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OBJECTIVE: To examine practice patterns of amiodarone use during in-hospital cardiac arrest. This study addresses the changing pattern of amiodarone use over time, following the publication of landmark studies and the inclusion of amiodarone in the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Furthermore, this study examines the impact of hospital and patient specific factors on the use of amiodarone. DESIGN: Retrospective cohort study, using the National Registry for Cardiopulmonary Resuscitation, an international registry of in-hospital resuscitation events. PATIENTS: All patients with an in-hospital ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) event reported to the national registry from January 1, 2000, to July 31, 2005. MEASUREMENTS AND MAIN RESULTS: During the study period, 14,854 of 29,552 (50%) adults (> 18 yrs old) with VF/pVT received an antiarrhythmic drug; 8,883 (60%) of these patients received amiodarone. In adults, amiodarone use for VF/pVT increased from 25% in 2000 to 72% in 2005 (p < .0001). Among children, 270 of 553 (49%) VF/pVT episodes were treated with an antiarrhythmic drug; 108 (40%) of these patients received amiodarone. Adults in institutions with larger intensive care units (> 50 beds) were more likely than those in institutions with smaller intensive care units (< or = 50 beds) to receive amiodarone; the association persisted in multivariable analysis (odds ratio [OR] = 1.825; 95% confidence interval [CI], 1.694-1.966). Thirty five percent of adults with VF/pVT who received amiodarone also received lidocaine, while 67% of children who received amiodarone also received lidocaine (p < .001). It is not possible to determine from the database the order in which medications were administered. CONCLUSIONS: There has been a significant increase in amiodarone use for VF/pVT events over the past 5 yrs. The frequency of amiodarone use in adults correlated positively with the number of intensive care beds. These results suggest that emerging data and national guidelines affect resuscitation practice patterns. [ABSTRACT FROM AUTHOR]

Abstract: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified syndrome that appears to be temporally associated with novel coronavirus 2019 infection. MIS-C presents with fever and evidence of systemic inflammation, which can manifest as cardiovascular, pulmonary, neurologic, and gastrointestinal (GI) system dysfunction. Presenting GI symptoms are seen in the majority, including abdominal pain, diarrhea, and vomiting. Any segment of the GI tract may be affected; however, inflammation in the ileum and colon predominates. Progressive bowel wall thickening can lead to luminal narrowing and obstruction. Most will have resolution of intestinal inflammation with medical therapies; however, in rare instances, surgical resection may be required., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Childhood cancer survivors (CCS) experience significant morbidity due to treatment- related late effects and benefit from late-effects surveillance. Adherence to screening recommendations is suboptimal. Survivorship care programs often struggle with resource limitations and may benefit from understanding institution-level financial outcomes associated with patient adherence to justify programmatic development and growth. The purpose of this study is to examine how CCS adherence to screening recommendations relates to the cost of care, insurance status, and institution-level financial outcomes. A retrospective chart review of 286 patients, followed in a structured survivorship program, assessed adherence to the Children's Oncology Group follow-up guidelines by comparing recommended versus performed screening procedures for each patient. Procedure cost estimates were based on insurance status. Institutional profit margins and profit opportunity loss were calculated. Bivariate statistics tested adherent versus nonadherent subgroup differences on cost variables. A generalized linear model predicted the likelihood of adherence based on cost of recommended procedures, controlling for age, gender, race, and insurance. Adherence to recommended surveillance procedures was 50.2%. Nonadherence was associated with higher costs of recommended screening procedures compared to the adherent group estimates ($2,469.84 vs. $1,211.44). Failure to perform the recommended tests resulted in no difference in reimbursement to the health system between groups ($1,249.63 vs. $1,211.08). For the nonadherent group, this represented $1,055.13 in "lost profit opportunity" per visit for patients, which totaled $311,850 in lost profit opportunity due to nonadherence in this subgroup. In the final model, nonadherence was related to higher cost of recommended procedures (p < .0001), older age at visit (p = .04), Black race (p = .02), and government-sponsored insurance (p = .03). Understanding institutional financial outcomes related to patient adherence may help inform survivorship care programs and resource allocation. Potential financial burden to patients associated with complex care recommendations is also warranted., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Childhood cancer survivors (CCSs) are at high risk of morbidity and mortality from long-term complications of their cancer treatment. The Children's Oncology Group developed screening guidelines to enable the early identification of and intervention for late effects of cancer treatment. There is a paucity of data on the adherence of CCSs to screening recommendations., Procedure: A retrospective analysis of medical records to evaluate the rate of adherence of CCSs to the personalized, risk-based recommendations provided to them in the context of a structured long-term follow-up program over a 3-year period., Results: Two hundred eighty-six CCSs visited the survivorship clinic 542 times during the 3-year study period. The overall rate of adherence to recommended screening was 74.2%. Using a univariate model and greater age at diagnosis and at screening recommendation were associated with decreased screening adherence. Gender, cancer diagnosis, radiation therapy, anthracycline exposure, and hematopoietic stem cell transplant were not significantly associated with adherence. In a multivariate model, age over 18 years at the time of the visit was significantly associated with decreased adherence (P < 0.0329) (odds ratio: 1.53, 95% confidence interval: 1.04-2.25)., Conclusions: Adherence to recommended screening tests is suboptimal among CCSs, with lower rates of adherence in CCSs older than 18 years of age compared with those younger than 18 years of age. Given the morbidity and mortality from the late effects of therapy among young adult CCSs, it is critically important to identify and remove barriers to late-effects screening among CCSs., (© 2016 Wiley Periodicals, Inc.)

Background: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited., Methods: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours 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 score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest., Results: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups., Conclusions: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

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 children's 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.).

The Pediatric Anesthesia NeuroDevelopment Assessment team at Columbia University Medical Center Department of Anesthesiology convened its fourth biennial Symposium to address unresolved issues concerning potential neurotoxic effects of anesthetic agents and sedatives on young children and to assess study findings to date. Dialogue initiated at the third Symposium was continued between anesthesiologists, researchers, and a panel of expert pediatric surgeons representing general surgery and dermatology, orthopedic, and urology specialties. The panel explored the need to balance benefits of early surgery using improved technologies against potential anesthetic risks, practice changes while awaiting definitive answers, and importance of continued interprofessional dialogue.

Objective: To describe the association of lactate levels within the first 12 hours after successful resuscitation from pediatric cardiopulmonary arrest with hospital mortality., Design: Retrospective cohort study., Setting: Fifteen children's hospital associated with the Pediatric Emergency Care Applied Research Network., Patients: Patients between 1 day and 18 years old who had a cardiopulmonary arrest, received chest compressions more than 1 minute, had a return of spontaneous circulation more than 20 minutes, and had lactate measurements within 6 hours of arrest., Interventions: None., Measurements and Main Results: Two hundred sixty-four patients had a lactate sampled between 0 and 6 hours (lactate(0-6)) and were evaluable. Of those, 153 patients had a lactate sampled between 7 and 12 hours (lactate(7-12)). One hundred thirty-eight patients (52%) died. After controlling for arrest location, total number of epinephrine doses, initial rhythm, and other potential confounders, the odds of death per 1 mmol/L increase in lactate(0-6) was 1.14 (1.08, 1.19) (p < 0.001) and the odds of death per 1 mmol/L increase in lactate(7-12) was 1.20 (1.11, 1.30) (p < 0.0001). Area under the curve for in-hospital arrest mortality for lactate(0-6) was 0.72 and for lactate(7-12) was 0.76. Area under the curve for out-of-hospital arrest mortality for lactate(0-6) was 0.8 and for lactate(7-12) was 0.75., Conclusions: Elevated lactate levels in the first 12 hours after successful resuscitation from pediatric cardiac arrest are associated with increased mortality. Lactate levels alone are not able to predict outcomes accurately enough for definitive prognostication but may approximate mortality observed in this large cohort of children's hospitals.

Objectives: To explore oxygenation and ventilation status early after cardiac arrest in infants and children. We hypothesize that hyperoxia is common and associated with worse outcome after pediatric cardiac arrest., Design: Retrospective cohort study., Setting: Fifteen hospitals within the Pediatric Emergency Care Applied Research Network., Patients: Children who suffered a cardiac arrest event and survived for at least 6 hours after return of circulation., Interventions: None., Measurements and Main Results: Analysis of 195 events revealed that abnormalities in oxygenation and ventilation are common during the initial 6 hours after pediatric cardiac arrest. Hyperoxia was frequent, affecting 54% of patients. Normoxia was documented in 34% and hypoxia in 22% of patients. These percentages account for a 10% overlap of patients who had both hyperoxia and hypoxia. Ventilation status was more evenly distributed with hyperventilation observed in 38%, normoventilation in 29%, and hypoventilation in 46%, with a 13% overlap of patients who had both hyperventilation and hypoventilation. Derangements in both oxygenation and ventilation were common early after cardiac arrest such that both normoxia and normocarbia were documented in only 25 patients (13%). Neither oxygenation nor ventilation status was associated with outcome. After controlling for potential confounders, arrest location and rhythm were significantly associated with worse outcome; however, hyperoxia was not (odds ratio for good outcome, 1.02 [0.46, 2.84]; p = 0.96)., Conclusions: Despite recent resuscitation guidelines that advocate maintenance of normoxia and normoventilation after pediatric cardiac arrest, this is uncommonly achieved in practice. Although we did not demonstrate an association between hyperoxia and worse outcome, the small proportion of patients kept within normal ranges limited our power. Preclinical data suggesting potential harm with hyperoxia remain compelling, and further investigation, including prospective, large studies involving robust recording of physiological derangements, is necessary to further advance our understanding of this important topic.

All pediatric intensivists need a primer on ICU finance. The author describes potential alternate revenue sources for the division. Differentiating units by size or academic affiliation, the author describes drivers of expense. Strategies to manage the bottom line including negotiations for hospital services are covered. Some of the current trends in physician productivity and its described metrics, with particular focus on clinical FTE management is detailed. Methods of using this data to enhance revenue are discussed. Some of the other current trends in the ICU business related to changes at the federal and state level as well as in the insurance sector, moving away from fee-for-service are covered., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To describe a large cohort of children with out-of-hospital cardiac arrest with return of circulation and to identify factors in the early postarrest period associated with survival. These objectives were for planning an interventional trial of therapeutic hypothermia after pediatric cardiac arrest., Methods: A retrospective cohort study was conducted at 15 Pediatric Emergency Care Applied Research Network clinical sites over an 18-month study period. All children from 1 day (24 hrs) to 18 yrs of age with out-of-hospital cardiac arrest and a history of at least 1 min of chest compressions with return of circulation for at least 20 mins were eligible., Measurements and Main Results: One hundred thirty-eight cases met study entry criteria; the overall mortality was 62% (85 of 138 cases). The event characteristics associated with increased survival were as follows: weekend arrests, cardiopulmonary resuscitation not ongoing at hospital arrival, arrest rhythm not asystole, no atropine or NaHCO3, fewer epinephrine doses, shorter duration of cardiopulmonary resuscitation, and drowning or asphyxial arrest event. For the 0- to 12-hr postarrest return-of-circulation period, absence of any vasopressor or inotropic agent (dopamine, epinephrine) use, higher lowest temperature recorded, greater lowest pH, lower lactate, lower maximum glucose, and normal pupillary responses were all associated with survival. A multivariate logistic model of variables available at the time of arrest, which controlled for gender, age, race, and asystole or ventricular fibrillation/ventricular tachycardia anytime during the arrest, found the administration of atropine and epinephrine to be associated with mortality. A second model using additional information available up to 12 hrs after return of circulation found 1) preexisting lung or airway disease; 2) an etiology of arrest drowning or asphyxia; 3) higher pH, and 4) bilateral reactive pupils to be associated with lower mortality. Receiving more than three doses of epinephrine was associated with poor outcome in 96% (44 of 46) of cases., Conclusions: Multiple factors were identified as associated with survival after out-of-hospital pediatric cardiac arrest with the return of circulation. Additional information available within a few hours after the return of circulation may diminish outcome associations of factors available at earlier times in regression models. These factors should be considered in the design of future interventional trials aimed to improve outcome after pediatric cardiac arrest.

We present 3 children with massive pulmonary embolism and review 17 recent pediatric reports. Malignancies were a frequent cause (40%), and sudden death was common (60%). Compared with adults, diagnosis was more likely to be made at autopsy (P < .0001), more children were treated with embolectomy/thrombectomy (P = .0006), and mortality was greater (P = .03).

Objective: To comprehensively evaluate the effect of parental presence on pediatric intensive care unit rounds., Study Design: A prospective, observational and survey-based study comprised of (1) observation of rounds (2) "rounding event assessments" (brief surveys specific to 1 rounding event, completed by health care providers [HCPs] n = 375) (3) qualitative interviews with parents (36 who joined rounds and 16 who elected not to join), and (4) qualitative written surveys from HCPs (63 nurses, 39 doctors)., Results: Eighty-one percent of parents who chose to join rounds reported that participation increased their overall satisfaction with their child's care. In 57% of rounding events, at least 1 HCP learned new, pertinent information from the parents. However, in 32% of rounding events, at least 1 HCP believed parental presence limited discussion. Forty-seven percent of parents who participated in rounds and 88% of those who chose not to participate volunteered that participation has the potential to increase parental confusion and anxiety (P = .02)., Conclusions: Most parents and physicians agree that parents should be invited to participate on rounds. Parents report increased satisfaction from participation, and parents provide new information when on rounds. However, parental presence may limit discussion during rounds which may adversely affect patient care.

Objectives: : To describe a large multicenter cohort of pediatric cardiac arrest (CA) with return of circulation (ROC) from either the in-hospital (IH) or the out-of-hospital (OH) setting and to determine whether significant differences related to pre-event, arrest event, early postarrest event characteristics, and outcomes exist that would be critical in planning a clinical trial of therapeutic hypothermia (TH)., Design: : Retrospective cohort study., Setting: : Fifteen Pediatric Emergency Care Applied Research Network sites., Patients: : Patients aged 24 hours to 18 years with either IH or OH CA who had a history of at least 1 minute of chest compressions and ROC for at least 20 minutes were eligible., Interventions: : None., Measurements and Main Results: : A total of 491 patients met study entry criteria with 353 IH cases and 138 OH cases. Major differences between the IH and OH cohorts were observed for patient prearrest characteristics, arrest event initial rhythm described, and arrest medication use. Several postarrest interventions were used differently, however, the use of TH was similar (<5%) in both cohorts. During the 0-12-hour interval following ROC, OH cases had lower minimum temperature and pH, and higher maximum serum glucose recorded. Mortality was greater in the OH cohort (62% vs. 51%, p = 0.04) with the cause attributed to a neurologic indication much more frequent in the OH than in the IH cohort (69% vs. 20%; p < 0.01)., Conclusions: : For pediatric CA with ROC, several major differences exist between IH and OH cohorts. The finding that the etiology of death was attributed to neurologic indications much more frequently in OH arrests has important implications for future research. Investigators planning to evaluate the efficacy of new interventions, such as TH, should be aware that the IH and OH populations differ greatly and require independent clinical trials.

Objective: We report our use of noninvasive ventilation (NIV) during pediatric interhospital ground transport., Methods: We retrospectively reviewed transport and hospital records for nonneonatal patients

Objective: To measure the effect of pre-ischemic administration of intraluminal epidermal growth factor on the changes in intestinal permeability induced by 30 mins of superior mesenteric artery occlusion, followed by 2 hrs of reperfusion., Design: Prospective, randomized, placebo-controlled experimental study., Setting: University basic science research laboratory., Subjects: Healthy, young, adult, male Sprague-Dawley rats., Interventions: A 10-cm segment of small intestine was isolated and studied in situ in rats that were anesthetized with fentanyl and mechanically ventilated. Intestinal ischemia-reperfusion injury was induced by temporary occlusion of the superior mesenteric artery for 30 mins, followed by 2 hrs of reperfusion. Three groups were studied: time controls with a sham operation, saline-treated ischemia-reperfusion, and epidermal growth factor-treated ischemia-reperfusion. Epidermal growth factor, 100 ng/min, was infused intraluminally, beginning 30 mins before and continued until 40 mins after ischemia., Measurements and Main Results: Intestinal permeability was measured for each 10-min time period by using chromium-labeled EDTA. Histopathologic injury was assessed by light microscopy. After superior mesenteric artery occlusion, intestinal permeability increased approximately ten-fold and was sustained for 2 hrs of reperfusion in saline-treated rats. Pretreatment with epidermal growth factor significantly reduced the permeability changes during reperfusion by >60% compared with saline-treated animals (p <.05). Histopathologic sections revealed apparently more extensive loss of epithelial cells and mucosal disruption in saline-treated intestine compared with epidermal growth factor-treated intestine., Conclusion: Pre-ischemic administration of intraluminal epidermal growth factor significantly protects against intestinal ischemia-reperfusion injury.

Objective: Measure the fraction of inspired oxygen (F(IO(2))) in infants receiving supplemental oxygen via nasal cannula and identify clinical variables that affect F(IO(2))., Methods: Hypopharyngeal gas samples were obtained from 20 infants receiving oxygen via nasal cannula at flows between 0 and 4 L/min. F(IO(2)) was calculated using the alveolar gas equation and measurements of partial pressure of oxygen in the samples and the barometric pressure., Results: F(IO(2)) increased as oxygen flow was increased. F(IO(2)) exceeded safe levels (> 60%) in two thirds of samples when the oxygen flow was 2 L/min or higher. Tachypnea (respiratory rate > 40 breaths/min) was associated with lower F(IO(2))., Conclusion: Infants receiving oxygen via nasal cannula at > or = 2 L/min may be at risk for hyperoxic lung injury. Therefore, we recommend using the lowest possible oxygen flow needed to maintain normoxia in infants requiring prolonged oxygen therapy via nasal cannula.

Central administration of interleukin-1 beta (IL-1 beta) increases cerebral blood flow (CBF) and body temperature, in part, through the production of prostaglandins. In previous studies, the temporal relationship between these effects of IL-1 beta have not been measured. In this study, we hypothesized that the increase in CBF occurs before any change in brain or body temperature and that the cerebrovascular and thermoregulatory effects of IL-1 beta would be attenuated by inhibiting the production of nitric oxide (NO). Adult male rats received 100 ng intracerebroventricular (icv) injection of IL-1 beta, and cortical CBF (cCBF) was measured by laser-Doppler in the contralateral cerebral cortex. A central injection of IL-1 beta caused a rapid increase in cCBF to 133 +/- 12% of baseline within 15 min and to an average of 137 +/- 12% for the remainder of the 3-h experiment. Brain and rectal temperature increased by 0.4 +/- 0.2 and 0.5 +/- 0.2 degrees C, but not until 45 min after IL-1 beta administration. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME; 5 mg/kg iv) completely prevented the changes in cCBF and brain and rectal temperature induced by IL-1 beta. L-Arginine (150 mg/kg iv) partially reversed the effects of L-NAME and resulted in increases in both cCBF and temperature. These findings suggest that the vasodilatory effects of IL-1 beta in the cerebral vasculature are independent of temperature and that NO plays a major role in both the cerebrovascular and thermoregulatory effects of centrally administered IL-1 beta.

OBJECTIVE: To test the hypothesis that cerebral and other regional organ blood flow would be maintained during partial liquid ventilation (PLV) in an animal model of acute lung injury during different ventilation strategies. DESIGN: A prospective, randomized study. SETTING: Animal research facility. SUBJECTS: Sixteen piglets, 2 to 4 wks of age. INTERVENTIONS: Severe lung injury was induced in infant piglets by repeated saline lavage and high tidal volume ventilation. Animals were then randomized to either conventional volume-controlled ventilation or PLV. MEASUREMENTS AND MAIN RESULTS: Organ blood flow was determined in both groups using radiolabeled microspheres under four conditions: high mean airway pressure, Paw; high Paco(2), high Paw; normal Paco(2); low Paw, high Paco(2); low Paw, normal Paco(2). There were no differences in cerebral blood flow during conventional ventilation and PLV, regardless of ventilation strategy. CONCLUSIONS: These results suggest in an acute lung injury model, PLV does not affect cerebral blood flow or other regional organ blood flow over a range of airway pressures.

OBJECTIVE: The most severe form of generalized junctional epidermolysis bullosa, the Herlitz variant, is associated with a number of extracutaneous manifestations. We report on a 45-day-old infant with laryngotracheobronchial mucosa involvement who underwent successful tracheal extubation after 10 days of orotracheal intubation and mechanical ventilatory support. Issues regarding airway management and mechanical ventilatory support in the pediatric intensive care unit are discussed.

Background: Surgical portosystemic shunting has been performed less frequently in recent years. In this retrospective study, recent outcomes of portosystemic shunting in children are described, to evaluate its role in the era of endoscopic therapy., Methods: Retrospective chart review of children who underwent surgical portosystemic shunt procedures between October 1994 and October 1997., Results: Twelve children (age range, 1-16 years) underwent shunting procedures. The causes of portal hypertension were extrahepatic portal vein thrombosis (n = 6), congenital hepatic fibrosis (n = 2), hepatic cirrhosis (n = 2), and other (n = 2). None of the patients were immediate candidates for liver transplantation. Types of shunt included: distal splenorenal (n = 10), portocaval (n = 1), and other (n = 1). Median follow-up was 35 months (range, 24-48 months). All patients are currently alive and well with patent shunts. The mean hospital stay was 8 days. Three patients required readmission for further interventions because of shunt stenosis in two and small bowel obstruction in the other. Mild portosystemic encephalopathy was seen in one child with pre-existing neurobehavioral disturbance. Excluding a patient who underwent placement of a portosystemic shunt for a complication of liver transplantation, mean weight-for-age z score in nine prepubertal patients improved from -1.16 SD to +0.15 SD (P = 0.023), and mean height-for-age z score from -1.23 SD to 0.00 SD (P = 0.048) by 2 years after surgery., Conclusions: Surgical portosystemic shunting is a safe and effective method for the management of portal hypertension in childhood. Patients show significant improvements in growth parameters after the procedure. Surgical portosystemic shunting should be actively considered in selected children with portal hypertension.

Using infant piglets, we studied the effects of nonspecific inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg) on vascular pressures, regional blood flow, and cerebral metabolism before 8 min of cardiac arrest, during 6 min of cardiopulmonary resuscitation (CPR), and at 10 and 60 min of reperfusion. We tested the hypotheses that nonspecific NO synthase inhibition 1) will attenuate early postreperfusion hyperemia while still allowing for successful resuscitation after cardiac arrest, 2) will allow for normalization of blood flow to the kidneys and intestines after cardiac arrest, and 3) will maintain cerebral metabolism in the face of altered cerebral blood flow after reperfusion. Before cardiac arrest, L-NAME increased vascular pressures and cardiac output and decreased blood flow to brain (by 18%), heart (by 36%), kidney (by 46%), and intestine (by 52%) compared with placebo. During CPR, myocardial flow was maintained in all groups to successfully resuscitate 24 of 28 animals [P value not significant (NS)]. Significantly, L-NAME attenuated postresuscitation hyperemia in cerebellum, diencephalon, anterior cerebral, and anterior-middle watershed cortical brain regions and to the heart. Likewise, cerebral metabolic rates of glucose (CMRGluc) and of lactate production (CMRLac) were not elevated at 10 min of reperfusion. These cerebral blood flow and metabolic effects were reversed by L-arginine. Flows returned to baseline levels by 60 min of reperfusion. Kidney and intestinal flow, however, remained depressed throughout reperfusion in all three groups. Thus nonspecific inhibition of NO synthase did not adversely affect the rate of resuscitation from cardiac arrest while attenuating cerebral and myocardial hyperemia. Even though CMRGluc and CMRLac early after resuscitation were decreased, they were maintained at baseline levels. This may be clinically advantageous in protecting the brain and heart from the damaging effects of hyperemia, such as blood-brain barrier disruption.

Objectives: To test the hypothesis that selective brain cooling could be performed in an infant model of cardiac arrest and resuscitation without changing core temperature and to study its acute effects on regional organ blood flow, cerebral metabolism, and systemic hemodynamics., Design: Prospective, randomized, controlled study., Setting: Research laboratory at a university medical center., Subjects: Fourteen healthy infant piglets, weighing 3.5 to 6.0 kg., Interventions: piglets were anesthetized and mechanically ventilated, and had vascular catheters placed. Parietal cortex (superficial brain), caudate nucleus (deep brain), esophageal, and rectal temperatures were monitored. All animals underwent 6 mins of cardiac arrest induced by ventricular fibrillation, 6 mins of external cardiopulmonary resuscitation (CPR), defibrillation, and 2 hrs of reperfusion. Normal core temperature (rectal) was regulated in all animals. In seven control animals (group 1), brain temperature was not manipulated. In seven experimental animals (group 2), selective brain cooling was begin during CPR, using a cooling cap filled with -30 degrees C solution. Selective brain cooling was continued for 45 mins of reperfusion after which passive rewarming was allowed. Regional blood flow (microspheres) and arterial and sagittal sinus blood gases were measured prearrest, during CPR, and at 10 mins, 45 mins, and 2 hrs of reperfusion., Measurements and Main Results: Rectal temperature did not change over time in either group. In group 1, brain temperature remained constant except for a decrease of 0.6 degrees C at 10 mins of reperfusion. In group 2, superficial and deep brain temperatures were lowered to 32.8 +/- 0.7 (SEM) degrees C and 34.9 +/- 0.4 degrees C, respectively, by 15 mins of reperfusion. Superficial and deep brain temperatures were further lowered to 27.8 +/- 0.8 degrees C and 31.1 +/- 0.3 degrees C, respectively, at 45 mins of reperfusion. Both temperatures returned to baseline by 120 mins. Cerebral blood flow was not different between groups at any time point, although there was a trend for higher flow in group 2 at 10 mins of reperfusion (314% of baseline) compared with group 1 (230% of baseline). Cerebral oxygen uptake was lower in group 2 than in group 1 (69% vs. 44% of baseline, p=.02) at 45 mins of reperfusion. During CPR, aortic diastolic pressure was lower in group 2 than in group 1 (27 +/- 1 vs. 23 +/- 1 mm Hg, p = .007). Myocardial blood flow during CPR was also lower in group 2 (80 +/- 7 vs. 43 +/- 7 mL/min/100 g, p=.002). Kidney and intestinal blood flows were reduced during CPR in both groups; however, group 2 animals also had lower intestinal flow vs. group 1 at 45 and 120 mins of reperfusion., Conclusions: Selective brain cooling by surface cooling can be achieved rapidly in an infant animal model of cardiac arrest and resuscitation without changing core temperature. Brain temperatures known to improve neurologic outcome can be achieved by this technique with minimal adverse effects. Because of its ease of application, selective brain cooling may prove to be an effective, inexpensive method of cerebral resuscitation during pediatric CPR.

The medical records of patients with acquired immunodeficiency syndrome were reviewed to evaluate the effect of our adoption to the pediatric population of the National Institutes of Health recommendation for adjunctive corticosteroid therapy in adults with Pneumocystis carinii pneumonia. In 21 episodes of P. carinii-related respiratory failure, only adjunctive corticosteroids were associated with a significant improvement in survival to successful removal of the tracheal tube, from a historical rate of 11% to 91%.

This study examined the early microvascular and neuronal consequences of cardiac arrest and resuscitation in piglets. We hypothesized that early morphological changes occur after cardiac arrest and reperfusion, and that these findings are partly caused by post-resuscitation hypertension. Three groups of normothermic piglets (37.5 degrees - 38.5 degrees C) were investigated: group 1, non-ischemic time controls; group 2, piglets undergoing 8 min of cardiac arrest by ventricular fibrillation, 6 min of cardiopulmonary resuscitation (CPR) and 4 h of reperfusion; and group 3, non-ischemic hypertensive controls, receiving 6 min of CPR after only 10 s of cardiac arrest followed by 4-h survival. Immediately following resuscitation, acute hypertension occurred with peak systolic pressure equal to 197 +/- 15 mm Hg usually lasting less than 10 min. In reacted vibratome sections, isolated foci of extravasated horseradish peroxidase were noted throughout the brain within surface cortical layers and around penetrating vessels in group 2. Stained plastic sections of leaky sites demonstrated variable degrees of tissue injury. While many sections were unremarkable except for luminal red blood cells and leukocytes, other specimens contained abnormal neurons, some appearing irreversibly injured. The number of vessels containing leukocytes was higher in group 2 than in controls (3.8 +/- 0.6% vs 1.4 +/- 0.4% of vessels, P < 0.05). Evidence for irreversible neuronal injury was only seen in group 2. Endothelial vacuolization was higher in groups 2 and 3 than in group 1 (P < 0.05). Ultrastructural examination of leaky sites identified mononuclear and polymorphonuclear leukocytes adhering to the endothelium of venules and capillaries only in group 2. The early appearance of luminal leukocytes in ischemic animals indicates that these cells may contribute to the genesis of ischemia reperfusion injury in this model. In both groups 2 and 3 endothelial cells demonstrated vacuolation and luminal discontinuities with evidence of perivascular astrocytic swelling. Widespread microvascular and neuronal damage is present as early as 4 h after cardiac arrest in infant piglets. Hypertension appears to play a role in the production of some of the endothelial changes.

Objectives: To determine cerebral and myocardial blood flow rates during vest cardiopulmonary resuscitation (CPR) without direct cardiac compression in an infant porcine model. Also, to determine if circumferential chest compression without the chest deformity ordinarily associated with precordial compression maintains cerebral and myocardial blood flow rates during prolonged CPR. Finally, to establish the effect of compression rate and duty cycle on cerebral and myocardial blood flow rates during vest CPR in this model., Design: Prospective, randomized comparison of two compression rates and two duty cycles in four groups during prolonged CPR., Setting: University cerebral resuscitation laboratory., Subjects: Thirty-two infant domestic swine., Interventions: Microsphere-determined cerebral and myocardial blood flow rates, perfusion pressures, and chest dimensions, were measured before and during prolonged vest CPR. Immediately after ventricular fibrillation, epinephrine administration was started and thoracic vest CPR was performed using a single combination of compression rates of 100 or 150/min and duty cycles of 30% or 60%. Measurements were made before and at 5, 10, 20, 35, and 50 mins of CPR., Measurements and Main Results: Five minutes into CPR, between-group comparisons showed that cerebral blood flow was 16 to 20 mL/min/100 g and myocardial blood flow was 34 to 45 mL/min/100 g (48% to 62% and 25% to 33% of prearrest values). When CPR was prolonged, cerebral blood flow deteriorated similarly in all groups. Myocardial blood flow decreased over time but was better maintained in the groups with a 30% duty cycle (24 vs. 4 mL/min/100 g; p < .006). There were no differences between the two compression rates. Chest deformity after cessation of 50 mins of compression was < 3%., Conclusions: Cerebral and myocardial blood flow rates produced by vest CPR are comparable with rates reported using other types of CPR in this model. Deterioration in blood flow during prolonged CPR occurs despite a lack of chest deformation. The deterioration in myocardial blood flow during prolonged CPR is greater when a long duty cycle is used in this model.

Background and Purpose: Cardiac arrest and resuscitation in immature piglets result in a delayed increase in blood-brain barrier permeability. We tested the hypothesis that pretreatment with oxygen radical scavengers reduces postischemic permeability., Methods: Permeability was assessed by measuring the plasma-to-brain transfer coefficient of the small amino acid, alpha-aminoisobutyric acid, in 2- to 3-week-old anesthetized piglets. Three groups were studied: (1) a nonischemic time control group (n = 5), (2) an ischemia group (n = 8) pretreated with 5 mL of polyethylene glycol vehicle, and (3) an ischemia group (n = 8) pretreated with polyethylene glycol conjugated to superoxide dismutase (10,000 U/kg) and to catalase (20,000 U/kg). The ischemia protocol consisted of 8 minutes of ventricular fibrillation, 6 minutes of cardiopulmonary resuscitation, defibrillation, and 4 hours of spontaneous circulation., Results: The mean +/- SEM of the transfer coefficient of alpha-aminoisobutyric acid in cerebrum was (in microL/g per minute): 1.54 +/- 0.37 in the nonischemic group, 2.04 +/- 0.26 in the ischemia group treated with vehicle, and 1.29 +/- 0.25 in the ischemia group treated with oxygen radical scavengers. Postischemic values with scavenger treatment were significantly lower than those with vehicle treatment in cerebrum, cerebellum, medulla and cervical spinal cord., Conclusions: Pretreatment with oxygen radical scavengers reduces postischemic blood-brain barrier permeability by a small amino acid. These data are consistent with oxygen radical-mediated dysfunction of cerebral endothelium in a pediatric model of cardiopulmonary resuscitation.

Background and Purpose: Previous in vitro and in vivo studies of the effects of nitric oxide synthase inhibition in the central nervous system have yielded conflicting results concerning the role of nitric oxide in the events that lead to ischemic injury. In this study, we tested the hypothesis that preischemic inhibition of nitric oxide synthase increases infarct volume after reversible focal cerebral ischemia in rats., Methods: NG-nitro-L-arginine methyl ester hydrochloride 15 mg/kg IV or an equivalent volume of saline was administered to adult Wistar rats 15 minutes before middle cerebral artery occlusion by the intraluminal suture method. After 2 hours of ischemia, the suture was withdrawn, and rats were allowed to survive for 3 days. Areas of infarction in 10 hematoxylin-eosin-stained sections were measured and used to determine infarct volume., Results: Administration of NG-nitro-L-arginine methyl ester hydrochloride increased hemispheric infarct volume by 137% over control (60.9 +/- 30.5 to 144.3 +/- 19.6 mm3, P < .05; mean +/- SEM). Cortical and subcortical infarct volumes were increased by 176% (33.8 +/- 21.9 to 93.3 +/- 15.2 mm3, P < .05) and 103% (25.1 +/- 9.4 to 51.0 +/- 5.5 mm3, P < .03), respectively., Conclusions: Nitric oxide synthase inhibition increases infarct volume and decreases the variability of the response to middle cerebral artery occlusion in Wistar rats, a strain that is normally resistant to focal cerebral ischemic injury owing to extensive collateralization. The mechanism of the deleterious effect of nitric oxide synthase inhibition likely involves a more severe degree of blood flow reduction during and after middle cerebral artery occlusion, primarily by preventing the vasodilatory response of collateral vessels to proximal middle cerebral artery occlusion. Maintenance of nitric oxide synthase activity during and after focal cerebral ischemia appears to minimize ischemic injury.

Background and Purpose: We tested the hypothesis that fructose-1,6-bisphosphate, when administered 10 minutes before the end of 2 hours of reversible middle cerebral artery occlusion, reduces ischemia-reperfusion injury and infarct volume measured after a 3-day survival period in rats., Methods: After 1 hour and 50 minutes of middle cerebral artery occlusion by the intraluminal suture method, fructose-1,6-bisphosphate, 500 mg/kg in group 1 and 350 mg/kg in group 2 (or an equivalent volume of 1.8% saline as placebo in each group), was given intravenously for a period of 15 minutes to fasted adult Sprague-Dawley rats. After 2 hours of ischemia, the suture was withdrawn and the rats allowed to survive for 3 days. The areas of infarction in 10 hematoxylin-eosin-stained coronal sections of the brain were measured and used to calculate infarct volume., Results: In group 1, fructose-1,6-bisphosphate decreased total cerebral hemispheric infarct volume by 43% (from 199.6 +/- 11.2 to 114.2 +/- 35.8 mm3, P < .04; mean +/- SEM). Cerebral cortical and subcortical infarct volumes were decreased by 46% (from 137.3 +/- 7.5 to 74.1 +/- 28.6 mm3, P < .04) and 36% (from 62.3 +/- 5.1 to 40.0 +/- 8.3 mm3, P < .04), respectively. In group 2, fructose-1,6-bisphosphate had no effect on infarct volume in rats that developed mild intraischemic hyperthermia, but in rats kept normothermic during ischemia, fructose-1,6-bisphosphate reduced subcortical infarct volume from 53.7 +/- 8.1 to 18.4 +/- 8.0 mm3 (P < .03)., Conclusions: Fructose-1,6-bisphosphate improves functional neurological outcome and reduces infarct volume after reversible middle cerebral artery occlusion in rats.

To evaluate the effect of selective brain cooling on cortical cerebral blood flow, we reduced brain temperature in nitrous oxide anesthetized adult rats using a high speed fan while keeping rectal temperature at 37-38 degrees C. During selective brain cooling, cortical cerebral blood flow, as measured by laser-Doppler flowmetry, increased to 215 +/- 26% (mean +/- SE) of baseline at a cortical brain temperature of 30.9 +/- 0.5 degrees C and a rectal temperature of 37.5 +/- 0.1 degrees C. During rewarming, as brain temperature increased, cortical cerebral blood flow decreased. The cerebral vasodilatory response to hypothermia may explain its protective effects during and after cerebral ischemia.

The diffuse inflammation produced by cardiopulmonary bypass might disrupt the blood-brain barrier and lead to the transient neurologic dysfunction occasionally seen after cardiac operations. To evaluate this possibility, blood-brain barrier integrity was measured by carbon 14-aminoisobutyric acid tracer technique after 2 hours of cardiopulmonary bypass in piglets. Six animals were cooled to 28 degrees C on cardiopulmonary bypass and then rewarmed to 38 degrees C before carbon 14-aminosisobutyric acid was injected intraarterially. A control group of six animals underwent median sternotomy and heparinization but were not placed on cardiopulmonary bypass. Blood-to-brain transfer coefficients for carbon 14-aminosisobutyric acid were calculated for multiple brain regions; higher coefficients reflect greater flux of carbon 14-aminosisobutyric acid and suggest loss of blood-brain barrier integrity. The brain regions examined and their transfer coefficients (cardiopulmonary bypass versus control mean +/- standard error of the mean ml/gm/min) were middle cerebral artery territory cortex (0.0032 +/- 0.0002 versus 0.0030 +/- 0.0002; p = 0.42), diencephalon (0.0031 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.50), midbrain (0.0028 +/- 0.0002 versus 0.0027 +/- 0.0002; p = 0.86), cerebellum (0.0036 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.22), and spinal cord (0.0035 +/- 0.0003 versus 0.0041 +/- 0.0008; p = 0.48). There were no significant differences in transfer coefficients between animals placed on cardiopulmonary bypass and control animals in any brain region examined. The pituitary gland lacks a blood-brain barrier and had a correspondingly high coefficient in control animals and those undergoing cardiopulmonary bypass (0.077 +/- 0.012 versus 0.048 +/- 0.008; p = 0.07). Two hours of moderately hypothermic cardiopulmonary bypass does not disrupt the blood-brain barrier.

Cardiac arrest causes a rapid loss of cerebral adenosine triphosphate [corrected] (ATP) and a decrease in cerebral intracellular pH (pHi). Depending on the efficacy of cardiopulmonary resuscitation (CPR), cerebral blood flow levels (CBF) ranging from near zero to near normal have been reported experimentally. Using 31P magnetic resonance spectroscopy, the authors tested whether experimental CPR with normal levels of cerebral blood flow can rapidly restore cerebral ATP and pHi despite the progressive systemic acidemia associated with CPR. After 6 min of ventricular fibrillation in six dogs anesthetized with fentanyl and pentobarbital, ATP was reduced to undetectable concentrations and pHi decreased from 7.11 +/- 0.02 to 6.28 +/- 0.09 (+/- SE) as measured by 31P magnetic resonance spectroscopy. Application of cyclic chest compression by an inflatable vest placed around the thorax and infusion of epinephrine (40 micrograms/kg bolus plus 8 micrograms/kg/min, intravenously) maintained cerebral perfusion pressure greater than 70 mmHg for 50 min with the dog remaining in the magnet. Prearrest cerebral blood flows were generated. Cerebral pHi recovered to 7.03 +/- 0.03 by 35 min of CPR, whereas arterial pH decreased from 7.41 +/- 0.4 to 7.08 +/- 0.04 and cerebral venous pH decreased from 7.29 +/- 0.03 to 7.01 +/- 0.04. Cerebral ATP levels recovered to 86 +/- 7% (+/- SE) of prearrest concentration by 6 min of CPR. There was no further recovery of ATP, which remained significantly less than control. Therefore, in contrast to hyperemic reperfusion with spontaneous circulation and full ATP recovery, experimental CPR may not be able to restore ATP completely after 6 min of global ischemia despite restoration of CBF and brain pHi to prearrest levels.

Although epinephrine increases cerebral blood flow (CBF) and left ventricular blood flow (LVBF) during cardiopulmonary resuscitation (CPR), the effects of high dosages on LVBF and CBF and cerebral O2 uptake have not been examined during prolonged CPR. We determined whether log increment dosages of epinephrine would enhance LVBF and CBF and cerebral O2 uptake in an infant swine CPR model. We compared these responses with epinephrine to those with the alpha-adrenergic agonist, phenylephrine. CPR was performed in five groups (n = 6) of pentobarbital-anesthetized piglets (3.5-5.6 kg) receiving a continuous epinephrine infusion (0, 1, 10, and 100 micrograms.kg-1.min-1) or phenylephrine infusion (40 micrograms.kg-1.min-1). Plasma epinephrine concentrations increased 10-100-fold in the control group during CPR and in a stepwise manner such that concentrations were increased by more than 10(4) in the 100 micrograms.kg-1.min-1 epinephrine group. In the control group with no epinephrine infusion, LVBF decreased to less than 10 ml.min-1.100 g-1 by 5 min of CPR. With epinephrine in dosages of 10 and 100 micrograms.kg-1.min-1, LVBF at 5 min was 75 +/- 19 and 44 +/- 15 ml.min-1.100 g-1, respectively, which was significantly greater than values in the control group. With more prolonged CPR, LVBF remained significantly greater than that in the control group but only at 10 micrograms.kg-1.min-1 of epinephrine. Phenylephrine also increased LVBF for 10 min of CPR when compared with the control group. All dosages of epinephrine and phenylephrine maintained CBF close to prearrest values for 20 min of CPR. With prolonged CPR, 10 and 100 micrograms.kg-1.min-1 epinephrine resulted in significantly greater CBF than that in the control group. Incremental dosages of epinephrine did not statistically increase cerebral O2 uptake or lower the cerebral fractional O2 extraction when compared with the control group, despite the higher CBF that was generated. In this immature animal CPR model, 10 micrograms.kg-1.min-1 epinephrine is an optimal dosage for maximizing both CBF and LVBF, a dosage that substantially exceeds the current recommended epinephrine dosage for human infant CPR. In addition, for short periods of CPR, 40 micrograms.kg-1.min-1 phenylephrine increases CBF and LVBF to levels similar to those generated by high dosages of epinephrine.

Background and Purpose: Epinephrine administration during cardiopulmonary resuscitation increases cerebral blood flow by increasing arterial pressure. We tested whether potential beta-adrenergic effects of epinephrine directly influence cerebral blood flow and oxygen consumption independently of raising perfusion pressure., Methods: Four groups of seven anesthetized dogs were subjected to 8 minutes of fibrillatory arrest followed by 6 minutes of chest compression, ventricular defibrillation, and 4 hours of spontaneous circulation. Cerebral perfusion pressure was increased to approximately equivalent ranges during resuscitation by either 1) epinephrine infusion, 2) epinephrine infusion after pretreatment with the lipophilic beta-adrenergic antagonist pindolol, 3) infusion of the alpha-adrenergic agonist phenylephrine, or 4) descending aortic balloon inflation without pressor agents., Results: We found no difference in cerebral blood flow, oxygen extraction, or oxygen consumption during chest compression among groups. After ventricular defibrillation, depressed levels of cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potential amplitude were not different among groups., Conclusions: We detected no evidence that after 8 minutes of complete ischemia, epinephrine administration during resuscitation substantially influences cerebral blood flow or cerebral oxygen consumption independent of its action of raising arterial pressure or or that epinephrine has a negative impact on immediate metabolic or electrophysiological recovery attributable to its beta-adrenergic activity.