Objective Venous to arterial carbon dioxide difference (AVCO2) correlates with cardiac output (CO) in critically ill adults, but its utility in pediatric patients is unclear. We sought to correlate AVCO2 with other CO surrogates (arteriovenous oxygen saturation difference [AVO2], central venous oxygen saturation [ScVO2], and lactate); as well as investigate its capacity to predict poor outcomes associated with low cardiac output (LCOS) in infants after cardiac surgery with cardiopulmonary bypass (CPB). Design Retrospective chart review. Poor outcome was defined as any: inotrope score > 15; death, cardiac arrest, ECMO, unplanned surgical re-intervention. Setting Pediatric cardiovascular intensive care unit Patients 139 infants <90d who underwent CPB, from October 2012 to May 2015. Measurement and Main Results 296 arterial and venous blood gas pairs from admission (n=139), 6hrs (n=62), 12hrs (n=73), 24hrs (n=22) were included in analysis. For all pairs, AVCO2 was moderately correlated with AVO2 (R2= 0.53, p<0.01) and ScVO2 (R2= −0.43, p<0.01), but not lactate. On admission AVCO2 was also moderately correlated with ScVO2 (R2= 0.-0.40, p<0.01) and AVO2 (R2= 0.55, p<0.01), but not lactate. 34/139 neonates (24.5%) had poor outcome. Median admission AVCO2 was 5.9 mm Hg (3.8, 9.2). Patients with poor outcome had median admission AVCO2 8.3 mmHg (5.6, 14.9) vs. 5.4 (3.0, 8.4) in those without poor outcome. AVCO2 (AUC=0.69, p<0.01), serum lactate (AUC=0.64, p=0.02) and ScVO2 (AUC=0.74, p<0.01) were predictive of poor outcome. After controlling for covariates, admission AVCO2 remained significantly associated with poor outcome [OR 1.3, 95% CI: 1.1–1.45], including independent association with mortality, [OR 1.2 (95% CI 1.07–1.31)]. Conclusions AVCO2 is correlated with important surrogates of CO, and is associated with poor outcome and mortality related to LCOS after cardiac surgery in infants. Prospective validation of these findings, including confirmation that AVCO2 can identify LCOS in real-time is warranted.
Fontan operation can be complicated by persistent chest tube output (CTO) leading to prolonged hospital length of stay (LOS). Postoperative sildenafil administration has been shown to improve clinical outcomes in selected patients after Fontan. We initiated a practice change utilizing intravenous (IV) sildenafil in early postoperative period in all patients undergoing Fontan operation with aim to decrease LOS and CTO. Nineteen patients (February 2014-May 2016) received 0.35 mg/kg sildenafil IV (three doses) followed by enteral, 1 mg/kg every eight hours until hospital discharge. Clinical outcomes were compared to 84 pre-protocol controls. Vital signs were recorded after second sildenafil dose. Demographics were similar between groups. Sildenafil group had longer median LOS [9 (7, 11) vs. 13 (8, 25) days, p = 0.016]. CTO days were longer [6 (5, 8) vs. 8 (6, 13) days, p = 0.011]. Sildenafil group had longer mechanical ventilation [6.9 (3.5, 11.1) vs. 4 (2, 7) h, p = 0.045] and longer oxygen therapy [99 (52, 225) vs. 14.5 (14, 56) h, p = 0.001]. There was a trend towards more albumin 5% resuscitation in first 24 h [17 (1, 30) vs. 21 (10, 40) ml/kg, p = 0.069]. There was no difference in inotrope score at 24 h, maximum lactate, or fluid balance. Readmission rates were similar. There was no mortality. IV sildenafil was well tolerated, and no doses were held. Routine early administration of sildenafil after Fontan operation is not associated with an improvement in any measured clinical outcome, including postoperative CTO, LOS, colloid administration, or duration of mechanical ventilation.
Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in SERT −/− mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin receptor (HTR) signaling. SERT activity was decreased in LL MVICs partially because of diminished membrane localization of SERT. In mice, fluoxetine treatment or SERT knockdown resulted in thickened MV leaflets. Similarly, silencing of SERT in normal human MVICs led to up-regulation of transforming growth factor β1 ( TGF β 1 ) and collagen ( COL1A1 ) in the presence of serotonin. In addition, treatment of MVICs with fluoxetine not only directly inhibited SERT activity but also decreased SERT expression and increased HTR2B expression. Fluoxetine treatment and LL genotype were also associated with increased COL1A1 expression in the presence of serotonin in MVICs, and these effects were attenuated by HTR2B inhibition. These results suggest that assessment of both 5-HTTLPR genotype and SERT-inhibiting treatments may be useful tools to risk-stratify patients with MV disease to estimate the likelihood of rapid disease progression.
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