Inhaled nitric oxide improves hemodynamics in patients with acute pulmonary hypertension after high-risk cardiac surgery

Severe pulmonary hypertension and right-sided circulatory failure (RSCF) represent an increasing cause of morbidity and mortality in patients undergoing high-risk cardiac surgery. Increased pulmonary vascular resistance in the setting of cardiopulmonary bypass (CPB) may further lead to decrease blood flow across the pulmonary vascular bed; thereby decreasing left ventricular filling and cardiac output. Current management techniques for RSCF include both nonspecific vasodilator and inotropic agents (often limited by systemic hypotension) and the placement of right ventricular assist devices (associated with increased perioperative morbidity). Inhaled nitric oxide (NOi) represents a novel, specific pulmonary vasodilator that has been proven efficacious in these clinical settings. We evaluated 34 patients in 38 operations who underwent cardiac surgery at Columbia Presbyterian Medical Center, and who received NOi (20 ppm) through a modified ventilatory circuit for hemodynamically significant elevations in pulmonary vascular resistance. Nine patients underwent cardiac transplantation, three patients bilateral lung transplantation, 16 patients left ventricular assist device placement and 10 patients routine cardiac surgery. Patients receiving NOi exhibited substantial reductions in mean pulmonary artery pressure (mPAP) (34.6 +/- 2.0 to 26.0 +/- 1.7 mmHg, p < 0.0001), with improvements in systemic hemodynamics, mean arterial pressure (68 +/- 3.1 to 75.9 +/- 2.0 mmHg, p = 0.006). In five cases, patients could not be weaned from CPB until NOi was administered. Patients were maintained on NOi from 6 to 240 h postoperatively (median duration 36 h). Inhaled NO induces substantial reductions in mPAP and increases in both cardiac index and systemic blood pressure in patients displaying elevated pulmonary hemodynamics after high-risk cardiac surgery. NO is, therefore, a useful adjunct in these patients in whom acute pulmonary hypertension threatens right ventricular function and hemodynamic stability.     

Comparison of inhaled and intravenous milrinone in patients with pulmonary hypertension undergoing mitral valve surgery

Introduction  Increased pulmonary vascular resistance (PVR) is detrimental to cardiac output in postoperative cardiac-surgery patients. The aim of this study was to investigate the postoperative hemodynamic effects of milrinone inhalation, and determine whether it has a selective effect of pulmonary vasodilation in patients with pulmonary hypertension undergoing mitral valve replacement surgery. Methods  In this study, 48 patients with pulmonary hypertension who underwent mitral valve replacement surgery were included. Patients were randomly divided into two groups with 24 patients in each: the inhaled group and the control group (intravenous [i.v.] milrinone). In the inhaled group, milrinone was administered with a jet nebulizer, and nebulized for 4 hours. In the control group, patients received a bolus of 50 μg/kg i.v. milrinone, then received a continuous milrinone infusion, 0.5 μg/kg/min, for 4 hours. A number of hemodynamic changes in all patients were evaluated. Results  With milrinone administration, mean pulmonary artery pressure (MPAP) and PVR showed a comparable decrease in both groups. However, after initiation of milrinone, both mean arterial pressure and systemic vascular resistance in the inhaled group were significantly higher than in the control group. MPAP and PVR returned to baseline values 60 minutes after termination of milrinone inhalation. In addition, in the inhaled group, there was a reduction in intrapulmonary shunt fraction (Qs/Qt), with an improvement in PaO₂/FiO₂ (arterial oxygen tension/fraction of inspired oxygen). Conclusion  The major advantage of inhaled milrinone is its pulmonary selectivity, thereby avoiding systemic side effects and ventilationperfusion mismatch. Inhaled milrinone is an effective pulmonary vasodilator and appears to be an alternative promising approach in addressing the problem of right-ventricular decompensation following cardiopulmonary bypass.     

Comparison of inhaled nitric oxide with aerosolized iloprost for treatment of pulmonary hypertension in children after cardiopulmonary bypass surgery

Objectives  

Pilot study to compare the effect of inhaled nitric oxide (iNO) and aerosolized iloprost in preventing perioperative pulmonary hypertensive crises (PHTCs).     

风湿性二尖瓣狭窄并重度肺动脉高压患者的术后监护

目的回顾性总结62例风湿性二尖瓣狭窄并重度肺动脉高压行二尖瓣置换术患者的术后监护经验。方法本组均为在全麻低温体外循环下施行二尖瓣置换术的术后患者,术后入住ICU监护,带呼吸机时间最短10 h,最长72h,平均38h。常规持续动态监测肺动脉压的变化,呼吸机支持呼吸及加强呼吸道管理,心功能的维护及减少肺渗出。结果术后并发肺动脉高压危象5例,心律失常3例,呼吸衰竭并肺部感染2例;经采取积极的治疗和护理措施,全部治愈出院。结论对术后患者持续动态监测肺动脉压的变化,控制肺动脉高压和预防肺动脉高压危象对提高风湿性二尖瓣狭窄并重度肺动脉高压患者的手术成功率起重要作用。     

Combined therapy with zaprinast and inhaled nitric oxide abolishes hypoxic pulmonary hypertension

OBJECTIVE: To determine whether the combination of the phosphodiesterase 5 inhibitor zaprinast and inhaled nitric oxide (NO) decreases hypoxic pulmonary hypertension in the rat. DESIGN: Prospective, experimental study. SETTING: Animal laboratory of a university medical center. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Anesthetized rats were mechanically ventilated and instrumented for measurement of mean systemic arterial pressure, pulmonary arterial pressure, and cardiac output. In group 1, four acute hypoxic challenges (FIO2 = 0.17 for 5 mins) were performed: initial, during 40 ppm inhaled NO, immediately after discontinuation of 5 mins of inhaled NO, and final. In group 2 rats, an initial hypoxic challenge was performed and rats then received zaprinast (3 mg/kg bolus followed by 0.3 mg/kg/min infusion). Four hypoxic challenges analogous to group 1 were then performed during zaprinast administration. MEASUREMENTS AND MAIN RESULTS: Initial hypoxic challenge produced similar increases in pulmonary arterial pressure in both groups. In group 1, inhaled NO either only before or only during hypoxia decreased the pulmonary hypertensive response to hypoxia. In group 2, zaprinast administration did not alter hemodynamics. Zaprinast alone decreased the pulmonary hypertensive response to hypoxia. The combination of zaprinast and inhaled NO (either before or during hypoxia) abolished the pulmonary hypertensive response to hypoxia. CONCLUSIONS: Treatment with inhaled NO for 5 mins before but not during hypoxia is as effective as inhaled NO during hypoxia. Inhaled NO and zaprinast both decrease the pulmonary hypertensive response to hypoxia, and the combination abolishes the response. The combination of a phosphodiesterase 5 inhibitor and inhaled NO may have clinical applicability in the treatment of pulmonary hypertension.     

Methemoglobin formation in children with congenital heart disease treated with inhaled nitric oxide after cardiac surgery

OBJECTIVE: Inhaled nitric oxide (NO) is used as a therapy of pulmonary hypertension in children after cardiac surgery. Hemoglobin binds to NO with great affinity and forms methemoglobin by oxidation in the erythrocyte. Once produced, methemoglobin is unable to transport and unload oxygen in the tissues. The amount of available hemoglobin in the body for oxygen transport is thereby reduced. Anemia, acidosis, respiratory compromise and cardiac disease may render patients more susceptible than expected for a given methemoglobin level. The goal of the present study was to review the cumulative effect of inhaled NO on methemoglobin formation in critically ill children. We therefore looked for methemoglobin levels in children with congenital heart disease after cardiac surgery who were treated with inhaled NO in a range of 5-40 ppm. METHODS: We retrospectively reviewed the medical charts of 38 children with congenital heart disease after cardiac surgery. We extracted demographic data and physiological measurements at the following time points: (1) T0 = before starting inhaled NO therapy, (2) T1 = 24 h after the beginning of inhaled NO therapy, (3) T2 = half-time therapy, (4) T3 = end of therapy, (5) T4 = 24 h after finishing inhaled NO therapy. RESULTS: The median duration of inhaled NO therapy was 5.5 days (interquartile range 6, range 2-29), NO concentrations at T1 and T2 were 16 ppm (10, 5-40) and 12.5 ppm (12.3, 2-40), respectively. The median cumulative dose of inhaled NO was 1699 ppm (2313, 193-7018). Methemoglobin levels increased moderately, but significantly, during therapy ( T0 vs T1 p<0.05 and T0 vs T2 p<0.001). The highest methemoglobin level measured was 3.9%. Methemoglobin levels correlated positively with the inhaled NO doses applied at T1 ( r(2)=0.8376; p<0.01) and at T2 ( r(2)=0.8945; p<0.01). At T1 the methemoglobin level correlated negatively with the T1 blood pH value. The overall mortality rate was 13.2% (5 of 38 study patients died). There was no significant difference in methemoglobin levels between survivors and non-survivors. CONCLUSION: We conclude from our data that the use of inhaled NO therapy for children with congenital heart disease after cardiac surgery in the described range of 5-40 ppm, resulting in a maximum of 4% methemoglobin blood level, is feasible and safe. However, we recommend the use of the minimal effective dose of inhaled NO and continuous monitoring of methemoglobin levels, especially in cases of anemia or sepsis in critically ill children.     

Relief of severe pulmonary hypertension after closure of a large ventricular septal defect using low dose inhaled nitric oxide

A 16-month-old girl developed severe pulmonary hyptertension after closure of a large ventricular septal defect. All conventional therapeutic measures failed; an attempt to add nitric oxide at a continous low dose to the inspired gas allowed resolution of pulmonary hypertension and low cardiac output. This report documents that continuous inhalation of low dose nitric oxide is capable of selective resolution of pulmonary hypertension following cardiac surgery for a large septal defect in a child. This suggests that a transient dysfunction in the release of nitric oxide by the pulmonary endothelial cell is responsible for the vasoconstriction.     

肺表面活性物质结合一氧化氮吸入治疗新生儿持续肺动脉高压的护理

总结11例新生儿持续肺动脉高压患儿肺表面活性物质气管内滴入结合一氧化氮(NO)吸入治疗的护理体会。主要护理措施包括注意正确清理呼吸道,配合医师使用肺表面活性物质(PS),重点加强NO使用过程中的护理及气道管理,密切观察不良反应。本组4~7d成功撤除呼吸机,未出现不良反应。     

Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery

Objective To investigate the acute effects of intravenous sildenafil on haemodynamics and oxygenation, and its interaction with inhaled nitric oxide (iNO) in infants at risk of pulmonary hypertension early after cardiac surgery.Design Prospective, randomised trial. Setting Paediatric intensive care unit of a childrens hospital.Patients and participants Sixteen ventilated infants early after closure of ventricular or atrioventricular septal defects, were randomly assigned to one of two groups. The study was completed in 15 infants.Interventions Studies were commenced within 7 h of separation from bypass. Seven infants received iNO (20 ppm) first, with the addition of intravenous sildenafil (0.35 mg/kg over 20 min) after 20 min. Eight infants received sildenafil first, iNO was added after 20 min. Vascular pressures, cardiac output and a blood gas were recorded at 0, 20 and 40 min.Measurements and results In infants receiving iNO first, iNO lowered the pulmonary vascular resistance index (PVRI) from 3.45 to 2.95 units (p=0.01); sildenafil further reduced PVRI to 2.45 units (p<0.05). In those receiving sildenafil first, PVRI was reduced from 2.84 to 2.35 units (p<0.05) with sildenafil, and fell to 2.15 units (p=0.01) with the addition of iNO. In both groups, sildenafil reduced the systemic blood pressure and systemic vascular resistance (p<0.01) and worsened arterial oxygenation and the alveolar-arterial gradient (p<0.05).Conclusion Intravenous sildenafil augmented the pulmonary vasodilator effects of iNO in infants early after cardiac surgery. However, sildenafil produced systemic hypotension and impaired oxygenation, which was not improved by iNO.     

心脏外科肺动脉高压患者围手术期一氧化氮的吸入治疗

目的 探讨一氧化氮(NO)吸入治疗对合并肺动脉高压心脏外科围手术期患者的有效性与安全性.方法 应用Servo 300A呼吸机或Aeronox NO释放与监测仪,对合并肺动脉高压且临床常规治疗效果不理想的27例成人和1例房间隔缺损修补术患儿进行围手术期NO吸入治疗,NO开始剂量(5～10)×10-6,然后根据病情可缓慢升高至20×10-6.于治疗前后监测患者的肺动脉压(PAP)、动脉压(AP)、肺血管阻力(PVR)和氧合指数(PaO2/FiO2).NO吸入治疗的有效标准为治疗开始后1 h内AP/PAP改善20%以上,或PaO2/FiO2改善20%以上.NO吸入治疗1.5 h后无效者终止该方法.结果 成人患者NO吸入治疗有效率为77.8%(21/27例),治疗持续时间为12～96 h,平均(32.6±10.3)h.1例房间隔缺损合并中度肺动脉高压患儿在房间隔缺损修补术后,肺动脉高压加重,合并严重的低氧血症[PaO2/FiO2为40 mm Hg(1 mm Hg=0.133 kPa),吸入氧浓度(FiO2)为1.00],经NO吸入等综合治疗后效果明显,4 d后撤离呼吸机.治疗中与治疗后,在患者与工作人员中未发现不良事件.结论 NO吸入治疗对心脏外科合并肺动脉高压围手术期病情加重者治疗有效,值得进一步临床探索.     

Additive effects of inhaled nitric oxide and intravenous milrinone in experimental pulmonary hypertension

OBJECTIVE: To determine whether inhaled nitric oxide (IN0) and intravenous milrinone have additive pulmonary vasodilator effects in a rat model of pulmonary hypertension. DESIGN: Prospective, experimental study. SETTING: Animal laboratory of a university medical center. SUBJECTS: Male New Zealand White rabbits. INTERVENTIONS: Anesthetized rabbits were mechanically ventilated and instrumented for measurement of systemic mean arterial pressure (MAP), pulmonary artery pressure (PAP), left atrial pressure, and cardiac output (CO). After baseline measurements, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg iv) was administered. Pulmonary hypertension was produced by the continuous infusion of U46619, a thromboxane A2 mimetic. INO (40 ppm) was added to the inspired gas, and hemodynamic measurements were obtained before and after INO. Milrinone was administered sequentially as a 30-mg/kg bolus followed by a 3-microg/kg/min infusion, a 100-mg/kg bolus followed by a 10-microg/kg/min infusion, and a 300-mg/kg bolus followed by a 30-microg/kg/min infusion (M3). Hemodynamic measurements were obtained with and without INO at each dose of milrinone. MEASUREMENTS AND MAIN RESULTS: During U46619-induced pulmonary hypertension, INO decreased PAP and pulmonary vascular resistance (PVR) but did not affect MAP, systemic vascular resistance (SVR), or CO. Milrinone dose dependently decreased PAP, PVR, MAP, and SVR and increased CO. At each dose of milrinone, INO further decreased PVR but not SVR. M3 decreased PVR 49%, and the addition of INO decreased PVR an additional 19% so that PAP and PVR decreased to baseline values. CONCLUSIONS: Milrinone and INO both decrease pulmonary hypertension individually, and the combination produces additive effects. Combination therapy may produce potent and selective pulmonary vasodilation during the treatment of pulmonary hypertension.     

Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease

BACKGROUND: Pulmonary hypertension is associated with congenital heart lesions with increased pulmonary blood flow. Acute increases in pulmonary vascular resistance (PVR) occur in the postoperative period after repair of these defects. These increases in PVR can be ablated by inducing an alkalosis with hyperventilation (HV) or bicarbonate therapy. Studies have shown that these patients also respond to inhaled nitric oxide (iNO), but uncertainty exists over the relative merits and undesirable effects of HV and iNO. HYPOTHESIS: Alkalosis and iNO are equally effective in reducing PVR and pulmonary artery pressure (PAP) in children with pulmonary hypertension after open heart surgery. SETTING: Critical care unit of a tertiary care pediatric hospital. DESIGN: Prospective, randomized, crossover design. PATIENTS: Twelve children with a mean PAP > 25 mm Hg at normal pH after biventricular repair of congenital heart disease. INTERVENTIONS: Patients were assigned to receive iNO or HV (pH > 7.5) in random order, and the effect on hemodynamics was measured. Each treatment was administered for 30 mins with a 30-min washout period between treatments. Finally, both treatments were administered together to look for a possible additive effect. MEASUREMENTS AND MAIN RESULTS: Cardiac output and derived hemodynamic parameters using the dye dilution technique. Hyperventilation, achieved by an increase in ventilator rate without a change in mean airway pressure, decreased Pa(CO2) from a mean (SD) of 43.7+/-5.3 to 32.3+/-5.4 mm Hg and increased pH from 7.40+/-0.04 to 7.50+/-0.03. This significantly altered both pulmonary and systemic hemodynamics with a reduction in PAP, PVR, central venous pressure, and cardiac output and an increase in systemic vascular resistance. In comparison, iNO selectively reduced PAP and PVR only. The reduction in PVR was comparable between treatments, although addition of iNO to HV resulted in a small additional reduction in PVR. An additional decrease in PAP was seen when HV was added to iNO, attributable to a reduction in cardiac output rather than a further decrease in PVR. CONCLUSIONS: Inhaled NO and HV are both effective at lowering PAP and PVR in children with pulmonary hypertension after repair of congenital heart disease. The selective action of iNO on the pulmonary circulation offers advantages over HV because a decrease in cardiac output and an increase in SVR are undesirable in the postoperative period.     

Direct comparison of the effects of nebulized nitroprusside versus inhaled nitric oxide on pulmonary and systemic hemodynamics during hypoxia-induced pulmonary hypertension in piglets

OBJECTIVE: To test the hypothesis that nebulized nitroprusside and inhaled nitric oxide would not differ in producing selective pulmonary vasodilation during hypoxia-induced pulmonary hypertension in piglets. SETTING: University laboratory. SUBJECTS: Five piglets. INTERVENTIONS: Piglets (n = 5) were anesthetized and instrumented to monitor systemic arterial pressure, pulmonary artery pressure, and cardiac output continuously. Hypoxia was induced (DeltaFio2 from 0.5 to 0.08), and either nebulized nitroprusside (5 mg/mL at 4 L/min flow; total dose 25 mg) or inhaled nitric oxide (20 ppm) was introduced into the ventilator circuit for 15 mins. Normoxia was then restored, and a repeat cycle of hypoxia followed by the alternate vasodilator treatment was initiated. MEASUREMENTS AND MAIN RESULTS: Hypoxia significantly reduced Pao2 (from 206 to 30 torr) and elevated pulmonary artery pressure (from 18 to 33 torr) while not significantly affecting systemic arterial pressure or cardiac output. During hypoxia, inhaled nitric oxide reduced pulmonary artery pressure from 33 to 21 torr (p <.01), whereas systemic arterial pressure and cardiac output were unchanged. During hypoxia, nebulized nitroprusside also reduced pulmonary artery pressure from 33 to 23 mm Hg (p <.01; p = nonsignificant vs. inhaled nitric oxide), whereas systemic arterial pressure and cardiac output again remained constant. The time course of the reduction in pulmonary artery pressure during inhaled nitric oxide was roughly ten-fold more rapid (<5 secs) than during nebulized nitroprusside ( approximately 1 min). Neither inhaled nitric oxide nor nebulized nitroprusside altered pH, Pao2, or Paco2. CONCLUSION: Both inhaled nitric oxide and nebulized nitroprusside produced prompt, significant, selective reduction of pulmonary artery pressure and pulmonary vascular resistance in piglets with hypoxia-induced pulmonary hypertension, without apparent effects on systemic hemodynamics or pulmonary gas exchange. The equivalence of the two effects in this animal model suggests that cautious extrapolation of the use of nebulized nitroprusside as a convenient bridge to inhaled nitric oxide in selected clinical contexts for human infants may be warranted.     

Effect of aerosolized prostacyclin and inhaled nitric oxide on experimental hypoxic pulmonary hypertension

Objective: To compare the effect of different concentrations of inhaled nitric oxide and doses of nebulized prostacyclin on hypoxia-induced pulmonary hypertension in pigs.¶Design: Prospective, controlled animal study.¶Setting: Animal research facilities of an university hospital.¶Interventions: After reducing the fraction of inspired oxygen (FIO₂) from 1.0 to 0.1, two groups of five pigs each were submitted to inhalation of three concentrations of nitric oxide (5, 10 and 20 ppm) or three doses of prostacyclin (2.5, 5, 10 ng × kg^–1× min^–1).¶Results: All doses of prostacyclin and concentrations of nitric oxide resulted in a decrease in mean pulmonary arterial pressure and pulmonary vascular resistance when compared to hypoxic ventilation (p < 0.001) which was independent of the dose or concentration of either drug used. While inhalation of nitric oxide caused a reduction in mean pulmonary arterial pressure back to values obtained during ventilation with FIO₂ 1.0, values achieved with prostacyclin were still significantly higher when compared to measurements prior to the initiation of hypoxic ventilation. However, direct comparison of the effect of 20 ppm nitric oxide and 10 ng × kg^–1× min^–1 prostacyclin on mean pulmonary arterial pressure revealed no differences between the drugs. All other hemodynamic and gas exchange parameters remained stable throughout the study.¶Conclusions: Inhalation of clinically used concentrations of nitric oxide and doses of prostacyclin can decrease elevated pulmonary arterial pressure in an animal model of hypoxic pulmonary vasoconstriction without impairing systemic hemodynamics or gas exchange.     

一氧化氮吸入对脓毒症幼猪血流动力学和氧合功能的影响

目的：研究脓毒症幼猪吸入一氧化氮（N0）后心脏指数（CI）与氧合指数的变化。方法：静脉注入革兰氏阴性杆菌内毒素（LPS）诱导脓毒症幼猪模型。随机分为两组：NO组（n＝8）为脓毒症模型建立后,在容量控制通气基础上持续吸入80 ppmNO 30 min;对照组（n＝4）为脓毒症模型建立后单纯容量控制通气,观察30 min以确定模型的稳定性并与NO组比较。利用脉波指示剂连续心排血量监测（PICC0）技术和动脉血气分析,测定各组血流动力学参数和肺气体交换。结果：静脉注射内毒素能够诱导稳定的脓毒症幼猪模型。该模型血气分析指标pH、HCO3－、股动脉血氧分压（PaO2）、平均动脉压（MAP）及心脏指数（CI）均较基础值明显降低（P＜0．01）。NO组PaO2及CI均较吸入前和同时点对照组明显升高（P＜0．01）。NO组及对照组心率（HR）、中心静脉压（CVP）、全心舒张末容积指数（GEDI）及胸腔内血容积指数（ITBI）均无明显变化。结论：吸入NO气体可以改善脓毒症幼猪的心功能及氧合功能。     

Acute ventilatory restriction in children after weaning off inhaled nitric oxide: relation to rebound pulmonary hypertension

Objective: To assess the interaction between pulmonary hemodynamics and respiratory mechanics during acute pulmonary hypertension. Patients: Ventilated and paralysed children treated with inhaled nitric oxide because of post-operative pulmonary hypertension. Interventions: Weaning of inhaled nitric oxide. Measurements: Air flow and airway pressure, calculation of dynamic respiratory system compliance and respiratory system resistance for each breath by multiple linear regression. Results: In four patients, increases in pulmonary arterial pressure from 26.1 to 56.7 mmg (p < 0.001) during weaning off nitric oxide were associated with decreases in tidal volume (from 9.7 → 8.2 ml/kg, p < 0.01) and reductions in dynamic respiratory system compliance (from 0.52 → 0.34 cmH₂0/ml/kg, p < 0.001), while respiratory system resistance was unchanged. Conclusions: Impaired ventilation during acute pulmonary hypertension is predominantly related to a reduction in respiratory system compliance. Received: 26 March 1998 Final revision received: 9 June 1998 Accepted: 30 July 1998     

Adapted ECMO criteria for newborns with persistent pulmonary hypertension after inhaled nitric oxide and/or high-frequency oscillatory ventilation

Purpose

Early prediction of extracorporeal membrane oxygenation (ECMO) requirement in term newborns with persistent pulmonary hypertension (PPHN), partially responding to inhaled nitric oxide (iNO) and/or high-frequency oscillatory ventilation (HFOV), based on oxygenation parameters.

Methods

This was a retrospective cohort study in 53 partial responders from among 133 term newborns with PPHN born between 2002 and 2007. Alveolar-to-arterial oxygen gradient (AaDO₂) values were determined in these 53 partial responders during the initial 72 h of iNO and/or HFOV treatment and compared between newborns who ultimately did (n = 11) and did not (n = 42) need ECMO.

Results

Over 72 h, partial responders not requiring ECMO showed a more profound AaDO₂ decrease than those who needed ECMO (median decline 242.5 mmHg, IQR 144 to 353 mmHg, vs. 35 mmHg, IQR ?15 to 123 mmHg; p = 0.0007). A decline of <123 mmHg over 72 h predicted the need for ECMO (sensitivity 82 %, specificity 79 %). At 72 h, AaDO₂ was significantly lower in partial responders without the need for ECMO than in those who did need ECMO (median 369 mmHg, IQR 258 to 478 mmHg, vs. 570 mmHg IQR 455 to 590 mmHg; p = 0.0008). An AaDO₂ >561 mmHg at 72 h predicted the need for ECMO (sensitivity 64 %, specificity 95 %, positive predictive value 78 %).

Conclusions

In term newborns with PPHN partially responding to iNO and/or HFOV, oxygenation-based prediction of the need for ECMO appears to be possible after 72 h. ECMO centers are encouraged to develop their own prediction model in order to prevent both lung damage and unnecessary ECMO runs.     

Effects of inhaled nitric oxide on pulmonary hemodynamics in a porcine model of endotoxin shock.

OBJECTIVE: To evaluate the effects of inhaled nitric oxide (NO) on pulmonary circulation in a porcine endotoxin shock model. DESIGN: Prospective, randomized trial. SETTING: Laboratory at a large university medical center. SUBJECTS: Twelve pathogen-free pigs weighing 15 to 31 kg. INTERVENTIONS: After surgical preparation, all pigs received a 0.5 mg/kg endotoxin infusion over 30 mins. One hour after the start of endotoxin, NO inhalation (40 ppm) was initiated in six pigs, whereas the six remaining pigs served to control the progression of shock in this model. Consecutive changes in systemic and pulmonary hemodynamics, including characteristic resistance, vascular compliance, peripheral vascular resistance, and inductance, were continuously assessed during the experimental protocol using a four-element Windkessel model of the pulmonary circulation. MEASUREMENTS AND MAIN RESULTS: Endotoxin insult resulted in a biphasic pulmonary artery pressure increase from 14 +/- 2 to 32 +/- 4 mm Hg. Inhaled NO reversed the resistance to blood flow in small pulmonary arteries from 596 +/- 69 to 424 +/- 36 dyne-sec/ cm5. In contrast, the vascular capacitance of the entire pulmonary circuit, which decreased from 2.4 +/- 0.2 to 0.8 +/- 0.1 mL/mm Hg throughout endotoxin challenge, remained insensitive to NO administration. CONCLUSION: In endotoxin-induced pulmonary hypertension, inhaled NO may function as a modulator of distal pulmonary arterial tone but fails to act as a regulator of larger capacitance pulmonary vessels.