John R. Charpie

Vasoactive–inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass*

Objective: Inotrope score has been proposed as a marker of illness severity after pediatric cardiac surgery despite a lack of data to support its use as such. The goal of this study was to determine the association between inotropic/vasoactive support and clinical outcome in infants after cardiac surgery. Design: Retrospective chart review. Setting: Dedicated pediatric cardiothoracic intensive care unit at an academic, tertiary care medical center. Patients: One hundred seventy-four patients 0 to 6 months of age admitted to the cardiothoracic intensive care unit after cardiac surgery with cardiopulmonary bypass between August 2007 and June 2008. Forty-three percent were neonates, and 39% had functional single ventricle physiology. Interventions: None. Measurements and Main Results: Hourly doses of all vasoactive medications were recorded for the first 48 hrs after admission to the cardiothoracic intensive care unit and a vasoactive–inotropic score was calculated. The maximum vasoactive–inotropic score level over the first 48 hrs was a good predictor of poor clinical outcome (death, cardiac arrest, mechanical circulatory support, renal replacement therapy, and/or neurologic injury). After controlling for diagnosis, high maximum vasoactive–inotropic score was strongly associated with a poor outcome with an adjusted odds ratio of 8.1 (95% confidence interval, 3.4–19.2; p < .001) compared with patients with a low maximum vasoactive–inotropic score. High vasoactive–inotropic score was also associated with prolonged cardiothoracic intensive care unit stay, duration of mechanical ventilation, and time to negative fluid balance. Conclusions: The amount of cardiovascular support in the first 48 hrs after congenital heart surgery with cardiopulmonary bypass predicts eventual morbidity and mortality in young infants. The degree of support is best characterized by a maximum vasoactive–inotropic score obtained during this period. The usefulness of vasoactive–inotropic score as an independent predictor of clinical outcome in infants after cardiac surgery may have important implications for future cardiothoracic intensive care unit research. (Pediatr Crit Care Med 2010; 11:234–238)

Clinical Outcomes of Palliative Surgery Including a Systemic-to-Pulmonary Artery Shunt in Infants With Cyanotic Congenital Heart Disease Does Aspirin Make a Difference?

Background— Aspirin (ASA) often is used to prevent thrombosis in infants with congenital heart disease after placement of a systemic-to–pulmonary artery shunt, but its effect on outcomes is unknown. Methods and Results— The present multicenter study prospectively collected data on 1-year postoperative rates of death, shunt thrombosis, or hospitalization age <4 months for bidirectional Glenn/hemi-Fontan surgery in 1004 infants. The use and dose of ASA were recorded. Kaplan-Meier event rates were calculated for each event and the composite outcome, and a Cox regression model was constructed for time to event. Model terms were ASA use and type of surgery, with adjustment for age at surgery. Diagnoses were hypoplastic left heart syndrome (n=346), tricuspid atresia (n=103), tetralogy of Fallot (n=127), pulmonary atresia (n=177), heterotaxy syndrome (n=38), and other (n=213). There were 344 shunts placed without cardiopulmonary bypass (closed shunt), 287 shunts with bypass (open shunt), 323 Norwood procedures, and 50 Sano procedures. Overall, 80% of patients received ASA. One-year postoperative events rates were high: 38% for the composite end point, 26% for death, and 12% for shunt thrombosis. After the exclusion of patients with early mortality, patients receiving ASA had a lower risk of shunt thrombosis (hazard ratio, 0.13; P=0.008) and death (closed shunt: hazard ratio, 0.41, P=0.057; open shunt: hazard ratio, 0.10, P<0.001; Norwood: hazard ratio, 0.34, P<0.001; Sano: hazard ratio, 0.68, P=NS) compared with those not receiving ASA. Conclusions— The morbidity and mortality for infants after surgical placement of a systemic-to–pulmonary artery shunt are high. ASA appears to lower the risk of death and shunt thrombosis in the present observational study.

Near-infrared spectroscopy: What we know and what we need to know—A systematic review of the congenital heart disease literature

OBJECTIVES Neurologic dysfunction is a problem in patients with congenital heart disease. Near-infrared spectroscopy may provide a real-time window into cerebral oxygenation. Enthusiasm for near-infrared spectroscopy has increased hopes of reducing neurologic dysfunction. However, potential gains need to be evaluated relative to cost before routine implementation. Responding to data in ways that seem intuitively beneficial can be risky when the long-term impact is unknown. Thus, we performed a systematic review of the literature on near-infrared spectroscopy in congenital heart disease. METHODS A literature search from 1950 to April 2007 for near-infrared spectroscopy in congenital heart disease was undertaken. We identified 54 manuscripts and\13 reviews. RESULTS There were 47 case series, 4 randomized trials, and 3 retrospective studies. Two studies had postdischarge follow-up, one incorporating neurologic testing. Neither of these studies demonstrated a benefit. One retrospective study, which included near-infrared spectroscopy and other intraoperative measures of cerebral perfusion, demonstrated a decrease in neurologic dysfunction using this combination of monitors. Three small studies were able to correlate near-infrared spectroscopy with other clinical and radiologic findings. CONCLUSIONS Many centers, and even entire countries, have adopted near-infrared spectroscopy as standard of care. The available data suggest that multimodality monitoring, including near-infrared spectroscopy, may be a useful adjunct. The current literature on the use of near-infrared spectroscopy alone, however, does not demonstrate improvement in neurologic outcome. The data correlating near-infrared spectroscopy findings with indirect measures of neurologic outcome or mortality are limited. Although near-infrared spectroscopy has promise for measuring regional tissue oxygen saturation, the lack of data demonstrating improved outcomes limits the support for widespread implementation.

Vascular Oxidative Stress Precedes High Blood Pressure in Spontaneously Hypertensive Rats

This study examines whether longitudinal antioxidant treatment initiated in prehypertensive spontaneously hypertensive rats (SHR) can attenuate vascular oxidant stress and prevent blood pressure elevation during development. Male SHR and age-matched Wistar-Kyoto rats (WKY) were treated from 6 and 11 weeks of age with Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl) (1 mmol/l in drinking water), a membrane-permeable superoxide dismutase mimetic. Mean systolic blood pressures (SBPs) were measured by tail-cuff. Agonist-induced and basal O2− production was measured in thoracic aortas of 6- and 11-week-old SHR and WKY by lucigenin-derived chemiluminescence and oxidative fluorescent microscopy, respectively. SBP of 6-week-old SHR (131 ± 5 mmHg) and WKY (130 ± 4 mmHg) were not different; however, 11-week-old SHR SBP (171 ± 4 mmHg) was significantly greater (p = .0001) than 11-week-old WKY SBP (143 ± 5 mmHg). Tempol treatment completely, but reversibly, prevented this age-related rise in SHR SBP (SHR + Tempol: 137 ± 4 mmHg; p < .0001 versus untreated SHR). Agonist-induced vascular O2− was increased in 6- (p = .03) and 11-week-old SHR (p < .0001) and 11-week-old WKY (p = .03) but not in 6-week-old WKY. Long-term Tempol treatment significantly lowered O2− production in both strains. Basal O2− measurements in both 6- and 11-week-old SHR were qualitatively increased compared with age-matched WKY; this increase in SHR was inhibited with in vitro Tempol treatment. These data show that antioxidant treatment to reduce oxidative stress prevents the age-related development of high blood pressure in an animal model of genetic hypertension.

Postoperative hemodynamics after norwood palliation for hypoplastic left heart syndrome

Hemodynamics after Norwood palliation for hypoplastic left heart syndrome (HLHS) have been incompletely characterized, although emphasis has been placed on the role that an excess pulmonary-to-systemic blood flow ratio (Qp/Qs) may play in causing hemodynamic instability. Studies suggest that maximal oxygen delivery occurs at a Qp/Qs < 1. However, it remains unclear to what extent cardiac output can increase with increasing pulmonary perfusion. One approach is to use the oxygen excess factor omega, an index of systemic oxygen delivery, and compare omega with measured Qp/Qs. We measured Qp/Qs and omega in neonates after Norwood palliation for HLHS, and determined how they were related. In addition, we determined the temporal course of surrogate indexes of systemic perfusion in the early postoperative period. Arteriovenous oxygen saturation difference, blood lactate, and omega were recorded on admission and every 3 to 12 hours for 2 days in 18 consecutive infants with HLHS or variant after Norwood palliation. Three infants required extracorporeal membrane oxygenation (ECMO) 6 to 9 hours after admission. These infants had higher Qp/Qs, blood lactate, arteriovenous oxygen saturation difference, and lower omega than non-ECMO patients. In non-ECMO patients between admission and 6 hours, omega decreased significantly despite no appreciable change in Qp/Qs. We conclude that: (1) Oxygen delivery is significantly decreased at 6 postoperative hours unrelated to Qp/Qs. This modest decline in oxygen delivery is insufficient to compromise tissue oxygenation. (2) Patients requiring ECMO have significant derangements in oxygen delivery.

Near infrared spectroscopy (NIRS) should not be standard of care for postoperative management

Neurologic dysfunction is a problem in patients with congenital heart disease. Near infrared spectroscopy (NIRS) may provide a real-time window into cerebral oxygenation. Enthusiasm for NIRS has increased in hopes of reducing neurologic dysfunction. However, potential gains need to be evaluated relative to cost and potential detriment of intervention before routine implementation. Responding to data in ways that seem intuitively beneficial can be risky when the long-term impact is unknown. Many centers, and even entire countries, have adopted NIRS as standard of care. Available data suggest that multimodality monitoring, including NIRS, may be a useful adjunct. However, the current literature on the use of NIRS alone does not demonstrate improvement in neurologic outcome. Data correlating NIRS findings with indirect measures of neurologic outcome or mortality are limited. Although NIRS has promise for measuring regional tissue oxygen saturation, the lack of data demonstrating improved outcomes limits the support for wide-spread implementation.

High systemic vascular resistance and sudden cardiovascular collapse in recovering norwood patients

BACKGROUND Sudden death, remote from surgery, in patients with hypoplastic left heart syndrome (HLHS) after Norwood palliation is an important problem. The episodic nature of this syndrome has made its cause(s) difficult to ascertain. Observations made in hospitalized Norwood patients may afford insight into the pathophysiology of sudden death among these patients. METHODS We conducted a retrospective chart review. RESULTS Five patients with HLHS experiencing unremarkable recoveries from Norwood palliation, still hospitalized but extubated (only 1 in intensive care), had unexpected, acute decompensation 8 to 15 days postoperatively. All had acutely decreased peripheral perfusion; severe metabolic acidosis (mean HCO(3) = 9 mEq/L, range 6 to 11 mEq/L; mean arterial lactate = 16 mmol/L, range 10 to 20 mmol/L, normal less than 2 mmol/L); relatively high arterial pO(2), especially considering their low systemic perfusion (mean = 57 mm Hg, range 50 to 66 mm Hg on fraction of inspired oxygen (FiO(2)) less than 0.3 in 4 of 5 patients); and relatively high systolic blood pressure (mean systolic blood pressure = 91 mm Hg, range 78 to 116 mm Hg). During the preceding 24 hours, all had had systolic blood pressures of more than 85 mm Hg at multiple times. All were resuscitated with mechanical ventilation and administration of HCO(3) and intravenous inotropic agents or vasodilators (1 also required extracorporeal membrane oxygenation), with rapid resolution of their acidosis. After decompensating, all were treated with oral antihypertensive agents; 1 had an early hemi-Fontan. All survived to discharge. CONCLUSIONS Increased systemic vascular resistance may be especially pernicious in Norwood patients-even remote from operation-as the condition increases myocardial work and O(2) consumption while diminishing systemic perfusion. Chronic and acutely increased systemic vascular resistance may account for some cases of sudden unexpected death in Norwood patients.

Management and long-term outcome of neonatal Ebstein anomaly

OBJECTIVE The objective of this study was to review the long-term results of symptomatic patients with Ebstein anomaly in the neonatal period. METHODS The medical records of 40 neonates with a diagnosis of Ebstein anomaly who were admitted to our institution between January 1988 and June 2008 were retrospectively reviewed. Primary outcomes studied included patient survival and need for reintervention. RESULTS No early intervention was required in 16 of the 40 patients with a hospital survival of 94% (15/16) and no late mortality. The remaining 24 patients underwent surgical intervention in the neonatal period. A shunt alone was performed in 9 patients with an actuarial survival of 88.9% at 1 year and 76.2% at 5 and 10 years. For the patients undergoing intervention on the tricuspid valve, survival estimates for the 11 patients with a right ventricular exclusion procedure were 63.6% at 1, 5, and 10 years and 47.7% at 15 years compared with 25.0% at 1, 5, and 10 years for the 4 patients with tricuspid valve repair. All long-term survivors were in New York Heart Association class I or II, and only 1 patient required antiarrhythmic medication. CONCLUSION Symptomatic neonates with Ebstein anomaly requiring no intervention or shunting alone have good long-term survival. For patients needing intervention on the tricuspid valve, overall survival is lower. For these patients, right ventricular exclusion may be superior to tricuspid valve repair.

Adrenocortical response in infants undergoing cardiac surgery with cardiopulmonary bypass and circulatory arrest.

Objective: To detail changes in adrenocorticotropic hormone (ACTH), cortisol, and aldosterone levels following cardiac surgery and to test the hypothesis that postcardiotomy infants requiring excessively high-dose vasopressor support will demonstrate adrenal insufficiency which will be proportional to cardiopulmonary bypass (CPB)/circulatory arrest times and vasopressor requirements. Design: Prospective observational pilot study. Setting: A tertiary care pediatric cardiac intensive care unit. Patients: Prospectively enrolled infants were divided into three subgroups: CPB, CPB with deep hypothermic circulatory arrest (DHCA), and control subjects. Interventions: None. Measurements and Main Results: A representative patient sample from each surgical group underwent preoperative synthetic ACTH testing. Postoperative serum samples for cortisol, ACTH, and inotrope score (IS) were collected at discrete intervals over 48 hrs along with patient demographics, surgical procedure, and CPB/DHCA times. Fifty-eight patients were classified by subgroup: 31 CPB, 22 DHCA, and 5 controls. Ten patients with DHCA, analyzed separately, received intraoperative steroids. Tested patients demonstrated preoperative adrenal competence. Cortisol peaked within 2 hrs of surgery without differences among groups. ACTH inversely correlated with bypass time in patients with DHCA (p = .03) but not with circulatory arrest time. Peak cortisol level did not correlate with simultaneous IS. Although not noted in any DHCA-steroid patients, nine patients had increased ACTH/cortisol ratios in association with elevated ISs suggesting inadequate adrenal responsiveness to endogenous ACTH. Conclusions: The majority of infants with congenital heart disease and intact hypothalamic-pituitary-adrenal axes demonstrated an appropriate adrenocortical stress response to cardiac surgery. Peak serum cortisol was unrelated to CPB/DHCA time and did not predict the level of inotrope support. However, a subset of patients with elevated ACTH/cortisol ratios seemed to have a clinical status consistent with adrenal insufficiency and may be a target group for early postoperative steroid therapy.

Collaborative quality improvement in the cardiac intensive care unit: development of the Paediatric Cardiac Critical Care Consortium (PC4)

Despite many advances in recent years for patients with critical paediatric and congenital cardiac disease, significant variation in outcomes remains across hospitals. Collaborative quality improvement has enhanced the quality and value of health care across specialties, partly by determining the reasons for variation and targeting strategies to reduce it. Developing an infrastructure for collaborative quality improvement in paediatric cardiac critical care holds promise for developing benchmarks of quality, to reduce preventable mortality and morbidity, optimise the long-term health of patients with critical congenital cardiovascular disease, and reduce unnecessary resource utilisation in the cardiac intensive care unit environment. The Pediatric Cardiac Critical Care Consortium (PC4) has been modelled after successful collaborative quality improvement initiatives, and is positioned to provide the data platform necessary to realise these objectives. We describe the development of PC4 including the philosophical, organisational, and infrastructural components that will facilitate collaborative quality improvement in paediatric cardiac critical care.