Christopher W. Mastropietro

N-3 Fatty Acid Rich Triglyceride Emulsions Are Neuroprotective after Cerebral Hypoxic-Ischemic Injury in Neonatal Mice

We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O2 for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1–0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans.

Cumulative Corticosteroid Exposure and Infection Risk After Complex Pediatric Cardiac Surgery

BACKGROUND Children undergoing cardiac surgery may receive corticosteroids preoperatively to temper cardiopulmonary bypass-related inflammation, postoperatively for hemodynamic instability, and periextubation to reduce airway edema. Recent data have associated preoperative corticosteroids with infection. We aimed to determine if there is a relationship between cumulative corticosteroid exposure and infection. METHODS A retrospective review of children who underwent cardiac surgery at our institution from January 2009 to July 2010 was performed. To limit study heterogeneity, patients who were 5 years or younger with basic Aristotle score of 7 or higher and intensive care unit stay of 7 days or more were included. Infections during the first 30 postoperative days were recorded, defined as clinically relevant positive blood, urine, respiratory, or wound cultures, or culture-negative sepsis treated with 7 or more days of antimicrobial therapy. Multivariate logistic regression analysis was performed to determine independent risk factors for infection. RESULTS Seventy-six patients were reviewed. All patients received intraoperative methylprednisolone, 48% received postoperative hydrocortisone, and 86% received periextubation dexamethasone. Twenty-six patients (36%) had 58 infections. On univariate analysis, patients with infection had greater median comprehensive Aristotle score (14.5 [intraquartile range (IQR): 12.5 to 16] versus 11.5 [IQR: 10 to 13.1], p = 0.001), maximum vasoactive inotrope score (29 [IQR: 24 to 40] versus 24 [IQR: 17 to 31], p = 0.031, days endotracheally intubated (12 [IQR: 7 to 30] versus 5 [IQR: 4 to 6.5], p < 0.001), and days of corticosteroid exposure (7 [IQR: 5 to 12] versus 4 [IQR: 2 to 5), p < 0.001). Also, patients with infections more often underwent delayed sternal closure (p = 0.008). On multivariate analysis, days endotracheally intubated (p = 0.023) and days of corticosteroid exposure (p = 0.015) remained significant. CONCLUSIONS For children undergoing complex cardiac surgery, greater cumulative duration of corticosteroid exposure is independently associated with postoperative infection.

Arginine vasopressin to manage hypoxemic infants after stage I palliation of single ventricle lesions

Objective: Management of patients with single ventricle physiology following stage I palliation procedures is often challenging, with optimization of the ratio of pulmonary-to-systemic blood flow as an important goal. Persistent hypoxemia may be a manifestation of elevated pulmonary vascular resistance and therefore decreased blood flow to the lungs. In such situations, the use of arginine vasopressin to increase systemic vascular resistance may be an effective strategy to improve pulmonary blood flow and maintain adequate pulmonary-to-systemic blood flow ratio. We describe three infants in whom persistent hypoxemia improved after institution of arginine vasopressin. Design: Retrospective chart review. Setting: Twenty-four bed medical-surgical pediatric intensive care unit at a large tertiary care academic hospital. Patients: Three neonates with single ventricle physiology who received arginine vasopressin in the setting of hypoxemia following stage I palliation. Results: Arginine vasopressin was initiated in all three patients for hypoxemia with a goal to increase systemic vascular resistance and generate a higher driving pressure for pulmonary blood flow. Twelve hours after arginine vasopressin initiation, systemic arterial saturation as determined by pulse oximetry and blood pressure increased, whereas heart rate, inotrope score, and Fio2 decreased in all three patients. Urine output was maintained and arterial lactate decreased during this time. Pulmonary-to-systemic flow ratio increased in one patient in whom it could be determined. Conclusion: In patients with single ventricle physiology and persistent hypoxemia following stage I palliation, administration of arginine vasopressin could improve oxygenation possibly by increasing systemic vascular resistance and therefore the pulmonary blood flow.

Relative deficiency of arginine vasopressin in children after cardiopulmonary bypass

Objective:To describe changes in plasma arginine vasopress in concentration in children following cardiopulmonary bypass and determine whether, in some patients, plasma arginine vasopressin remains relatively low despite hemodynamic instability. Design:Prospective observational study. Setting:Pediatric intensive care unit at a tertiary care university hospital. Patients:One hundred twenty patients ≤18 yrs of age undergoing open heart surgery requiring cardiopulmonary bypass at Childrens Hospital of Michigan between January 2008 and January 2009. Interventions:Blood samples were collected before cardiopulmonary bypass and 4, 24, and 48 hrs after cardiopulmonary bypass for measurement of plasma arginine vasopressin concentration. Measurements and Main Results:Mean plasma arginine vasopressin (pg/mL) for all patients was 21 ± 63 before cardiopulmonary bypass and 80 ± 145, 43 ± 79, and 19 ± 25 at 4, 24, and 48 hrs, respectively, after cardiopulmonary bypass. Patients with plasma arginine vasopressin below the lower quartile (<9.2 pg/mL) at 4 hrs after cardiopulmonary bypass (n = 29), labeled group A, were examined separately and compared with the rest of the study population, labeled group B. Mean plasma arginine vasopressin was 4.9 ± 2.6 in group A at 4 hrs after cardiopulmonary bypass, statistically unchanged from its baseline mean plasma arginine vasopressin of 5.0 ± 10.4 (p = .977). Mean plasma arginine vasopressin in group B was 104 ± 160 at 4 hrs after cardiopulmonary bypass. Mean plasma arginine vasopressin of group A was also significantly lower as compared with group B before and 24 and 48 hrs after cardiopulmonary bypass. Hemodynamics, inotrope score, and serum sodium did not differ between groups at any time point. Plasma arginine vasopressin was measured immediately before exogenous arginine vasopressin administration in 10 patients; only those (n = 3) with hemodynamic instability and relatively low plasma arginine vasopressin concentration (<9.2 pg/mL) had notable hemodynamic improvement. Conclusions:In some children undergoing open heart surgery, plasma arginine vasopressin concentration is relatively low at baseline and remains low after cardiopulmonary bypass regardless of hemodynamic stability and serum osmolality. These children are likely the optimal candidates for exogenous arginine vasopressin should hemodynamic compromise occur.

Passive peritoneal drainage improves fluid balance after surgery for congenital heart disease

OBJECTIVE In some centers, passive peritoneal drainage (PD) is implemented following surgery for congenital heart disease. The utility of this practice has yet to be studied. We hypothesized that passive PD can promote negative fluid balance without compromising intravascular volume. METHODS A retrospective review of infants who underwent repair of complete atrioventricular septal defect (AVSD) between 6/2006 and 8/2010 was completed. Data are represented as mean ± standard deviation. RESULTS Thirty-six infants underwent AVSD repair, 18 of whom had PD catheters placed without complication. Infants with passive PD had longer duration of cardiopulmonary bypass (211 ± 59 vs 137 ± 41 min, P < 0.001) and aortic cross-clamp (148 ± 29 vs 102 ± 21 min, P < 0.001); had higher Aristotle complexity score (12.6 ± 3 vs 10.7 ± 2, P = 0.03) and ventilatory support immediately after surgery (ventilation index score 19.5 ± 6.5 vs 14.3 ± 2.5, P = 0.004); and received greater fluid administration (225 ± 6 3 vs 168 ± 45 ml kg(-1), P = 0.002) in the first 48 postoperative hours. Despite these differences, infants with passive PD achieved negative fluid balance more rapidly (12 ± 10 vs 27.3 ± 13 h, P < 0.0001) and to a greater extent (-73 + 55 vs +2.6 + 39 mL kg(-1) at 48 h, P = 0.002). Moreover, postoperative hemodynamics, urine output, creatinine clearance, blood urea nitrogen, peak lactate, and duration of mechanical ventilation were similar between groups. CONCLUSIONS Passive PD is safe and promotes negative fluid balance after repair of complete AVSD without adversely affecting intravascular volume.

Risk Factors for Extubation Failure Following Neonatal Cardiac Surgery.

Objective: Extubation failure after neonatal cardiac surgery has been associated with considerable postoperative morbidity, although data identifying risk factors for its occurrence are sparse. We aimed to determine risk factors for extubation failure in our neonatal cardiac surgical population. Design: Retrospective chart review. Setting: Urban tertiary care free-standing children’s hospital. Patients: Neonates (0–30 d) who underwent cardiac surgery at our institution between January 2009 and December 2012 was performed. Interventions: Extubation failure was defined as reintubation within 72 hours after extubation from mechanical ventilation. Multivariate logistic regression analysis was performed to determine independent risk factors for extubation failure. Measurements and Main Results: We included 120 neonates, of whom 21 (17.5%) experienced extubation failure. On univariate analysis, patients who failed extubation were more likely to have genetic abnormalities (24% vs 6%; p = 0.023), hypoplastic left heart (43% vs 17%; p = 0.009), delayed sternal closure (38% vs 12%; p = 0.004), postoperative infection prior to extubation (38% vs 11%; p = 0.002), and longer duration of mechanical ventilation (median, 142 vs 58 hr; p = 0.009]. On multivariate analysis, genetic abnormalities, hypoplastic left heart, and postoperative infection remained independently associated with extubation failure. Furthermore, patients with infection who failed extubation tended to receive fewer days of antibiotics prior to their first extubation attempt when compared with patients with infection who did not fail extubation (4.9 ± 2.6 vs 7.3 ± 3; p = 0.073). Conclusions: Neonates with underlying genetic abnormalities, hypoplastic left heart, or postoperative infection were at increased risk for extubation failure. A more conservative approach in these patients, including longer pre-extubation duration of antibiotic therapy for postoperative infections, may be warranted.

Clinical response to arginine vasopressin therapy after paediatric cardiac surgery.

OBJECTIVE To describe the haemodynamic response of children who receive arginine vasopressin for haemodynamic instability after cardiac surgery and to identify clinical variables associated with a favourable response. Materials and Methods We reviewed patients less than or equal to 6 years undergoing open heart surgery in our institution between January, 2009 and July, 2010 who received arginine vasopressin during the first 7 days post operation. Favourable responders were defined as those in whom blood pressure was increased or maintained and catecholamine score was decreased, or blood pressure was increased by greater than or equal to 10% of baseline and catecholamine score was unchanged at 6 hours following arginine vasopressin initiation. RESULTS Of the 34 patients identified, 17 (50%) patients responded favourably to arginine vasopressin. At 6 hours, the mean blood pressure was increased by 32.2% in responders as compared with 4.6% in non-responders, with a p-value less than 0.001. The mean catecholamine score decreased by 30.1% in responders and increased by 7.6% in non-responders, with a p-value less than 0.001. Anthropometric, demographic, and intra-operative variables were similar in both groups, as was maximum dose of arginine vasopressin. The median time after arrival to the intensive care unit at which arginine vasopressin was initiated, however, was later in those who responded, 20 hours as compared with those who did not, 6 hours, with a p-value equal to 0.032. CONCLUSIONS Arginine vasopressin therapy led to haemodynamic improvement in only half of the children in this study, and improvement was more likely to occur if arginine vasopressin was initiated after the post-operative night.

Prior Cardiac Surgery Is Independently Associated With Decreased Survival Following Infant Tracheostomy

INTRODUCTION: Previous reports have demonstrated that prior cardiac surgery is independently associated with in-hospital mortality after infant tracheostomy. We aimed to determine whether these infants would continue to be at increased risk for death following hospital discharge. METHODS: A retrospective review was performed on subjects < 2 y of age who recovered from tracheostomy in the pediatric ICU at our institution between January 2007 and December 2011, with follow-up to December 2013. Survival to 1 y following tracheostomy was the primary outcome variable for the study. Multivariate Cox regression analysis was then performed to determine independent risk factors for death after infant tracheostomy. RESULTS: Forty-two subjects met inclusion criteria, 18 of whom had undergone prior cardiac surgery. Twenty-six subjects (62%) were alive at 1 y post-tracheostomy. Age at tracheostomy, concomitant genetic abnormalities or prematurity, and ventilator dependence at discharge were not statistically different between survivors and those who died. Subjects who died, however, were more likely to have had cardiac surgery prior to tracheostomy (11 [69%] vs 7 [27%], P = .008) and had longer hospital stay (median 3.4 months [interquartile range: 2.6–4.6] vs 2.2 months [interquartile range: 1.1–3.5], P = .045). Multivariate Cox regression analysis revealed only prior cardiac surgery to be independently associated with decreased survival after tracheostomy (hazard ratio 4.7, 95% CI 1.3–16.4, P = .02). CONCLUSIONS: Prior cardiac surgery is independently associated with decreased survival within 1 y following tracheostomy. Clinicians and families of infants with prior cardiac surgery in whom tracheostomy after cardiac surgery is deemed necessary should consider this risk when planning long-term care.

Early Administration of Intratracheal Surfactant (Calfactant) After Hydrocarbon Aspiration

Hydrocarbon ingestions account for a substantial number of accidental poisonings; when aspirated, it can lead to severe pneumonitis. Treatment for severe pneumonitis is generally supportive, and outcomes are frequently poor. We report here the case of a 19-month-old girl who was treated successfully with early administration of exogenous surfactant for acute respiratory distress syndrome secondary to aspiration of lamp oil. Approximately 7 hours after aspiration, she required mechanical ventilation and had an oxygenation index (OI) of 13.2. Approximately 10 hours after ingestion, exogenous surfactant (calfactant) was instilled intratracheally, after which her OI improved markedly to 4.3. She received a second dose ∼19 hours after ingestion, after which her OI remained at <5 and she was progressively weaned from mechanical ventilation. She was extubated 64 hours after the ingestion with no residual lung disease. This case illustrates the importance of considering exogenous surfactant therapy early in the course of acute respiratory failure secondary to hydrocarbon aspiration. Because of the putative mechanisms of lung injury involved in hydrocarbon aspiration, surfactant-replacement therapy is a reasonable therapeutic intervention based on pathophysiologic rationale.

Flexible bronchoscopy for children on extracorporeal membrane oxygenation for cardiac failure.

Objective: To describe the safety and use of flexible bronchoscopy in the management of respiratory complications in patients on extracorporeal membrane oxygenation for cardiac failure. Design: Retrospective cohort study. Setting: Pediatric intensive care unit at a tertiary care university hospital. Patients: Patients requiring extracorporeal membrane oxygenation for cardiac failure in the pediatric intensive care unit between 2003 and 2008. Interventions: None. Measurements and Main Results: Forty-eight patients required extracorporeal membrane oxygenation for cardiac failure (32 after surgery for congenital heart disease, 16 for acquired heart disease) during the study period. Seven patients (15%) underwent 17 flexible bronchoscopies. Median age and weight at extracorporeal membrane oxygenation cannulation was 10 days (range, 4 days to 27 yrs) and 3.2 kg (range, 2.8–66 kg), respectively. Median duration of extracorporeal membrane oxygenation in this group was longer than those not undergoing flexible bronchoscopy (314 vs. 114 hrs, p < .001). In all cases, flexible bronchoscopy indication was persistent atelectasis despite conventional ventilator adjustments. Activated clotting time during flexible bronchoscopy was maintained between 180 and 220 secs (normal, 80–150 secs) in all patients. No major complications occurred. A minor complication occurred in one of 17 flexible bronchoscopies (6%), scant oozing that stopped with epinephrine lavage. Findings included bronchus compression or narrowing in four patients and mucous plugging in three patients. Bronchoalveolar lavage specimens identified new ventilator-associated infections in three patients. In two patients with mucous plugging, serial bronchoscopies were accompanied by stepwise decreases in extracorporeal membrane oxygenation flow, thereby facilitating discontinuation from extracorporeal membrane oxygenation support. Conclusions: In patients requiring extracorporeal membrane oxygenation for cardiac failure, flexible bronchoscopy can be performed safely, provide important diagnostic information to the bedside clinician, and, perhaps, therapeutic benefit to the patient.