Jamie Hutchison

Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada

CONTEXT Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. OBJECTIVE To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. DESIGN, SETTING, AND PATIENTS A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. MAIN OUTCOME MEASURES The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. RESULTS Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29). CONCLUSION Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

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.).

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

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 childrens 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.)

Critical illness in children with influenza A/pH1N1 2009 infection in Canada*

Objective: To describe characteristics, treatment, and outcomes of critically ill children with influenza A/pandemic influenza A virus (pH1N1) infection in Canada. Design: An observational study of critically ill children with influenza A/pH1N1 infection in pediatric intensive care units (PICUs). Setting: Nine Canadian PICUs. Patients: A total of 57 patients admitted to PICUs between April 16, 2009 and August 15, 2009. Interventions: None. Measurements and Main Results: Characteristics of critically ill children with influenza A/pH1N1 infection were recorded. Confirmed intensive care unit cases were compared with a national surveillance database containing all hospitalized pediatric patients with influenza A/pH1N1 infection. Risk factors were assessed with a Cox proportional hazard model. The PICU cohort and national surveillance data were compared, using chi-square tests. Fifty-seven children were admitted to the PICU for community-acquired influenza A/pH1N1 infection. One or more chronic comorbid illnesses were observed in 70.2% of patients, and 24.6% of patients were aboriginal. Mechanical ventilation was used in 68% of children, 20 children (35.1%) had acute lung injury on the first day of admission, and the median duration of ventilation was 6 days (range, 0–67 days). The PICU mortality rate was 7% (4 of 57 patients). When compared with nonintensive care unit hospitalized children, PICU children were more likely to have a chronic medical condition (relative risk, 1.73); aboriginal ethnicity was not a risk factor of intensive care unit admission. Conclusions: During the first outbreak of influenza A/pH1N1 infection, when the population was naïve to this novel virus, severe illness was common among children with underlying chronic conditions and aboriginal children. Influenza A/pH1N1-related critical illness in children was associated with severe hypoxemic respiratory failure and prolonged mechanical ventilation. However, this higher rate and severity of respiratory illness did not result in an increased mortality when compared with seasonal influenza.

A quantitative analysis of out-of-hospital pediatric and adolescent resuscitation quality – A report from the ROC epistry-cardiac arrest☆

AIM High-quality cardiopulmonary resuscitation (CPR) may improve survival. The quality of CPR performed during pediatric out-of-hospital cardiac arrest (p-OHCA) is largely unknown. The main objective of this study was to describe the quality of CPR performed during p-OHCA resuscitation attempts. METHODS Prospective observational multi-center cohort study of p-OHCA patients ≥ 1 and < 19 years of age registered in the Resuscitation Outcomes Consortium (ROC) Epistry database. The primary outcome was an a priori composite variable of compliance with American Heart Association (AHA) guidelines for both chest compression (CC) rate and CC fraction (CCF). Event compliance was defined as a case with 60% or more of its minute epochs compliant with AHA targets (rate 100-120 min(-1); depth ≥ 38 mm; and CCF ≥ 0.80). In a secondary analysis, multivariable logistic regression was used to evaluate the association between guideline compliance and return of spontaneous circulation (ROSC). RESULTS Between December 2005 and December 2012, 2564 pediatric events were treated by EMS providers, 390 of which were included in the final cohort. Of these events, 22% achieved AHA compliance for both rate and CCF, 36% for rate alone, 53% for CCF alone, and 58% for depth alone. Over time, there was a significant increase in CCF (p < 0.001) and depth (p = 0.03). After controlling for potential confounders, there was no significant association between AHA guideline compliance and ROSC. CONCLUSIONS In this multi-center study, we have established that there are opportunities for professional rescuers to improve prehospital CPR quality. Encouragingly, CCF and depth both increased significantly over time.

A cross-sectional survey of levels of care and response mechanisms for evolving critical illness in hospitalized children.

OBJECTIVES. Recognition and treatment of evolving critical illness is a fundamental element of hospital care. Hospital systems should triage patients to receive appropriate levels of care. We describe here the levels of care, the frequency of near or actual cardiopulmonary arrest (code-blue events), identification mechanisms, and responses to evolving critical illness in hospitalized children. METHODS. A cross-sectional telephone survey of Canadian and American hospitals with ≥50 pediatric acute care beds or ≥2 pediatric wards was performed. Regression analysis identified factors associated with the frequency of code-blue events after adjustment for hospital volume. RESULTS. Responses from 388 (84%) hospitals identified the 181 eligible pediatric hospitals included in this survey. All had a PICU, 99 (55%) had high-dependency units, 101 (56%) had extracorporeal membrane oxygenation therapy, and 69 (38%) used extracorporeal membrane oxygenation therapy for refractory cardiopulmonary arrest. All of the hospitals had immediate-response teams. They were activated 4676 times in the previous 12 months. Twenty-four percent of hospitals had activation criteria for immediate-response teams. Urgent-response teams to treat children who were clinically deteriorating but not at immediate risk of cardiopulmonary arrest were available in 136 (75%) hospitals; 29 (17%) had formal medical emergency teams, and 92 (51%) consulted the PICU. Code-blue events were more common in hospitals with extracorporeal membrane oxygenation therapy, cardiopulmonary bypass, and larger PICU size. CONCLUSIONS. Currently, the organization of Canadian and American pediatric hospitals includes dedicated areas to match patient acuity and additional personnel to stabilize and facilitate transfer. The functioning of these systems of care results in calls for immediate medical assistance for ward patients ∼5000 times annually.

Adaptive behavior, functional outcomes, and quality of life outcomes of children requiring urgent ICU admission.

Objective: To describe the adaptive behavior and functional outcomes, and health-related quality of life of children who were urgently admitted to the ICU. Design: Prospective observational study. Setting: Critical Care Medicine program at a University-affiliated pediatric institution. Patients: Urgently admitted patients, aged 1 month to 18 yrs. Interventions: None. Measurements and Main Results: We evaluated children’s adaptive behavior functioning with the Vineland Adaptive Behavior Scale-2, functional outcomes with the pediatric cerebral performance category and pediatric overall performance category, and health-related quality of life with the Pediatric Quality of Life Inventory 4 and Visual Analogue Scale. We enrolled 91 children and 65 (71%) completed the 1-month assessment. Patients had a mean (SD) Vineland Adaptive Behavior Scale-2 rating of 83.2 (±24.8), considered to be moderate-low adaptive behavior functioning. From baseline to 1 month, pediatric cerebral performance category ratings did not significantly change (p = 0.59) and pediatric overall performance category ratings significantly improved (p = 0.03). Visual Analogue Scale ratings significantly worsened from baseline to 1wk (p < 0.0001) and significantly improved from 1 wk to 1 month (p=0.002). At 1 month, patients had a mean (SD) Pediatric Quality of Life Inventory 4 rating of 52.8 (±27.9) of 100, a poor quality of life rating. Circulatory admissions, worse pediatric cerebral performance category score at baseline, worse transcutaneous oxygen saturation, and longer cardiac compression duration were independently associated with worse adaptive behavior functioning. Neurological admissions, worse pediatric cerebral performance category score at baseline, longer ICU stay, and longer duration of extracorporeal membrane oxygenation were independently associated with worse functional outcome. Worse pediatric cerebral performance category score at baseline, longer ICU stay, and longer duration of extracorporeal membrane oxygenation were independently associated with worse health-related quality of life. Conclusions: Children surviving PICU have significant adaptive behavior functioning and functional morbidity and reduced health-related quality of life. Although neurologic morbidity following ICU was associated with baseline state, we found that resuscitation intensity and illness severity factors were independently associated with the development of acquired brain injury and reduced quality of life.

Unchanged pediatric out-of-hospital cardiac arrest incidence and survival rates with regional variation in North America

AIM Outcomes for pediatric out-of-hospital cardiac arrest (OHCA) are poor. Our objective was to determine temporal trends in incidence and mortality for pediatric OHCA. METHODS Adjusted incidence and hospital mortality rates of pediatric non-traumatic OHCA patients from 2007-2012 were analyzed using the 9 region Resuscitation Outcomes Consortium-Epidemiological Registry (ROC-Epistry) database. Children were divided into 4 age groups: perinatal (<3 days), infants (3days-1year), children (1-11 years), and adolescents (12-19 years). ROC regions were analyzed post-hoc. RESULTS We studied 1738 children with OHCA. The age- and sex-adjusted incidence rate of OHCA was 8.3 per 100,000 person-years (75.3 for infants vs. 3.7 for children and 6.3 for adolescents, per 100,000 person-years, p<0.001). Incidence rates differed by year (p<0.001) without overall linear trend. Annual survival rates ranged from 6.7-10.2%. Survival was highest in the perinatal (25%) and adolescent (17.3%) groups. Stratified by age group, survival rates over time were unchanged (all p>0.05) but there was a non-significant linear trend (1.3% increase) in infants. In the multivariable logistic regression analysis, infants, unwitnessed event, initial rhythm of asystole, and region were associated with worse survival, all p<0.001. Survival by region ranged from 2.6-14.7%. Regions with the highest survival had more cases of EMS-witnessed OHCA, bystander CPR, and increased EMS-defibrillation (all p<0.05). CONCLUSIONS Overall incidence and survival of children with OHCA in ROC regions did not significantly change over a recent 5year period. Regional variation represents an opportunity for further study to improve outcomes.

Brain death in Canadian PICUs: demographics, timing, and irreversibility.

Objectives: To determine any discordance between first and second brain death examinations and investigate the quality of brain death determination in Canadian PICUs. Design: Multicenter retrospective chart review. Setting: Four Canadian PICUs. Patients: All deaths from 1999 to 2003 were screened. Patients included were 36 wks corrected gestation to 17 yrs old and had at least one brain death examination documented in the chart. Interventions: None. Measurements and Main Results: Medical records were reviewed to determine demographics, results of the brain death examinations, ancillary tests, and time intervals between injury event, fixed dilated pupils, first brain death examination, second brain death examination, and terminal event. Discordance between brain death examinations was defined as the medical conclusion documented in the chart as brain death followed by no brain death. Prespecified subgroups were age <1 yr vs. ≥1 yr and organ donor vs. nonorgan donor. Mann-Whitney-Wilcoxon and unpaired t tests compared time intervals between subgroups; p value ⩽ 0.05 was consi dered significant. Of those screened, 135 of 907 (15%) met the study eligibility criteria and 110 of 135 (81%) had at least two brain death examinations. The prevalence of discordance between brain death examinations was 1 of 110 (0.91%) (95% confidence interval <0.01%–5.5%). In those who had two apnea tests, the prevalence of discordance between brain death examinations was 1 of 63 (1.6%) (95% confidence interval <0.01%–9.3%). Twenty-five (19%) patients had only one brain death examination, and one of these became an organ donor without ancillary testing. Twenty-four (18%) patients did not have an apnea test. Of the 48 (36%) who had only one apnea test, 16 became organ donors without any ancillary test. Patients <1 yr old had a longer time interval between the first and second brain death examinations than those >1 yr old. Conclusions: Some brain death diagnoses were not based on two examinations, and some did not include an apnea test. In patients who had two brain death examinations, discordant results were uncommon.

Abnormal fatty acid metabolism in spinal muscular atrophy may predispose to perioperative risks

A 15 year old boy with SMA type II underwent spinal fusion and suffered a mitochondrial Reye-like catabolic crisis 4 days postop with hypoketotic hypoglycemia, lactic acidaemia, hyperammonemia and liver failure, with 90% coagulative necrosis and diffuse macro- and microvesicular steatosis, requiring orthotopic liver transplantation. This crisis responded in part to mitochondrial therapy and anabolic rescue. He made a dramatic sustained neurological recovery, though his post-transplant liver biopsies revealed micro- and macrosteatosis. We hypothesize that a combination of surgical stress-catecholamine induced lipolysis, prolonged general anaesthesia with propofol and sevoflurane, and perioperative fasting on a background of decreased β-oxidation were potential risk factors for the mitochondrial decompensation.