Karen Lidsky

Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children

BACKGROUND Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS We conducted this trial of two targeted temperature interventions at 38 childrens hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Pharmacology of inotropic agents in infants and children.

Inotropic agents are drugs which increase the stroke work of the heart at a given pre-load and after-load. All of these agents work through a final common pathway involving the modulation of calcium interactions with various myocardial contractile proteins. The agents employed with pediatric patients include the cardial glycosides, catecholamine beta-agonists and the selective phosphodiesterase III inhibitors. Digoxin is the prototypic cardiac glycoside which has a long history of safe and effective use in infants and children. Its utility in improving right ventricular dysfunction in patients with cor pulmonale leading to biventricular dysfunction makes it ideally suited to the pediatric population. Monitoring digoxin pharmacokinetics in infants is confounded by the presence of an endogenous digoxin-like substance. Nevertheless, the drug is well suited for subacute and chronic myocardial support. In contrast, the catecholamines are the drugs of choice for acute intervention. Their pharmacokinetics permit rapid dosing titration. In infants and children the greatest experience has been accrued with dopamine, a mixed alpha- and beta-agonist but both epinephreine and norepinephrine are being used with increasing frequency as the need for drugs with increased potency and pressor activity becomes more common. The phosphodiesterase inhibitors amrinone and milrinone are the newest additions to our therapeutic armamentarium. In addition to their modest inotropic effects, amrinone and to a greater extent, milrinone offer significant pulmonary vasodilatation as part of their therapeutic package. These effects occur with little or any impact on myocardial oxygen consumpton while their lusitropic effects enhance relaxation in hypertrophied ventricular muscle. Of the two agents milrinone is probably preferred due to its greater therapeutic index and shorter elimination half-life. All of these agents remain important tools in the care of critically ill infants and children. The rational use of these drugs based upon their pharmacokinetic and pharmacodynamic properties is essential to achieve their optimal effects.

Predictors of Complications of Tonsillectomy With or Without Adenoidectomy in Hospitalized Children and Adolescents in the United States, 2001-2010: A Population-Based Study

Outcomes of tonsillectomy (with or without adenoidectomy [w/woA]) in hospitalized children are unclear. We sought, to describe the characteristics of hospitalized children who underwent tonsillectomy (w/woA), to estimate the prevalence of complications and to evaluate the relative impact of different comorbid conditions (CMC) on the risk of occurrence of common complications following these procedures. All patients aged ≤21years who underwent a tonsillectomy (w/woA) were selected from the Nationwide Inpatient Sample (NIS 2001-2010). The associations between several patient/hospital-level factors and occurrence of complications were generated using multivariable logistic regression models. Over a decade, a total of 141 599 hospitalized patients underwent tonsillectomy (w116 319; woA 25 280). A total of 58.1% were males. Majority of the procedures were performed in teaching hospitals (TH, 73.7%), in large (bed-size) hospitals (LH, 57.8%), and in those who were electively admitted (EA, 67.3%). Frequently present CMC in patients included obstructive sleep apnea (OSA, 26.4%), chronic pulmonary disease (CPD, 14.6%), neurological disorders (ND, 6.7%), and obesity (4.8%). Majority of patients were discharged routinely (98%). Overall complication rate was 6.4% with common complications being postoperative pneumonia (2.3%), bacterial infections (1.4%), respiratory complications (1.3%), and hemorrhage (1.2%). All-cause mortality included a total of 60 patients. Patients in TH (odds ratio [OR] = 0.72, 95%CI = 0.62-0.85), LH (OR = 0.80, 95% CI = 0.69-0.93), and those who had the procedures during EA (OR = 0.64, 95% CI = 0.56-0.74) had significantly lower odds of complications compared with their counterparts. CMC such as anemia, CPD, coagulopathy, HT, ND, and fluid/electrolyte disorders were independent predictors of significantly higher complication risk (P < .05). In conclusion, hospitalized children who underwent tonsillectomy (w/woA) in large or teaching hospitals, or during elective admissions had lower risk of complications. Comorbidity is an important independent predictor of complications in this cohort.

Feasibility Study Evaluating Therapeutic Hypothermia for Refractory Status Epilepticus in Children

Pediatric refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality, which lacks consensus regarding diagnosis and treatment(s). Therapeutic hypothermia (TH) is an effective treatment for RSE in preclinical models and small series. In addition, TH is a standard care for adults after cardiac arrest and neonates with hypoxic-ischemic encephalopathy. The purpose of this study was to identify the feasibility of a study of pediatric RSE within a research group (Pediatric Neurocritical Care Research Group [PNCRG]). Pediatric intensive care unit (PICU) admissions at seven centers were prospectively screened from October 2012 to July 2013 for RSE. Experts within the PNCRG estimated that clinicians would be unwilling to enroll a child, unless the child required at least two different antiepileptic medications and a continuous infusion of another antiepileptic medication with ongoing electrographic seizure activity for ≥2 hours after continuous infusion initiation. Data for children meeting the above inclusion criteria were collected, including the etiology of RSE, history of epilepsy, and maximum dose of continuous antiepileptic infusions. There were 8113 PICU admissions over a cumulative 52 months (October 2012-July 2013) at seven centers. Of these, 69 (0.85%) children met inclusion criteria. Twenty children were excluded due to acute diagnoses affected by TH, contraindications to TH, or lack of commitment to aggressive therapies. Sixteen patients had seizure cessation within 2 hours, resulting in 33 patients who had inadequate seizure control after 2 hours and a continuous antiepileptic infusion. Midazolam (21/33, 64%) and pentobarbital (5/33, 15%) were the most common infusions with a wide maximum dose range. More than one infusion was required for seizure control in four patients. There are substantial numbers of subjects at clinical sites within the PNCRG with RSE that would meet the proposed inclusion criteria for a study of TH. The true feasibility of such a study depends on the sample size necessary to achieve therapeutic effects on justifiable clinical outcomes.

Association of early postresuscitation hypotension with survival to discharge after targeted temperature management for pediatric out-of-hospital cardiac arrest secondary analysis of a randomized clinical trial

Importance Out-of-hospital cardiac arrest (OHCA) occurs in more than 6000 children each year in the United States, with survival rates of less than 10% and severe neurologic morbidity in many survivors. Post–cardiac arrest hypotension can occur, but its frequency and association with survival have not been well described during targeted temperature management. Objective To determine whether hypotension is associated with survival to discharge in children and adolescents after resuscitation from OHCA. Design, Setting, and Participants This post hoc secondary analysis of the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trial included 292 pediatric patients older than 48 hours and younger than 18 years treated in 36 pediatric intensive care units from September 1, 2009, through December 31, 2012. Participants underwent therapeutic hypothermia (33.0°C) vs therapeutic normothermia (36.8°C) for 48 hours. All participants had hourly systolic blood pressure measurements documented during the initial 6 hours of temperature intervention. Hourly blood pressures beginning at the time of temperature intervention (time 0) were normalized for age, sex, and height. Early hypotension was defined as a systolic blood pressure less than the fifth percentile during the first 6 hours after temperature intervention. With use of forward stepwise logistic regression, covariates of interest (age, sex, initial cardiac rhythm, any preexisting condition, estimated duration of cardiopulmonary resuscitation [CPR], primary cause of cardiac arrest, temperature intervention group, night or weekend cardiac arrest, witnessed status, and bystander CPR) were evaluated in the final model. Data were analyzed from February 5, 2016, through June 13, 2017. Exposures Hypotension. Main Outcomes and Measure Survival to hospital discharge. Results Of 292 children (194 boys [66.4%] and 98 girls [33.6%]; median age, 23.0 months [interquartile range, 5.0-105.0 months]), 78 (26.7%) had at least 1 episode of early hypotension. No difference was observed between the therapeutic hypothermia and therapeutic normothermia groups in the prevalence of hypotension during induction and maintenance (73 of 153 [47.7%] vs 72 of 139 [51.8%]; P = .50) or rewarming (35 of 118 [29.7%] vs 19 of 95 [20.0%]; P = .10) during the first 72 hours. Participants who had early hypotension were less likely to survive to hospital discharge (20 of 78 [25.6%] vs 93 of 214 [43.5%]; adjusted odds ratio, 0.39; 95% CI, 0.20-0.74). Conclusions and Relevance In this post hoc secondary analysis of the THAPCA trial, 26.7% of participants had hypotension within 6 hours after temperature intervention. Early post–cardiac arrest hypotension was associated with lower odds of discharge survival, even after adjusting for covariates of interest.

Immediate effects of use of recombinant bone morphogenetic protein in children having spinal fusion and refusion procedures in United States

Study Design. Retrospective study of Nationwide Inpatient Sample (NIS). Objective. The objective of this study is to estimate the prevalence of complications in children who had insertion of recombinant human bone morphogenetic protein (rhBMP) at the time of spinal fusion procedures (SFP) and to examine if the use of rhBMP is associated with an increased risk of complications. Summary of Background Data. Use of rhBMP for SFP has been associated with conflicting safety profile reports in adults. Methods. NIS (years 2004–2010) was used. All patients with age  < 18 years who had a SFP during hospitalization with or without insertion of rhBMP were selected. Complications were selected based on a literature review of studies examining outcomes of SFP. Association between insertion of rhBMP and occurrence of complications was examined by multivariable logistic regression models. Results. Of the 72,898 children who underwent SFP, 7.1% children had insertion of rhBMP. Overall complication rate was 14.34% (15.2% in rhBMP group and 14.3% in no-rhBMP group). There was no statistically significant difference in the overall complication rate [odds ratio (OR) = 1.08, 95% confidence intervals (CI) = 0.89–1.30] or among 14 different complications between rhBMP and no-rhBMP groups. Children who had rhBMP were associated with higher odds for “other infections” (OR = 2.09, 95% CI = 1.26–3.48, P = 0.004) when compared with their counterparts. Conclusion. Despite the lack of Food and Drug Administration approval, rhBMP was not infrequently used in pediatric SFP. In this large retrospective study using administrative data, the use of rhBMP in children during SFP was not associated with higher risks for majority of assessed complications with the exception of “other infections”. Future studies must examine the long-term impact of use of rhBMP in children with SFP. Level of Evidence: 3

Prevalence and predictors of gastrostomy tube and tracheostomy placement in anoxic/hypoxic ischemic encephalopathic survivors of in-hospital cardiopulmonary resuscitation in the United States

Introduction Current prevalence estimates of gastrostomy tube (GT) /tracheostomy placement in hospitalized patients with anoxic/hypoxic ischemic encephalopathic injury (AHIE) post cardiopulmonary resuscitation (CPR) are unknown. We sought, to estimate the prevalence of AHIE in hospitalized patients who had CPR and to identify patient/hospital level factors that predict the performance of GT/tracheostomy in those with AHIE. Methods We performed a retrospective analysis of the Nationwide Inpatient Sample (years 2004–2010). All patients who developed AHIE following CPR were included. In this cohort the odds of having GT and tracheostomy was computed by multivariable logistic regression analysis. Patient and hospital level factors were the independent variables. Results During the study period, a total of 686,578 CPR events occurred in hospitalized patients. Of these, 94,336 (13.7%) patients developed AHIE. In this AHIE cohort, 6.8% received GT and 8.3% tracheostomy. When compared to the 40–49 yrs age group, those aged >70 yrs were associated with lower odds for GT (OR = 0.65, 95% CI:0.53–0.80, p<0.0001). Those aged <18 years & those >60 years were associated with lower odds for having tracheostomy when compared to the 40–49 years group (p<0.0001). Each one unit increase in co-morbid burden was associated with higher odds for having GT (OR = 1.23,p<0.0001) or tracheostomy (OR = 1.17, p<0.0001). Blacks, Hispanics, Asians/Pacific Islanders, and other races were associated with higher odds for having GT or tracheostomy when compared to whites (p<0.05). Hospitals located in northeastern regions were associated with higher odds for performing GT (OR = 1.48, p<0.0001) or tracheostomy (OR = 1.63, p<0.0001) when compared to those in Western regions. Teaching hospitals (TH) were associated with higher odds for performing tracheostomy when compared to non-TH (OR = 1.36, 1.20–1.54, p<0.0001). Conclusions AHIE injury occurs in a significant number of in-hospital arrests requiring CPR. Certain predictors of GT/ Tracheostomy placement are identified. Patients in teaching hospitals were more likely to receive tracheostomy than their counterparts.

A 3-Month-Old With Failure to Thrive and Persistent Vomiting

A 3-month-old boy presented with failure to thrive and vomiting and was diagnosed with a well-known condition that is rare in young infants. A 3-month-old boy was admitted from his pediatrician’s office for failure to thrive and vomiting. On admission, he weighed barely more than his birth weight and was cachectic with muscle wasting. His abdomen was grossly distended but soft and nontender. A trial of nasogastric feeds resulted in a worsening of his clinical status. He was transferred to the ICU, and diagnostic imaging was concerning for a distal bowel obstruction. Surgical pathology revealed a surprising diagnosis, which is described in detail in the following case.

Firearm injuries by legal personnel in the USA: a new public health burden

Objective and background: Violence necessitating legal intervention is a common occurrence in the USA. Such legal intervention may include the use of firearms by law enforcement personnel. However, very little is known about such firearm related injuries necessitating medical care. The objective of the present study is to characterize the burden in terms of mortality and emergency department charges of firearm related interventions requiring ED care in USA. Further we sought to identify high-risk cohorts for such injuries. Methods: A nationwide (USA) emergency department sample for the year 2008 through 2010 was used for the present study. All patients treated in an emergency department (ED) due to firearm injuries by law enforcement personnel were selected for analysis. Outcomes examined including mortality in the ED and ED charges. Findings: There were 6144 ED visits due to firearm injuries caused by law enforcement. The mean age was 33 years. Most patients (69.1%) resided in geographic regions designated as low income areas, and the vast majority were males (91.8%). Many patients (39%) were uninsured. For those with insurance, payers included Medicare (5%), Medicaid (13.5%), private (26.5%), and other insurance (15.6%). Following an ED visit 56.9% were discharged as routine, 25.5% were admitted as inpatients, 3.5% were transferred to another short-term hospital, and 2.8% were transferred to a long-term facility. 338 patients died in the ED and 102 patients died following admission as an inpatient. The mean ED charge was US

945: PREVALENCE AND PREDICTORS OF SEPTICEMIA IN PATIENTS WHO UNDERWENT MAJOR SURGICAL PROCEDURES IN USA.

3631 and total ED charges across the USA was US