Transient Improvement In Oxygenation Research Articles

Acute Respiratory Distress Syndrome and the Use of Inhaled Pulmonary Vasodilators in the COVID-19 Era: A Narrative Review.

The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. COVID-19-associated ARDS (CARDS) differs from the typical ARDS due to distinct pathology involving the pulmonary vasculature endothelium, resulting in diffuse thrombi in the pulmonary circulation and impaired gas exchange. The National Institute of Health and the Society of Critical Care Medicine recommend lung-protective ventilation, prone ventilation, and neuromuscular blockade as needed. Further, a trial of pulmonary vasodilators is suggested for those who develop refractory hypoxemia. A review of the prior literature on inhaled pulmonary vasodilators in ARDS suggests only a transient improvement in oxygenation, with no mortality benefit. This narrative review aims to highlight the fundamental principles in ARDS management, delineate the fundamental differences between CARDS and ARDS, and describe the comprehensive use of inhaled pulmonary vasodilators. In addition, with the differing pathophysiology of CARDS from the typical ARDS, we sought to evaluate the current evidence regarding the use of inhaled pulmonary vasodilators in CARDS.

Tissue plasminogen activator for the treatment of adults with critical COVID-19: A pilot randomized clinical trial

Tissue plasminogen activator for the treatment of adults with critical COVID-19: A pilot randomized clinical trial

OVERUSE OF AEROSOLIZED PROSTACYCLIN IN THE MANAGEMENT OF ARDS

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Prone ventilation is often under-utilized in the management of acute respiratory distress syndrome (ARDS). One potential reason could be due to use of aerosolized prostacyclin which is known to improve the oxygenation status. As a result of improved oxygenation, clinicians may delay other treatment modalities such as proning which has been associated with both improved oxygenation and mortality. Therefore, we aimed to look at our institutions’ use of aerosolized prostacyclin in patients who might be eligible for proning instead. METHODS: We performed a retrospective chart review of patients admitted to the medical intensive care unit (MICU) between 2016 and 2018 for ARDS using the Berlin definition. We enrolled patients only if they were on mechanical ventilation for = 48 hours. We collected the following data: age, gender, body mass index (BMI), PaO2/FiO2 (P/F) ratios on days 1-3, comorbidities, aerosolized prostacyclin use and adjunctive therapies (proning, neuromuscular blockade). We defined patients with BMI = 36 kg/m2 and P/F = 150 as those eligible for proning. RESULTS: Eighty six patients with ARDS were identified of which 41 (48%) received aerosolized prostacyclin. On day 1, twenty four patients had P/F = 150. Amongst this group, 13 (54%) patients eligible for proning continued to receive prostacyclin instead. On day 2, four (31%) out of the 13 patients had P/F = 150 but were not proned. Overall, aerosolized prostacyclin was used in 52% of patients in 2016, 65% of patients in 2017 and 30% of patients in 2018. CONCLUSIONS: We found that aerosolized prostacyclin was administered frequently in managing patients with severe ARDS and proning was under-utilized. This could be due to three reasons: transient improvement in oxygenation after starting prostacyclin therapy thus discouraging the clinician to consider proning, patient’s body habitus and the laborious nature of prone positioning. The reduction in prostacyclin over the 3-year study period use could be due to increased awareness of adjunctive measures for ARDS. Our study did not account for contraindications to proning such as spinal instability, unstable fractures, burns and high intra-cranial pressure; however, at our institution such patients are admitted to the surgical ICU. The major limitations of our study are its small sample size and retrospective methodology. Therefore, the generalizability is limited. In summary, aerosolized prostacyclin use in ARDS treatment continues to remain high. CLINICAL IMPLICATIONS: Overuse of nebulized prostacyclin may lead to under utilization of proning due to the transient improvement of hypoxemia seen with prostacyclin use in the management of ARDS. DISCLOSURES: No relevant relationships by Ryan Hyde, source=Web Response No relevant relationships by Johnny Jaber, source=Web Response No relevant relationships by Saminder Kalra, source=Web Response No relevant relationships by Sarina Parikh, source=Web Response No relevant relationships by Raju Reddy, source=Web Response No relevant relationships by Daniel Urbine, source=Web Response

The effect of inhaled nitric oxide in acute respiratory distress syndrome in children and adults: a Cochrane Systematic Review with trial sequential analysis

Acute respiratory distress syndrome is associated with high mortality and morbidity. Inhaled nitric oxide has been used to improve oxygenation but its role remains controversial. Our primary objective in this systematic review was to examine the effects of inhaled nitric oxide administration on mortality in adults and children with acute respiratory distress syndrome. We included all randomised, controlled trials, irrespective of date of publication, blinding status, outcomes reported or language. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity analyses to assess the effect of inhaled nitric oxide. There was no statistically significant effect of inhaled nitric oxide on longest follow-up mortality (inhaled nitric oxide group 250/654 deaths (38.2%) vs. control group 221/589 deaths (37.5%; relative risk (95% CI) 1.04 (0.9-1.19)). We found a significant improvement in PaO2 /FI O2 ratio at 24 h (mean difference (95% CI) 15.91 (8.25-23.56)), but not at 48 h or 72 h, while four trials indicated improved oxygenation in the inhaled nitric oxide group at 96 h (mean difference (95% CI) 14.51 (3.64-25.38)). There were no statistically significant differences in ventilator-free days, duration of mechanical ventilation, resolution of multi-organ failure, quality of life, length of stay in intensive care unit or hospital, cost-benefit analysis and methaemoglobin and nitrogen dioxide levels. There was an increased risk of renal impairment (risk ratio (95% CI) 1.59 (1.17-2.16)) with inhaled nitric oxide. In conclusion, there is insufficient evidence to support inhaled nitric oxide in any category of critically ill patients with acute respiratory distress syndrome despite a transient improvement in oxygenation, since mortality is not reduced and it may induce renal impairment.

Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults.

Acute hypoxaemic respiratory failure (AHRF) and mostly acute respiratory distress syndrome (ARDS) are critical conditions. AHRF results from several systemic conditions and is associated with high mortality and morbidity in individuals of all ages. Inhaled nitric oxide (INO) has been used to improve oxygenation, but its role remains controversial. This Cochrane review was originally published in 2003, and has been updated in 2010 and 2016. The primary objective was to examine the effects of administration of inhaled nitric oxide on mortality in adults and children with ARDS. Secondary objectives were to examine secondary outcomes such as pulmonary bleeding events, duration of mechanical ventilation, length of stay, etc. We conducted subgroup and sensitivity analyses, examined the role of bias and applied trial sequential analyses (TSAs) to examine the level of evidence. In this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 Issue 11); MEDLINE (Ovid SP, to 18 November 2015), EMBASE (Ovid SP, to 18 November 2015), CAB, BIOSIS and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We handsearched the reference lists of the newest reviews and cross-checked them with our search of MEDLINE. We contacted the main authors of included studies to request any missed, unreported or ongoing studies. The search was run from inception until 18 November 2015. We included all randomized controlled trials (RCTs), irrespective of publication status, date of publication, blinding status, outcomes published or language. We contacted trial investigators and study authors to retrieve relevant and missing data. Two review authors independently extracted data and resolved disagreements by discussion. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity analyses to assess the effects of INO in adults and children and on various clinical and physiological outcomes. We presented pooled estimates of the effects of interventions as risk ratios (RRs) with 95% confidence intervals (CIs). We assessed risk of bias through assessment of trial methodological components and risk of random error through trial sequential analysis. Our primary objective was to assess effects of INO on mortality. We found no statistically significant effects of INO on longest follow-up mortality: 250/654 deaths (38.2%) in the INO group compared with 221/589 deaths (37.5%) in the control group (RR 1.04, 95% CI 0.9 to 1.19; I² statistic = 0%; moderate quality of evidence). We found no statistically significant effects of INO on mortality at 28 days: 202/587 deaths (34.4%) in the INO group compared with 166/518 deaths (32.0%) in the control group (RR 1.08, 95% CI 0.92 to 1.27; I² statistic = 0%; moderate quality of evidence). In children, there was no statistically significant effects of INO on mortality: 25/89 deaths (28.1%) in the INO group compared with 34/96 deaths (35.4%) in the control group (RR 0.78, 95% CI 0.51 to 1.18; I² statistic = 22%; moderate quality of evidence).Our secondary objective was to assess the benefits and harms of INO. For partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2), we found significant improvement at 24 hours (mean difference (MD) 15.91, 95% CI 8.25 to 23.56; I² statistic = 25%; 11 trials, 614 participants; moderate quality of evidence). For the oxygenation index, we noted significant improvement at 24 hours (MD -2.31, 95% CI -2.73 to -1.89; I² statistic = 0%; five trials, 368 participants; moderate quality of evidence). For ventilator-free days, the difference was not statistically significant (MD -0.57, 95% CI -1.82 to 0.69; I² statistic = 0%; five trials, 804 participants; high quality of evidence). There was a statistically significant increase in renal failure in the INO groups (RR 1.59, 95% CI 1.17 to 2.16; I² statistic = 0%; high quality of evidence). Evidence is insufficient to support INO in any category of critically ill patients with AHRF. Inhaled nitric oxide results in a transient improvement in oxygenation but does not reduce mortality and may be harmful, as it seems to increase renal impairment.

Exogenous surfactant in the treatment of neonatal meconium aspiration syndrome

Dysfunction of pulmonary surfactant is one of the key pathogenic features in meconium aspiration syndrome. Surfactant function may be affected by components of meconium, by inflammatory mediators (e.g., tumor necrosis factor alpha and interleukin-1), proteolytic enzymes, phospholipase A2, reactive oxygen species, and by plasma proteins leaking into the alveolar space. Administration of exogenous surfactant may at least partially alleviate the inactivation of pulmonary surfactant present in meconium aspiration syndrome. In experimental and clinical studies, intratracheal administration of a surfactant bolus significantly improved both lung function and survival. However, some patients are non-responders and there is only transient improvement in oxygenation. A repeat dose of surfactant may be required in these patients. Bronchoalveolar lavage with diluted exogenous surfactant is another technique for surfactant administration that may be more effective in partially removing meconium from the lungs, and thereby reducing surfactant inhibition, inflammation and mechanical obstruction of the airways. There is also a growing body of evidence suggesting that exogenous surfactant may be more effective when combined with pulmonary vasodilators, anti-inflammatory and antioxidant treatment.

Acute respiratory distress syndrome in the pediatric age: an update on advanced treatment.

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that lacks definitive treatment. The cornerstone of management is sound intensive care treatment and early anticipatory ventilation support. A mechanical ventilation strategy aiming at optimal alveolar recruitment, judicious use of positive end-respiratory pressure (PEEP) and low tidal volumes (VT) remains the mainstay for managing this lung disease. Several treatments have been proposed in rescue settings, but confirmation is needed from large controlled clinical trials before they be recommended for routine care. Non-invasive ventilation (NIV) is suggested with a cautious approach and a strict selection of candidates for treatment. Mild and moderate cases can be efficiently treated by NIV, but this is contra-indicated with severe ARDS. The extra-corporeal carbon dioxide removal (ECCO2 R), used as an integrated tool with conventional ventilation, is playing a new role in adjusting respiratory acidosis and CO2. The proposed benefits of ECCO2 R over extra-corporeal membrane oxygenation (ECMO) consist in a reduction of artificial surface contact, avoidance of pump-related side effects and technical complications, as well as lower costs. The advantages and disadvantages of inhaled nitric oxide (iNO) are better recognized today and iNO is not recommended for ARDS and acute lung injury (ALI) in children and adults because iNO results in a transient improvement in oxygenation but does not reduce mortality, and may be harmful. Several trials have found no clinical benefit from various surfactant supplementation methods in adult patients with ARDS. However, studies which are still controversial have shown that surfactant supplementation can improve oxygenation and decrease mortality in pediatric and adolescent patients in specific conditions and, when applied in different modes and doses, also in neonatal respiratory distress syndrome (RDS) of preemies. Management of ARDS remains supportive, aimed at improving gas exchange and preventing complications. Progress in the treatment of ARDS must be addressed toward the new paradigm of the disease pathobiology to be applied to the disease definition and to predict the treatment outcome, also with the perspective to develop predictive and personalized medicine that highlights new and challenging opportunities in terms of benefit for patient's safety and doctor's responsibility, with further medico-legal implication.

Inhaled Nitric Oxide for Acute Respiratory Distress Syndrome and Acute Lung Injury in Adults and Children

Acute hypoxemic respiratory failure, defined as acute lung injury and acute respiratory distress syndrome, are critical conditions associated with frequent mortality and morbidity in all ages. Inhaled nitric oxide (iNO) has been used to improve oxygenation, but its role remains controversial. We performed a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials (RCTs). We searched CENTRAL, Medline, Embase, International Web of Science, LILACS, the Chinese Biomedical Literature Database, and CINHAL (up to January 31, 2010). Additionally, we hand-searched reference lists, contacted authors and experts, and searched registers of ongoing trials. Two reviewers independently selected all parallel group RCTs comparing iNO with placebo or no intervention and extracted data related to study methods, interventions, outcomes, bias risk, and adverse events. All trials, irrespective of blinding or language status were included. Retrieved trials were evaluated with Cochrane methodology. Disagreements were resolved by discussion. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effect of iNO in adults and children and on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components. We assessed the risk of random error by applying trial sequential analysis. We included 14 RCTs with a total of 1303 participants; 10 of these trials had a high risk of bias. iNO showed no statistically significant effect on overall mortality (40.2%versus 38.6%) (relative risks [RR] 1.06, 95% confidence interval [CI] 0.93 to 1.22; I² = 0) and in several subgroup and sensitivity analyses, indicating robust results. Limited data demonstrated a statistically insignificant effect of iNO on duration of ventilation, ventilator-free days, and length of stay in the intensive care unit and hospital. We found a statistically significant but transient improvement in oxygenation in the first 24 hours, expressed as the ratio of Po₂ to fraction of inspired oxygen (mean difference [MD] 15.91, 95% CI 8.25 to 23.56; I² = 25%). However, iNO appears to increase the risk of renal impairment among adults (RR 1.59, 95% CI 1.17 to 2.16; I² = 0) but not the risk of bleeding or methemoglobin or nitrogen dioxide formation. iNO cannot be recommended for patients with acute hypoxemic respiratory failure. iNO results in a transient improvement in oxygenation but does not reduce mortality and may be harmful.

The short‐term effect of hyperoncotic albumin, given alone or with furosemide, on oxygenation in sepsis‐induced Acute Respiratory Distress Syndrome

Two prospective non-randomised interventional case series were conducted consecutively at a single university hospital mixed intensive care unit, in patients with severe sepsis and acute respiratory distress syndrome. The first series describes the administration of 200 ml of 20% human albumin solution over 120 s in 13 patients, examining the hypothesis that raising plasma albumin should improve oxygenation. The second series describes the effect of administering 30 mg of furosemide intravenously along with the albumin in 15 patients, exploring whether this would produce more sustained improvement in oxygenation than albumin only. Oxygenation and haemodynamic parameters were measured for 4 h, during the period of peak oncotic effect. Hyperoncotic albumin given alone or with furosemide produced only transient improvement in oxygenation and haemodynamics, which was statistically significant only in the patients given albumin alone. Although the plasma albumin remained significantly elevated at 4 h in both series, no sustained improvement in oxygenation was seen.

Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults.

Acute hypoxemic respiratory failure affects all age groups and may result from a number of systemic diseases. It continues to be associated with high mortality and morbidity. Initial studies examining the effect of inhaled nitric oxide in respiratory failure demonstrated transient improvement in oxygenation but did not examine mortality or other significant morbidity outcomes. To systematically examine randomized controlled trials addressing the effect of inhaled nitric oxide, compared with placebo inhaled gas, on mortality and morbidity in patients with acute hypoxemic respiratory failure. Randomized controlled trials were identified from electronic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2002;MEDLINE (January 1966-August 2002); EMBASE (1980-March 2001); CINAHL (1982-July 2002), as well as from bibliographies of retrieved articles. Relevant journals and conference proceedings were hand searched and authors published in this field were contacted for knowledge of unpublished ongoing trials. Randomized controlled trials comparing inhaled nitric oxide with maximal conventional therapy and inhaled placebo, in either children or adults with acute hypoxemic respiratory failure. Qualitative assessment of each trial was made and analyses performed according to statistical methods in Review Manager MetaView 4.1. A sub-group analysis was performed to assess the impact of inhaled nitric oxide at varied doses. Five randomized controlled trials were evaluated, assessing 535 patients with acute hypoxemic respiratory failure (Age range not provided). Lack of data prevented assessment of all outcomes. There was no significant difference of nitric oxide on mortality in trials without cross-over (RR 0.98, 95%CI 0.66,1.44). Published evidence from one study demonstrated nitric oxide to transiently improve oxygenation in the first 72 hours of treatment. Limited data demonstrated no significant difference in ventilator-free days between treatment and placebo groups, and no specific dose of nitric oxide was significantly advantageous over another. Other clinical indicators of effectiveness, such as duration of hospital and intensive care stay, were inconsistently reported. There were no significant complications directly attributable to this treatment. Nitric oxide did not demonstrate any statistically significant effect on mortality and transiently improved oxygenation in patients with hypoxemic respiratory failure. Lack of data prevented assessment of other clinically relevant end points. If further trials comparing inhaled nitric oxide with an inhaled placebo are to proceed, they should be stratified for primary disease, assess the impact of other combined treatment modalities for respiratory failure, and must specifically evaluate clinically relevant outcomes, before any benefit of inhaled nitric oxide for respiratory failure can be excluded.

Brief report. Early dexamethasone treatment in preterm infants treated with surfactant: a double blind controlled trial

The objective of the study was to test the hypothesis that early postnatal dexamethasone administration (days 1-5) in preterm infants with respiratory distress syndrome would improve acute respiratory status and therefore decrease long-term neonatal morbidity. This was a prospective, blind randomized controlled trial. Eligible neonates were preterm infants with birthweight < or = 1500 g who developed respiratory distress syndrome requiring mechanical ventilation and surfactant. A 5-day course of dexamethasone or placebo was initiated within the first 6 h after birth. The starting dose of dexamethasone was 0.5 mg/kg/day and it was tapered progressively. Results were analysed with t-test chi 2, Wilcoxon test, and ANOVA. Twenty-nine infants (n = 15 of early dexamethasone and n = 14 of placebo group) fulfilled the inclusion criteria. The dexamethasone group exhibited a significant improvement in arterial to alveolar oxygen ratio only between postnatal days 2 and 5 (p = 0.02). This initial improvement was not associated with long-term benefits. Infants who received dexamethasone had increased systolic blood pressure (p = 0.0001), diastolic blood pressure (p = 0.001), blood sugar (p = 0.02, serum urea (p = 0.03), and creatinine level (p = 0.02). All these side-effects were resolved by postnatal day 7. We concluded that a 5-day course of early postnatal dexamethasone was associated with only a transient improvement in oxygenation with no long-term benefits. Side-effects were more common in the dexamethasone group.

Inhaled and exhaled nitric oxide.

. Inhaled nitric oxide (NO) is used to treat various cardiopulmonary disorders associated with pulmonary hypertension. The rationale is based on the fact that NO, given by inhalation, only dilates those pulmonary vessels that perfuse well-ventilated lung units. As a result, pulmonary gas exchange is improved while pulmonary vascular resistance is reduced and pulmonary blood flow is increased. Inhaled NO has been succesfully applied to treat persistent pulmonary hypertension of the newborn, reducing the need for extracorporeal life support. Although pulmonary hypertension and altered vasoreactivity contribute to profound hypoxaemia in adult and paediatric acute respiratory distress syndrome (ARDS), the benefit of inhaled NO still remains to be established in patients with ARDS. ARDS is a complex response of the lung to direct or indirect insults, leading to pulmonary vasoconstriction and various inflammatory responses. Recent randomized trials suggest that inhaled NO only causes a transient improvement in oxygenation. Whether this effect is important in the long-term management of ARDS remains to be established. NO, measured in the exhaled breath, is an elegant and non-invasive means to monitor inflammation of the upper and lower respiratory tract. In the normal upper airways, the bulk of exhaled NO originates from the paranasal sinuses. Exhaled NO is increased in nasal allergy and decreased in cystic fibrosis, nasal polyposis and chronic sinusitis. That NO production is increased in asthmatic airways is also well established. However, several questions still need to be addressed, in particular evaluation of the sensitivity and specificity of the measurement techniques, and assessment of the bronchodilator action of endogenous NO.

Inhaled nitric oxide in term infants with hypoxemic respiratory failure

OBJECTIVE: To determine whether inhaled nitric oxide (NO) administered during conventional mechanical ventilation could produce improvements in oxygenation and reduce the incidence of meeting extracorporeal membrane oxygenation (ECMO) criteria in infants with hypoxemia. DESIGN: Prospective, randomized, controlled trial. Enrolled infants were assigned to conventional treatment with or without adjunctive inhaled NO. Control infants meeting failure criteria (partial pressure of arterial oxygen [PaO 2]<80 mm Hg [10.7 kPa]) were allowed to cross over. Caregivers were not masked to group assignment. SETTING: Neonatal intensive care units at the University of Alabama Hospital and the Children's Hospital of Alabama, October 1993 to May 1994. PATIENTS: Newborn infants, both term and near-term, with PaO 2 less than 100 mm Hg (13.3 kPa) who were receiving mechanical ventilation with 100% oxygen. Exclusion criteria included major congenital anomalies, diaphragmatic hernia, profound asphyxia, and significant bleeding. INTERVENTIONS: Inhaled NO was initiated in the NO group at a dose of 20 to 40 ppm and advanced stepwise to 80 ppm if PaO 2 remained less than 100 mm Hg (13.3 kPa). OUTCOME MEASURES: Primary outcome variables were treatment failure and meeting of ECMO criteria before crossover. Improvement in oxygenation and ultimate use of ECMO or high-frequency oscillatory ventilation were secondary outcome variables. RESULTS: Seventeen neonates with hypoxemia were enrolled; 16 had echocardiographic evidence of pulmonary hypertension, and eight had extrapulmonary shunting. At 1 hour of treatment, two infants in the NO group responded with increases in PaO 2 of more than 100 mm Hg (13.3 kPa); after crossover, two had increases in PaO 2 of more than 10 mm Hg (1.3 kPa) and one control infant had an increase in PaO 2 of more than 10 mm Hg (1.3 kPa). All control infants met failure criteria and crossed over to receive NO; two had increases in PaO 2 of more than 10 mm Hg (1.3 kPa) with NO treatment. Despite initial responses, all subjects in both groups eventually met failure criteria. There were no differences between groups in primary outcome variables. CONCLUSIONS: Although inhaled NO produced a transient improvement in oxygenation in some infants, it did not reduce the incidence of meeting ECMO criteria in this population. (J P EDIATR 1996;129:279-86)

EFFECTS OF PARTIAL LIQUID VENTILATION (PLV) WITH PERFLUORODECALIN IN THE SALINE INJURED LUNG OF THE JUVENILE RABBIT MODEL. † 2286

Several perfluorochemical (PFC) liquids with different and specific physical properties have been used as a means of improving pulmonary gas exchange and lung mechanics during respiratory distress. We evaluated APF-140M(Air Product and Chemicals, Inc.) with respect to gas exchange and lung mechanics in healthy and saline injured(SI) lungs of the juvenile New Zealand White rabbit. SI was created by repeated lung lavages (4-16 times, 10 cc/kg/lavage) with warm saline solution. PLV treated animals received intratracheal APF-140M at a volume equal to the measured pre-injury gas functional residual capacity (FRC = 18.6 ± 1.5 ml/kg). Seventeen rabbits, (age: 7-9 wks; wt. = 1.59 ± 0.1 kg SE) were assigned to three groups. Gr I (n=5) was treated with conventional mechanical ventilation (CMV) after establishing SI, Gr II (n=6) was treated with PLV after SI. Gr III (n=6) was supported with PLV without injury. All rabbits were supported with CMV gas ventilator strategy in which frequency was maintained constant and ventilatory pressures were adjusted to maintain constant tidal volume and minute ventilation. Sequential measurements of dynamic compliance(C) and arterial blood chemistry were performed in all groups (ie. after instrumentation, injury) and hourly for 4 hours thereafter. Oxygenation index (OI), and ventilation efficiency index(VEI) were calculated. Mean±SEM data at baseline(BI), Injury (Inj), 1 hour (1H), and 4 hours(4H) were:Table These data demonstrate: 1) following lung injury there was a significant (p<0.05) decrease in PaO2, C, VEI and increase in OI. 2) In Gr II, PLV significantly (p<0.05) improved PaO2 and OI. C was significantly (p<0.05) higher than Gr I at 1H. 3) there was a significant (p<0.05) decrease in C following PLV in Gr III. These results indicate that PLV with APF-140M caused a transient improvement in oxygenation and lung mechanics in the saline injured lung and sustained impairment of C in healthy lung of the juvenile rabbit model.(Supp in part by R29HD26341)

Nitric oxide treatment for pulmonary hypertension after neonatal cardiac operation

This report describes a newborn with transposition of the great arteries who underwent a Blalock-Taussig shunt with transient improvement in oxygenation, but required emergent insertion of a central shunt later the same day due to progressive hypoxia and cardiac arrest. Two hours after central shunt insertion, sudden episodes of hypoxia and hypotension developed that were resistant to all pharmacologic therapy. Inhaled nitric oxide (25 ppm) was then administered with dramatic improvement in oxygenation and hemodynamics within minutes. The patient's condition stabilized after these measures, and nitric oxide therapy was discontinued after 2 days.