Stuart H. Friess

Diffuse optical monitoring of hemodynamic changes in piglet brain with closed head injury.

We used a nonimpact inertial rotational model of a closed head injury in neonatal piglets to simulate the conditions following traumatic brain injury in infants. Diffuse optical techniques, including diffuse reflectance spectroscopy and diffuse correlation spectroscopy (DCS), were used to measure cerebral blood oxygenation and blood flow continuously and noninvasively before injury and up to 6 h after the injury. The DCS measurements of relative cerebral blood flow were validated against the fluorescent microsphere method. A strong linear correlation was observed between the two techniques (R=0.89, p<0.00001). Injury-induced cerebral hemodynamic changes were quantified, and significant changes were found in oxy- and deoxy-hemoglobin concentrations, total hemoglobin concentration, blood oxygen saturation, and cerebral blood flow after the injury. The diffuse optical measurements were robust and also correlated well with recordings of vital physiological parameters over the 6-h monitoring period, such as mean arterial blood pressure, arterial oxygen saturation, and heart rate. Finally, the diffuse optical techniques demonstrated sensitivity to dynamic physiological events, such as apnea, cardiac arrest, and hypertonic saline infusion. In total, the investigation corraborates potential of the optical methods for bedside monitoring of pediatric and adult human patients in the neurointensive care unit.

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 …

Electrographic status epilepticus is associated with mortality and worse short-term outcome in critically ill children.

Objectives:Electrographic seizures and electrographic status epilepticus are common in critically ill children. We aimed to determine whether electrographic seizures and electrographic status epilepticus are associated with higher mortality or worse short-term neurologic outcome. Design:Prospective observational study. Setting:PICU of a tertiary children’s hospital. Patients:Non-neonatal children admitted to a PICU with acute encephalopathy underwent continuous electroencephalographic monitoring. Electroencephalographs were scored as 1) no seizures, 2) electrographic seizures, or 3) electrographic status epilepticus. Covariates included age, acute neurologic disorder category, prior neurodevelopmental status, sex, and electroencephalographic background category. Outcomes were mortality and worsening of pediatric cerebral performance category from preadmission to PICU discharge. Chi-square analysis, Fisher’s exact test, and multivariable logistic regression were used to evaluate the associations between electrographic seizures or electrographic status epilepticus and mortality or short-term neurologic outcome, using odds ratios and 95% confidence intervals. Interventions:None. Main Results:Two hundred children underwent continuous electroencephalographic monitoring. Eighty-four (42%) had seizures, which were categorized as electrographic seizures in 41 (20.5%) and electrographic status epilepticus in 43 (21.5%). Thirty-six subjects (18%) died, and 88 subjects (44%) had pediatric cerebral performance category worsening. In multivariable analysis, electrographic status epilepticus was associated with an increased risk of mortality (odds ratio 5.1; 95% confidence interval 1.4, 18; p = 0.01) and pediatric cerebral performance category worsening (odds ratio 17.3; 95% confidence interval 3.7, 80; p < 0.001), whereas electrographic seizures were not associated with an increased risk of mortality (odds ratio 1.3; 95% confidence interval 0.3, 5.1; p = 0.74) or pediatric cerebral performance category worsening (odds ratio 1.2; 95% confidence interval 0.4, 3.9; p = 0.77). Conclusions:Electrographic status epilepticus, but not electrographic seizures, is associated with mortality and worse short-term neurologic outcome in critically ill children with acute encephalopathy.

Hemodynamic directed CPR improves short-term survival from asphyxia-associated cardiac arrest

AIM Adequate coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) is essential for establishing return of spontaneous circulation. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus an absolute depth-guided approach in a porcine model of asphyxia-associated cardiac arrest. We hypothesized that a hemodynamic directed approach would improve short-term survival compared to depth-guided care. METHODS After 7 min of asphyxia, followed by induction of ventricular fibrillation, 19 female 3-month old swine (31±0.4 kg) were randomized to receive one of three resuscitation strategies: (1) hemodynamic directed care (CPP-20): chest compressions (CCs) with depth titrated to a target systolic blood pressure of 100 mmHg and titration of vasopressors to maintain CPP>20 mmHg; (2) depth 33 mm (D33): target CC depth of 33 mm with standard American Heart Association (AHA) epinephrine dosing; or (3) depth 51 mm (D51): target CC depth of 51 mm with standard AHA epinephrine dosing. All animals received manual CPR guided by audiovisual feedback for 10 min before first shock. RESULTS 45-Min survival was higher in the CPP-20 group (6/6) compared to D33 (1/7) or D51 (1/6) groups; p=0.002. Coronary perfusion pressures were higher in the CPP-20 group compared to D33 (p=0.011) and D51 (p=0.04), and in survivors compared to non-survivors (p<0.01). Total number of vasopressor doses administered and defibrillation attempts were not different. CONCLUSIONS Hemodynamic directed care targeting CPPs>20 mmHg improves short-term survival in an intensive care unit porcine model of asphyxia-associated cardiac arrest.

Hemodynamic Directed Cardiopulmonary Resuscitation Improves Short-term Survival From Ventricular Fibrillation Cardiac Arrest*

Objectives:During cardiopulmonary resuscitation, adequate coronary perfusion pressure is essential for establishing return of spontaneous circulation. Current American Heart Association guidelines recommend standardized interval administration of epinephrine for patients in cardiac arrest. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus chest compression depth-directed cardiopulmonary resuscitation in a porcine model of cardiac arrest. Design:Randomized interventional study. Setting:Preclinical animal laboratory. Subjects:Twenty-four 3-month-old female swine. Interventions:After 7 minutes of ventricular fibrillation, pigs were randomized to receive one of three resuscitation strategies: 1) Hemodynamic directed care (coronary perfusion pressure-20): chest compressions with depth titrated to a target systolic blood pressure of 100 mm Hg and titration of vasopressors to maintain coronary perfusion pressure greater than 20 mm Hg; 2) Depth 33 mm: target chest compression depth of 33 mm with standard American Heart Association epinephrine dosing; or 3) Depth 51 mm: target chest compression depth of 51 mm with standard American Heart Association epinephrine dosing. All animals received manual cardiopulmonary resuscitation guided by audiovisual feedback for 10 minutes before first shock. Measurements and Main Results:Forty-five–minute survival was higher in the coronary perfusion pressure-20 group (8 of 8) compared to depth 33 mm (1 of 8) or depth 51 mm (3 of 8) groups; p equals to 0.002. Coronary perfusion pressures were higher in the coronary perfusion pressure-20 group compared to depth 33 mm (p = 0.004) and depth 51 mm (p = 0.006) and in survivors compared to nonsurvivors (p < 0.01). Total epinephrine dosing and defibrillation attempts were not different. Conclusions:Hemodynamic directed resuscitation targeting coronary perfusion pressures greater than 20 mm Hg during 10 minutes of cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest improves short-term survival, when compared to resuscitation with depth of compressions guided to 33 mm or 51 mm and standard American Heart Association vasopressor dosing.

Physiological and histopathological responses following closed rotational head injury depend on direction of head motion

Rotational inertial forces are thought to be the underlying mechanism for most severe brain injuries. However, little is known about the effect of head rotation direction on injury outcomes, particularly in the pediatric population. Neonatal piglets were subjected to a single non-impact head rotation in the horizontal, coronal, or sagittal direction, and physiological and histopathological responses were observed. Sagittal rotation produced the longest duration of unconsciousness, highest incidence of apnea, and largest intracranial pressure increase, while coronal rotation produced little change, and horizontal rotation produced intermediate and variable derangements. Significant cerebral blood flow reductions were observed following sagittal but not coronal or horizontal injury compared to sham. Subarachnoid hemorrhage, ischemia, and brainstem pathology were observed in the sagittal and horizontal groups but not in a single coronal animal. Significant axonal injury occurred following both horizontal and sagittal rotations. For both groups, the distribution of injury was greater in the frontal and parietotemporal lobes than in the occipital lobes, frequently occurred in the absence of ischemia, and did not correlate with regional cerebral blood flow reductions. We postulate that these direction-dependent differences in injury outcomes are due to differences in tissue mechanical loading produced during head rotation.

Neurobehavioral Functional Deficits Following Closed Head Injury in the Neonatal Pig

Neurobehavioral deficits in higher cortical systems have not been described previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day old piglets were subjected to either mild (142 rad/s) or moderate (188 rad/s) rapid non-impact axial rotations of the head. Multiple domains of cortical function were evaluated 5 times during the 12 day post-injury period using tests of neurobehavioral function devised for piglets. There were no observed differences in neurobehavioral outcomes between mild injury pigs (N=8) and instrumented shams (N=4). Moderately injured piglets (N=7) had significantly lower interest in exploring their environment and had higher failure rates in visual-based problem solving compared to instrumented shams (N=5) on days 1 and 4 after injury. Neurobehavioral functional deficits correlated with neuropathologic damage in the neonatal pigs after inertial head injury. Injured axons detected by immunohistochemistry (beta-APP) were absent in mild injury and sham piglets, but were observed in moderately injured piglet brains. In summary, we have developed a quantitative battery of neurobehavioral functional assessments for large animals that correlate with neuropathologic axonal damage and may have wide applications in the fields of cardiac resuscitation, stroke, and hypoxic-ischemic brain injury.

Use of recombinant factor VIIa for refractory hemorrhage during extracorporeal membrane oxygenation.

Objective: To describe the outcome and treatment of two patients with recombinant factor VIIa (rFVIIa) for severe hemorrhage associated with extracorporeal membrane oxygenation (ECMO). Design: Case report. Setting: A 38-bed pediatric intensive care unit and 20-bed pediatric cardiac intensive care unit at a tertiary care children’s hospital. Patient: Two patients with life-threatening hemorrhagic complications associated with ECMO requiring massive transfusion of blood products. Interventions: Administration of repeated doses of rFVIIa at 90 &mgr;g/kg/dose. Measurement and Main Results: Patient 1 was an 11-yr-old male with a dilated cardiomyopathy who had undergone an orthotopic heart transplant treated with venoarterial ECMO postoperatively for right ventricular dysfunction. Patient 2 was a 13-yr-old male treated with venoarterial ECMO for cardiopulmonary failure from necrotizing staphylococcal pneumonia. Both patients had severe hemorrhage from the cannulation sites and thoracostomy tubes requiring massive transfusion to maintain intravascular blood volume and replace clotting factors. Both patients were treated with rFVIIa every 2–4 hrs and attained hemostasis. Patient 1 was administered three doses and Patient 2 was administered ten doses. No evidence of abnormal thrombus formation was noted in their respective ECMO circuits. Conclusions: The efficacy of rFVIIa in reducing intractable bleeding postcardiac surgery and in other coagulopathic states is being investigated. Despite theoretical concerns of thrombosis, these cases illustrate that there may be a role for the cautious use of rFVIIa in treating severe and intractable hemorrhage associated with ECMO.

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 …

Hemodynamic directed CPR improves cerebral perfusion pressure and brain tissue oxygenation

AIM Advances in cardiopulmonary resuscitation (CPR) have focused on the generation and maintenance of adequate myocardial blood flow to optimize the return of spontaneous circulation and survival. Much of the morbidity associated with cardiac arrest survivors can be attributed to global brain hypoxic ischemic injury. The objective of this study was to compare cerebral physiological variables using a hemodynamic directed resuscitation strategy versus an absolute depth-guided approach in a porcine model of ventricular fibrillation (VF) cardiac arrest. METHODS Intracranial pressure and brain tissue oxygen tension probes were placed in the frontal cortex prior to induction of VF in 21 female 3-month-old swine. After 7 min of VF, animals were randomized to receive one of three resuscitation strategies: (1) hemodynamic directed care (CPP-20): chest compressions (CCs) with depth titrated to a target systolic blood pressure of 100 mmHg and titration of vasopressors to maintain coronary perfusion pressure (CPP)>20 mmHg; (2) depth 33 mm (D33): target CC depth of 33 mm with standard American Heart Association (AHA) epinephrine dosing; or (3) depth 51 mm (D51): target CC depth of 51 mm with standard AHA epinephrine dosing. RESULTS Cerebral perfusion pressures (CerePP) were significantly higher in the CPP-20 group compared to both D33 (p<0.01) and D51 (p=0.046), and higher in survivors compared to non-survivors irrespective of treatment group (p<0.01). Brain tissue oxygen tension was also higher in the CPP-20 group compared to both D33 (p<0.01) and D51 (p=0.013), and higher in survivors compared to non-survivors irrespective of treatment group (p<0.01). Subjects with a CPP>20 mmHg were 2.7 times more likely to have a CerePP>30 mmHg (p<0.001). CONCLUSIONS Hemodynamic directed resuscitation strategy targeting coronary perfusion pressure>20 mmHg following VF arrest was associated with higher cerebral perfusion pressures and brain tissue oxygen tensions during CPR.