Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inhalation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,225 records · Page 68Linked to original sources
PubMed2002

Inhalation and deposition of nebulized sodium cromoglycate in two different particle size distributions in children with asthma.

The relative deposition of two inhaled droplet size distributions of sodium cromoglycate produced by a Hudson Updraft II nebulizer was evaluated, using a setup modified from the proposed Comité Européen Normalisé (CEN) standard prEN 13544-1. The modified setup comprised an Andersen 296 impactor and a Spira Electro 2 dosimeter. The setup was characterized prior to use in children with sodium cromoglycate (SCG) and sodium fluoride as tracer aerosol. The main in vivo study was designed to allow nine children with a mean age of 10 years to inhale SCG aerosol at two different relative humidities (RH), a high RH (> 90%) and a low RH (13%), which in turn resulted in two different droplet size distributions. The nebulizer/dosimeter was set to provide 1-sec nebulization during 50 inhalations. Throughout the exposures, the children were instructed to inhale in a consistent manner with target tidal volumes (0.5 L) and inhalation flows (0.4 L/sec). Blood samples were taken at predefined time intervals, and the area under the curve (AUC) was calculated. A lung deposition program, TGLD2, was used to calculate the expected deposition, using the droplet sizes and inhalation parameters obtained during in vivo exposures. The in vivo monitoring of droplet size distribution during the exposure showed that the low, intermediate (room air), and high RHs gave a mean droplet size distribution with a mass median aerosol diameter (MMAD) of 1.2, 1.7, and 2.0 microm, respectively. The average tidal volume over all exposures was 0.51 +/- 0.12 L. The total deposition fraction was 33.4% of the estimated nebulizer output. A correlation was found between tidal volume and the calculated deposited fraction. The results indicate that there is a difference in total deposition, depending on the size of the droplet size distribution, with the larger droplet size distribution (MMAD, 2.0 microm) having a higher total deposition than the smaller droplet size distribution (MMAD, 1.2 microm). The deposition results were in good agreement with the deposition fractions estimated using the TGLD2 software for the inhalation parameters found in the study. The obtained study results can arise from differences in regional deposition, but may also be explained by differences in extrathoracic deposition.

Administration, Inhalation↗
PubMed2003

Majority of children aged 3 years and above can reliably inhale through the Clickhaler.

Guidelines suggest that pressurized metered dose inhalers (pMDI) plus spacers are the delivery system of choice for children. However, they are bulky, which makes them inconvenient. It was suggested that the smaller dry-powder inhalers (DPIs) may be suitable for delivering short-acting bronchodilators to preschool children. This study considered whether preschool children could reliably generate sufficient inspiratory flows to use the Clickhaler DPI. Twenty-seven asthmatic and 34 nonasthmatic children, aged 2-5 years, were recruited. Following training, they were asked to inhale four times through a Clickhaler flow monitoring system, twice "steadily" and twice "forcefully." Inspiratory flow data were collected during each inhalation. Of the 3-, 4-, and 5-year-old asthmatics, 62.5, 100, and 100%, respectively, could reliably differentiate between inhaling and exhaling through the DPI. For nonasthmatics, the figures were 66, 60, and 88%, respectively. All but one of the children who understood the instructions generated a PIF of greater than 15 l/min (range, 13.9-88.3 l/min and 21.2-84.5 l/min in asthmatic and nonasthmatic children, respectively). These data indicate that the majority of children aged 3 years and above could reliably inhale rather than exhale through a dry-powder inhaler, and that they generate inspiratory flows sufficient to use the Clickhaler effectively. The results indicate that the device could be a suitable delivery system for beta(2)-agonists in preschool children.

Administration, Inhalation↗
PubMed1995

A comparison of the inflammatory response of the lung to inhaled versus instilled particles in F344 rats.

The potential pulmonary toxicity of poorly soluble airborne dusts generated in industrial and environmental settings is often evaluated by inhalation studies in rodents. Studies using intratracheal instillation of particles have been suggested as a less expensive alternative. We conducted a study to compare the inflammatory response of the lung to instilled versus inhaled particles. In one study, female F344/N rats, 11-13 weeks of age, were exposed for 6 hr/day, 5 days/week for 4 weeks by inhalation to 0, 0.1, 1.0, or 10 mg/m3 of either alpha-quartz (toxic particle) or TiO2 (relatively low toxicity particle) and the lung burdens were determined at 1 week after the end of the exposure. The lungs were evaluated by analysis of bronchoalveolar lavage fluid (BALF) at 1, 8, and 24 weeks after the end of the exposure and by histopathology at 24 weeks. In a second study, rats were exposed by instillation to the lung burdens present in the preceding study at 1 week after the inhalation exposure, and the rats were evaluated in the same manner as in the inhalation study. In general, the degree of alveolitis, as evaluated by histopathology and BALF analysis, was similar by the two methods of exposure. With lung burdens up to 750 micrograms/g lung, the TiO2 elicited no changes in BALF parameters at any time by either method of exposure, nor was any histopathology observed. The BALF changes elicited by alpha-quartz were of approximately the same magnitude and followed the same time course by either exposure method with the lowest dose delivered to the lung by either method being a "no-effect" dose. At the highest dose, microgranulomas were observed in bronchial-associated lymphoid tissue (BALT) in both sets of rats. However, the highest inhalation exposure induced pleural granulomatous lesions that were not observed in the animals instilled with alpha-quartz. The results indicate that the relative potentials of the two materials to produce bronchoalveolitis and granulomatous lesions in BALT could be appropriately evaluated using either intratracheal or inhalation exposures.

Administration, Inhalation↗
PubMed1996

Use of lung toxicity and lung particle clearance to estimate the maximum tolerated dose (MTD) for a fiber glass chronic inhalation study in the rat.

Short-term toxicity and lung clearance were assessed in rats exposed by inhalation to size-selected fibrous glass (FG) for 13 weeks. Results from this study and from a recent FG chronic inhalation study are presented here as guidelines for the selection of a maximum tolerated dose (MTD) for chronic inhalation studies of fibers. Fischer 344 rats were exposed using nose-only inhalation chambers, 6 hr/day, 5 days/week, for 13 weeks to one of five concentrations of FG (36, 206, 316, 552, or 714 fibers/cc; expressed gravimetrically, 3, 16, 30, 45, or 60 mg/m3) or to filtered air. Rats were then held for an additional 10 weeks of postexposure recovery. Test fiber was size-selected from glass wool having a chemical composition representative of building insulation. Rats were terminated at 7, 13, 19, and 23 weeks after the onset of exposure to evaluate pulmonary pathology, lung epithelium cell proliferation, lung fiber burden, and lung lavage cells and chemistry. The effect of fiber inhalation on lung clearance of innocuous microspheres was also evaluated: following fiber exposure, six rats/group were exposed to 85Sr-labeled 3.0-microns polystyrene microspheres by intratracheal inhalation and then monitored for whole-body radioactivity during the 10-week recovery period. Data from the short-term study support the choice of 30 mg/m3 as the MTD for the previous chronic FG study and also provide indicators of long-term lung toxicity and functional impairment that can be used to estimate the MTD for future chronic fiber inhalation studies.

Administration, Inhalation↗
PubMed2001

Relative lung bioavailability of generic sodium cromoglycate inhalers used with and without a spacer device.

The relative lung bioavailability of sodium cromoglycate following inhalation has been evaluated using urinary drug excretion in nine healthly volunteers. Each inhaled four 5 mg sodium cromoglycate doses from a generic metered dose inhaler (MDI) and when it was attached to large volume spacer (MDI + VOL). A breath-actuated MDI was also evaluated either used on its own (EB) or attached to a small volume spacer tube (EBO). The mean (SD) urinary excretion of sodium cromoglycate in the first 30 min post-inhalation was 34.1 (20.2), 211.7 (123.5), 29.3 (19.5) and 52.8 (36.0) microg following MDI, MDI+VOL, EB and EBO, respectively. The cumulative mean (SD) urinary excretion of sodium cromoglycate over the 24 h post-inhalation was 364.7 (266.2), 1227.1 (459.0), 280.2 (155.4) and 429.5 (176.7) microg. A metered dose inhaler attached to a large volume spacer delivers more sodium cromoglycate to the lungs than any other inhalation method.

Administration, Inhalation↗
PubMed1996

Combined effects of NO inhalation and intravenous PGF2 alpha on pulmonary circulation and gas exchange in an ovine ARDS model.

OBJECTIVES: Inhalation of nitric oxide (NO) selectively dilates pulmonary vessels in well-ventilated regions. Prostaglandin F2 alpha (PGF2 alpha) is a vasoconstrictor and is reported to enhance hypoxic pulmonary vasoconstriction. The objective of this study was to examine whether the combination of intravenous PGF2 alpha and inhaled NO in ARDS lungs has a beneficial effect on oxygenation. DESIGN: We investigated the effect of intravenous PGF2 alpha infusion (0.05-10.0 micrograms/kg per min) with and without NO inhalation (60 ppm) on the hemodynamics and gas exchange in an ovine ARDS model, examining the pulmonary artery pressure versus the flow plot by varying cardiac output. MEASUREMENTS AND RESULTS: After lung lavage, NO inhalation reduced the mean pulmonary arterial pressure (MPAP) by decreasing the zero-flow pressure intercept from 10.6 +/- 3.8 (mean +/- SD) to 8.5 +/- 3.8 mmHg (p < 0.05) with no significant change in slope. NO inhalation improved PaO2 from 56 +/- 12 to 84 +/- 38 mmHg (p < 0.005) and reduced pulmonary shunt from 65 +/- 5 to 53 +/- 8% (Qs/Qt) (p < 0.001). The dose-dependent effects of PGF2 alpha infusion were: (1) increased MPAP attributed to an increased slope in pulmonary artery pressure-flow plot; (2) decreased cardiac index; (3) decreased Qs/Qt with unchanged PaO2. The dose-dependent decrease in Qs/Qt after PGF2 alpha infusion was attributed to the decreased cardiac output. CONCLUSIONS: It is suggested that inhalation of NO reduced the critical vascular pressure near alveoli without affecting upstream vessels, while infused PGF2 alpha constricted the larger upstream pulmonary artery vessels without appreciably affecting the critical pressure. Inhalation of NO into well-ventilated lung areas shifted perfusion to well-oxygenated areas, and there was no supplemental shift in blood flow by adding an infusion of PGF2 alpha.

Administration, Inhalation↗
PubMed1998

Combined nitric oxide inhalation, prone positioning and almitrine infusion improve oxygenation in severe ARDS.

PURPOSE: To determine the efficacy and side effects of prone positioning (PP) and nitric oxide (NO) inhalation, alone, associated, or combined with i.v. almitrine for the treatment of hypoxaemia in severe acute respiratory distress syndrome (ARDS). METHODS: Over a period of 20 months, 27 consecutive critically ill patients with severe ARDS (Murray score > 2.5, PaO2/FiO2 < 170 after alveolar recruitment) were prospectively and randomly included. They inhaled NO for two hours at concentrations of 5 and 10 ppm for one hour each (H0-H2). One hour later, they were returned to the prone position for four hours (H3-H7). During the last two hours in this position (H5-H7), they were assigned to further inhalation of 10 ppm NO (Group B, n = 9) or to no further inhalation (Group A, n = 9). In group C (n = 9), the procedure for group B was combined with perfusion of 16 mg.kg-1.min-1 almitrine throughout the study. RESULTS: Compared with control values, two hours NO inhalation improves PaO2/FiO2 and shunt effect by +28% and -9%, PP by +88% and -27%, PP + almitrine by +132% and -28%, NO + almitrine by +153 and -28%, PP + NO by +94% and -29%, NO + PP + almitrine by +327 and -48%. NO inhalation reduces pulmonary vascular resistance. Other haemodynamic parameters remain unchanged, whatever the treatment. NO inhalation improves PaO2/FiO2 by over 20% in 50% of the patients and PP is effective in 78% of the cases. CONCLUSION: Prone Position improves PaO2/FiO2 significantly more than NO alone but less than PP + almitrine or NO + almitrine. The best results are obtained with the association of NO + Prone position + Almitrine.

Administration, Inhalation↗
PubMed2002

Inhaled iloprost controls pulmonary hypertension after cardiopulmonary bypass.

PURPOSE: Severe pulmonary hypertension (PH) is a major cause of right ventricular (RV) dysfunction. Various iv vasodilator modalities have been used with limited results because of lack of pulmonary selectivity. The aim of the present controlled study was to evaluate the efficacy of inhaled iloprost, a synthetic prostacyclin analogue, in patients with elevated pulmonary vascular resistance (PVR) immediately after separation from cardiopulmonary bypass (CPB). METHODS: Twelve patients with persistent PH after discontinuation of CPB were included in the study. In all patients standard hemodynamic monitoring was used. Inhaled iloprost was administered via nebulized aerosol at a cumulative dose of 0.2 micro g*kg(-1) for a total duration of 20 min. Complete sets of hemodynamic measurements were performed before inhalation (baseline), during and after cessation of the inhalation period. Echocardiographic monitoring of RV function was also used. RESULTS: Inhaled iloprost induced a reduction in the transpulmonary gradient at the end of the inhalation period in comparison to baseline (9.33 +/- 3.83 mmHg vs 17.09 +/- 6.41 mmHg, P < 0.05). The mean pulmonary artery pressure to systemic artery pressure ratio decreased over this period (0.28 +/- 0.08 vs 0.45 +/- 0.17, P < 0.05). A statistically significant decrease of the PVR to systemic vascular resistance ratio was also observed (0.15 +/- 0.05 vs 0.21 +/- 0.05, P < 0.05). Improved indices of RV function were observed in echocardiographic monitoring. CONCLUSION: Inhaled iloprost appears to be a selective pulmonary vasodilator and may be effective in the initial treatment of PH and the improvement of RV performance in the perioperative setting.

Administration, Inhalation↗
PubMed2003

Acute asthma in children and adolescents: should inhaled anticholinergics be added to beta(2)-agonists?

Children and adolescents experiencing acute exacerbations of asthma benefit from the use of beta(2)-adrenoceptor agonists (beta(2)-agonists) and systemic corticosteroids. However, there have been conflicting reports regarding the efficacy of inhaled anticholinergic agents. This article summarizes the evidence provided by randomized controlled trials studying the efficacy of adding inhaled anticholinergic agents to beta(2)-agonists in nonhospitalized children and adolescents with acute exacerbations of asthma. This systematic review of randomized controlled trials suggests that the addition of inhaled anticholinergic agents to beta(2)-agonists is beneficial in children and adolescents, particularly those with severe exacerbations of asthma. When given in repeated doses, the addition of inhaled anticholinergic agents to beta(2)-agonists improves lung function and reduces the risk of hospital admission by 25%. Several treatment regimens, namely ipratropium bromide (250 or 500 microg per dose) every 20-60 minutes for two to three doses have been tested with similar beneficial effects. The addition of a single dose of an inhaled anticholinergic agent to beta(2)-agonists improves lung function but does not prevent hospital admission. The review did not identify any beneficial effects of anticholinergic agents in children with nonsevere asthma. Use of anticholinergic agents was not associated with increase in the incidence of nausea, vomiting or tremor. In conclusion, the addition of repeated doses of an inhaled anticholinergic agent to inhaled beta(2)-agonist is indicated in the emergency room management of children and adolescents with acute asthma, particularly those with severe exacerbations.

Acute Disease↗
PubMed1997

Hemodynamic and gas exchange responses to inhalation of nitric oxide in patients with the acute respiratory distress syndrome and in hypoxemic patients with chronic obstructive pulmonary disease.

OBJECTIVE: Inhalation of nitric oxide (NO) can improve oxygenation and decrease mean pulmonary artery pressure (MPAP) in patients with the acute respiratory distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective clinical study. SETTING: General intensive care unit in Sabadell, Spain. PATIENTS: Nine mechanically ventilated COPD patients (mean age 72 +/- 2 years; forced expiratory volume in 1 s 0.91 +/- 0.11 l) and nine ARDS patients (mean age 57 +/- 6 years; mean lung injury score 2.8 +/- 0.1). MEASUREMENTS AND RESULTS: We measured hemodynamic and gas exchange parameters before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20 min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group, these parameters were measured before NO inhalation (basal 1), during different doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued (basal 2). A positive response to NO was defined as a 20% increment in basal arterial partial pressure of oxygen (PaO2). MPAP and pulmonary vascular resistance (PVR) decreased significantly, while other hemodynamic parameters remained unchanged after NO-10 in both groups. Basal oxygenation was higher in the COPD group (PaO2/FIO2 (fractional inspired oxygen) 190 +/- 18 mmHg) than in the ARDS group (PaO2/FIO2 98 +/- 12 mmHg), (p < 0.01). After NO-10, PaO2/FIO2 increased (to 141 +/- 17 mmHg, p < 0.01) and Qva/Qt decreased (39 +/- 3 to 34 +/- 3%, p < 0.01) in the ARDS group. There were no changes in PaO2/FIO2 and Qva/Qt when the NO concentration was increased to 30 ppm in the COPD group. In both groups, a correlation was found between basal MPAP and basal PVR, and between the NO-induced decrease in MPAP and in PVR. The NO-induced increase in PaO2/FIO2 was not correlated with basal PaO2/FIO2. In the ARDS group, six of the nine patients (66%) responded to NO and in the COPD group, two of nine (22%) (p = 0.05). CONCLUSIONS: NO inhalation had similar effects on hemodynamics but not on gas exchange in ARDS and COPD patients, and this response probably depends on the underlying disease.

Administration, Inhalation↗
PubMed1999

Effect of inhaled nitric oxide on respiratory mechanics in ventilated infants with RSV bronchiolitis.

OBJECTIVE: To evaluate the bronchodilator effect of inhaled nitric oxide (NO) in infants with respiratory failure caused by respiratory syncytial virus (RSV) bronchiolitis and to compare the effect with the one obtained by salbutamol. DESIGN: Prospective study. SETTING: Pediatric intensive care unit of a university children's hospital. PATIENTS: Twelve acutely ill, intubated infants (mean age 4.5 months, mean weight 4.9 kg) with respiratory failure due to documented RSV bronchiolitis. INTERVENTIONS: Total respiratory system resistance (Rrs) was measured by single breath occlusion at the baseline and after inhaling NO at 20, 40 and 60 ppm for 1 h, and after inhalation of a standard beta2-agonist, salbutamol. Arterial blood gas analysis was performed at each study level on 6 of the 12 patients. RESULTS: The baseline mean Rrs (SE) was 0.29 (0.04) cm H2O/ml per s. At each dose of NO, the mean Rrs (SE) was 0.28 (0.04) cm H2O/ml per s. With salbutamol, the mean Rrs (SE) was 0.21 (0.03) cm H20/ml per s. These values were not significantly different from each other (by ANOVA). Inhaled NO produced a significant decrease in Rrs of greater than 4 times the coefficient of variation of the baseline measurement in 3 of 12 patients. Seven of 12 patients had no significant change while two patients had a significant increase in Rrs. Inhaled salbutamol produced a significant decrease in Rrs in 5 of 11 patients, while 6 showed no change in Rrs. CONCLUSION: Inhaled NO has no apparent bronchodilator effect in the majority of acutely ill infants with RSV bronchiolitis and does not appear to provide any additional benefit over the use of salbutamol. The clinical benefit of inhaled NO as a bronchodilator is questionable under these conditions.

Administration, Inhalation↗
PubMed1999

Pharmacokinetics and tolerability of formoterol in healthy volunteers after a single high dose of Foradil dry powder inhalation via Aerolizer.

OBJECTIVE: The pharmacokinetics of the long-acting beta2-agonist formoterol fumarate, which is a racemate of the (S,S)- and (R,R)-enantiomers were evaluated in 12 healthy (eight male, four female) volunteers after a single inhaled high dose of 120 microg of formoterol fumarate. The tolerability and safety were also assessed. METHODS: Each volunteer inhaled the single 120-microg dose through the Aerolizer device within 2-5 min, using ten 12-microg dry powder capsules for inhalation. Formoterol, i.e., the sum of both enantiomers, was determined in plasma over 24 h, whereas the separate enantiomers were determined in urine over 48 h. Incidence, seriousness and severity of adverse experiences, electrocardiogram (ECG), including the corrected QT interval (QTc) calculation, systolic blood pressure, heart rate, and plasma potassium levels were recorded. RESULTS: In nine of the 12 volunteers, the peak plasma concentration of formoterol was observed already at 5 min after inhalation. The absorption kinetics were complex, as depicted by multiple peaks or shoulders within 0.5-6 h after inhalation. Mean with (SD; n = 12) of maximum concentration (Cmax) and area under the curve (AUC) of formoterol in plasma were 266 (108) pmol x l(-1) and 1330 (398) pmol x l(-1), respectively. The moderate inter-individual variability in systemic exposure of formoterol reflects the homogeneous pharmacokinetics of the drug. A predominant slow elimination of formoterol from plasma with a mean half-life (t1/2) of 10 h was demonstrated. Assuming linear kinetics in plasma suggested by urinary data, the steady-state trough plasma levels of formoterol for a b.i.d. dosing regimen are predicted to amount to 20% of Cmax. In urine, mean with (SD; n = 10) of the amount excreted over 48 h was 3.61 (0.89)% of dose for the pharmacologically active (R,R)-enantiomer and 4.80 (1.33)% of dose for the (S,S)-enantiomer. The terminal half-lives calculated from the excretion rate-time curves, i.e., 13.9 h and 12.3 h for the (R,R)- and (S,S)-enantiomer, respectively, confirm the slow elimination of formoterol from plasma. The dose inhaled was 10 times the most frequently recommended dose (12 microg) and 5 times the highest recommended dose (24 microg). Ten of 12 subjects experienced mild and transient nervousness. Pulse readings demonstrated the maximum mean increase of 25.8 beats x min(-1) at 6 h. The mean maximum QTc increase was 25 msec at 6 h. Pulse and QTc values returned to baseline or close to baseline values at 24 h or before. Potassium levels in plasma decreased in eight out of 12 subjects; the lowest mean value was 3.53 mmol x l(-1) at 2 h post-dose. The lowest individual potassium measurement was 2.95 mmol x l(-1) between 15 min and 6 h. By 8 h post-dose all values had returned to within the normal ranges. CONCLUSIONS: The extremely fast appearance of formoterol in plasma shows the predominance of airways absorption shortly after inhalation. Due to a terminal elimination half-life of about 10 h, sustained systemic concentrations of formoterol are predicted for a twice daily treatment regimen without noteworthy accumulation. The excreted amounts in percent of dose of the enantiomers in urine and the enantiomer ratio are similar to data reported previously after lower doses and suggest linear kinetics for doses between 12 microg and 120 microg of formoterol fumarate. The expected side effects on heart rate, QTc interval, and plasma potassium were small and had no clinical consequences in spite of the very high dose of 120 microg (5 to 10 times the recommended therapeutic dose of Foradil). It should be noted that the impact of high doses may be greater in patients. Nevertheless these findings provide reassurance on the safety margin of formoterol after accidental and intentional overdosing.

Administration, Inhalation↗
PubMed1998

[Duplex ultrasound examinations of retinal circulation after inhalation of various mixed respiratory gases].

BACKGROUND: Hyperoxic-hypercapnic inhalation is a therapeutic option in vascular disorders of the retina. The effect of hyperoxic and/or hypercapnic inhalation on the perfusion of the retina was examined. METHODS: Twenty-five young adults between 18 and 35 years were investigated in a prospective study. They inhaled one of three different mixtures of breathing gases: (1) 100% O2, (2) Carbogen 240 (95% O2 and 5% CO2), (3) 92% O2 with 8% CO2 and were examined by color Doppler imaging of the CRA and OA before and after inhalation. The resistance index (RI) was calculated. RESULTS: The majority of the subjects showed an Increase in the RI in both ophthalmic vessels after inhalation of pure O2, a decrease after breathing in 92% O2 and 8% CO2 and it remained almost constant with inhalation of 95% O2 and 5% CO2. CONCLUSIONS: Inhalation of 92% O2 and 8% CO2 is a possibility for decreasing the peripheral resistance of OA and CRA. No change in blood flow was observed with Carbogen 240.

Adolescent↗
PubMed2005

Inhaled nitric oxide therapy after Fontan-type operations.

PURPOSE: Inhaled nitric oxide (NO) therapy is a newly developed strategy designed to reduce pulmonary vascular resistance after the Fontan-type operation. We reviewed our experience to evaluate its efficacy and true indications. METHODS: We retrospectively examined 47 children who received inhaled NO therapy after the Fontan-type operation between August 1996 and December 2002. The maximal dose of NO ranged from 5 to 30 ppm (median 10 ppm), and the duration of inhaled NO therapy ranged from 5 h to 52 days (median 2 days). RESULTS: Inhaled NO significantly decreased the central venous pressure (CVP), from 16.2 +/- 2.2 to 14.6 +/- 2.2 mmHg (P < 0.0001), and the transpulmonary pressure gradient between the CVP and left atrial pressure, from 9.9 +/- 2.9 to 8.4 +/- 2.7 mmHg (P < 0.0001). It also increased the systolic systemic arterial pressure from 71.9 +/- 15.2 to 76.8 +/- 14.5 mmHg (P < 0.05). In 26 patients with additional fenestration, inhaled NO led to a significant improvement in SaO(2) from 90.1% +/- 9.6% to 93.3% +/- 7.9% (P < 0.01). However, patients with a CVP <15 mmHg or a transpulmonary pressure gradient <8 mmHg, or both, after the Fontan-type operation, showed no significant changes in hemodynamics during inhaled NO therapy. CONCLUSIONS: We propose that a CVP >/=15 mmHg or a transpulmonary pressure gradient >/=8 mmHg, or both, after Fontan-type operations are appropriate indications for inhaled NO therapy.

Administration, Inhalation↗
PubMed1985

Effect of inhalation injury on fluid resuscitation requirements after thermal injury.

The presence of inhalation injury has been reported to increase fluid requirements for resuscitation from burn shock after thermal injury. To evaluate the effect of inhalation injury on the magnitude of burn-induced shock, the characteristics of resuscitation of 171 patients with burns covering at least 25 percent of the total body surface area were reviewed. When inhalation injury was suspected, confirmation by xenon-133 scanning, bronchoscopy, or both was obtained. Initial fluid resuscitation was calculated according to the Parkland formula, and titration was initiated to maintain a urine output of 30 to 50 ml/hour. Fifty-one patients had inhalation injuries. Patients with inhalation injuries had a mean fluid requirement of 5.76 ml/kg per percentage of total body surface area burned and a mean sodium requirement of 0.94 mEq/kg per percentage of total body surface area burned to achieve successful resuscitation, compared with a fluid requirement of 3.98 ml/kg per percentage of total body surface area burned and a sodium requirement of 0.68 mEq/kg per percentage of total body surface area burned for the group without inhalation injury (p less than 0.05). These data confirm and quantitate that inhalation injury accompanying thermal trauma increases the magnitude of total body injury and requires increased volumes of fluid and sodium to achieve resuscitation from early burn shock.

Adolescent↗
PubMed1995

Inhaled nitric oxide for children with congenital heart disease and pulmonary hypertension.

BACKGROUND: Endothelium-derived nitric oxide (NO) is a potent vasodilator and a major mediator of pulmonary vascular tone. METHODS: Five infants underwent a trial of inhaled NO with hemodynamic monitoring in the operating room after atrioventricular canal repair. An additional 15 patients with congenital heart disease and refractory pulmonary hypertension were treated with inhaled NO for 1 day to 10 days postoperatively. RESULTS: In the 5 infants with atrioventricular canal, corrective surgical intervention and conventional therapy (hyperventilation, inspired oxygen fraction of 0.80, and inotropic agents) lowered mean pulmonary artery pressure from 49.5 +/- 10.5 to 20.0 +/- 2.2 mm Hg (p < 0.001). Adding inhaled NO further decreased mean pulmonary artery pressure to 18.0 +/- 2.8 mm Hg (p = not significant). Inhaled NO had no effect on ventricular function curves (inflow occlusion) in this group. In the 15 patients with refractory postoperative pulmonary hypertension, 11 had a favorable response to inhaled NO, with a decrease in mean pulmonary artery pressure from 30.9 +/- 5.8 to 23.1 +/- 5.4 mm Hg (p < 0.01) in 8 patients with pulmonary artery catheters. CONCLUSIONS: These studies demonstrate that inhaled NO has minimal beneficial effect on pulmonary artery pressure or cardiac output in infants after repair of atrioventricular canal. Inhaled NO is effective in decreasing PAP postoperatively in select patients with congenital heart disease and pulmonary hypertension refractory to conventional therapeutic modalities.

Administration, Inhalation↗
PubMed1994

Inhaled nitric oxide in congenital diaphragmatic hernia.

Pulmonary hypertension is a major complication of congenital diaphragmatic hernia (CDH). Inhaled nitric oxide (NO) is a selective pulmonary vasodilator because it produces vasodilatation of the pulmonary vasculature without systemic hypotension. In experimental and clinical studies, inhaled NO ameliorates pulmonary hypertension and improves gas exchange. The goal of the present study was to determine the extent to which infants with CDH respond to inhaled NO. Four newborn infants with CDH complicated by severe respiratory insufficiency and right-to-left shunting received inhaled NO. In three patients, postductal oxygenation improved in response to small concentrations of NO (5 to 10 ppm); two received NO after operative repair, and the third both before and after repair. However, tachyphylaxis developed in all cases within 1 to 6 days. A fourth patient received inhaled NO in an attempt at weaning from ECMO. He did not respond, remaining hypoxic despite 80 ppm NO, and continued to require ECMO. In the three patients who responded to inhaled NO, plasma nitrites and nitrates (stable oxidative end products of NO) accumulated over time, but not in the patient who did not respond. The accumulation of nitrite and nitrate in plasma may reflect alveolar-capillary NO absorption, and may identify patients who will respond to continued inhaled NO. Methemoglobin remained below 1.9% in all four babies. Selected infants with CDH may respond to NO, but the benefit may be temporary.

Administration, Inhalation↗
PubMed1996

Vagal bronchopulmonary C-fibers and acute ventilatory response to inhaled irritants.

Experiments were carried out in anesthetized Sprague-Dawley rats to determine the role of vagal bronchopulmonary C-fiber afferents in regulating the respiratory responses to inhaled irritants. Spontaneous inhalation of 2 tidal breaths of a known airway irritant (sulfur dioxide, 0.5%; ammonia, 1%; cigarette smoke, 50%) into the lower airways invariably elicited an immediate and transient inhibitory effect on breathing, characterized by apnea or bradypnea and accompanied by bradycardia, which lasted for 3-8 breaths. A delayed hyperpnea was also induced by inhalation of cigarette smoke, but not by sulfur dioxide or ammonia. After perineural capsaicin treatment of both cervical vagi to selectively block the conduction of capsaicin-sensitive C-fibers, these inhaled irritants no longer evoked any inhibitory effect on breathing; conversely, an augmented inspiration was triggered within the first 3 breaths from the onset of cigarette smoke inhalation in > 85% of the rats studied, but after a delay of several breaths following inhalation of ammonia or sulfur dioxide in only 30% of the rats. The augmented breaths were completely abolished when both cervical vagi were cooled to 6-7 degrees C. Bilateral vagotomy eliminated all the immediate responses to these irritants. These results suggest that both vagal C-fiber endings and irritant receptors in the airways are activated by these inhaled irritants, but the more dominant and consistent inhibitory effect on breathing is elicited primarily by stimulation of C-fiber afferents.

Administration, Inhalation↗