Maryam Y. Naim

Cerebral oxygen metabolism in neonates with congenital heart disease quantified by MRI and optics.

Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO2) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (SvO2) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO2 in physiologic units. In addition, microvascular tissue oxygenation (StO2) and indices of microvascular CBF (BFI) and CMRO2 (CMRO2i) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO2 were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O2/minute per 100 g, respectively. These CBF and CMRO2 values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Comparison of MRI measurements of global SvO2, CBF, and CMRO2 with corresponding local DOS/DCS measurements demonstrated strong linear correlations (R2=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The results suggest that MRI and optics offer new tools to evaluate cerebral hemodynamics and metabolism in CHD neonates.

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.

Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome

OBJECTIVE Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately one half of HLHS survivors will exhibit neurobehavioral symptoms believed to be associated with this injury, although the exact timing of the injury is unknown. METHODS Neonates with HLHS were recruited for pre- and postoperative monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using 2 noninvasive optical-based techniques: diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomic magnetic resonance imaging was performed before and approximately 1 week after surgery to quantify the extent and timing of the acquired white matter injury. The risk factors for developing new or worsened white matter injury were assessed using uni- and multivariate logistic regression. RESULTS A total of 37 neonates with HLHS were studied. On univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time to surgery (P=.0003). In a multivariate model, a longer time between birth and surgery, delayed sternal closure, and greater preoperative cerebral blood flow were predictors of postoperative white matter injury. Additionally, a longer time to surgery and greater preoperative cerebral blood flow on the morning of surgery correlated with lower cerebral oxygen saturation (P=.03 and P=.05, respectively) and greater oxygen extraction fraction (P=.05 for both). CONCLUSIONS A longer time to surgery was associated with new postoperative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation might decrease the likelihood of acquiring postoperative white matter injury.

Feeding, growth, and nutrition in children with congenitally malformed hearts

In the United States of America, approximately 40,000 infants are born annually with congenitally malformed hearts. Children with defects that require complex surgical palliation, or definitive repair, face many challenges in achieving optimal short-term and long-term growth. The presence of associated chromosomal abnormalities, cyanosis, and cardiac failure adds to the complexity and challenge. In this review, we address three themes related to feeding, growth, and nutrition of infants after neonatal cardiac surgery: nutritional challenges after chylothorax; breastfeeding after surgery; and the challenges of feeding after discharge. Chylothorax is a rare complication following cardiothoracic surgery in children. Children with chylothorax have nutritional depletion secondary to protein losses in chylous fluid, hypovolaemia, and electrolyte losses. In spite of the evidence supporting the use of human milk and breastfeeding in preterm infants, barriers to its use appear to persist in infants with critical cardiac disease. Yet, human milk is the preferred form of nutrition for well, preterm, or ill infants. It is well documented that after complex neonatal cardiac surgery medical teams and families struggle with infant feeding problems. Parents have described feeding their children as difficult, time consuming, and anxiety producing. Medical complications such as chylothorax, limited access to human milk, and parental concerns and stress about feeding are but three of the myriad of factors that may contribute to poor outcomes regarding nutrition and growth. Compelling evidence exists that this multi-factorial problem must be addressed with both physiological and behavioural strategies.

The Children's Hospital of Philadelphia's experience with donation after cardiac death

Objective:To describe our experience with pediatric donation after cardiac death. Design:Retrospective chart review of all cases of donation after cardiac death from 1995 to 2005. Setting:The Children’s Hospital of Philadelphia pediatric intensive care unit. Patients:Twelve patients who were pediatric organ donors after cardiac death. Interventions:None. Measurements and Main Results:Charts for 12 patients were located, and donation after cardiac death was confirmed. There were two females and ten males. Patient age ranged from 1 to 17 yrs (mean 8 yrs). Four patients had severe traumatic brain injury, and eight patients had hypoxic ischemic encephalopathy. The organs procured were 24 kidneys, eight livers, four lungs, and one pancreas. The organs transplanted were 23 kidneys, four livers, and one pancreas. Ten of 12 cases of withdrawal of life-sustaining support occurred in the operating room area; the other two occurred in the holding area and the postanesthesia care unit. Children received a wide range of medications at the time of extubation. No neuromuscular blockers were used. The time of extubation to time of death ranged from 4 mins to 30 mins, with a mean of 14.5 mins. Death was declared based on cardiac asystole confirmed by auscultation and transthoracic impedance, with organ procurement initiated 5 mins later. Regarding who initiated conversation about donation after cardiac death, nine cases were family initiated, one case was physician initiated, and in two there was a collaborative approach with the physician and representative from the organ procurement organization. Of the organs transplanted, all organs other than one kidney and one split liver graft were functioning at 1 yr post-transplant. Conclusions:Pediatric donation after cardiac death can be performed successfully; its impact on end-of-life care and bereavement needs further investigation.

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.

Patient-centric blood pressure-targeted cardiopulmonary resuscitation improves survival from cardiac arrest.

RATIONALE Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival. OBJECTIVES To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF). METHODS After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure-targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival. MEASUREMENTS AND MAIN RESULTS The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9-13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0-12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0-3] vs. 2 [range, 2-2]; P = 0.003). CONCLUSIONS Blood pressure-targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest.

Hemodynamic-directed cardiopulmonary resuscitation during in-hospital cardiac arrest.

Cardiopulmonary resuscitation (CPR) guidelines assume that cardiac arrest victims can be treated with a uniform chest compression (CC) depth and a standardized interval administration of vasopressor drugs. This non-personalized approach does not incorporate a patients individualized response into ongoing resuscitative efforts. In previously reported porcine models of hypoxic and normoxic ventricular fibrillation (VF), a hemodynamic-directed resuscitation improved short-term survival compared to current practice guidelines. Skilled in-hospital rescuers should be trained to tailor resuscitation efforts to the individual patients physiology. Such a strategy would be a major paradigm shift in the treatment of in-hospital cardiac arrest victims.

Association of Bystander Cardiopulmonary Resuscitation With Overall and Neurologically Favorable Survival After Pediatric Out-of-Hospital Cardiac Arrest in the United States: A Report From the Cardiac Arrest Registry to Enhance Survival Surveillance Registry

Importance There are few data on the prevalence or outcome of bystander cardiopulmonary resuscitation (BCPR) in children 18 years and younger. Objective To characterize BCPR in pediatric out-of-hospital cardiac arrests (OHCAs). Design, Setting, and Participants This analysis of the Cardiac Arrest Registry to Enhance Survival database investigated nontraumatic OHCAs in children 18 years and younger from January 2013 through December 2015. Exposures Bystander CPR, which included conventional CPR and compression-only CPR. Main Outcomes and Measures Overall survival and neurologically favorable survival, defined as a Cerebral Performance Category score of 1 or 2, at the time of hospital discharge. Results Of the 3900 children younger than 18 years with OHCA, 2317 (59.4%) were infants, 2346 (60.2%) were female, and 3595 (92.2%) had nonshockable rhythms. Bystander CPR was performed on 1814 children (46.5%) and was more common for white children (687 of 1221 [56.3%]) compared with African American children (447 of 1134 [39.4%]) and Hispanic children (197 of 455 [43.3%]) (P < .001). Overall survival and neurologically favorable survival were 11.3% (440 of 3900) and 9.1% (354 of 3900), respectively. On multivariable analysis, BCPR was independently associated with improved overall survival (adjusted proportion, 13.2%; 95% CI, 11.81-14.58; adjusted odds ratio, 1.57; 95% CI, 1.25-1.96) and neurologically favorable survival (adjusted proportion, 10.3%; 95% CI, 9.10-11.54; adjusted odds ratio, 1.50; 95% CI, 1.21-1.98) compared with no BCPR (overall survival: adjusted proportion, 9.5%; 95% CI, 8.28-10.69; neurologically favorable survival: adjusted proportion, 7.59%; 95% CI, 6.50-8.68). For those with data on type of BCPR, 697 of 1411 (49.4%) received conventional CPR and 714 of 1411 (50.6%) received compression-only CPR. On multivariable analysis, only conventional CPR (adjusted proportion, 12.89%; 95% CI, 10.69-15.09; adjusted odds ratio, 2.06; 95% CI, 1.51-2.79) was associated with improved neurologically favorable survival compared with no BCPR (adjusted proportion, 9.59%; 95% CI, 6.45-8.61). There was a significant interaction of BCPR with age. Among infants, conventional BCPR was associated with improved overall survival and neurologically favorable survival while compression-only CPR had similar outcomes to no BCPR. Conclusions and Relevance Bystander CPR is associated with improved outcomes in pediatric OHCAs. Improving the provision of BCPR in minority communities and increasing the use of conventional BCPR may improve outcomes for children with OHCA.