Jonathan R. Egan

Part 10: Acute Coronary Syndromes 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

There has been tremendous progress in reducing disability and death from ACS. But many patients still die before reaching the hospital because patients and family members fail to recognize the signs of ACS and fail to activate the EMS system. Once the patient with ACS contacts the healthcare system, providers must focus on support of cardiorespiratory function, rapid transport, and early classification of the patient based on ECG characteristics. Patients with STEMI require prompt reperfusion; the shorter the interval from symptom onset to reperfusion, the greater the benefit. In the STEMI population, mechanical reperfusion with percutaenous coronary intervention improves survival and decreases major cardiovascular events compared to fibrinolysis. Patients with UA/NSTEMI (non-STEMI ACS) or nonspecific or normal ECGs require risk stratification and appropriate monitoring and therapy. Healthcare providers can improve survival rates and myocardial function of patients with ACS by providing skilled, efficient, and coordinated out-of-hospital and in-hospital care.

Part 6: Pediatric basic life support and pediatric advanced life support. 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations

The Pediatric Task Force reviewed all questions submitted by the International Liaison Committee on Resuscitation (ILCOR) member councils in 2010, reviewed all council training materials and resuscitation guidelines and algorithms, and conferred on recent areas of interest and controversy. We identified a few areas where there were key differences in council-specific guidelines based on historical recommendations, such as the A-B-C (Airway, Breathing, Circulation) versus C-A-B (Circulation, Airway, Breathing) sequence of provision of cardiopulmonary resuscitation (CPR), initial back blows versus abdominal thrusts for foreign-body airway obstruction, an upper limit for recommended chest compression rate, and initial defibrillation dose for shockable rhythms (2 versus 4 J/kg). We produced a working list of prioritized questions and topics, which was adjusted with the advent of new research evidence. This led to a prioritized palate of 21 PICO (population, intervention, comparator, outcome) questions for ILCOR task force focus. The 2015 process was supported by information specialists who performed in-depth systematic searches, liaising with pediatric content experts so that the most appropriate terms and outcomes and the most relevant publications were identified. Relevant adult literature was considered (extrapolated) in those PICO questions that overlapped with other task forces, or when there were insufficient pediatric data. In rare circumstances (in the absence of sufficient human data), appropriate animal studies were incorporated into reviews of the literature. However, these data were considered only when higher levels of evidence were not available and the topic was deemed critical. When formulating the PICO questions, the task force felt it important to evaluate patient outcomes that extend beyond return of spontaneous circulation (ROSC) or discharge from the pediatric intensive care unit (PICU). In recognition that the measures must have meaning, not only to clinicians but also to parents and caregivers, longer-term outcomes at 30 …

Levosimendan for low cardiac output: a pediatric experience.

This was a retrospective observational study in a pediatric intensive care unit, in which 19 patients received levosimendan. There were no adverse events attributable to levosimendan and no instances where the clinical condition worsened after administration. Arterial lactate levels decreased significantly following levosimendan administration during cardiopulmonary bypass for anticipated low cardiac output. In those with established low cardiac output, trends toward improved hemodynamics were seen, with heart rate reduction, an increase in mean blood pressure, a reduction in arterial lactate, and reduced conventional inotrope use. Levosimendan was safely used in a small number of pediatric patients with established low cardiac output state who demonstrated improved hemodynamics and tissue perfusion, with a tendency to reduced conventional inotrope usage, and this warrants its evaluation as an inotrope in the pediatric population.

Increased connective tissue growth factor associated with cardiac fibrosis in the mdx mouse model of dystrophic cardiomyopathy

Cardiomyopathy contributes to morbidity and mortality in Duchenne muscular dystrophy (DMD), a progressive muscle‐wasting disorder. A major feature of the hearts of DMD patients and the mdx mouse model of the disease is cardiac fibrosis. Connective tissue growth factor (CTGF) is involved in the fibrotic process in many organs. This study utilized the mdx mouse model to assess the role of CTGF and other extracellular matrix components during the development of fibrosis in the dystrophic heart. Left ventricular function of mdx and control mice at 6, 29 and 43 weeks was measured by echocardiography. Young (6 weeks old) mdx hearts had normal function and histology. At 29 weeks of age, mdx mice developed cardiac fibrosis and increased collagen expression. The onset of fibrosis was associated with increased CTGF transcript and protein expression. Increased intensity of CTGF immunostaining was localized to fibrotic areas in mdx hearts. The upregulation of CTGF was also concurrent with increased expression of tissue inhibitor of matrix metalloproteinases (TIMP‐1). These changes persisted in 43 week old mdx hearts and were combined with impaired cardiac function and increased gene expression of transforming growth factor (TGF)‐β1 and matrix metalloproteinases (MMP‐2, MMP‐9). In summary, an association was observed between cardiac fibrosis and increased CTGF expression in the mdx mouse heart. CTGF may be a key mediator of early and persistent fibrosis in dystrophic cardiomyopathy.

Part 6: Pediatric basic life support and pediatric advanced life support

The Pediatric Task Force reviewed all questions submitted by the International Liaison Committee on Resuscitation (ILCOR) member councils in 2010, reviewed all council training materials and resuscitation guidelines and algorithms, and conferred on recent areas of interest and controversy. We identified a few areas where there were key differences in council-specific guidelines based on historical recommendations, such as the A-B-C (Airway, Breathing, Circulation) versus C-A-B (Circulation, Airway, Breathing) sequence of provision of cardiopulmonary resuscitation (CPR), initial back blows versus abdominal thrusts for foreign-body airway obstruction, an upper limit for recommended chest compression rate, and initial defibrillation dose for shockable rhythms (2 versus 4 J/kg). We produced a working list of prioritized questions and topics, which was adjusted with the advent of new research evidence. This led to a prioritized palate of 21 PICO (population, intervention, comparator, outcome) questions for ILCOR task force focus. The 2015 process was supported by information specialists who performed in-depth systematic searches, liaising with pediatric content experts so that the most appropriate terms and outcomes and the most relevant publications were identified. Relevant adult literature was considered (extrapolated) in those PICO questions that overlapped with other task forces, or when there were insufficient pediatric data. In rare circumstances (in the absence of sufficient human data), appropriate animal studies were incorporated into reviews of the literature. However, these data were considered only when higher levels of evidence were not available and the topic was deemed critical. When formulating the PICO questions, the task force felt it important to evaluate patient outcomes that extend beyond return of spontaneous circulation (ROSC) or discharge from the pediatric intensive care unit (PICU). In recognition that the measures must have meaning, not only to clinicians but also to parents and caregivers, longer-term outcomes at 30 …

Myocardial ischemia is more important than the effects of cardiopulmonary bypass on myocardial water handling and postoperative dysfunction: A pediatric animal model

OBJECTIVES Low cardiac output state is the principal cause of morbidity after surgical intervention for congenital heart disease. Myocardial ischemia-reperfusion injury, apoptosis, capillary leak syndrome, and myocardial edema are associated factors. We established a clinically relevant model to examine relationships between myocardial ischemia, edema, and cardiac dysfunction and to assess the role of the water transport proteins aquaporins. METHODS Sixteen lambs were studied. Seven were control animals not undergoing cardiopulmonary bypass, and 9 underwent bypass. Six had 90 minutes of aortic crossclamping with blood cardioplegia and moderate hypothermia. The remaining 3 underwent cardiopulmonary bypass without aortic crossclamping. Hemodynamic and biochemical data were recorded, and myocardial edema, apoptotic markers, and aquaporin expression were determined after death. RESULTS The group undergoing cardiopulmonary bypass with aortic crossclamping had a low cardiac output state, with early postoperative tachycardia, hypotension, increased serum lactate levels, and impaired tissue oxygen delivery (P < .05) compared with the group undergoing cardiopulmonary bypass without aortic crossclamping. The lambs undergoing cardiopulmonary bypass with aortic crossclamping had increased myocardial water (P < .05) compared with those not undergoing cardiopulmonary bypass and a 2-fold increase in aquaporin 1 mRNA expression (P < .05) compared with those not undergoing cardiopulmonary bypass and those undergoing cardiopulmonary bypass without aortic crossclamping. CONCLUSIONS A temporal association between hemodynamic dysfunction, myocardial edema, and increased aquaporin 1 expression was demonstrated. Cardiopulmonary bypass without ischemia was associated with minimal edema, negligible myocardial dysfunction, and static aquaporin expression. Ischemic reperfusion injury is the main cause of myocardial edema and myocardial dysfunction, but a causal relationship between edema and dysfunction remains to be proved.

Part 2: Evidence Evaluation and Management of Conflicts of Interest: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

This Part describes the process of creating the 2015 American Heart Association (AHA) Guidelines Update for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC), informed by the 2015 International Consensus on CPR and ECC Science With Treatment Recommendations (CoSTR) publication.1,2 The process for the 2015 International Liaison Committee on Resuscitation (ILCOR) systematic review is quite different when compared with the process used in 2010.1–3 For the 2015 systematic review process, ILCOR used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) (www.gradeworkinggroup.org) approach to systematic reviews and guideline development. For the development of this 2015 Guidelines Update, the AHA used the ILCOR reviews as well as the AHA definition of Classes of Recommendation (COR) and Levels of Evidence (LOE) (Table 1). This Part summarizes the application of the ILCOR GRADE process to inform the creation of 2015 Guidelines Update, and the process of assigning the AHA COR and LOE. View this table: Table 1. Applying Class of Recommendations and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* ### Grading of Recommendations Assessment, Development, and Evaluation The 2015 CoSTR summarizes the published scientific evidence that was identified to answer specific resuscitation questions. ILCOR uses the GRADE system to summarize evidence and determine confidence in estimates of effect as well as to formulate treatment recommendations. GRADE is a consensus-crafted tool in wide use by many professional societies and reference organizations, including the American College of Physicians, the American Thoracic Society, and the Cochrane Collaboration, as well as the Centers for Disease Control and the World Health Organization. The choice of the GRADE approach was based on its increasingly ubiquitous use, practicality, and unique features. To our knowledge, the ILCOR evidence review process represents the largest application of the GRADE system in a healthcare-related review. GRADE is a system to review evidence to determine …

Zolpidem for persistent vegetative state - a placebo-controlled trial in pediatrics

OBJECTIVE The aim of this study was to determine if zolpidem is associated with improved responsiveness or regional cerebral perfusion in patients with persistent vegetative states. METHODS Following ethics approval, children with persistent vegetative state were enrolled in a prospective, double-blind, placebo-controlled randomised trial. Patients underwent 2 treatments of 4 days, separated by 10 days. Each child received either a daily dose of zolpidem or placebo with a dosage of 0.14-0.2 mg/kg. Responsiveness and regional cerebral perfusion were the outcomes of interest. These were assessed using the Rancho levels of cognitive functioning scale, the coma/near-coma scale and F (18)-FDG positron emission tomography. These were conducted at baseline and after completion of the treatments. RESULTS 3 children were enrolled. The Rancho assessment scales showed no change with treatment. The coma/near-coma scale showed a tendency to increase with zolpidem, suggesting reduced responsiveness - when compared to baseline or placebo. The positron emission tomography scans showed no significant changes between treatments. CONCLUSION Zolpidem was associated with a tendency towards reduced responsiveness in patients with persistent vegetative states. There were no objective changes on positron emission tomography suggestive of an associated increase in cerebral blood flow with zolpidem. It would appear that zolpidem does not offer a beneficial effect in this setting.

Dysfunction induced by ischemia versus edema: Does edema matter?

OBJECTIVES Recovery from pediatric cardiac surgery is affected by ischemia-reperfusion injury, cardiac edema, and in some cases a low cardiac output syndrome. Although association has been made between the development of edema and dysfunction, modeling is confounded by intercurrent injurious stimuli that also cause cardiac edema and dysfunction. We tested whether a true causal relationship exists between edema and cardiac dysfunction. METHODS We induced either ischemia or edema alone in isolated cardiomyocytes and whole Langendorff-perfused hearts. Function was measured as shortening dynamics and developed pressure, respectively. RESULTS Ischemic injury impaired function in both cardiomyocytes and whole hearts. Isolated cells showed significant reduction in peak shortening and departure and relaxation velocities. Whole hearts displayed severely reduced developed pressures. Hyposmotic solution forced cardiomyocytes to swell to 7% greater than their normal size. No significant effect on shortening was seen. Similarly, Langendorff-perfused hearts were induced to take on 3% more water than control-perfused hearts and 9% more water than nonperfused hearts. This additional water was associated with mild dysfunction. CONCLUSIONS We demonstrate the capacity of the heart to tolerate edema greater than that seen in clinical settings without residual effect. Ischemia results in ongoing contractile dysfunction of both isolated cardiomyocytes and whole hearts. We conclude that dysfunction resulting from edema in ex vivo cardiac models is mild and suggest review of the importance given to edema-mediated dysfunction after cardiac surgery.

Recombinant Activated Factor VII Following Pediatric Cardiac Surgery

Objective: Review the use of recombinant activated Factor VII following cardiac surgery. Specifically, we sought to define our current therapeutic practice indications and outcomes to assess the impact of recombinant activated factor VII on postoperative bleeding. Design: Retrospective case series. Setting: The study was conducted at the University affiliated pediatric intensive care unit. Patients and participants: All postcardiac surgical patients who received recombinant activated Factor VII between June 2002 and July 2006. Results: Cardiac surgery requiring cardiopulmonary bypass was performed on 1010 children during this period. In all, 25 (2.5%) children received recombinant activated factor VII for excessive bleeding. A single dose (180 μg/kg) of recombinant activated factor VII was given to 11 patients and 2 doses of 180 μg/kg to 14 patients. Intercostal drain losses were reduced from 12 (6.7-20.8) mL/kg/h to 3 (1-4.1) mL/kg/h, P = .018 following 1 dose of recombinant activated factor VII. In those receiving 2 doses; initial losses were 19.1 (7.5-31.7) mL/kg/h, after the first dose were 7.5 (3.6-13.7) mL/kg/h, P = .046, and after the second dose were 2 (1-2.9) mL/kg/h, P = .008. The plasma prothrombin time decreased in both the 1 dose, P = .003 and 2 dose, P = .009 groups. The activated partial thromboplastin time also decreased in the 1 dose group, P = .007 and 2 dose group, P = .03. There were no side effects attributable to recombinant activated factor VII. Annual rates of return to the operating theatre for excessive bleeding were coincidentally reduced in association with the routine use of recombinant activated factor VII from 4.3% to 1.5%, P = .019. Conclusions: Hemostasis occurred in 25 postoperative pediatric cardiac patients after recombinant activated Factor VII was given. In this setting, once conventional hemostatic therapy was optimized, recombinant activated Factor VII 180 μg/kg initially with intercostal losses greater than 10 mL/kg/h and a repeat dose after 2 hours if losses remained greater than 5 mL/kg/h was effective. No complications were found to have occurred and there was a coincidental reduction in annual returns to theatre for excessive bleeding.