Echocardiographic assessment of cardiovascular physiology of preterm miniature piglets supported with a pumped artificial placenta system.

OBJECTIVES: We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit. METHODS: Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status. In utero scans were used as control data. RESULTS: AP fetuses (n = 13; 102±4d gestational age [term 115d]; 616 ± 139 g [g]; survival 46.4 ± 46.8 h) were tachycardic and hypertensive with initially supraphysiologic circuit flows. Increased myocardial wall thickness was observed. Signs of fetal hydrops were present in all piglets. Global longitudinal strain (GLS) measurements increased in the left ventricle (LV) after transition to the circuit. Right ventricle (RV) and LV strain rate decreased early during AP support compared with in utero measurements but recovered toward the end of the experiment. Fetuses supported for >24 h had similar RV GLS to in utero controls and significantly higher GLS compared to piglets surviving only up to 24 h. CONCLUSIONS: Fetuses on a pump-supported AP circuit experienced an increase in afterload, and redistribution of blood flow between the AP and systemic circulations, associated with elevated end-diastolic filling pressures. This resulted in heart failure and hydrops. These preterm fetuses were unable to tolerate the hemodynamic changes associated with connection to the current AP circuit. To better mimic the physiology of the native placenta and preserve normal fetal cardiovascular physiology, further optimization of the circuit will be required.

Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort.

OBJECTIVES: During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined. DESIGN: Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion. SETTING: PICU and cardiac ICU in a quaternary-care center. PATIENTS: Patients 0-18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014-2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37-101 mcg/kg), with the last dose given 6 minutes (2-16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO ( p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, -0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance. CONCLUSIONS: There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

Reintervention Before Bidirectional Cavopulmonary Shunt and Intermediate Outcomes in Children with Single Ventricle Who Underwent Main Pulmonary Artery Banding.

Unplanned reinterventions following pulmonary artery banding (PAB) in single ventricle patients are common before stage 2 palliation (S2P) but associated risk factors are unknown. We hypothesized that reintervention is more common when PAB is placed at younger age and with a looser band, reflected by lower PAB pressure gradient. Retrospective single center study of single ventricle patients undergoing PAB between Jan 2000 and Dec 2020. The association with reintervention and successful S2P was modeled using exploratory cause-specific hazard regression. A multivariable model was developed adjusting for clinical and statistically relevant predictors. The cumulative proportion of patients undergoing reintervention were summarized using a competing risk model. 77 patients underwent PAB at median (IQR) 47 (24-66) days and 3.73 (3.2-4.5) kg. Within18 months of PAB, 60 (78%) reached S2P, 9 (12%) died, 1 (1%) transplanted and 7 (9%) were alive without S2P. Within 18 months of PAB 10 (13%) patients underwent reintervention related to pulmonary blood flow modification: PAB adjustment (n = 6) and conversion to Damus-Kaye-Stansel/Blalock-Taussig-Thomas shunt (n = 4). 6/10 (60%) reached S2P following reintervention. A trend toward higher intervention in patients with a genetic syndrome (p-0.06) and weight < 3 kg (p-0.057) at time of PAB was noted. Only genetic syndrome was a risk factor associated with poor outcome (p-0.025). PAB has a reasonable outcome in SV patients with unobstructed systemic and pulmonary blood flow, but with a high reintervention rate. Only a quarter of patients with genetic syndromes reach S2P and further study is required to explore the benefits from an alternative palliative strategy.

Comparison between Del Nido and conventional blood cardioplegia in pediatric open-heart surgery.

BACKGROUND: Del Nido cardioplegia (DNc) was designed for superior myocardial protection during cardiopulmonary bypass (CPB). We conducted a retrospective review to explore if DNc was associated with increase in systemic ventricle dysfunction (sVD) following pediatric CPB. METHODS AND RESULTS: This single-center, retrospective study included 1534 patients undergoing CPB between 2013 and 2016, 997 prior to center-wide conversion to DNc and 537 following. The primary outcome was new postoperative ≥moderate sVD by echocardiogram. Secondary outcomes included sVD of any severity and right ventricular dysfunction. Data was evaluated by interrupted time-series analysis. Groups had similar cardiac diagnoses and surgical complexity. Del Nido cardioplegia was associated with longer median (IQR) CPB [117 (84-158) vs 108 (81-154), p = 0.04], and aortic cross-clamp [83 (55-119) vs 76 (53-106), p = 0.03], and fewer cardioplegia doses [2 (1-2) vs 3 (2-4), p < 0.0001]. Mortality was similar in both groups. Frequency of sVD was unchanged following DNc, including predetermine subgroups (neonates, infants, and prolonged cross-clamp). Logistic regression showed a significant rise in right ventricular dysfunction (OR 5.886 [95% CI: 0.588, 11.185], p = 0.03) but similar slope. CONCLUSIONS: Use of DNc was not associated with increased in reported sVD, and provided similar myocardical protection to the systemic ventricle compared to conventional cardioplegia but may possibly impact right ventricular function. Studies evaluating quantitative systolic and diastolic function are needed.

Standardisation of management after Norwood operation has not improved 1-year outcomes.

INTRODUCTION: Treatment of hypoplastic left heart syndrome varies across institutions. This study examined the impact of introducing a standardised programme. METHODS: This retrospective cohort study evaluated the effects of a comprehensive strategy on 1-year transplant-free survival with preserved ventricular and atrioventricular valve (AVV) function following a Norwood operation. This strategy included standardised operative and perioperative management and dedicated interstage monitoring. The post-implementation cohort (C2) was compared to historic controls (C1). Outcomes were assessed using logistic regression and Kaplan-Meier analysis. RESULTS: The study included 105 patients, 76 in C1 and 29 in C2. Groups had similar baseline characteristics, including percentage with preserved ventricular (96% C1 versus 100% C2, p = 0.28) and AVV function (97% C1 versus 93% C2, p = 0.31). Perioperatively, C2 had higher indexed oxygen delivery (348 ± 67 ml/minute/m2 C1 versus 402 ± 102ml/minute/m2 C2, p = 0.015) and lower renal injury (47% C1 versus 3% C2, p = 0.004). The primary outcome was similar in both groups (49% C1 and 52% C2, p = 0.78), with comparable rates of death and transplantation (36% C1 versus 38% C2, p = 0.89) and ventricular (2% C1 versus 0% C2, p = 0.53) and AVV dysfunction (11% C1 versus 11% C2, p = 0.96) at 1-year. When accounting for cohort and 100-day freedom from hospitalisation, female gender (OR 3.7, p = 0.01) increased and ventricular dysfunction (OR 0.21, p = 0.02) and CPR (OR 0.11, p = 0.002) or ECMO use (OR 0.15, p = 001) decreased the likelihood of 1-year transplant-free survival. CONCLUSIONS: Standardised perioperative management was not associated with improved 1-year transplant-free survival. Post-operative ventricular or AVV dysfunction was the strongest predictor of 1-year mortality.

Rapid Advancement in Enteral Nutrition Does Not Affect Systemic Inflammation and Insulin Homeostasis Following Pediatric Cardiopulmonary Bypass Surgery.

OBJECTIVES: To determine impact of enteral nutrition delivery on the relationship among inflammation, insulin resistance, and outcomes following pediatric cardiopulmonary bypass surgery. DESIGN: Pilot, randomized study analyzed according to intention-to-treat analysis. SETTING: Pediatric cardiac ICU. PATIENTS: Infants (≤ 6 mo) undergoing cardiopulmonary bypass. INTERVENTIONS: Patients randomly assigned to receive rapid escalation to enteral nutrition reaching goal feeds by 27 hours or standard feeding practice reaching goal feeds by 63 hours. Feeds were initiated on the first postoperative day. MEASUREMENTS AND MAIN RESULTS: Fifty patients were randomized equally to study arms. Patients were a median (interquartile range) of 16 days old (7-110 d old), undergoing biventricular surgery (88%) with a median cardiopulmonary bypass time of 125 minutes (105-159 min). Serial blood samples were drawn before and after cardiopulmonary bypass, cardiac ICU admission, and every 12 hours (up to 96 hr) for glucose, insulin, and cytokines (interleukin-1α, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) levels. Glucose-insulin ratio was calculated to quantify insulin resistance. Patient characteristics, time to enteral nutrition initiation, enteral nutrition interruptions, and insulin administration were similar across intervention arms. FF reached goal feeds at similar intervals as standard feeding (39 hr [30-60 hr] vs 60 hr [21-78 hr]; p = 0.75). No difference in cytokine, insulin, or glucose-insulin ratio was noted between groups. Higher inflammation was associated with increased glucose-insulin ratio and higher risk of adverse events. In multivariable models of interleukin-8, FF was associated with increased glucose-insulin ratio (estimate of effect [95% CI], 0.152 [0.033-0.272]; p = 0.013). Although higher interleukin-8 was associated with an elevated risk of adverse event, this relationship was possibly mitigated by FF (odds ratio [95% CI], 0.086 [0.002-1.638]; p = 0.13). CONCLUSIONS: A FF strategy was not associated with changes to early enteral nutrition delivery. Inflammation, insulin resistance, and morbidity were similar, but FF may modify the relationship between inflammation and adverse event. Multicenter nutrition studies are possible and necessary in this vulnerable population.

Intranasal glucagon acutely increases energy expenditure without inducing hyperglycaemia in overweight/obese adults.

AIM: To assess the acute effects of 0.7 mg intranasal glucagon (ING) vs intranasal placebo (INP) on food intake and resting energy expenditure (REE). METHODS: A single-blind, crossover study was conducted in 19 overweight/obese adults (15 men, 4 women). REE was assessed by indirect calorimetry over 90 minutes, after which appetite was assessed using a visual analogue scale, and ad libitum caloric intake was assessed. Plasma samples were obtained at baseline and at 15-minute intervals post-treatment up to 90 minutes. RESULTS: ING increased total REE (INP 61.5 ± 1.2 kcal vs ING 69.4 ± 1.2 kcal; P = 0.027). There were no between-treatment differences in blood glucose, food intake and appetite. There were no adverse effects. CONCLUSION: ING acutely increases REE without increasing plasma glucose. Longer term studies with multiple daily dosing will establish whether this affects body weight.

Retrospective Application of New Pediatric Ventilator-Associated Pneumonia Criteria Identifies a High-Risk Population.

OBJECTIVES: To promote standardization, the Centers for Disease Control and Prevention introduced a new ventilator-associated pneumonia classification, which was modified for pediatrics (pediatric ventilator-associated pneumonia according to proposed criteria [PVAP]). We evaluated the frequency of PVAP in a cohort of children diagnosed with ventilator-associated pneumonia according to traditional criteria and compared their strength of association with clinically relevant outcomes. DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. PATIENTS: Critically ill children (0-18 yr) diagnosed with ventilator-associated pneumonia between January 2006 and December 2015 were identified from an infection control database. Patients were excluded if on high frequency ventilation, extracorporeal membrane oxygenation, or reintubated 24 hours following extubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for PVAP diagnosis. Primary outcome was the proportion of subjects diagnosed with PVAP. Secondary outcomes included association with intervals of care. Two hundred seventy-seven children who had been diagnosed with ventilator-associated pneumonia were eligible for review; 46 were excluded for being ventilated under 48 hours (n = 16), on high frequency ventilation (n = 12), on extracorporeal membrane oxygenation (n = 8), ineligible bacteria isolated from culture (n = 8), and other causes (n = 4). ICU admission diagnoses included congenital heart disease (47%), neurological (16%), trauma (7%), respiratory (7%), posttransplant (4%), neuromuscular (3%), and cardiomyopathy (3%). Only 16% of subjects (n = 45) met the new PVAP definition, with 18% (n = 49) having any ventilator-associated condition. Failure to fulfill new definitions was based on inadequate increase in mean airway pressure in 90% or FIO2 in 92%. PVAP was associated with prolonged ventilation (median [interquartile range], 29 d [13-51 d] vs 16 d [8-34.5 d]; p = 0.002), ICU (median [interquartile range], 40 d [20-100 d] vs 25 d [14-61 d]; p = 0.004) and hospital length of stay (median [interquartile range], 81 d [40-182 d] vs 54 d [31-108 d]; p = 0.04), and death (33% vs 16%; p = 0.008). CONCLUSIONS: Few children with ventilator-associated pneumonia diagnosis met the proposed PVAP criteria. PVAP was associated with increased morbidity and mortality. This work suggests that additional study is required before new definitions for ventilator-associated pneumonia are introduced for children.

Assessment of Growth 6 Years after the Norwood Procedure.

At 6 years of age, patients with hypoplastic left heart syndrome had mean age-adjusted z-scores for weight and height below the normative population, and body mass index was similar to the normative population. Males had the greatest increase in z-scores for body mass index. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00115934.

Nutrition and Mesenteric Issues in Pediatric Cardiac Critical Care.

OBJECTIVES: The objectives of this review are to discuss the challenges of delivering adequate nutrition to children with congenital heart disease, including pre- and postoperative factors and the role of enteral and parenteral nutrition, as well as the evidence supporting current practices. DATA SOURCE: MEDLINE and PubMed. CONCLUSION: Providing adequate nutritional support is paramount for critically ill infants with congenital heart disease, a population at particular risk for malnutrition. Improved nutritional support has been associated with increased survival and reduction in overall morbidity. Further gains can be achieved by creating a clinical culture that emphasizes optimal perioperative nutritional support. Additional research is required to identify the specific nutrient composition, optimal mode, and timing of delivery to maximize clinical benefit.

Outcomes in Patients with Persistent Ventricular Dysfunction After Stage I Palliation for Hypoplastic Left Heart Syndrome.

We sought to describe the clinical course for patients with hypoplastic left heart syndrome and persistent ventricular dysfunction and identify risk factors for death or transplantation before stage II palliation. 138 children undergoing stage I palliation from 2004 to 2011 were reviewed. Twenty-two (16 %) patients (seven Hybrid, 15 Norwood) with two consecutive echocardiograms reporting at least moderate dysfunction were included and compared to case-matched controls. Eleven of the 22 patients with dysfunction (50 %) underwent stage II, seven (32 %) were transplanted, and four (18 %) died prior to stage II. Of the patients who survived to hospital discharge (n = 17) following stage 1, 14 (82 %) required readmission for heart failure (HF) compared to only two (10 %) for controls (p < 0.001). Among patients with ventricular dysfunction, there was an increased use of ACE inhibitors or beta-blockers (82 vs. 25 %; p = 0.001), inotropes (71 vs. 15 %; p = 0.001), ventilation (58 vs. 10 %; p = 0.001), and ECMO (29 vs. 0 %; p = 0.014) for HF management post-discharge when compared to controls. There was a lower heart transplant-free survival at 7 months in patients with dysfunction compared to controls (50.6 vs. 90.9 %; p = 0.040). ECMO support (p = 0.001) and duration of inotropic support (p = 0.04) were significantly associated with death or transplantation before stage II palliation. Patients with ventricular dysfunction received more HF management and related admissions. Longer inotropic support should prompt discussion regarding alternative treatment strategies given its association with death or transplant.

Systemic inflammation increases energy expenditure following pediatric cardiopulmonary bypass.

OBJECTIVES: To examine the association between cardiopulmonary bypass-related systemic inflammation and resting energy expenditure in pediatric subjects following cardiac surgery. DESIGN: Single-center, prospective cohort study. SETTING: Pediatric cardiac critical care unit in Toronto, Canada. PATIENTS: Children with congenital heart disease undergoing cardiopulmonary bypass surgery. INTERVENTIONS: Resting energy expenditure was determined by indirect calorimetry and the modified Weir equation, using VO2 and VCO2 measured by in-line respiratory mass spectrometry. Measurements were taken at baseline and 6-hour intervals from separation from cardiopulmonary bypass for a maximum of 72 hours. Plasma interleukin-6, glucose delivery, feeding status, and cardiac output (calculated by Fick equation) were monitored at each resting energy expenditure measurement. MEASUREMENTS AND MAIN RESULTS: We studied 111 subjects at a median (interquartile range) age of 5.3 months (0.8-10.5 mo), weighing 5.7 kg (3.9-8.1 kg), of whom 88% underwent biventricular repair. Resting energy expenditure decreased from 51 kcal/kg/d to 45 kcal/kg/d during the study period. Resting energy expenditure was positively associated with increased plasma interleukin-6 (estimate variable, 1.76; p = 0.001) and inversely associated with preoperative methylprednisolone use (estimate variable, -6.7; p = 0.003) even after accounting for other predictors. Increase in cardiac output was also associated (estimate variable, 13.7; p < 0.0001) with higher resting energy expenditure. CONCLUSIONS: Resting energy expenditure ranges between 40 and 60 kcal/kg/d and decreases progressively in children following cardiopulmonary bypass surgery. It is directly associated with increased inflammation and higher cardiac output and inversely associated with anti-inflammatory strategies. Further studies are required to predict the appropriate caloric delivery in this cohort.

Cased-based education rounds-the eternal heart of an international training program.

Case-based teaching or "Morning Rounds" have been used in medical education for more than a century and remain a cornerstone for teaching in many training programs. Our Pediatric Critical Care Medicine (PCCM) program was established forty years ago and has retained this form of teaching since its inception. Case-based rounds have consistently had the highest evaluation of all curricula in our program. Here we review the history of how these rounds were introduced in medical education, provide data from the learners' evaluation of these case-based rounds, and discuss the strengths and potential drawbacks of this form of teaching from an educational theories perspective with the hope that they can be used by other Pediatric Critical Care training programs.

Outcomes of Children With Hypoplastic Left Heart Syndrome and Heart Failure on Medical Therapy.

Background: Systemic right ventricle (RV) dysfunction is associated with lower transplant-free survival (TFS) in hypoplastic left heart syndrome (HLHS), but the likelihood of functional improvement and utility of heart failure (HF) medications is not understood. Objectives: The authors aimed to describe TFS, HF medication use, and surgical interventions in HLHS patients with RV dysfunction with and without subsequent improvement in function. Methods: The SickKids HF Database is a retrospective cohort that includes all pediatric HLHS patients with RV dysfunction lasting >30 days. We compared TFS, HF medications, and surgical interventions in HLHS patients with and without functional normalization. Results: Of 99 patients with HLHS and RV dysfunction, 52% had normalized function for ≥30 days. TFS at 2 years after dysfunction onset was lower in those without normalization (14% vs 78%, P < 0.001). Patients without normalization were less likely to reach target dosing (TD) of HF medications (27% vs 47% on 1 medication at TD, P < 0.001) and undergo Fontan completion (7% vs 53%, P < 0.001). Clinical factors associated with improved TFS were normalization of function for ≥30 days, onset of dysfunction after bidirectional Glenn, and exposure to ACE inhibition. Conclusions: Our cohort of HLHS patients with systemic RV dysfunction demonstrated a novel finding of improved TFS in those with functional normalization for ≥30 days. Achieving TD of HF medications was associated with improved outcomes. This may reflect patient stability and tolerance for HF medication more than its therapeutic effect, but it can help inform decisions to proceed with surgical palliation or list for transplant.

Early outcomes of moderate-to-high-risk pediatric congenital cardiac surgery and predictors of extracorporeal circulatory life support requirement.

Background: Cardiopulmonary failure refractory to medical management after moderate-to-high-risk congenital cardiac surgery may necessitate mechanical support with veno-arterial extracorporeal membrane oxygenation (ECMO). On the extreme, ECMO can also be initiated in the setting of cardiac arrest (extracorporeal cardiopulmonary resuscitation, ECPR) unresponsive to conventional resuscitative measures. Methods: This was a single-center retrospective cohort study of patients (n = 510) aged <3 years old who underwent cardiac surgery with cardiopulmonary bypass with a RACHS-1 score ≥3 between 2011 and 2014. Perioperative factors were reviewed to identify predictors of ECMO initiation and mortality in the operating room (OR) and the intensive care unit (ICU). Results: A total of 510 patients with a mean surgical age of 10.0 ± 13.4 months were included. Among them, 21 (4%) patients received postoperative ECMO-12 were initiated in the OR and 9 in the ICU. ECMO cannulation was associated with cardiopulmonary bypass duration, aortopulmonary shunt, residual severe mitral regurgitation, vaso-inotropic score, and postprocedural lactate (p < 0.001). Of the 32 (6%) total deaths, 7 (22%) were ECMO patients-4 were elective OR cannulations and 3 were ICU ECPR. Prematurity [hazard ratio (HR): 2.61, p < 0.01), Norwood or Damus-Kaye-Stansel procedure (HR: 4.29, p < 0.001), postoperative left ventricular dysfunction (HR: 5.10, p = 0.01), residual severe tricuspid regurgitation (HR: 6.06, p < 0.001), and postoperative ECMO (ECPR: HR: 15.42, p < 0.001 vs. elective: HR: 5.26, p = 0.01) were associated with mortality. The two patients who were electively cannulated in the ICU survived. Discussion: Although uncommon, postoperative ECMO in children after congenital cardiac surgery is associated with high mortality, especially in cases of ECPR. Patients with long cardiopulmonary bypass time, residual cardiac lesions, or increased vaso-inotropic requirement are at higher risk of receiving ECMO. Pre-emptive or early ECMO initiation before deterioration into cardiac arrest may improve survival.

Successful Pediatric Mechanical Thrombectomy for HeartMate 3-Related Intracranial Thromboembolism.

Thromboembolic events post left ventricular assist devices (LVAD) implantation remain a major cause of morbidity and mortality. Mechanical thrombectomy for the treatment of pediatric intracranial thromboembolic events have been reported in LVADs, but never following HeartMate 3 (HM3) implantation. We present the case of an 8-year-old, 26.5 kg male with dilated cardiomyopathy and decompensated heart failure who presented with extensive intracranial thromboembolism in the early postoperative period following HM3 implantation and underwent successful mechanical thrombectomy with a favorable neurological outcome.

Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit (n = 12; 98 ± 4 days; 743 ± 350 g). The umbilical vessels were cannulated, and fetuses were supported for 46.4 ± 46.8 h using the pumped AP versus 11 ± 13 h on the pumpless AP circuit. Upon initiation of AP support on the pumped system, we observed supraphysiologic circuit flows, tachycardia, and hypertension, while animals maintained on a pumpless AP circuit exhibited subphysiologic flows. On the pumped AP circuit, there was a progressive decline in umbilical vein (UV) flow and oxygen delivery. We conclude that the addition of a centrifugal pump to the AP circuit improves survival of preterm pigs by augmenting UV flow through the reduction of right ventricular afterload. However, we continued to observe the development of heart failure within a matter of days.

Achieving sustained extrauterine life: Challenges of an artificial placenta in fetal pigs as a model of the preterm human fetus.

Artificial placenta (AP) technology aims to maintain fetal circulation, while promoting the physiologic development of organs. Recent reports of experiments performed in sheep indicate the intrauterine environment can be recreated through the cannulation of umbilical vessels, replacement of the placenta with a low-resistance membrane oxygenator, and incubation of the fetus in fluid. However, it remains to be seen whether animal fetuses similar in size to the extremely preterm human infant that have been proposed as a potential target for this technology can be supported in this way. Preterm Yucatan miniature piglets are similar in size to extremely preterm human infants and share similar umbilical cord anatomy, raising the possibility to serve as a good model to investigate the AP. To characterize fetal cardiovascular physiology, the carotid artery (n = 24) was cannulated in utero and umbilical vein (UV) and umbilical artery were sampled. Fetal UV flow was measured by MRI (n = 16). Piglets were delivered at 98 ± 4 days gestation (term = 115 days), cannulated, and supported on the AP (n = 12) for 684 ± 228 min (range 195-3077 min). UV flow was subphysiologic (p = .002), while heart rate was elevated on the AP compared with in utero controls (p = .0007). We observed an inverse relationship between heart rate and UV flow (r2  = .4527; p < .001) with progressive right ventricular enlargement that was associated with reduced contractility and ultimately hydrops and circulatory collapse. We attribute this to excessive afterload imposed by supraphysiologic circuit resistance and augmented sympathetic activity. We conclude that short-term support of the preterm piglet on the AP is feasible, although we have not been able to attain normal fetal physiology. In the future, we propose to investigate the feasibility of an AP circuit that incorporates a centrifugal pump in our miniature pig model.