An Imbalance of Pathophysiologic Factors in Late Postprandial Hypoglycemia Post Bariatric Surgery: A Narrative Review.

With a rise in obesity and more patients opting for bariatric surgery, it becomes crucial to understand associated complications like postprandial hypoglycemia (PPH). After bariatric surgery, significant changes are seen in insulin sensitivity, beta cell function, glucagon-like peptide 1 (GLP-1) levels, the gut microbiome, and bile acid metabolism. And in a small subset of patients, exaggerated imbalances in these functional and metabolic processes lead to insulin-glucose mismatch and hypoglycemia. The main treatment for PPH involves dietary modifications. For those that do not respond, medications or surgical interventions are considered to reverse some of the imbalances. We present a few case reports of patients that safely tolerated GLP-1 agonists. However, larger randomized control trials are needed to further characterize PPH and understand its treatment.

Abnormal flow conduction through pulmonary arteries is associated with right ventricular volume and function in patients with repaired tetralogy of Fallot: does flow quality affect afterload?

OBJECTIVES: Flow through the proximal pulmonary arteries (PAs) of patients with repaired Tetralogy of Fallot (TOF) is known to be highly disordered and associated with significant regurgitation. The purpose of this study was to evaluate 4D-Flow MRI-derived viscous energy loss [Formula: see text])-as a result of non-efficient flow propagation, and relate this parameter to standard right ventricular (RV) size and function markers in patients with repaired TOF. METHODS: Thirty-five patients with TOF and 14 controls underwent comprehensive 4D-Flow MRI evaluation for qualitative flow analysis and to calculate [Formula: see text] in the main and right pulmonary arteries. Sampled [Formula: see text] indices were correlated with the MRI-derived RV size and functional indices. RESULTS: All patients with TOF exhibited abnormal, supra-physiologic helical/vortical formations in the PAs. Patients with TOF had significantly increased peak systolic [Formula: see text] (8.0 vs 0.5 mW, p < 0.001), time-averaged [Formula: see text] (2.5 vs. 0.2 mW, p < 0.001), and peak systolic [Formula: see text] indexed to stroke volume (0.082 vs. 0.012 mW/mL, p < 0.001). [Formula: see text] indexed to stroke volume correlated with the RV end-diastolic volume (R = 0.68, p < 0.001), end-systolic volume (R = 0.62, p < 0.001), ejection fraction (R = -0.45, p = 0.002), and cardiac index (R = 0.45, p = 0.002). The mean estimated energy loss due to [Formula: see text] with regard to input RV mechanical power was 4.7%. CONCLUSION: This study demonstrates that patients with repaired TOF have highly abnormal flow conduction through the PAs which result into extensive viscous energy loss. This significant flow-mediated energy loss is associated with the RV volume and function, and might represent considerable loss of mechanical power generated by each cardiac cycle. Future studies are required to assess whether the abnormal flow conduction adds to the RV afterload and remodeling. KEY POINTS: • Abnormal flow patterns through proximal pulmonary arteries in patients with TOF are associated with excessive viscous energy loss. • Inefficient flow conduction is associated with the RV dilation and reduced function and might contribute to the RV adaptive remodeling.

Multi-Disciplinary Management and Surgical Resection of Intracardiac Fibromas Causing Bilateral Ventricular Outflow Tract Obstructions in an Infant.

Cardiac tumors remain rare in children with benign pathologies predominating. Indications for surgical management often result from compromised ventricular chamber size, biventricular outflow tract obstruction, impaired ventricular function, or the presence of medically refractory dysrhythmias. We present a case of a six-month-old infant with two intracardiac fibromas originating in the interventricular septum. The fibromas were causing significant biventricular outflow obstruction. The patient successfully underwent tumor resection on cardiopulmonary bypass The literature on pediatric cardiac tumors is reviewed. Multi-disciplinary medical planning is necessary for successful anesthetic and surgical treatment of this high-risk patient population.

Changes in infant porcine pulmonary tissue oxylipins induced by cardiopulmonary bypass.

BACKGROUND: Oxylipins are metabolites derived from fatty acids such as arachidonic acid (AA) and are key mediators in inflammation, host defense, and tissue injury. Serum oxylipins increase in adults after cardiopulmonary bypass (CPB) but tissue-level changes are poorly defined. The objective of this study was to characterize pulmonary tissue oxylipins in an infant porcine model of CPB with deep hypothermic circulatory arrest (DHCA). METHODS: Infant pigs underwent CPB with DHCA. Controls received anesthesia only. Right upper and lower lobes of the lung underwent oxylipin analysis via liquid chromatography-tandem mass spectrometry. One-way ANOVA was utilized to assess differences in oxylipin concentrations across groups, followed by pairwise comparisons. RESULTS: AA and multiple AA metabolites via cytochrome P450 (CYP450), lipoxygenase (LOX), and cyclooxygenase (COX) pathways were significantly increased in the upper and lower lobe of pigs exposed to CPB/DHCA as compared to controls. Multiple prostaglandin metabolites produced via COX were also significantly elevated in the lower lobes of control animals. CONCLUSIONS: CPB/DHCA induces a significant increase in pulmonary tissue AA, with subsequent metabolism via COX, LOX, and CYP450 pathways. Interestingly, prostaglandins were also elevated in the lower lobes of the controls, suggesting a mechanism separate from CPB/DHCA. Future oxylipin studies are needed to better understand CPB-induced acute lung injury. IMPACT: CPB/DHCA and, to a lesser extent, lung region influence pulmonary tissue-level AA metabolite production. Inflammatory mediator AA metabolites have been noted in previous studies to increase following CPB; however, this is the first study to look at pulmonary tissue-level differences following CPB/DHCA. Increases in many AA metabolites, including LOX- and CYP450-derived products, were seen in both upper and lower lobe of piglets following CPB/DHCA. COX-derived prostaglandin metabolites were increased not only in CPB upper and lower lobe but also in mechanically ventilated control lower lobe, suggesting an additional, separate mechanism from CPB/DCHA.

Metabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury.

Acute kidney injury (AKI) is a common cause of morbidity after congenital heart disease surgery. Progress on diagnosis and therapy remains limited, however, in part due to poor mechanistic understanding and a lack of relevant translational models. Metabolomic approaches could help identify novel mechanisms of injury and potential therapeutic targets. In the present study, we used a piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB/DHCA) and targeted metabolic profiling of kidney tissue, urine, and serum to evaluate metabolic changes specific to animals with histological acute kidney injury. CPB/DHCA animals with acute kidney injury were compared with those without acute kidney injury and mechanically ventilated controls. Acute kidney injury occurred in 10 of 20 CPB/DHCA animals 4 h after CPB/DHCA and 0 of 7 control animals. Injured kidneys showed a distinct tissue metabolic profile compared with uninjured kidneys (R2 = 0.93, Q2 = 0.53), with evidence of dysregulated tryptophan and purine metabolism. Nine urine metabolites differed significantly in animals with acute kidney injury with a pattern suggestive of increased aerobic glycolysis. Dysregulated metabolites in kidney tissue and urine did not overlap. CPB/DHCA strongly affected the serum metabolic profile, with only one metabolite that differed significantly with acute kidney injury (pyroglutamic acid, a marker of oxidative stress). In conclusion, based on these findings, kidney tryptophan and purine metabolism are candidates for further mechanistic and therapeutic investigation. Urine biomarkers of aerobic glycolysis could help diagnose early acute kidney injury after CPB/DHCA and warrant further evaluation. The serum metabolites measured at this early time point did not strongly differentiate based on acute kidney injury.NEW & NOTEWORTHY This project explored the metabolic underpinnings of postoperative acute kidney injury (AKI) following pediatric cardiac surgery in a translationally relevant large animal model of cardiopulmonary bypass with deep hypothermic circulatory arrest. Here, we present novel evidence for dysregulated tryptophan catabolism and purine catabolism in kidney tissue and increased urinary glycolysis intermediates in animals who developed histological AKI. These pathways represent potential diagnostic and therapeutic targets for postoperative AKI in this high-risk population.

Regional lung metabolic profile in a piglet model of cardiopulmonary bypass with circulatory arrest.

INTRODUCTION: Acute lung injury is common following cardiopulmonary bypass and deep hypothermic circulatory arrest for congenital heart surgery with the most severe injury in the dorsocaudal lung. Metabolomics offers promise in deducing mechanisms of disease states, providing risk stratification, and understanding therapeutic responses in regards to CPB/DHCA related organ injury. OBJECTIVES: Using an infant porcine model, we sought to determine the individual and additive effects of CPB/DHCA and lung region on the metabolic fingerprint, metabolic pathways, and individual metabolites in lung tissue. METHODS: Twenty-seven infant piglets were divided into two groups: mechanical ventilation + CPB/DHCA (n = 20) and mechanical ventilation only (n = 7). Lung tissue was obtained from dorsocaudal and ventral regions. Targeted analysis of 235 metabolites was performed using HPLC/MS-MS. Data was analyzed using Principal Component Analysis (PCA), Partial Least Square Discriminant Analysis (PLS-DA), ANOVA, and pathway analysis. RESULTS: Profound metabolic differences were found in dorsocaudal compared to ventral lung zones by PCA and PLS-DA (R2 = 0.7; Q2 = 0.59; p < 0.0005). While overshadowed by the regional differences, some differences by exposure to CPB/DHCA were seen as well. Seventy-four metabolites differed among groups and pathway analysis revealed 20 differential metabolic pathways. CONCLUSION: Our results demonstrate significant metabolic disturbances between dorsocaudal and ventral lung regions during supine mechanical ventilation with or without CPB/DHCA. CPB/DHCA also leads to metabolic differences and may have additive effects to the regional disturbances. Most pathways driving this pathology are involved in energy metabolism and the metabolism of amino acids, carbohydrates, and reduction-oxidation pathways.

Selected 2020 Highlights in Congenital Cardiac Anesthesia.

This article is a review of the highlights of pertinent literature published during the 12 months of 2020 that are of interest to the congenital cardiac anesthesiologist. After a search of the US National Library of Medicine's PubMed database, several topics emerged for which significant contributions were made in 2020. The authors of the present article considered the following topics noteworthy to be included in this review: pediatric cardiac care in the coronavirus disease 2019 era, the use of mechanical circulatory support in coronavirus disease 2019-related multisystem inflammatory syndrome in children, transfusion and coagulation management in children undergoing congenital heart surgery, and pulmonary vein stenosis.

Short-Term Effects of Inhaled Nitric Oxide on Right Ventricular Flow Hemodynamics by 4-Dimensional-Flow Magnetic Resonance Imaging in Children With Pulmonary Arterial Hypertension.

Background Pulmonary arterial hypertension (PAH) manifests with progressive right ventricular (RV) dysfunction, which eventually impairs the left ventricular function. We hypothesized that 4-dimensional-flow magnetic resonance imaging can detect flow hemodynamic changes associated with efficient intracardiac flow during noninvasive inhaled nitric oxide (iNO) challenge in children with PAH. Methods and Results Children with PAH (n=10) underwent 2 same-day separate iNO challenge tests using: (1) 4-dimensional-flow magnetic resonance imaging and (2) standard catheterization hemodynamics. Intracardiac flow was evaluated using the particle tracking 4-flow component analysis technique evaluating the direct flow, retained inflow, delayed ejection flow, and residual volume. Respective flow hemodynamic changes were compared with the corresponding catheterization iNO challenge results. The RV analysis revealed decreased direct flow in patients with PAH when compared with controls (P<0.001) and increase in residual volume (P<0.001). Similarly, the left ventricular analysis revealed decreased direct flow in patients with PAH when compared with controls (P=0.004) and increased proportion of the residual volume (P=0.014). There was an increase in the RV direct flow during iNO delivery (P=0.009), with parallel decrease in the residual volume (P=0.008). Conclusions Children with PAH have abnormal biventricular flow associated with impaired diastolic filling. The flow efficiency is significantly improved in the RV on iNO administration with no change in the left ventricle. The changes in the RV flow have occurred despite the minimal change in catheterization hemodynamics, suggesting that flow hemodynamic evaluation might provide more quantitative insights into vasoreactivity testing in PAH.

Clonidine as an Adjuvant to Bupivacaine for Suprazygomatic Maxillary Nerve Blocks in Cleft lip and Palate Repair: A Randomized, Prospective, Double-Blind Study.

OBJECTIVES: Does clonidine, as adjuvant to bupivacaine for suprazygomatic maxillary nerve blocks, reduce emergence agitation in patients undergoing cleft lip and cleft palate surgery? DESIGN: Randomized, controlled, and double-blind study. SETTING: Guwahati Comprehensive Cleft Care Center, Guwahati (Assam, India). PARTICIPANTS: A total of 124 patients; with a median age of 5 years in the clonidine group (CLG) and 7 years in the control group (CG), who underwent cleft lip or cleft palate surgery were included. Exclusion criteria included lack of consent from patients or their guardians, allergy to local anesthetics, coagulation disorders, local infection at the puncture site before performing the block, and language difficulties or cognitive disorders. INTERVENTIONS: Patients were randomized into 2 groups to receive bilateral suprazygomatic maxillary nerve blocks with either a bupivacaine/clonidine mixture for the CLG or bupivacaine alone in the CG. MAIN OUTCOME MEASURE: The primary end point was the incidence of emergence agitation. RESULTS: There was a statistically significant difference in the incidence of emergence agitation (30.2% in the CG compared to 15.2% in the CLG; difference of incidences: 15%, 95% CI: 0.1-30.1). The percentage of patients requiring intraoperative Fentanyl was lower in the CLG (10.6% compared to 26.4%; difference of incidences: 15.8%, 95% CI: 1.8-29). No other differences were observed. Further research in a more typically aged children population undergoing cleft surgery is needed. CONCLUSIONS: The use of clonidine as an adjuvant to bupivacaine in maxillary nerve block reduces the incidence of emergence agitation and intraoperative opioid consumption without hemodynamic or sedative side effects in patients undergoing cleft lip and palate surgery.

Tissue alkaline phosphatase activity and expression in an experimental infant swine model of cardiopulmonary bypass with deep hypothermic circulatory arrest.

BACKGROUND: Infant cardiac surgery with cardiopulmonary bypass results in decreased circulating alkaline phosphatase that is associated with poor postoperative outcomes. Bovine intestinal alkaline phosphatase infusion represents a novel therapy for post-cardiac surgery organ injury. However, the effects of cardiopulmonary bypass and bovine-intestinal alkaline phosphatase infusion on tissue-level alkaline phosphatase activity/expression are unknown. METHODS: Infant pigs (n = 20) underwent cardiopulmonary bypass with deep hypothermic circulatory arrest followed by four hours of intensive care. Seven control animals underwent mechanical ventilation only. Cardiopulmonary bypass/deep hypothermic circulatory arrest animals were given escalating doses of bovine intestinal alkaline phosphatase infusion (0-25 U/kg/hr.; n = 5/dose). Kidney, liver, ileum, jejunum, colon, heart and lung were collected for measurement of tissue alkaline phosphatase activity and mRNA. RESULTS: Tissue alkaline phosphatase activity varied significantly across organs with the highest levels found in the kidney and small intestine. Cardiopulmonary bypass with deep hypothermic circulatory arrest resulted in decreased kidney alkaline phosphatase activity and increased lung alkaline phosphatase activity, with no significant changes in the other organs. Alkaline phosphatase mRNA expression was increased in both the lung and the ileum. The highest dose of bovine intestinal alkaline phosphatase resulted in increased kidney and liver tissue alkaline phosphatase activity. CONCLUSIONS: Changes in alkaline phosphatase activity after cardiopulmonary bypass with deep hypothermic circulatory arrest and bovine intestinal alkaline phosphatase delivery are tissue specific. Kidneys, lung, and ileal alkaline phosphatase appear most affected by cardiopulmonary bypass with deep hypothermic circulatory arrest and further research is warranted to determine the mechanism and biologic importance of these changes.