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PubMed2004

Measurement of the ductal L-R shunt during extracorporeal membrane oxygenation in the lamb.

OBJECTIVE: In neonates, initially a ductal shunt is often observed during veno-arterial extracorporeal membrane oxygenation (ECMO). Depending on the degree of pulmonary hypertension in these patients, the ductal shunt will be right to left (R-L), left to right (L-R), or bidirectional. A ductal L-R shunt will possibly lead to pulmonary hyperperfusion and interact with ECMO weaning. The aim of this study was to give more insight in this ductal L-R shunt during ECMO by quantification of this shunt in relation to cardiac output and ECMO flow. METHODS: In 7 lambs, closure of the duct was prevented by infiltration of the ductal wall with 10% formaline. This patent duct could be closed using a vesselloop around the duct. Ultrasound flowprobes were installed around the pulmonary artery, ascending aorta, and around the ECMO circulation tube. Right and left ventricular output and ECMO flow were measured. Ductus flow was defined as ductal left to right shunt (Qduct L-R) = flow in ascending aorta (Qao) - flow in central pulmonary artery (Qpa) and Qduct R-L = Qpa = Qao. RESULTS: In 6 of 7 lambs a ductal L-R shunt was observed with a mean shunt of 44% (range, 11 to 79) of left ventricular output (Qduct L-R/Qao). Comparison with ECMO flow (Qduct L-R/Qecmo) showed a mean shunt of 76% (range 15 to 230). When compared with the total systemic circulating volume (Qpa + flow in the ECMO circuit [Qecmo]), the mean ductal L-R shunt showed a percentage of 51% (range, 7% to 142%). CONCLUSIONS: During ECMO, mostly a ductal L-R shunt is observed in this lamb model. This ductal shunt is hemodynamically important. The percentages of this shunt in comparison with left ventricular output, and total circulating volume will support the idea that a ductal L-R shunt during ECMO could be another deteriorating factor in the often critical circulation of the neonate on veno-arterial ECMO.

Animals↗
PubMed2004

Venovenous extracorporeal membrane oxygenation in neonatal respiratory failure: does routine, cephalad jugular drainage improve outcome?

BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO), may be life saving for infants with severe respiratory failure, and when possible, veno-venous bypass through a jugular double lumen cannula, can be expected to provide satisfactory support for most patients. Some ECMO centers favor routine placement of a cephalad jugular cannula for the theoretical benefits of augmented (desaturated) venous return, reduction of atrial recirculation, and cerebral venous decompression. The purpose of this study was to querie the ELSO registry for patients who had undergone VV-ECMO and compare outcomes for patients with a double lumen cannula only (VVDL), with those who had both a double lumen and cephalad jugular cannula (VVDL + V). METHODS: With institutional review board (IRB) approval, the Extracorporeal Life Support Organization (ELSO) registry (Ann Arbor, MI) was queried from January 1, 1989 to December 31, 2001, and all "neonatal respiratory" patients undergoing VV-ECMO via either the VVDL or VVDL + V modes were identified. Group comparisons by age, diagnosis, hours on bypass, mean flow rates (Q) at 4 and 24 hours, mean airway pressures (MAP) at initiation and at 24 hours of bypass, complications (including neurologic and cannula-specific), need for conversion to veno-arterial (VA) ECMO, and survival were performed. A similar analysis was performed on a congenital diaphragmatic hernia (CDH) patient subgroup. Student's t tests were used to compare means between groups, with P values of less than.05 considered significant. RESULTS: The querie generated a total of 2,471 patients: 2,379 (96.3%) VVDL, and 92 (3.7%) VVDL + V. The groups were comparable with the only significant differences being a higher mean airway pressure at 24 hours of bypass and a more frequent use of inotropes during extracorporeal life support (ECLS) in the VVDL + V group. Comparison of a CDH patient subset (280 from the VVDL group and 25 from the VVDL + V group) showed the following significant differences: more frequent use of inotropes, higher MAP at 24 hours, and higher mean flow rates at 4 and 24 hours, all in the VVDL + V group. Patient outcomes, including survival, complications, and rates of conversion to VA bypass were comparable between like groups. CONCLUSIONS: The theoretical benefits of routine placement of a cephalad jugular cannula during VV-ECMO via a jugular double lumen cannula are not substantiated by critical analysis of ELSO data.

Catheterization, Central Venous↗
PubMed2005

A proposal of new therapeutic strategy for antenatally diagnosed congenital diaphragmatic hernia.

PURPOSE: The prognosis of antenatally diagnosed congenital diaphragmatic hernia (ADCDH) is still very poor despite of innovation of various therapeutics. The authors reviewed their new therapeutic strategy of ADCDH from a viewpoint of cardiologic function. METHODS: The cardiac function in 19 cases of ADCDH was reviewed. The patients, at the age of 0 days, were divided into 2 groups, PG (+) and PG (-), according to the requirement of prostaglandin E1 (PGE1) to attenuate pulmonary hypertension. The left ventricular (LV) end-diastolic dimension (LV diastolic diameter index [LVDI]) and bilateral pulmonary arterial diameters (total pulmonary artery index [TPAI]) were measured on days 0 and 2. RESULT: Only 1 patient died of cardiac or respiratory failure, and the survivors' postoperative course was uneventful. Eleven patients needed inhalation of nitric oxide (NO), and in 9 of those, PGE1 was administered. The LVDI and TPAI of day 0 in PG (+) were significantly smaller than those in PG (-) and the controls. The LVDI increased from postnatal day 0 to day 2 in both PG (+) and PG (-). Although the LV was too small to output enough volume, the right ventricle successfully compensated for the low output through the ductus arteriosus, kept patent by NO and PGE1. CONCLUSION: For ADCDH with sever pulmonary hypertension, keeping patent ductus arteriosus with NO and PGE1 plays a critical role in obtaining excellent clinical outcome. Thus, the authors proposed a new therapeutic strategy for ADCDH based on a circulatory management.

Alprostadil↗
PubMed2026

Meta-analysis of prostacyclin therapy for persistent pulmonary hypertension with congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the efficacy and safety of prostacyclin in the treatment of persistent pulmonary hypertension in congenital diaphragmatic hernia. METHODS: A systematic literature search was conducted in four main databases (PubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The protocol was registered in advance in the International Prospective of Systematic Reviews (CRD420261325458). RESULTS: A total of nine studies were included involving a total of 7009 infants in this systematic review and meta-analysis. GRADE assessment revealed substantial heterogeneity in the quality of evidence across outcomes, with most outcomes rated very low quality and only one rated moderate quality. Studies were performed meta-analysis, which showed the use of prostacylin resulted a statistically significant decrease in the OI compared to the control group (Mean Difference (MD), 9.34; I2 0%; p < 0.00001), no statistically significant in mortality (OR, 0.83; I2 84%; p = 0.70), ECMO (OR = 4.9; I2 98%; p = 0.27), BNP (std MD, 6.98; I2 98%; p = 0.31), FiO2 (SMD = 8.0;, I2 64%; p = 0.11), Systolic orientation of IVS curvature (SMD = 0.69; I2 97%; p = 0.32), Diastolic orientation of IVS differences (MD = 0.62; I2 93% p = 0.26). After applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. CONCLUSION: In conclusion, this meta-analysis has confirmed that prostacyclin may temporarily improve oxygenation. However, after applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. Further validation through high-quality studies are still needed. TRIAL REGISTRATION: PROSPERO: CRD420261325458.

Humans↗
PubMed2003

Molecular mechanisms of nitric oxide-induced growth arrest and apoptosis in fetal pulmonary arterial smooth muscle cells.

Superoxide plays an important role in pulmonary arterial smooth muscle cell (SMC) proliferation and survival. The rapid reaction between superoxide and nitric oxide (NO) to form peroxynitrite suggests that endothelium-derived NO may influence adjacent SMC growth. To investigate this possibility, we determined the dose-dependent effects of NO on the proliferation and viability of pulmonary arterial SMC isolated from fetal lambs (FPASMC). Using fluorescence microscopy we found a dose-dependent decrease in superoxide levels in FPASMC treated with the NO donor spermine NONOate. This was associated with an increase in peroxynitrite-mediated protein nitration. At doses between 50 and 250 microM, spermine NONOate attenuated serum-induced FPASMC proliferation resulting in a G(0)/G(1) cell cycle arrest. This process involved a decrease in levels of cyclin A and an increase in the nuclear localization of p21 and p27. Furthermore, 500 microM spermine NONOate decreased viable cell number by inducing programmed cell death: FPASMC treated with 500 microM spermine NONOate displayed a loss of mitochondrial membrane potential, followed by caspase activation and DNA fragmentation. These data suggest that NO inhibits superoxide-induced proliferation of FPASMC and at higher doses induces apoptosis. NO donors may therefore prove to be useful therapeutic tools to treat diseases resulting from excessive proliferation of vascular smooth muscle.

Animals↗
PubMed2006

Persistent pulmonary hypertension of the newborn.

In utero, fetal pulmonary vascular resistance (PVR) is high, but rapidly falls after birth. Expansion of the lungs, increase in oxygenation, release of vasoactive mediators, growth factors and remodeling of the vascular wall, all contribute to the reduction in PVR. Persistent pulmonary hypertension of the newborn (PPHN) is defined as a failure of the pulmonary vasculature to relax at birth, resulting in hypoxemia. PPHN is in fact a variety of disorders that have a common presentation. Some of the pathophysiological mechanisms and the therapeutic approaches are discussed below.

Administration, Inhalation↗
PubMed2003

Expression of heme oxygenase-1 and endothelial nitric oxide synthase in the lung of newborns with congenital diaphragmatic hernia and persistent pulmonary hypertension.

BACKGROUND/PURPOSE: Heme oxygenase (HO-1), an inducible isoform of HO is a regulator of vascular tone and cell proliferation through the production of endogenous carbon monoxide (CO). Endothelium-derived nitric oxide (NO) occurs in the endothelial layers of blood vessels and mediates vasorelaxation. Both CO and NO have similar properties and are potent vasodilators. The aim of this study was to examine the expression of HO-1 and endothelial nitric oxide synthase (eNOS) in the Congenital diaphragmatic hernia (CDI) lung. METHODS: RNA was extracted from archival formalin-fixed paraffin-embedded lung tissue from 11 patients with CDH complicated by persistent pulmonary hypertension (PPH). Five age-matched newborns served as controls. Reverse transcription polymerase chain reaction (RT-PCR) was performed using specific primers for human HO-1 and eNOS. Immunohistochemistry using HO-1 and eNOS antibodies was performed and examined using laser scanning microscope. RESULTS: HO-1 and eNOS mRNA expression was significantly decreased in CDH lung compared with controls (P <.05). HO-1 and eNOS immunoreactivity was reduced markedly reduced in the endothelium and arterial wall in the CDH samples compared with normal lung. CONCLUSIONS: Decreased expression of HO-1 and eNOS in the CDH lung suggests deficiency of endogenous NO and CO, which may contribute to altered vascular tone causing PPH.

Analysis of Variance↗
PubMed2003

Complications in infants undergoing surgery for congenital cataract in the first 12 weeks of life: is early surgery better?

PURPOSE: To determine if there is an association between the timing of surgical intervention for congenital cataract within the first 12 weeks of life and the prevalence of postoperative complications. METHODS: We performed a retrospective review of records from 1990 to 2000 of infants who underwent surgery for congenital cataract within the first 12 weeks of life. Eighty eyes in 55 children were involved with a minimum follow up of 6 months. Bilateral cataracts were present in 25 and monocular cataracts in 30 infants. A limbal approach lensectomy-vitrectomy was performed in all infants. Children with aphakia were rehabilitated with contact lens or glasses. Operative and postoperative complications-including glaucoma, nystagmus, strabismus, retinal detachment, and posterior capsule opacification/secondary membranes-were recorded. Ocular and systemic associations were noted. Statistical analysis was carried out with classification and regression trees (CART). RESULTS: The mean age at the time of surgery was 31.5 +/- 23.3 days (median, 26.5; range, 2 to 84). Mean follow up from the time of surgery was 2.85 +/-1.9 years (median, 2; range, 0.5 to 8). Persistent fetal vasculature (persistent hyperplastic primary vitreous) was present in 14 eyes. One infant with bilateral persistent fetal vasculature had bilateral retinal dysplasia and was excluded from the analysis. Glaucoma developed in 12 infants (22%); nystagmus was present in 18 infants (33%); strabismus developed in 28 infants (52%); and secondary membranes developed in 7 eyes (13%). CART analysis suggests that glaucoma is more prevalent in infants when the surgery was performed between 13.5 and 43 days of life (CART = 0.370); nystagmus when surgery is performed between 48 and 84 days of life (CART = 0.500); strabismus when surgery is performed between 55.5 and 84 days of life (CART = 0.600); and secondary membranes when surgery is performed between 26.5 and 40 days of life (CART = 0.4). CONCLUSIONS: Our data suggest that the first 2 weeks of life comprise the most favorable time for decreasing postoperative complications resulting from surgical intervention for infants presenting with cataracts within the first 12 weeks of life.

Cataract↗
PubMed1984

Use of the rebreathing method in the differential diagnosis of congenital heart disease and persistent fetal circulation.

The differential diagnosis of congenital heart disease from persistent fetal circulation is clinically difficult and cardiac catheterization is often needed. The development of a safe, new technique for use of the rebreathing method has allowed the determination of effective pulmonary blood flow, lung tissue volume, lung diffusion capacity and functional residual capacity in 7 critically ill, ventilator-dependent infants at the bedside. Analysis of the data revealed highly significant differences for lung tissue volume and diffusion capacity, a minimally significant difference for effective pulmonary blood flow and no difference for functional residual capacity between the groups. Use of this method allows not only attainment of clinically useful information but also permits better insight into the pathophysiology of the disease state.

Animals↗
PubMed1985

Association of elective repeat cesarean delivery and persistent pulmonary hypertension of the newborn.

Seventy-one cases of persistent pulmonary hypertension of the newborn have been reviewed in an attempt to identify possibly preventable causes. Three groups of infants were identified. The first group consisted of 36 infants with evidence of perinatal asphyxia. The second group was made up of 23 infants who exhibited a variety of associated factors including pneumonia, septic shock, and congenital diaphragmatic hernia. A third group included 12 infants delivered by elective repeat cesarean section. Infants in the third group did not have evidence of perinatal asphyxia, meconium aspiration, or infection. Chest roentgenograms revealed amniotic fluid aspiration in seven cases, retained lung fluid in three cases, and normal findings in two cases. All 12 infants in the third group developed respiratory distress which eventually progressed to respiratory failure and persistent pulmonary hypertension of the newborn. These data suggest that infants of elective repeat cesarean deliveries are at risk for developing persistent pulmonary hypertension of the newborn and constitute a group of patients with a potentially preventable course of events.

Asphyxia Neonatorum↗
PubMed1986

Improving survival in the treatment of congenital diaphragmatic hernia.

Thirty-two infants were treated for congenital diaphragmatic hernia at our institution from 1979 to 1984. Eight were in no or minimal distress at birth and had operative intervention when they were more than 24 hours old; survival was 100%. The remaining 24 neonates required immediate intubation and ventilation followed by operation at less than 12 hours of age. Overall survival was 54%; survival was 31% (4 of 13 patients, Group 1) in the first three years of the series and 82% (9 of 11 patients, Group 2) in the last three years (p less than 0.001). Apgar score, gestational age, birth weight, and incidence of associated congenital heart disease were equal for the two groups (all, p greater than 0.05). The two groups also were examined with reference to alveolar-arterial oxygen differences P(A-a)O2 and mean airway pressure (MAP). The best preoperative P(A-a)O2 was greater than 600 mm Hg for 7 neonates in Group 1 and 6 in Group 2, and survival was 0% and 71%, respectively (p less than 0.001). Infants with a postoperative MAP of 13 cm H2O or greater had a higher mortality (100% in Group 1 and 50% in Group 2, p greater than 0.05). Our treatment protocol was studied to determine those methods related to improved survival. Sodium bicarbonate infusion was used earlier in Group 2 as a prophylaxis against persistent fetal circulation (PFC) (p greater than 0.05). The incidence of severe PFC dropped from 85 to 54% (p greater than 0.05). Higher ventilator rates rather than pressures were used to achieve equally effective ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Apgar Score↗
PubMed1997

Pulmonary hypertension caused by medial hypertrophy associated with aortic stenosis and preductal coarctation.

A 7-month-old female infant with aortic stenosis, preductal coarctation, and pulmonary hypertension underwent operation. Intraoperative lung biopsy revealed marked medial hypertrophy of the pulmonary arterioles. This histopathology is compatible with persistent pulmonary hypertension in the newborn. She is alive about 5 years after the operation, but pulmonary hypertension remains. The pathogenesis is discussed.

Aortic Coarctation↗
PubMed1979

Respiratory paralysis to improve oxygenation and mortality in large newborn infants with respiratory distress.

The nonsynchronous respiratory efforts of neonates with surgically correctable disorders may inhibit effective mechanical ventilation. The records of 25 infants treated with metocurine for muscular paralysis to improve mechanical ventilation were reviewed. All patients were greater than 35 (37.6 +/- 2.1) weeks gestation and 2.27 (2.98 +/- .47) kg. All required ventilatory support with an FiO2 of 100%. The mortality rate of this group of infants was 20% as compared with 73% (p < .001) in a similar group of 26 infants managed without paralysis. In 10 of the 25 infants treated with metocurine, pre- and 1 hr postparalysis paO2 values were available. The mean paO2 prior to paralysis was 62 (45--111) mm Hg and the mean post-paralysis paO2 was 144 (75--227) mm Hg, representing at 132% increase in paO2 (p < .001). The mean dosage for metocurine was 3.5 (1.45--6.79) mg/kg/day; however, those requiring paralysis for greater than 7 days showed a dramatically increasing requirement. These preliminary data suggest that respiratory paralysis reduces right-to-left shunting, improves paO2 and decreases mortality in large infants with severe respiratory distress requiring ventilatory support.

Diaphragm↗
PubMed1980

An analysis of tolazoline therapy in the critically-ill neonate.

There were 47 seriously-ill neonates with medical causes of respiratory distress and 10 infants with severe respiratory distress secondary to a congenital diaphragmatic hernia treated with tolazoline according to a strict protocol designed to manage persistent fetal circulation (PFC). Of the 47 infants, 28 (60%) had a positive response defined as an increase in the pO2 greater than or equal to 24 mm Hg within 4 hr of beginning the drug. Of 7 infants, 4 with congenital diaphragmatic hernia had a positive response. The mean increase in the pO2 for the 47 infants was statistically significant (p less than .05). Of the 47 infants with medical disorders, 27 survived (survival 57%), whereas only 2 of the 10 infants with congenital diaphragmatic hernia and severe persistent fetal circulation survived (survival 28%). Erythema (60%), hematest positive gastric aspirates (55%), thrombocytopenia (45%), hyponatremia (40%) and increased gastric aspirates (36%) were the most common adverse effects occurring during tolazoline infusion. Hypotension occurred in nine cases, but was transient. Of the 27 survivors, 20 with medical causes of persistent fetal circulation were evaluated at age 1 yr. Eighty percent of these infants studied were considered normal as defined by an MDI and PI of the Bayley Scales of greater than or equal to 70. These data suggest that tolazoline is a useful adjunct in the management of neonates with PFC. In addition, tolazoline was more effective in mechanically ventilated neonates treated with respiratory paralytic agents. Although tolazoline resulted in a significant improvement in the paO2 in 4 infants with congenital diaphragmatic hernia, it did not appear to improve mortality in these infants.

Erythema↗