Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia

Kashyap, Aidan J.; Hodges, Ryan; Thió, Marta; Rodgers, Karyn; Amberg, Ben J; McGillick, Erin V.; Hooper, Stuart B.; Crossley, Kelly J.; DeKoninck, Philip

doi:10.1136/archdischild-2019-316906

Cited by 29 publications

(20 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an ovine diaphragmatic hernia (DH) model, the lambs developed respiratory acidosis and poor cerebral oxygenation immediately after birth, confirming the hypothesised worsening of hypoxia after ICC 30. Hypoxia may result in an enhanced vasoconstrictive response since the pulmonary vasculature in CDH infants is hyper-reactive 30.…”

Section: Transition Periodmentioning

confidence: 78%

“…29 In particular, airway liquid clearance will be impeded because of an increased resistance to liquid flow down through the airways due to their smaller total cross-sectional area, in combination with a reduced surface area for liquid movement into the perialveolar tissue 29. Since lung aeration is the most important trigger for decreasing PVR and augmenting PBF, impaired airway liquid clearance and thus delayed lung aeration results in a delay in the sequence of physiological changes that transform the fetal circulation into a neonatal circuit 5 25 30. Accordingly, after cord clamping there is a prolonged period of reduced cardiac output, resulting in gradually worsening of hypoxia and blood pressure fluctuations in the pulmonary and systemic vasculature.…”

Section: Transition Periodmentioning

confidence: 99%

“…Hypoxia may result in an enhanced vasoconstrictive response since the pulmonary vasculature in CDH infants is hyper-reactive 30. The resulting increase in vascular resistance could worsen PH, ultimately leading to an increase in the pre-existing right-to-left shunt, which in turn would aggravate the hypoxia and trigger an ongoing cycle of worsening PH 5 8 30 34…”

Section: Transition Periodmentioning

confidence: 99%

See 2 more Smart Citations

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: a review of current concepts

Horn-Oudshoorn

Knol

Pas

et al. 2020

Arch Dis Child Fetal Neonatal Ed

Self Cite

View full text Add to dashboard Cite

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, the physiological changes occurring during the fetal-to-neonatal transition in CDH, novel delivery room strategies and early predictors of adverse outcomes. The combination of improvements in the perinatal stabilisation period and early prediction of adverse outcomes may mitigate the need for specific postnatal management strategies.copyright.on July 4, 2020 by guest. Protected by

show abstract

Section: Transition Periodmentioning

confidence: 78%

Section: Transition Periodmentioning

confidence: 99%

Section: Transition Periodmentioning

confidence: 99%

See 1 more Smart Citation

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: a review of current concepts

Horn-Oudshoorn

Knol

Pas

et al. 2020

Arch Dis Child Fetal Neonatal Ed

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have shown previously that DH lambs experience severe hypoxia at birth if the umbilical cord is immediately clamped. This is because the hypoplastic lungs of DH lambs are slow to aerate and perfuse at birth, so they cannot take over the role of gas exchange from the placenta as rapidly as can age‐matched control lambs.…”

Section: Discussionmentioning

confidence: 99%

Antenatal sildenafil treatment improves neonatal pulmonary hemodynamics and gas exchange in lambs with diaphragmatic hernia

Kashyap

DeKoninck

Rodgers

et al. 2019

Ultrasound in Obstet & Gyne

View full text Add to dashboard Cite

Objectives Infants with congenital diaphragmatic hernia (CDH) are predisposed to pulmonary hypertension after birth, owing to lung hypoplasia that impairs fetal pulmonary vascular development. Antenatal sildenafil treatment attenuates abnormal pulmonary vascular and alveolar development in rabbit and rodent CDH models, but whether this translates to functional improvements after birth remains unknown. We aimed to evaluate the effect of antenatal sildenafil on neonatal pulmonary hemodynamics and lung function in lambs with diaphragmatic hernia (DH). Methods DH was surgically induced at approximately 80 days' gestation in 16 lamb fetuses (term in lambs is approximately 147 days). From 105 days' gestation, ewes received either sildenafil (0.21 mg/kg/h intravenously) or saline infusion until delivery (n = 8 fetuses in each group). At approximately 138 days' gestation, all lambs were instrumented and then delivered via Cesarean section. The lambs were ventilated for 120 min with continuous recording of physiological (pulmonary and carotid artery blood flow and pressure; cerebral oxygenation) and ventilatory parameters, and regular assessment of arterial blood gas tensions. Only lambs that survived until delivery and with a confirmed diaphragmatic defect at postmortem examination were included in the analysis; these comprised six DH‐sildenafil lambs and six DH‐saline control lambs. Results Lung‐to‐body‐weight ratio (0.016 ± 0.001 vs 0.013 ± 0.001; P = 0.06) and dynamic lung compliance (0.8 ± 0.2 vs 0.7 ± 0.2 mL/cmH2O; P = 0.72) were similar in DH‐sildenafil lambs and controls. Pulmonary vascular resistance decreased following lung aeration to a greater degree in DH‐sildenafil lambs, and was 4‐fold lower by 120 min after cord clamping than in controls (0.6 ± 0.1 vs 2.2 ± 0.6 mmHg/(mL/min); P = 0.002). Pulmonary arterial pressure was also lower (46 ± 2 vs 59 ± 2 mmHg; P = 0.048) and pulmonary blood flow higher (25 ± 3 vs 8 ± 2 mL/min/kg; P = 0.02) in DH‐sildenafil than in DH‐saline lambs at 120 min. Throughout the 120‐min ventilation period, the partial pressure of arterial carbon dioxide tended to be lower in DH‐sildenafil lambs than in controls (63 ± 8 vs 87 ± 8 mmHg; P = 0.057), and there was no significant difference in partial pressure of arterial oxygen between the two groups. Conclusions Sustained maternal antenatal sildenafil infusion reduced pulmonary arterial pressure and increased pulmonary blood flow in DH lambs for the first 120 min after birth. These findings of improved pulmonary vascular function are consistent with improved pulmonary vascular structure seen in two previous animal models. The data support the rationale for a clinical trial investigating the effect of antenatal sildenafil in reducing the risk of neonatal pulmonary hypertension in infants with CDH. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

show abstract

“…Physiologically based cord clamping may stabilise gas exchange during neonatal transition among infants with CDH by supporting aeration of the hypoplastic lung and increasing pulmonary blood flow through the thickened pulmonary vasculature before UCC. In an ovine CDH model, ventilation onset before UCC resulted in improved cerebral tissue oxygenation and increased pulmonary blood flow compared with UCC before ventilation 12. A physiologically based approach to UCC for infants with CDH may smooth the postnatal transition and prevent acidosis and hypoxaemia.…”

Section: Introductionmentioning

confidence: 99%

Initiating resuscitation before umbilical cord clamping in infants with congenital diaphragmatic hernia: a pilot feasibility trial

Foglia

Ades

Hedrick

et al. 2019

Arch Dis Child Fetal Neonatal Ed

View full text Add to dashboard Cite

BackgroundInfants with congenital diaphragmatic hernia (CDH) often experience hypoxaemia with acidosis immediately after birth. The traditional approach in the delivery room is immediate cord clamping followed by intubation. Initiating resuscitation prior to umbilical cord clamping (UCC) may support this transition.ObjectivesTo establish the safety and feasibility of intubation and ventilation prior to UCC for infants with CDH. To compare short-term outcomes between trial participants and matched controls treated with immediate cord clamping before intubation and ventilation.DesignSingle-arm, single-site trial of infants with CDH and gestational age ≥36 weeks. Infants were placed on a trolley immediately after birth and underwent intubation and ventilation, with UCC performed after qualitative CO2 detection. The primary feasibility endpoint was successful intubation prior to UCC. Prespecified safety and physiological outcomes were compared with historical controls matched for prognostic variables using standard bivariate tests.ResultsOf 20 enrolled infants, all were placed on the trolley, and 17 (85%) infants were intubated before UCC. The first haemoglobin and mean blood pressure at 1 hour of life were significantly higher in trial participants than controls. There were no significant differences between groups for subsequent blood pressure values, vasoactive medications, inhaled nitric oxide or extracorporeal membrane oxygenation. Blood gas and oxygenation index values did not differ between groups at any point.ConclusionsIntubation and ventilation prior to UCC is safe and feasible among infants with CDH. The impact of this approach on clinically relevant outcomes deserves investigation in a randomised trial.

show abstract

Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia

Cited by 29 publications

References 34 publications

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: a review of current concepts

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: a review of current concepts

Antenatal sildenafil treatment improves neonatal pulmonary hemodynamics and gas exchange in lambs with diaphragmatic hernia

Initiating resuscitation before umbilical cord clamping in infants with congenital diaphragmatic hernia: a pilot feasibility trial

Contact Info

Product

Resources

About