Phenylephrine and inhaled nitric oxide in adult respiratory distress syndrome. When are two better than one?
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Administration, Inhalation↗
Biomedical subjects
R G Pearl
Publications and source records attributed to R G Pearl.
Prediction of poor outcome of intensive care unit patients admitted from the emergency department.
OBJECTIVE: To assess whether physicians can identify very low likelihood of survival and very low likelihood of favorable functional outcome in adult nontrauma patients before admission to the intensive care unit (ICU) from the emergency department (ED). DESIGN: Prospective survey. SETTING: University hospital ED and ICU. PARTICIPANTS AND PATIENTS: Critical care fellows and ED physicians and all adult nontrauma patients admitted to the ICU from the ED over 1 yr. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The survey compared predictions of poor outcome from three sources: critical care fellows, ED physicians, and the admission Mortality Probability Model (MPM0). All patients were followed until hospital death or hospital discharge. Six-month follow-up data were obtained for patients predicted to have a < 2% chance of surviving with favorable functional outcome. In the ED, critical care fellows and ED physicians predicted likelihood of patient survival and likelihood of favorable functional outcome. MPM0 estimates of mortality were determined. The sensitivities, specificities, and positive predictive values were calculated for the predictions of < 2% survival and the predictions of < 2% chance of favorable functional outcome made by each prediction group. Complete data were obtained on 236 (96%) of 243 eligible patients. With regard to hospital mortality rate, fellows' predictions had a sensitivity of 27%, a specificity of 99%, and a positive predictive value of 88%; ED physicians' predictions had a sensitivity of 24%, a specificity of 98%, and a positive predictive value of 81%; and MPM0 predictions had a sensitivity of 2%, a specificity of 100%, and a positive predictive value of 100%. With regard to mortality rate combined with poor functional outcome, fellows' predictions had a sensitivity of 35%, a specificity of 99%, and a positive predictive value of 96%; ED physicians' predictions had a sensitivity of 37%, a specificity of 99%, and a positive predictive value of 96%. CONCLUSIONS: If a cutoff point of < 2% predicted survival is used in the triage of patients away from the ICU, the MPM0 has too low a sensitivity to be used as an effective screen. The low sensitivities and relatively low positive predictive values with wide confidence intervals of physician predictions of < 2% survival also preclude their use in triage. The addition of functional outcome as an end point improves the sensitivity, specificity, and positive predictive value of subjective predictions, making triage of patients away from the ICU at the time of ED evaluation a realistic possibility.
Adult↗
Mechanical ventilation and adjuncts in acute respiratory distress syndrome.
Acute respiratory distress syndrome is a response of the lung to both direct and indirect insults. Although much knowledge has been gained in understanding the pathophysiology of the syndrome, overall mortality in the past 25 years remains unchanged. Application of scientific knowledge to present-day technology has yielded advances in ventilator and pharmacological support for the patient with ARDS. Emphasis is now made on the prevention of iatrogenic lung injury with the use of pressure-limited mechanical ventilation, permissive hypercapnia, and artificial means of gas exchange (discussed in the chapter by Dr Furukawa). The role of INO and surfactant, as well as antimediator therapy, in the armamentarium against ARDS appears promising but awaits definitive clinical trials. Only with progress and newer therapies will we be able to improve the outlook for patients and families in the future.
Administration, Inhalation↗
Improved gastric tonometry for monitoring tissue perfusion: the canary sings louder.
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Carbon Dioxide↗
Crystalloid versus colloid versus colloid: all colloids are not created equal.
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Colloids↗
Plasma potentiates the priming effects of endotoxin on platelet activating factor-induced pulmonary hypertension in the rabbit lung.
During Gram-negative sepsis, endotoxin lipopolysaccharide (LPS) may activate host inflammatory responses, resulting in the systemic inflammatory response syndrome and the adult respiratory distress syndrome. In cell culture systems, LPS activation of cellular responses may be potentiated by plasma proteins. In the isolated perfused rabbit lung, LPS administration markedly increases the pulmonary hypertensive response to subsequent administration of platelet activating factor (PAF). We examined whether plasma would potentiate the priming effects of LPS in this model. Male New Zealand White rabbits were used in a standard, isolated buffer-perfused rabbit lung preparation, and the pulmonary hypertensive response to 5 nM PAF was measured after 2 h of perfusion with different LPS doses (0, 1, and 10 ng/mL), with and without plasma (10% by volume). In the absence of plasma, 10 ng/mL LPS, but not 1 ng/mL LPS, increased the pulmonary hypertensive response to subsequent administration of 5 nM PAF. However, in the presence of plasma, 1 ng/mL LPS significantly increased the hypertensive response to subsequent administration of 5 nM PAF. We conclude that components of plasma--possibly LPS binding protein and soluble CD14--potentiate the priming effect of endotoxin, resulting in an augmented pulmonary hypertensive response to PAF. Thus, plasma proteins decrease the threshold at which endotoxin primes the lung and may have a critical role in the pathogenesis of endotoxin-induced acute lung injury.
Acute-Phase Proteins↗
Delayed time response of the continuous cardiac output pulmonary artery catheter.
Previous studies of the accuracy of pulmonary artery catheters (PAC) which provide continuous cardiac output (CCO) monitoring have investigated the performance during steady-state conditions. We compared the response time to hemodynamic change using a CCO PAC and an ultrasonic flow probe (UFP). In five sheep, a CCO PAC was inserted, and an UFP for measurement of CCO was placed around the pulmonary artery via a left thoracotomy. Six interventions which rapidly alter cardiac output were studied: crystalloid bolus, balloon inflation in the inferior vena cava (IVC), IVC balloon deflation, dobutamine infusion, hemorrhage, and reinfusion of blood. Cardiac output measured before and after each intervention was used to calculate the total change caused by the intervention, and the time intervals from intervention to 20%, 50%, and 80% of that change were noted. For all interventions, the time response of CCO was significantly slower than UFP. The largest differences were seen with the rapid infusion of lactated Ringer's solution for which the time interval for 20% change was 7.3 +/- 2.3 min (mean +/- SD) for CCO versus 0.5 +/- 0.3 min for UFP. The time interval for 80% change was 14.5 +/- 4.1 min for CCO versus 1.8 +/- 0.9 min with UFP. The current study demonstrates clinically important time delays in the response of the CCO catheter. This delay must be considered when rapid alterations of the hemodynamic state may occur.
Adrenergic beta-Agonists↗
Inhibition of endogenous nitric oxide synthase potentiates nitrovasodilators in experimental pulmonary hypertension.
BACKGROUND: The role of endogenous nitric oxide (NO) in the regulation of pulmonary vascular tone is complex. Inhibition of endogenous NO synthase, potentially through upregulation of guanylyl cyclase, results in an increase in potency of nitrovasodilators in the systemic circulation. This study considered whether inhibition of endogenous NO synthase would increase the potency of nitrovasodilators, but not of cyclic adenosine monophosphate-dependent vasodilators, in the pulmonary vasculature. METHODS: We used the isolated buffer-perfused rabbit lung. Preparations were randomized to receive either pretreatment with NG-nitro-L-arginine methyl ester (or L-NAME, an inhibitor of endogenous NO synthase) or no pretreatment. Stable pulmonary hypertension was then produced by infusing the thromboxane A2 analog U46619. The dose-response characteristics of two nitrovasodilators, sodium nitroprusside and nitroglycerin, and two nonnitrovasodilators, prostaglandin E2 and 5'-N-ethylcarboxamidoadenosine, were studied. RESULTS: Inhibition of endogenous NO synthase caused no significant changes in baseline pulmonary artery pressure but did significantly reduce the U46619 infusion rate required to produce pulmonary hypertension. Pretreatment with L-NAME (vs. no L-NAME) resulted in significantly lower values of the log median effective dose with sodium nitroprusside and nitroglycerin. In contrast, pretreatment with L-NAME resulted in no changes in the dose-response characteristics of the cyclic adenosine monophosphate-mediated, NO-independent vasodilators prostaglandin E1 and 5'-N-ethylcarboxamidoadenosine. CONCLUSIONS: These data suggest that endogenous NO synthase is not an important regulator of basal pulmonary tone in this model but is an important modulator of pulmonary vascular responses to vasoconstriction and to nitrovasodilators. The pulmonary vasodilator effects of nitrovasodilators, but not of nonnitrovasodilators, may depend on the level of activity of NO synthase.
Adenosine↗
Pulmonary capillary pressure measurement from pulmonary artery occlusion pressure decay profile analysis in sheep.
Pulmonary capillary pressure (Ppc), the major factor responsible for pulmonary edema, cannot be directly measured in intact subjects but may be estimated by analysis of the pressure decay profile after pulmonary artery catheter balloon inflation. We compared three different methods of pulmonary artery occlusion pressure (Ppao) decay profile analysis to estimates of Ppc derived from lymph flow measurements in halothane-anesthesized sheep. The relationship between Ppc and lymph flow was first determined by increasing Ppc by left atrial balloon inflation, and was then used to determine Ppc during pulmonary hypertension produced by infusion of a thromboxane analog. All three methods of Ppao decay profile analysis demonstrated a correlation with Ppc estimated from lymph flow. However, the method using a single exponential analysis significantly overestimated Ppc, and none of the methods reliably estimated changes in the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension. These results suggest that Ppao decay profile analysis as currently performed has limited application.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Risk of pulmonary angiography.
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Angiography↗
Inhaled nitric oxide does not alter the longitudinal distribution of pulmonary vascular resistance.
Because the effects of inhaled nitric oxide (NO) may be localized to its site of delivery, we studied the effects of inhaled NO on the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension in perfused rabbit lungs. Before NO administration, pulmonary hypertension was produced by infusion of the thromboxane A2 mimetic U-46619 in all lungs. Pulmonary vascular resistance was divided into arterial, microvascular, and venous components by arterial and venous occlusion techniques. In the buffer-perfused lung, all doses of inhaled NO (5, 20, and 80 ppm) produced small decreases (approximately 3 mmHg) in pulmonary arterial pressure (Ppa), with equivalent proportional reductions in all segmental vascular resistances. Similar results were obtained after an extended inhaled NO dose range of 20, 80, and 240 ppm. In the buffer-perfused lung, inhibition of endogenous NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME) potentiated the effects of U-46619. Subsequent inhaled NO administration produced larger decreases (approximately 7 mmHg) in Ppa with equivalent proportional reductions in all segmental vascular resistances. In the blood-perfused lung, L-NAME did not alter baseline pulmonary pressures. Administration of inhaled NO during U-46619-induced pulmonary hypertension produced dose-related decreases in Ppa. The highest dose (80 ppm) of inhaled NO decreased Ppa by 3.5 mmHg, with equivalent proportional reductions in all segmental vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Effect of blood and albumin on pulmonary hypertension and edema in perfused rabbit lungs.
Perfusate composition may alter pulmonary hemodynamics and edema formation in perfused lungs. Perfusion for 3 h with Krebs-Henseleit solution with 3% bovine serum albumin did not produce pulmonary hypertension, pulmonary edema (assessed by lung wet-to-dry wt ratio), or increased macromolecular permeability (assessed by 125I-albumin uptake). Addition of blood to hematocrit levels of 10 or 20% resulted in pulmonary hypertension during the final hour of perfusion but not pulmonary edema or increased macromolecular permeability. Pulmonary hypertension during blood perfusion was primarily due to increased precapillary resistance. Perfusion with buffer solution without albumin produced edema and increased macromolecular permeability but not pulmonary hypertension. In lungs perfused with blood (20% hematocrit), thromboxane B2 levels increased in parallel with the pulmonary hypertension, and inhibition of cyclooxygenase or thromboxane synthase with indomethacin or dazmegrel prevented pulmonary hypertension. Perfusion with leukopenic blood (from prior nitrogen mustard administration or from filtration) also prevented pulmonary hypertension. We conclude that blood perfusion produces pulmonary hypertension via thromboxane A2 generation, which depends on leukocyte activation, and that perfusion with buffer solutions without albumin produces edema and increased permeability without pulmonary hypertension.
Albumins↗
Inhaled nitric oxide in anesthesia and critical care medicine.
Inhaled NO is an exciting new drug and has enormous potential in the therapy of a wide variety of acute, and possibly chronic, cardiopulmonary disorders. No reports of controlled, randomized, and blinded trials have been published concerning the use of inhaled NO in any clinical condition. In the United States, use of inhaled NO currently requires an investigational new drug approval from the Food and Drug Administration. Physicians involved in anesthesia and critical care medicine have a unique opportunity to validate a new mode of therapy in acute care, and optimal evaluation should be undertaken so that the real therapeutic role of inhaled NO may be defined.
Administration, Inhalation↗
Inhaled nitric oxide.
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Administration, Inhalation↗
Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant-induced acute lung injury.
Inhaled nitric oxide (NO) decreases pulmonary arterial pressure (Ppa) and improves oxygenation in the adult respiratory distress syndrome. Endogenous NO can modulate the development of acute tissue injury. We investigated the effects of inhaled NO and of inhibition of endogenous NO synthase in oxidant-induced acute lung injury in the isolated buffer-perfused rabbit lung. A rapid (45 min) and a more gradual (3 h) model of oxidant-induced acute lung injury were developed using the production of superoxide free radicals from the reaction of purine with low and high doses of xanthine oxidase, respectively. The effects of rapid injury included increases in Ppa, precapillary pulmonary vascular resistance, capillary filtration coefficient (Kfc), and lung weight. In the gradual-injury model, only lung weight and Kfc increased. Pretreatment with inhaled NO (90-120 ppm) prevented the rise in Ppa and precapillary pulmonary vascular resistance in the rapid-injury model and prevented elevation of Kfc in the gradual-injury model. Pretreatment with an inhibitor of endogenous NO synthase (NG-nitro-L-arginine methyl ester) resulted in increased pulmonary capillary pressure and postcapillary pulmonary vascular resistance in the rapid-injury model and increased peak Ppa, pulmonary capillary pressure, and pulmonary vascular resistance in the gradual-injury model. These data suggest that in oxidant-induced acute lung injury 1) inhaled NO may attenuate increases in capillary permeability and 2) endogenous NO may function as a modulator of pulmonary vascular tone without affecting capillary permeability.
Administration, Inhalation↗
Effect of l-glutamine on pulmonary hypertension in the perfused rabbit lung.
The effects of l-glutamine on pulmonary hypertension in the isolated perfused rabbit lung were investigated. Pulmonary hypertension was produced by the thromboxane-A2 mimetic U46619. l-Glutamine at a dose of 0.04 mM produced a sustained increase in pulmonary artery pressure (PAP) and subsequent administration of an equimolar dose of l-arginine did not affect PAP. l-Glutamine at a dose of 0.5 mM transiently increased PAP, which then decreased to baseline (pre-glutamine) values. When endogenous nitric oxide (NO) synthesis was inhibited with NG-nitro-l-arginine methylester, l-glutamine at a dose of 0.04 mM decreased PAP. These results demonstrate that the effect of l-glutamine on PAP during pulmonary hypertension depends upon dose, time and the presence of endogenous NO synthesis. We believe that the results can be explained by two different effects of l-glutamine, namely a direct inhibition of NO release by glutamine and the donation of nitrogen atoms by glutamine for additional NO or other vasodilator synthesis. Since plasma glutamine levels are 0.4-0.7 mM, endogenous l-glutamine may play a modulatory role during pulmonary hypertension.
Animals↗
Serum but not plasma produces injury in the perfused rabbit lung.
Serum contains proteins that may produce lung injury directly by affecting endothelial cells and indirectly by modulating the effects of endotoxin (lipopolysaccharide). We studied the effects of 10% serum, 10% plasma, and 10% plasma plus 2 micrograms/mL lipopolysaccharide on pulmonary hypertension and vascular permeability in the isolated perfused rabbit lung. Control lungs perfused with Krebs-Henseleit buffer containing 3% albumin for 2 h had stable pulmonary vascular pressures and permeability (measured by the capillary filtration coefficient). Serum produced pulmonary hypertension and increased pulmonary vascular permeability. In contrast, plasma, with and without lipopolysaccharide, did not alter pulmonary vascular pressures or permeability. Pretreatment with the cyclooxygenase inhibitor indomethacin prior to the addition of serum prevented the serum-induced increase in pulmonary vascular pressures and permeability. We conclude that the deleterious effects of serum are not due to plasma proteins per se, but instead are related to activation of the coagulation cascade during preparation of the serum. The deleterious effects of serum appear to be mediated by cyclooxygenase metabolites of arachidonic acid. Finally, endotoxin, even with the addition of plasma, does not directly produce lung injury.
Animals↗