Postoperative Hydrocortisone Infusion Reduces the Prevalence of Low Cardiac Output Syndrome After Neonatal Cardiopulmonary Bypass.

OBJECTIVE: Neonatal cardiac surgery with cardiopulmonary bypass is often complicated by morbidity associated with inflammation and low cardiac output syndrome. Hydrocortisone "stress dosing" is reported to provide hemodynamic benefits in some patients with refractory shock. Development of cardiopulmonary bypass-induced adrenal insufficiency may provide further rationale for postoperative hydrocortisone administration. We sought to determine whether prophylactic, postoperative hydrocortisone infusion could decrease prevalence of low cardiac output syndrome after neonatal cardiac surgery with cardiopulmonary bypass. DESIGN: Double-blind, randomized control trial. SETTING: Pediatric cardiac ICU and operating room in tertiary care center. PATIENTS: Forty neonates undergoing cardiac surgery with cardiopulmonary bypass were randomized (19 hydrocortisone and 21 placebo). Demographics and known risk factors were similar between groups. INTERVENTIONS: After cardiopulmonary bypass separation, bolus hydrocortisone (50 mg/m²) or placebo was administered, followed by continuous hydrocortisone infusion (50 mg/m²/d) or placebo tapered over 5 days. Adrenocorticotropic hormone stimulation testing (1 µg) was performed before and after cardiopulmonary bypass, prior to steroid administration. Blood was collected for cytokine analysis before and after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Subjects receiving hydrocortisone were less likely to develop low cardiac output syndrome (5/19, 26% vs 12/21, 57%; p = 0.049). Hydrocortisone group had more negative net fluid balance at 48 hours (-114 vs -64 mL/kg; p = 0.01) and greater urine output at 0-24 hours (2.7 vs 1.2 mL/kg/hr; p = 0.03). Hydrocortisone group weaned off catecholamines and vasopressin sooner than placebo, with a difference in inotrope-free subjects apparent after 48 hours (p = 0.033). Five placebo subjects (24%) compared with no hydrocortisone subjects required rescue steroids (p = 0.02). Thirteen (32.5%) had adrenal insufficiency after cardiopulmonary bypass. Patients with adrenal insufficiency randomized to receive hydrocortisone had lower prevalence of low cardiac output syndrome compared with patients with adrenal insufficiency randomized to placebo (1/6 vs 6/7, respectively; p = 0.02). Hydrocortisone significantly reduced proinflammatory cytokines. Ventilator-free days, hospital length of stay, and kidney injury were similar. CONCLUSIONS: Prophylactic, postoperative hydrocortisone reduces low cardiac output syndrome, improves fluid balance and urine output, and attenuates inflammation after neonatal cardiopulmonary bypass surgery. Further studies are necessary to show if these benefits lead to improvements in more important clinical outcomes.

Peritoneal dialysis: an alternative modality of fluid removal in neonates requiring extracorporeal membrane oxygenation after cardiac surgery.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy for patients with cardiopulmonary failure after cardiac surgery. Fluid overload (FO) is associated with increased morbidity and mortality in this population. We present our experience using peritoneal dialysis (PD) as an adjunct for fluid removal in eight consecutive neonates requiring ECMO after cardiac surgery between 2010 and 2012. PD was added to FO management when fluid removal goals were not being met by hemofiltration (HF) or hemodialysis (HD). Percent FO was 36% at ECMO initiation; 88% (seven of eight) achieved negative fluid balance before discontinuation of ECMO. PD removed median 119 mL/kg/day (interquartile range [IQR], 70-166) compared with median 132 mL/kg/day (IQR, 47-231) removed by HF/HD. PD and HF/HD fluid removal were performed concurrently 38% of the time. Unlike HF/HD, PD was never stopped secondary to hemodynamic compromise. Median duration of ECMO was 155 hours (IQR, 118-215). Six of eight patients were successfully decannulated. These results suggest PD safely and effectively removes fluid in neonates on ECMO after cardiac surgery. PD may increase total fluid removal potential when combined with other modalities.

Hypogammaglobulinemia after cardiopulmonary bypass in infants.

BACKGROUND: Hypogammaglobulinemia has been reported after cardiac surgery and may be associated with adverse outcomes. We sought to define baseline immunoglobulin (Ig) concentration in neonates and infants with congenital heart disease, determine their course after cardiopulmonary bypass (CPB), and determine if post-CPB hypogammaglobulinemia was associated with increased morbidity. METHODS: This was a single-center, retrospective analysis of infants who underwent cardiac surgery with CPB between June 2010 and December 2011. The Ig concentration was obtained from banked plasma of 47 patients from a prior study (pre-CPB, immediately post-CPB, and 24 and 48 hours post-CPB). In addition, any Ig levels drawn for clinical purposes after CPB were included. Ig levels were excluded if drawn after chylothorax diagnosis or intravenous IgG administration. RESULTS: The median age was 7 days. Preoperative Ig concentration was similar to that described in healthy children. IgG level decreased to less than 50% of preoperative concentration by 24-hour post-CPB and failed to recover by 7 days. Of 47 patients, 25 (53%) had low IgG (<248 mg/dL) after CPB. Despite no difference in demographics or risk factors between patients with low and normal IgG, low IgG patients had more positive fluid balance at 24 hours and increased proinflammatory plasma cytokine levels, duration of mechanical ventilation, and cardiac intensive care unit length of stay. In addition, low IgG patients had an increased incidence of postoperative infections (40% vs 14%; P = .056). CONCLUSIONS: Hypogammaglobulinemia occurs in half of infants after CPB. Its association with fluid overload and increased inflammatory cytokines suggests it may result from capillary leak. Postoperative hypogammaglobulinemia is associated with increased morbidity, including more secondary infections.

Inferior vena cava oxygen saturation monitoring after the Norwood procedure.

BACKGROUND: Superior vena cava oxygen saturation monitoring in the early postoperative period after the Norwood procedure (NP) has been associated with improved survival and decreased adverse events (AE). There is no data describing inferior vena cava saturation (Sivo2) monitoring after NP. We sought to investigate the utility of intermittent Sivo2 monitoring after NP and to assess the correlation of Sivo2 with renal near-infrared spectroscopy (rNIRS). We hypothesized failure to achieve Sivo2 greater than 45% within the first 4 hours after NP is predictive of AE, and that rNIRS correlates with Sivo2. METHODS: A retrospective study of 26 consecutive NP patients who received postoperative management with Sivo2 monitoring according to a strict protocol was conducted. Primary outcome was AE, defined as cardiopulmonary resuscitation, extracorporeal membrane oxygenation, death before discharge, or residual surgical defects. RESULTS: Ten (38%) patients had one or more AE; mortality was 23%. On admission to the cardiac intensive care unit, patients with AE had lower Sivo2 (45% ± 9.4% versus 62% ± 12.0%; p < 0.001) and lower rNIRS (56 ± 6.5 versus 77 ± 7.2; p < 0.001). At 4 hours, 90% of AE patients had an Sivo2 less than 45% versus 6% of non-AE patients. Both Sivo2 and rNIRS were highly predictive of AE: the area under the receiver-operating characteristic curve was greater than 0.86 and 0.95, respectively. Two hours after admission, an Sivo2 less than 45% predicted AE with a specificity of 93%, a sensitivity of 70%, and a positive predictive value of 82%. The Sivo2 was strongly correlated with rNIRS (r = 0.81). CONCLUSIONS: Intermittent Sivo2 can be used to guide early postoperative NP management; rNIRS is an accurate continuous, noninvasive surrogate for Sivo2. An Sivo2 of less than 45% in the first 4 hours after the NP is predictive of AE.

Postoperative serum cortisol concentration and adrenal insufficiency in neonates undergoing open-heart surgery.

BACKGROUND: We sought to determine whether immediate postoperative serum cortisol concentration predicts adrenal insufficiency in neonates after cardiac surgery with cardiopulmonary bypass. We hypothesized that cortisol <10 µg/dL would be associated with increased catecholamine requirements and fluid resuscitation and would predict hemodynamic responsiveness to exogenous steroids. METHODS: Retrospective study of 41 neonates was carried out for the levels of cortisol in the immediate postoperative period; of whom, 15 received steroids due to high levels of inotropic support. Laboratory and clinical outcomes were collected. RESULTS: Median cortisol was 12 µg/dL (interquartile range: 5.2-27.4). Levels of cortisol <10 µg/dL was not associated with any clinical variable indicative of increased illness severity. Peak lactate (9.1 vs 11.8 mmol/L, P = .04) and maximum arteriovenous saturation difference ([Sao 2 - Svo 2] 28% vs 32%, P = .05) were both lower among patients with levels of cortisol <10 µg/dL. Six (40%) patients had a significant hemodynamic improvement within 24 hours after receiving steroids (responders), although there was no statistical difference between levels of cortisol in responders versus nonresponders. Level of cortisol was positively correlated with maximum lactate (P < .001), maximum Sao 2 - Svo 2 (P < .001), maximum inotrope score (P = .014), initial 24-hour fluid intake (P = .012), and time to negative fluid balance (P = .008) and was negatively correlated with initial 24-hour urine output (P < .001). CONCLUSIONS: Low cortisol obtained in the immediate postoperative period is not associated with worse postoperative outcomes or predictive of steroid responsiveness. In contrast, elevated levels of cortisol are positively correlated with severity of illness. The use of an absolute cortisol threshold to identify adrenal insufficiency and/or guide steroid therapy in neonates after cardiac surgery is unjustified.

Preconditioning with high mobility group box 1 (HMGB1) induces lipoteichoic acid (LTA) tolerance.

High mobility group box chromosomal protein 1 (HMGB1) is a DNA-binding protein that exhibits proinflammatory properties when present in the extracellular compartment. Putative receptors for HMGB1 include Toll-like receptor (TLR)4, TLR2, and the receptor for advanced glycation end products (RAGE). We tested the hypothesis that extracellular HMGB1 can induce tolerance to the bacterial product, lipoteichoic acid (LTA). Pretreatment of human monocyte-like THP-1 cells with 1 µg/mL HMGB1 18 hours before exposure to LTA (10 µg/mL) decreased secretion of tumor necrosis factor, nuclear factor-κB DNA-binding, and degradation of IκBα. Denaturation of HMGB1 with boiling water or coincubation with anti-HMGB1 antibody abrogated the induction of tolerance to LTA. In contrast, coincubation with polymyxin B failed to diminish HMGB1-induced tolerance to LTA. These findings support the view that the induction of LTA tolerance by HMGB1 was not due to lipopolysaccharide contamination. Bone marrow-derived macrophages obtained from C57Bl/6 wild-type and RAGE-deficient mice became LTA-tolerant after HMGB1 exposure ex vivo. We were unable to demonstrate LTA tolerance in TLR2 and TLR4-deficient macrophages, as they are hyporesponsive to LTA. These findings suggest that extracellular HMGB1 induces LTA tolerance, and RAGE receptor is not required for this induction.