What Are the Etiology and Epidemiology of Out‐of‐hospital Pediatric Cardiopulmonary Arrest in Ontario,Canada?

Background: Pediatric cardiopulmonary arrest (CPA) outside of the hospital has a very high mortality rate. Objectives: To evaluate the etiology and initial compromise of pediatric CPA cases in hopes of developing strategies to improve out‐of‐hospital resuscitation. Methods: The Ontario Prehospital Advanced Life Support (OPALS) study was a large multicenter initiative to evaluate the impact of emergency medical services (EMS) programs on 17 communities with 40,000 critically ill and injured patients who were older than 11 years. As part of this study, the authors conducted a retrospective observational cohort study that included all children younger than 18 years of age with out‐of‐hospital CPA, during an 11‐year period from 1991–2002. CPA was defined as patient being pulseless, apneic, and requiring chest compressions. Data were collected from ambulance call reports and centralized dispatch data and were reviewed by two independent investigators. Results: There were 503 children with CPA in the sample. Mean age was 5.6 years (range, 0–17 yr); 58.4% of patients were male, and 37.8% were younger than 1 year of age. Cardiopulmonary resuscitation (CPR) first was started by a bystander in 32.4% of cases, whereas 66.0% were unwitnessed arrests. Initial rhythms were asystole 77.2% of the time, pulseless electrical activity 16.4% of the time, and ventricular fibrillation or ventricular tachycardia 4% of the time. Annual incidence was 9.1/100,000 children. CPA was witnessed in 34.0% of cases; 80.7% of these were bystander‐witnessed, and 18.1% were EMS‐witnessed. Primary pathogenic cause of arrest was medical in 61.2% of cases, trauma in 37.2% of cases, and indeterminate in 1.6% of cases. Initial underlying physiologic compromise of witnessed arrests was judged to be respiratory in 39.8% of cases, sudden collapse (presumed electrical) in 16.4% of cases, progressive shock in 1.2% of cases, and indeterminate in 42.6% of cases. Presumed etiology was trauma, 37.6%; sudden infant death syndrome (SIDS), 20.3%; and respiratory disease, 11.6%, most commonly. Survival to hospital discharge was 2.0%. Conclusions: This is one of the largest population‐based, prospective cohorts of pediatric CPA reported to date, and it reveals that most pediatric arrests are unwitnessed and receive no bystander CPR. Those that are witnessed most often are caused by respiratory arrests or trauma. Trauma, SIDS, and respiratory disease are the most common etiologies overall. These data are vital to planning large resuscitation trials looking at specific interventions (i.e., increasing bystander CPR) and highlight the need for better strategies for prevention and early recognition.     

CPR-only survivors of out-of-hospital cardiac arrest: implications for out-of-hospital care and cardiac arrest research methodology

STUDY OBJECTIVE: There is little evidence that cardiopulmonary resuscitation (CPR) alone may lead to the resuscitation of cardiac arrest victims with other than respiratory causes (eg, pediatric arrest, drowning, drug overdose). The objective of this study was to identify out-of-hospital cardiac arrest survivors resuscitated without defibrillation or advanced cardiac life support. METHODS: This observational cohort included all adult survivors of out-of-hospital cardiac arrest of a cardiac cause from phases I and II of the Ontario Prehospital Advanced Life Support Study. During the study period, the system provided a basic life support/defibrillation level of care but no advanced life support. CPR-only patients were patients determined to be without vital signs by EMS personnel who regained a palpable pulse in the field with precordial thump or CPR only and then were admitted alive to the hospital. Six members of a 7-member expert review panel had to rate the patient as either probably or definitely having an out-of-hospital cardiac arrest, and a rhythm strip consistent with a cardiac arrest rhythm had to be present to be considered a patient. Criteria considered were witness status, citizen or first responder CPR, CPR duration, arrest rhythm and rate, and performance of precordial thump. RESULTS: From January 1, 1991, to June 30, 1997, 9,667 patients with out-of-hospital cardiac arrest were treated. The overall survival rate to hospital discharge was 4.6%. There were 97 apparent CPR-only patients admitted to the hospital. Application of the inclusion criteria yielded 24 CPR-only patients who had true out-of-hospital cardiac arrest and 73 patients judged not to have cardiac arrest. Of the 24 true CPR-only patients admitted to the hospital, 15 patients were discharged alive, 10 patients were witnessed by bystanders, and 7 patients were witnessed by EMS personnel. The initial arrest rhythm was pulseless electrical activity in 9 patients, asystole in 12 patients, and ventricular tachycardia in 3 patients. One patient with ventricular tachycardia converted to sinus tachycardia with a single precordial thump. CONCLUSION: CPR-only survivors of true out-of-hospital cardiac arrest do exist; some victims of out-of-hospital cardiac arrest of primary cardiac cause can survive after provision of out-of-hospital basic life support care only. However, many patients found to be pulseless by means of out-of-hospital evaluation likely did not have a true cardiac arrest. This has implications for the survival rates of most, if not all, previous cardiac arrest reports. Survival rates from cardiac arrest may actually be lower if one excludes survivors who never had a true arrest. The absence of vital signs by out-of-hospital assessment alone is not adequate to include patients in research reports or quality evaluations for cardiac arrest.     

Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells

Cytokine-induced killer (CIK) cells are non-major histocompatibility complex-restricted cytotoxic cells generated by incubation of peripheral blood lymphocytes with anti-CD3 monoclonal antibody (MoAb), interleukin-2 (IL-2), IL-1, and interferon-gamma. Cells with the greatest effector function in CIK cultures coexpress CD3 and CD56 surface molecules. CIK cell cytotoxicity can be blocked by MoAbs directed against the cell surface protein leukocyte function associated antigen-1 but not by anti-CD3 MoAbs. CIK cells undergo release of cytoplasmic cytotoxic granule contents to the extracellular space upon stimulation with anti-CD3 MoAbs or susceptible target cells. Maximal granule release was observed from the CD3+ CD56+ subset of effector cells. The cytoplasmic granule contents are lytic to target cells. Treatment of the effector cells with a cell-permeable analog of cyclic adenosine monophosphate (cAMP) inhibited anti-CD3 MoAb and target cell- induced degranulation and cytotoxicity of CIK cells. The immunosuppressive drugs cyclosporin (CsA) and FK506 inhibited anti-CD3- mediated degranulation, but did not affect cytotoxicity of CIK cells against tumor target cells. In addition, degranulation induced by target cells was unaffected by CsA and FK506. Our results indicate that two mechanisms of cytoplasmic granule release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity proceeds through a cAMP- sensitive, CsA- and FK506-insensitive pathway triggered by yet-to-be- identified target cell surface molecules.