Murray Kesselman

Severe traumatic brain injury in children elevates glial fibrillary acidic protein in cerebrospinal fluid and serum

Objectives: 1) To determine the levels of glial fibrillary acidic protein (GFAP) in both cerebrospinal fluid and serum; 2) to determine whether serum GFAP levels correlate with functional outcome; and 3) to determine whether therapeutic hypothermia, as compared with normothermia, alters serum GFAP levels in children with severe traumatic brain injury (TBI). Design: Laboratory-based analyses; postrandomized, controlled trial. Setting: Four Canadian pediatric intensive care units and a university-affiliated laboratory. Patients: Twenty-seven children, aged 2–17 yrs, with severe TBI (Glasgow Coma Scale score of ≤8). Interventions: Hypothermia therapy (32.5°C) for 24 hrs with cooling started within 8 hrs of injury and rewarming at a rate of 0.5°C every 2 hrs or normothermia (37.0°C). Measurements and Main Results: GFAP was measured in cerebrospinal fluid and serum, using enzyme-linked immunosorbent assay. Levels of GFAP were maximal on day 1 post-TBI, with cerebrospinal fluid GFAP (15.5 ± 6.1 ng/mL) 25-fold higher than serum GFAP (0.6 ± 0.2 ng/mL). Cerebrospinal fluid GFAP normalized by day 7, whereas serum GFAP decreased gradually to reach a steady state by day 10. Serum GFAP measured on day 1 correlated with Pediatric Cerebral Performance Category scores determined at 6 months post-TBI (&rgr; = 0.527; p = .008) but failed to correlate with the injury scoring on admission, physiologic variables, or indices of injury measured on computerized tomography imaging. The areas under the receiver operating characteristic curves for pediatric intensive care unit day 1 serum GFAP in determining good outcome were 0.80 (pediatric cerebral performance category, 1–2; normal-mild disability) and 0.91 (pediatric cerebral performance category, 1–3; normal-moderate disability). For a serum GFAP cutoff level of 0.6 ng/mL, sensitivity and specificity were 88% to 90% and 43% to 71%, respectively. Serum GFAP levels were similar among children randomized to either therapeutic hypothermia or normothermia. Conclusions: GFAP was markedly elevated in cerebrospinal fluid and serum in children after severe TBI and serum GFAP measured on pediatric intensive care unit day 1 correlated with functional outcome at 6 months. Hypothermia therapy did not alter serum GFAP levels compared with normothermia after severe TBI in children. Serum GFAP concentration, together with other biomarkers, may have prognostic value after TBI in children.

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.

Potential pediatric intensive care unit demand/capacity mismatch due to novel pH1N1 in Canada.

Objective: To investigate the possibility of pediatric intensive care unit shortfalls, using pandemic models for a range of attack rates and durations. The emergence of the swine origin pH1N1 virus has led to concerns about shortfalls in our ability to provide pediatric ventilation and critical care support. Design: Modeling of pediatric intensive care demand based on pH1N1 predictions using simulation techniques. Setting: Simulation laboratory. Patients: None. Interventions: None. Measurements and Main Results: Data collected during the first wave of the pH1N1 in children in Canada were applied to several second wave pandemic models to explore potential pediatric intensive care unit ventilatory demands for Canada and to investigate the impact of vaccination upon these demands. In almost all cases studied, even for relatively low attack rates of 15%, significant pediatric intensive care unit shortages would be expected to occur. Vaccination strategies targeting 50% of the population significantly reduced demand, but shortages may still be expected. Although shortfalls can occur in all provinces, Ontario and British Columbia may experience the greatest supply-demand difference, even at low attack rates. Conclusion: Reducing the attack rate among children, whether through vaccination or additional measures, such as social distancing, will be critical to ensure sufficient pediatric intensive care unit capacity for continued pediatric care.

Air Transported Pediatric Rescue Extracorporeal Membrane Oxygenation: A Single Institutional Review

Background: Pediatric extracorporeal membrane oxygenation (ECMO) programs are sophisticated endeavors usually found only in high-volume cardiac surgical programs. Worldwide, many cardiology programs do not have on-site pediatric cardiac surgery expertise. Our single-center experience shows that an organized multidisciplinary rescue-ECMO program, in collaboration with an accepting facility, can achieve survival rates comparable to modern era on-site ECMO. Methods: A retrospective review was conducted of all patients initiated on rescue-ECMO from 2004 to 2009 in a single academic pediatric hospital without a pediatric cardiac surgery program. All aspects of ECMO were formalized using Failure Mode Effects Analysis. Results: Eight patients were initially cannulated for ECMO at our institution. Six were subsequently transported by air to the receiving facility 1,305 km away. Extracorporeal membrane oxygenation was initiated in 0.2% of our Pediatric Intensive Care Unit admissions and in 0.52% of all our pediatric cardiac patients. Mean age was 4.0 years (7 weeks to 15 years). Indications for ECMO initiations were cardiogenic shock (n = 5) and acute respiratory distress syndrome (n = 3). Six had veno-arterial- and two had veno-veno ECMO. Two patients were not transported (one death and one weaned locally). Six patients were successfully transported within 2 to 24 hours, with a survival to hospital discharge rate of 67% (four of six). Median total time on ECMO was 5.5 days. Complication rate was 50% (4/8). Conclusions: Our rescue-ECMO survival results were comparable to that of current published results from established pediatric ECMO programs. Air transport of ECMO patients can be performed safely using an organized multidisciplinary team approach.

Severe Mitral Insufficiency Associated with Kawasaki's Valvulitis

SummaryA two-month-old male infant with Kawasakis disease, severe mitral insufficiency, and normal coronary arteries is described. We postulate the mitral insufficiency was secondary to Kawasakis valvulitis, and that this occurred in the absence of other forms of cardiac involvement characteristic of Kawasakis disease.

Delivering Prolonged Intensive Care to a Non-human Primate: A High Fidelity Animal Model of Critical Illness

Critical care needs have been rising in recent decades as populations age and comorbidities increase. Sepsis-related admissions to critical care contribute up to 50% of volume and septic shock carries a 35–54% fatality rate. Improvements in sepsis-related care and mortality would have a significant impact of a resource-intensive area of health care delivery. Unfortunately, research has been hampered by the lack of an animal model that replicates the complex care provided to humans in an intensive care unit (ICU). We developed a protocol to provide full ICU type supportive care to Rhesus macaques. This included mechanical ventilation, continuous sedation, fluid and electrolyte management and vasopressor support in response to Ebolavirus-induced septic shock. The animals accurately recapitulated human responses to a full range of ICU interventions (e.g. fluid resuscitation). This model can overcome current animal model limitations by accurately emulating the complexity of ICU care and thereby provide a platform for testing new interventions in critical care and sepsis without placing patients at risk.