Airway trauma.

Traumatic airway injuries fortunately are rare. While sometimes injuries are obvious and initial management straightforward, frequently the diagnosis is difficult. Prompt diagnosis of airway injuries requires a high index of clinical suspicion, complemented by judicious use of endoscopy and radiological imaging. Initial management can be complicated by associated head, neck, and thoracic injuries. Importantly, a patient's airway can be lost because of injudicious use of sedation or failure to be properly cautious during attempts at airway management and endotracheal intubation. Mortality rates and the incidence of late complications remain high and have been related to delays in diagnosis and definitive treatment.

Effects of intravenous Zaprinast and inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of acute respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide (No) selectively dilates the pulmonary vasculature and improves gas exchange in acute respiratory distress syndrome. Because of the very short half-life of NO, inhaled NO is administered continuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a cyclic guanosine monophosphate phosphodiesterase inhibitor, increases the efficacy and prolongs the duration of action of inhaled NO in models of acute pulmonary hypertension. Its efficacy in lung injury models is uncertain. The authors hypothesized that the use of intravenous Zaprinast would have similar beneficial effects when used in combination with inhaled NO to improve oxygenation and dilate the pulmonary vasculature in a diffuse model of acute lung injury. METHODS: The authors studied two groups of sheep with lung injury produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO were administered in a random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus followed by 0.1 mg. kg-1. min-1). In the second group, inhaled NO was administered at the same concentrations before and after an intravenous infusion of Zaprinast solvent (0.05 m NaOH). RESULTS: After lavage, inhaled NO decreased pulmonary arterial pressure and resistance with no systemic hemodynamic effects, increased arterial oxygen partial pressure, and decreased venous admixture (all P < 0.05). The intravenous administration of Zaprinast alone decreased pulmonary artery pressure but worsened gas exchange (P < 0.05). Zaprinast infusion abolished the beneficial ability of inhaled NO to improve pulmonary gas exchange and reduce pulmonary artery pressure (P < 0. 05 vs. control). CONCLUSIONS: This study suggests that nonselective vasodilation induced by intravenously administered Zaprinast at the dose used in our study not only worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.

Inhaled nitric oxide delivery by anesthesia machines.

UNLABELLED: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator used to treat intraoperative pulmonary hypertension and hypoxemia. In contrast to NO delivered by critical care ventilators, NO delivered by anesthesia machines can be complicated by rebreathing. We evaluated two methods of administering NO intraoperatively: via the nitrous oxide (N(2)O) flowmeter and via the INOvent (Datex-Ohmeda, Madison, WI). We hypothesized that both systems would deliver NO accurately when the fresh gas flow (FGF) rate was higher than the minute ventilation (VE). Each system was set to deliver NO to a lung model. Rebreathing of NO was obtained by decreasing FGF and by simulating partial NO uptake by the lung. At FGF > or = VE (6 L/min), both systems delivered an inspired NO concentration ([NO]) within approximately 10% of the [NO] set. At FGF < VE and complete NO uptake, the N(2)O flowmeter delivered a lower [NO] (70 and 40% of the [NO] set at 4 and 2 L/min, respectively) and the INOvent delivered a higher [NO] (10 and 23% higher than the [NO] set at 4 and 2 L/min, respectively). Decreasing the NO uptake increased the inspired [NO] similarly with both systems. At 4 L/min FGF, [NO] increased by 10%-20% with 60% uptake and by 18%-23% with 30% uptake. At 2 L/min, [NO] increased by 30%-33% with 60% uptake and by 60%-69% with 30% uptake. We conclude that intraoperative NO inhalation is accurate when administered either by the N(2)O flowmeter of an anesthesia machine or by the INOvent when FGF > or = VE. IMPLICATIONS: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In a lung model, we demonstrated that NO can be delivered accurately by a N(2)O flowmeter or by a commercial device. We provide guidelines for intraoperative NO delivery.

Delivery of inhaled nitric oxide using the Ohmeda INOvent Delivery System.

OBJECTIVES: We evaluated the Ohmeda INOvent Nitric Oxide Delivery System, which uses an inspiratory flow sensor to inject a synchronized and proportional nitric oxide (NO) flow into the mechanical ventilator circuit. This system should deliver a constant NO concentration independent of ventilator mode, minute ventilation, fraction of inspired oxygen, or ventilator brand. It should also minimize nitrogen dioxide (NO2) formation. METHODS: NO delivery by the INOvent and a premixing NO delivery system were compared using two ventilators (Puritan-Bennett 7200 and Servo 900C). NO concentration was measured within the trachea of an attached lung model using a fast-response chemiluminescence NO analyzer. NO concentration was also measured in the inspiratory limb using the electrochemical analyzer of the INOvent. For three NO concentrations (2, 5, and 20 ppm), the ventilators were set for constant flow volume control ventilation, pressure control ventilation, and spontaneous breathing with pressure support ventilation or synchronized intermittent mandatory ventilation. Different tidal volumes (300, 500, 750, and 1,000 mL) and inspiratory times (1 and 2 s) were evaluated. NO2 formation for both ventilators and delivery systems were evaluated at 20 ppm and 95% O2-. RESULTS: Regardless of ventilatory pattern, both systems delivered a constant NO concentration. The error between the target and the delivered NO dose for the INOvent was -1.3+/-3.6% with the Puritan-Bennett 7200 and -3.9+/-4.3% with the Servo 900C. For the premixing system, the error was -5.5+/-4.8% with the Puritan-Bennett 7200 and -6.7+/-6.2% with the Servo 900C. NO2 concentrations were 0.5+/-0.1 ppm during NO delivery by the INOvent, 5.8+/-1.6 ppm when NO was premixed with air, 0.3+/-0.1 ppm when NO was premixed with N2. CONCLUSION: The INOvent provides a constant NO concentration independent of the ventilatory pattern, and NO2 formation is minimal.

Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension.

Sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO; Et2N-[N(O)NO]Na) is a compound that spontaneously generates nitric oxide (NO). Because of its short half-life (2.1 min), we hypothesized that inhaling DEA/NO aerosol would selectively dilate the pulmonary circulation without decreasing systemic arterial pressure. We compared the pulmonary selectivity of this new NO donor with two other reference drugs: inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheep with pulmonary hypertension induced by the infusion of U-46619, we compared the hemodynamic effects of DEA/NO with those of incremental doses of inhaled NO gas. In seven additional awake sheep, we examined the hemodynamic effects of incremental doses of inhaled nitroprusside (i.e., SNP). Inhaled NO gas selectively dilated the pulmonary vasculature. Inhaled DEA/NO produced nonselective vasodilation; both systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were reduced. Inhaled SNP selectively dilated the pulmonary circulation at low concentrations (< or = 10(-2)M), inducing a decrease of PVR of up to 42% without any significant decrease of SVR(-5%), but nonselectively dilated the systemic circulation at larger doses (> 10(-2)M). In conclusion, despite its short half-life, DEA/NO is not a selective pulmonary vasodilator compared with inhaled NO. Inhaled SNP appears to be selective to the pulmonary circulation at low doses but not at higher levels.

Selective pulmonary vasodilation induced by aerosolized zaprinast.

BACKGROUND: Zaprinast, an inhibitor of guanosine-3',5'-cyclic monophosphate (cGMP)-selective phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators (including inhaled nitric oxide [NO]). The present study was designed to examine the effects of inhaled nebulized zaprinast, alone, and combined with inhaled NO. METHODS: Eight awake lambs with U46619-induced pulmonary hypertension sequentially breathed two concentrations of NO (5 and 20 ppm), followed by inhalation of aerosols generated from solutions containing four concentrations of zaprinast (10, 20, 30, and 50 mg/ml). The delivered doses of nebulized zaprinast at each concentration (mean +/- SD) were 0.23 +/- 0.06, 0.49 +/- 0.14, 0.71 +/- 0.24, and 1.20 +/- 0.98 mg x kg(-1) x min(-1), respectively. Each lamb also breathed NO (5 and 20 ppm) and zaprinast (0.23 +/- 0.06 mg x kg[-1] x min[-1]) in combination after a 2-h recovery period. RESULTS: Inhaled NO selectively dilated the pulmonary vasculature. Inhaled zaprinast selectively dilated the pulmonary circulation and potentiated and prolonged the pulmonary vasodilating effects of inhaled NO. The net transpulmonary release of cGMP was increased by inhalation of NO, zaprinast, or both. The duration of the vasodilation induced by zaprinast inhalation was greater than that induced by NO inhalation. CONCLUSIONS: Aerosolization of a cGMP-selective phosphodiesterase inhibitor alone or combined with NO may be a useful noninvasive therapeutic method to treat acute or chronic pulmonary hypertension.

Selective pulmonary vasodilation by intravenous infusion of an ultrashort half-life nucleophile/nitric oxide adduct.

BACKGROUND: PROLI/NO (C5H7N3O4Na2 x CH3OH) is an ultrashort-acting nucleophile/NO adduct that generates NO (half-life 2 s at 37 degrees C and pH 7.4). Because of its short half-life, the authors hypothesized that intravenous administration of this compound would selectively dilate the pulmonary vasculature but cause little or no systemic hypotension. METHODS: In eight awake healthy sheep with pulmonary hypertension induced by 9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha, the authors compared PROLI/NO with two reference drugs-inhaled NO, a well-studied selective pulmonary vasodilator, and intravenous sodium nitroprusside (SNP), a nonselective vasodilator. Sheep inhaled 10, 20, 40, and 80 parts per million NO or received intravenous infusions of 0.25, 0.5, 1, 2, and 4 microg x kg-1 x min-1 of SNP or 0.75, 1.5, 3, 6, and 12 microg x kg-1 x min-1 of PROLI/NO. The order of administration of the vasoactive drugs (NO, SNP, PROLI/NO) and their doses were randomized. RESULTS: Inhaled NO selectively dilated the pulmonary vasculature. Intravenous SNP induced nonselective vasodilation of the systemic and pulmonary circulation. Intravenous PROLI/NO selectively vasodilated the pulmonary circulation at doses up to 6 microg x kg-1 x min-1, which decreased pulmonary vascular resistance by 63% (P < 0.01) from pulmonary hypertensive baseline values without changing systemic vascular resistance. At 12 microg x kg-1 x min-1, PROLI/NO decreased systemic and pulmonary vascular resistance and pressure. Exhaled NO concentrations were higher during PROLI/NO infusion than during SNP infusion (P < 0.01 with all data pooled). CONCLUSIONS: The results suggest that PROLI/NO could be a useful intravenous drug to vasodilate the pulmonary circulation selectively.

Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection.

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.

The biologic basis for inhaled nitric oxide.

Nitric oxide is produced by nitric oxide synthase enzymes, which cleave the amino acid L-arginine to form nitric oxide and the amino acid L-citrulline. Many of the biologic actions of nitric oxide occur because nitric oxide activates guanylate cyclase, which in turn synthesizes a second-messenger molecule, cyclic guanosine 3',5'-monophosphate (cGMP). The increased concentration of cGMP activates cGMP-dependent protein kinase, reducing intracellular concentrations of calcium and relaxing smooth muscle. Nitric oxide also has many important effects that may not be mediated through increases of pulmonary cGMP activity. These include the ability to scavenge oxygen free radicals, reduce oxygen toxicity, and inhibit platelet and leukocyte aggregation. Nitric oxide is metabolized and excreted via a number of diverse pathways that may modify the toxicity of the molecule.

Use of inhaled nitric oxide for ARDS.

Inhalation of low inspired concentration of nitric oxide reduces pulmonary hypertension and increases arterial oxygen tension in patients with acute respiratory distress syndrome (ARDS), and appears to be safe. Research on the physiologic mechanisms regulating the action of inhaled nitric oxide may provide clinicians with ways to further potentiate and prolong its beneficial effects.