The Effects of Inhaled Nitric Oxide on Postoperative Pulmonary Hypertension in Infants and Children Undergoing Surgical Repair of Congenital Heart Disease

Russell, Isobel A.; Zwass, Maurice S.; Fineman, Jeffrey R.; Balea, Michel; Rouine‐Rapp, Kathryn; Brook, Michael M.; Hanley, Frank L.; Silverman, Norman H.; Cahalan, Michael K.

doi:10.1097/00000539-199807000-00011

Cited by 42 publications

(24 citation statements)

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“…Previous reports have highlighted the complexity of this phenotype (Russell, et al, 1998 ). In these previous reports, age at the time of surgery has been identified as an important factor in the development of elevated PAP, with younger children being at increased risk for this complication (Steinhorn and Fineman, 1999;Schulze-Neick et al, 2001).…”

Section: Discussionmentioning

confidence: 87%

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study

et al. 2007

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Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI). A well-characterized polymorphism in the gene encoding CPSI (T1405N) has previously been implicated in neonatal pulmonary hypertension. A consecutive modeling cohort of children (N=131) with congenital heart defects requiring surgery was prospectively evaluated to determine key factors associated with increased postoperative PAP, defined as a mean PAP > 20mmHg for at least one hour during the 48 hours following surgery measured by an indwelling pulmonary artery catheter. Multiple Dimensionality Reduction (MDR) was used to both internally validate observations and develop optimal two-variable through five-variable models that were tested prospectively in a validation cohort (N= 41). Unconditional logistic regression analysis of the modeling cohort revealed that age (OR= 0.92, p=0.01), CPSI T1405N genotype (AC vs. AA: OR=4.08, p=0.04, CC vs. AA: OR=5.96, p=0.01), and Down syndrome (OR=5.25, p=0.04) were independent predictors of this complex phenotype. MDR predicted that the best two-variable model consisted of age and CPSI T1405N genotype (p<0.001). This two-variable model correctly predicted 73% of the outcomes from the validation cohort. A five-variable model that added race, gender and Down's syndrome was not significantly better than the two-variable model. In conclusion, the CPSI T1405N genotype appears to be an important new factor in predicting susceptibility to increased PAP following surgical repair of congenital cardiac defects in children.

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Section: Discussionmentioning

confidence: 87%

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study

et al. 2007

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“…17 Other studies demonstrate its effectiveness in the management of postoperative pulmonary hypertension in congenital heart disease patients. 18,19 Large multi-center trials have demonstrated that INO reduces the need for extracorporeal membranous oxygenation in newborns with persistent pulmonary hypertension. 20,21 Given the high cost of INO and the lack of demonstrable effect on mortality, utilization of a protocol to minimize costs without adversely affecting outcomes is prudent.…”

Section: Discussionmentioning

confidence: 99%

Implementation of an Inhaled Nitric Oxide Protocol Decreases Direct Cost Associated With Its Use

Tzanetos

Housley

Barr³

et al. 2015

Respir Care

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BACKGROUND: The objective of this study was to determine whether the implementation of an inhaled nitric oxide protocol (INO) in a pediatric ICU (PICU) would reduce cost associated with its use without negatively affecting patient outcomes. METHODS: This is a retrospective cohort study of 76 subjects who required INO therapy in the PICU during the study period. A nitric oxide setup and weaning protocol was implemented in the PICU. The medical records of subjects who had received INO 18 months after protocol implementation, as well as the medical records of subjects who had received INO in the 18 months before protocol implementation, were reviewed. Length of time on INO, cost of INO per subject, mortality, stay, and ventilator hours were recorded. RESULTS: There were 38 subjects in the pre-protocol group and 38 subjects in the post-protocol group. There was a statistically significant decrease in the median per subject cost of INO between the pre-and post-protocol groups (P < .01). There was no statistically significant difference in the median duration of INO use (P ‫؍‬ .06), median PICU (P ‫؍‬ .42) or hospital (P ‫؍‬ .58) stay, median duration of mechanical ventilation (P ‫؍‬ .79) or percent mortality (P ‫؍‬ .28) between the 2 groups. CONCLUSIONS: Implementation of an INO setup and weaning protocol in a PICU reduces the cost associated with its use without a statistically significant difference in mortality. In an era of increased awareness regarding healthcare spending, implementation of evidence-based protocols can provide a way to ensure the judicious utilization of medical resources.

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“…[6,7] The first reported randomized clinical trial was conducted by Russell et al, and included 35 patients with specific congenital heart defects and documented preoperative PH. [8] These patients, who were to undergo cardiopulmoFive Group I patients died in the early postoperative period; 2 had complete atrioventricular septal defect, 1 had TA, and 2 had hypoplastic left heart syndrome. One patient with complete atrioventricular septal defect and 1 with TA died from persistent pulmonary hypertensive crisis.…”

Section: Discussionmentioning

confidence: 99%

Use of inhaled nitric oxide in pediatric cardiac intensive care unit

Öztürk¹

2016

Arch Turk Soc Cardiol

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Objective: Experience with administration of inhaled nitric oxide (iNO) in pediatric cardiac intensive care unit was retrospectively reviewed. Methods:Data from 32 pediatric patients treated with iNO between 2011 and 2012 were collected. Patients were divided into 3 groups: Group I comprised postoperative patients, Group II comprised newborns with persistent pulmonary hypertension (PPH), and Group III comprised patients with primary pulmonary hypertension (PH) or Eisenmenger's syndrome. Age, sex, weight, primary diagnosis, arterial blood sample, pulmonary artery pressure (PAP), systemic arterial pressure (SAP), and oxygen saturation levels were analyzed.Results: Groups I, II, and III included 25, 3, and 4 patients, respectively. Median weight was 8 kg (range: 3-40 kg), and median age was 7 months (range: 2 days-10 years). On average, iNO treatment was initiated at the 12th hour after admission to the unit (range: 1-48 hours) and continued for a median duration of 24 hours (range: 12-168 hours). Systolic PAP was 40±15 mmHg, mean SAP was 57±18 mmHg, PAP/SAP ratio was 0.69, and oxygen saturation levels were 88% prior to iNO treatment. Following iNO treatment, PAP decreased to 24±9 mmHg (p<0.05), PAP/SAP ratio decreased to 0.4 (p<0.05), SAP showed no change (60±12 mmHg), and saturation levels increased to 98% (p<0.05). Seven patients died during follow-up (Group I, n=5; Group II, n=1; Group III, n=1).Conclusion: iNO seems to effectively reduce PAP, and can be used effectively and safely to prevent pulmonary hypertensive crises in pediatric cardiac intensive care units. Amaç:Bu çalışmada pediatrik kardiyoloji yoğun bakım ünitesi'nde tedavi amaçlı inhale nitrik oksit (iNO) kullanılan olgular değerlendirildi.Yöntemler: 2011-2012 yılları arasında pediatrik kardiyoloji yoğun bakım ünitesinde iNO kullanılan 32 olgu çalışmaya alındı. Hastalar üç gruba ayrıldı. Grup I (ameliyat sonrası hastalar), Grup II (diretken pulmoner hipertansiyonlu yenidoğan hastalar), Grup III (primer hipertansiyon veya Eisenmenger Sendrom'lu hastalar). Yaş, cinsiyet, ağırlık, primer tanı, kan örneği, pulmoner arter basıncı (PAB), sistemik arteryel basınç (SAB), oksijen satürasyonu değerleri incelendi. Bulgular: Grup I'de 25 olgu, Grup II'de 3 olgu, Grup III'te 4 olgu mevcuttu. Olguların ortanca yaşı 7 ay (dağılım, 2 gün-10 yaş) ve ortanca ağırlığı 8 kg (dağılım, 3-40 kg) idi. iNO ortanca başlama zamanı 12 saat (dağılım, 1-48 saat) ve ortanca kullanım süresi 24 saat (dağılım, 12-168 saat) idi. İNO öncesi ortalama sistolik PAB 40±15 mmHg, ortalama SAB 57±18 mmHg, PAB/SAB=0.69, oksijen satürasyonu %88'idi. Olguların iNO sonrası PAB 24±9 mmHg, SAB 60±12 mmHg, PAB/SAB=0.40, oksijen satürasyonu %98'idi. Pulmoner arter basıncı ve PAB/SAB oranı anlamlı olarak düşerken, satüras-yonda yükselme saptandı (p<0.05). Yedi hasta takip sırasında kaybedildi (Grup I, n=5; Grup II, n=1; Grup III, n=1

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The Effects of Inhaled Nitric Oxide on Postoperative Pulmonary Hypertension in Infants and Children Undergoing Surgical Repair of Congenital Heart Disease

Abstract: In a randomized double-blind study, inhaled nitric oxide selectively reduced pulmonary artery pressures in pediatric patients who developed pulmonary hypertension (high blood pressure in the lungs) immediately after cardiopulmonary bypass and surgical repair.

Cited by 42 publications

References 10 publications

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study

Implementation of an Inhaled Nitric Oxide Protocol Decreases Direct Cost Associated With Its Use

Use of inhaled nitric oxide in pediatric cardiac intensive care unit

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