OBJECTIVE Ketamine is widely used in emergency departments (EDs) to facilitate painful procedures; however, existing descriptors of predictors of emesis and recovery agitation are derived from relatively small studies. METHODS We pooled individual-patient data from 32 ED studies and performed multiple logistic regression to determine which clinical variables would predict emesis and recovery agitation. The first phase of this study similarly identified predictors of airway and respiratory adverse events. RESULTS In 8,282 pediatric ketamine sedations, the overall incidence of emesis, any recovery agitation, and clinically important recovery agitation was 8.4%, 7.6%, and 1.4%, respectively. The most important independent predictors of emesis are unusually high intravenous (IV) dose (initial dose of > or =2.5 mg/kg or a total dose of > or =5.0 mg/kg), intramuscular (IM) route, and increasing age (peak at 12 years). Similar risk factors for any recovery agitation are low IM dose (<3.0 mg/kg) and unusually high IV dose, with no such important risk factors for clinically important recovery agitation. CONCLUSION Early adolescence is the peak age for ketamine-associated emesis, and its rate is higher with IM administration and with unusually high IV doses. Recovery agitation is not age related to a clinically important degree. When we interpreted it in conjunction with the separate airway adverse event phase of this analysis, we found no apparent clinically important benefit or harm from coadministered anticholinergics and benzodiazepines and no increase in adverse events with either oropharyngeal procedures or the presence of substantial underlying illness. These and other results herein challenge many widely held views about ED ketamine administration.

Effect of Ondansetron on the Incidence of Vomiting Associated With Ketamine Sedation in Children: A Double-Blind, Randomized, Placebo-Controlled Trial

STUDY OBJECTIVE We investigate the effect of ondansetron on the incidence of vomiting in children who receive intravenous (IV) ketamine for procedural sedation and analgesia in the emergency department (ED). METHODS In this double-blind, randomized, placebo-controlled trial in a childrens hospital ED, patients receiving IV ketamine (1 mg/kg) for ED procedures were randomized to receive either IV ondansetron (0.15 mg/kg; maximum 4 mg) or identical placebo. We recorded whether vomiting occurred in the ED postsedation or up to 12 hours after discharge with telephone follow-up and compared ED length of stay and parental satisfaction. RESULTS One hundred twenty-seven children were randomized to placebo and 128 to ondansetron. The groups were similar in age, sex, and fasting duration. ED vomiting was less common with ondansetron: 6 of 128 (4.7%) versus 16 of 127 (12.6%), P=.02, difference 7.9% (95% confidence interval 1.1% to 14.7%), number needed to treat 13. Follow-up was successful in 82.7%, with vomiting in the ED or after discharge less frequent with ondansetron: 10 of 128 (7.8%) versus 24 of 127 (18.9%), P=.01, difference 11.1% (95% confidence interval 2.7% to 19.5%), number needed to treat 9. ED length of stay and parental satisfaction were similar between groups. CONCLUSION IV ondansetron significantly reduces the incidence of vomiting associated with IV ketamine procedural sedation in children.

Pediatric rapid sequence intubation: Incidence of reflex bradycardia and effects of pretreatment with Atropine

Background: The American College of Emergency Physicians (ACEP) recommends atropine as adjunctive therapy to prevent reflex bradycardia prior to laryngoscopy/tracheal intubation (L/TI) in pediatric patients. Objective: To describe the incidence of reflex bradycardia and its relationship to the administration of atropine during L/TI in a Pediatric Emergency Department. Design/Methods: A retrospective cohort study was designed through review of records of all patients who received L/TI in the ED at an urban childrens hospital from January 1997 to March 2001. Patients meeting inclusion criteria were placed into cohorts defined by whether they had received atropine prior to L/TI or not. Results: One hundred sixty-three patients received L/TI during the study period. One hundred forty-three patients met inclusion criteria. Sixty-eight patients received atropine (atropine group) prior to L/TI. Seventy-two percent of atropine group patients met ACEP criteria for atropine pretreatment. Seventy-five patients did not receive atropine pretreatment (no-atropine group). Forty-three percent of no-atropine group patients met ACEP criteria for pretreatment with atropine. The atropine group was younger [mean 22.5 vs. 36.4 months, P = 0.003, 95% CI (−28.5, 0.70)], averaged the same number of intubation attempts [1.6 vs. 1.5, P = 0.941, 95% CI 0.1 (−0.3,0.4)], and had normal or elevated HR for age prior to L/TI (mean 159 bpm). Hypoxia occurred more often in the atropine group [28% vs. 16%, P = 0.046, 95% CI for difference (0.3, 27.1)]. Bradycardia was noted in 6 patients during L/TI; 3 in the atropine group and 3 in the no-atropine group. Conclusion: Atropine is not routinely administered prior to L/TI in this pediatric ED. Pretreatment with atropine did not prevent bradycardia in all cases. These data suggest that use of atropine prior to L/TI may not be required for all pediatric patients. Some patients will experience bradycardia regardless of atropine pretreatment.

Chest radiograph in the evaluation of first time wheezing episodes: Review of current clinical practice and efficacy

Objective To evaluate the current clinical use and utility of chest radiographs (CXR) in the workup of pediatric patients with first time wheezing (FTW) episodes. Setting Urban childrens hospital. Design Retrospective review of medical records of patients seen in the emergency department in 1994 with disposition diagnoses of asthma or reactive airways disease, bronchiolitis, pneumonia, congenital heart disease, congestive heart failure, or foreign body aspiration to identify those patients presenting with FTW episodes. Methods Clinical findings in FTW were compared in patients receiving a CXR (121,41%) and those who did not (177, 59%). Comparisons were made between patients with a clinically significant CXR (CXR-pos) (29, 24%) and those without (92,76%). CXR-pos was defined as a CXR result which would be expected to alter patient management. Comparisons between groups were analyzed using the two-tailed Students t test for continuous variables and the χ2 statistic for categorical data. The level of significance was determined at P < 0.05. Results Two hundred ninety-eight episodes of FTW were identified of 1984 patient charts reviewed. Patients receiving CXR differed from those who did not by being of a greater age (39 vs 20 months, P < 0.01), having lower pulse oximetry (89.7 vs. 92.7%, P < 0.01), being less likely to have a family history of asthma (47.5 vs 63.2%, P < 0.01), or history of atopy (40.6 vs 59.4%, P < 0.01). Those with localized wheezes (59.4 vs 40.6% P < 0.01), localized rales (593 vs 40.7% P < 0.01), and localized decreased breath sounds (59.3 vs 40.7%, P = 0.01) were also more likely to receive a CXR. Among patients receiving CXR, clinical characteristics associated with CXR-pos were elevated temperature (37.9 vs 37.5°C, P = 0.04), absence of family history of asthma 72.6 vs 27.4%, P < 0.01), and the presence of localized wheezes (76.0 vs 24.0%, P = 0.02), or localized rales (76.0 vs 24.0%, P < 0.01). Conclusions Clinicians in this setting do not routinely obtain a CXR in patients with FTW episodes. Retrospective examination of clinician practice revealed several clinical characteristics that were associated with increased use of CXR in FTW. Increased utility of the CXR was associated with patients having elevated temperature, an absence of a family history of asthma, and localized wheezes or rales by ausculatory examination.

Failure of oxygen saturation and clinical assessment to predict which patients with bronchiolitis discharged from the emergency department will return requiring admission

Objective. To determine if there is a difference between patients with bronchiolitis who are discharged from the emergency department (ED) but return requiring admission and those who do not return. Design. Retrospective, case control study. Setting. Tertiary care childrens hospital emergency department Participants. Fifty-seven study patients under one year of age with bronchiolitis seen from November 1991 to April 1993 who were discharged but returned requiring admission within 96 hours, and 124 controls, matched by diagnosis, who did not return. Results No differences were found between cases and controls in duration of illness (3.0 vs 3.7 days, P = 0.08), gestational age (39.3 vs 38.8 weeks, P = 0.32), chronologic age (20.9 vs 22.9 weeks, P = 0.31), respiratory rate (49.9 vs 48.0 respirations/ min, P = 0.18), presence of retractions (54.8 vs 54.4%, P = 0.97), oxygen saturation (SaO2; 97.6 vs 98.0%, P = 0.29), or number of nebulized β-agonists administered in the ED (1.4 vs 1.2 P = 0.35). Cases had higher mean heart rates (HR) than controls (154.8 vs 148.8, P = 0.006). Patients with HR >150 were more likely to return requiring admission (odds ratio = 2.45, 95% confidence intervals 1.2–4.9). However, only 36 of 57 patients who returned requiring admission had HR >150 (sensitivity = 0.63), and 73 of 124 who did not return had HR ≥

Activated protein C concentrate for the treatment of meningococcal endotoxin shock in rabbits

150 (specificity = 0.59). None of the returns required admission to the intensive care unit, and their mean duration of admission was 59 hours. At the time of admission the cases had lower SaO2 (95.9 vs 97.7 %, P = 0.001) and a higher frequency of retractions (83.3 vs 52.6%, P = 0.02) than when seen initially. Conclusions. Oxygen saturation and clinical assessment failed to differentiate between patients with bronchiolitis who returned requiring admission and patients who did not return.