Information de reference pour ce titreAccession Number: | 00002953-200003000-00035.
|
Author: | van Heerden, P. Vernon MD; Barden, Anne PhD; Michalopoulos, Nicholas BSc; Bulsara, Max K. MSc; Roberts, Brigit L. RN
|
Institution: | *From the Department of Pharmacology (Dr. van Heerden), University Department of Medicine (Dr. Barden), and Biostatistical Consulting Service (Mr. Bulsara), Department of Public Health, University of Western Australia, Nedlands, Australia; Department of Haematology (Mr. Michalopoulos), PathCentre, Perth, Australia; and Department of Intensive Care (Ms. Roberts), Sir Charles Gairdner Hospital, Perth, Australia.
|
Title: | Dose-Response to Inhaled Aerosolized Prostacyclin for Hypoxemia Due to ARDS*.[Article]
|
Source: | Chest. 117(3):819-827, March 2000.
|
Abstract: | Study objectives: This study was carried out to determine the efficacy of and dose-response relationships to inhaled aerosolized prostacyclin (IAP), when used as a selective pulmonary vasodilator (SPV) in patients with severe hypoxemia due to ARDS.
Design: Unblinded, interventional, prospective clinical study.
Setting: A general ICU in a university-affiliated, tertiary referral center.
Patients: Nine adult patients with severe ARDS (lung injury score, >= 2.5).
Interventions: All patients received IAP over the dose range 0 to 50 ng/kg/min. The IAP was delivered via a jet nebulizer placed in the ventilator circuit. Dose increments were 10 ng/kg/min every 30 min.
Measurements and results: Cardiovascular parameters (cardiac index and mean pulmonary and systemic pressures), indexes of oxygenation (PaO2/fraction of inspired oxygen [FIO2] ratio and alveolar-arterial oxygen partial pressure difference [P(A-a)O2]) and shunt fraction were measured or calculated at each dose interval, as were platelet aggregation and systemic levels of prostacyclin metabolite (6-keto prostaglandin F1[alpha]). A generalized linear regression model was used to determine a dose effect of IAP on these parameters. The Wilcoxon rank sum test for related measures was used to compare the effects of various doses of IAP. IAP acted as an SPV, with a statistically significant dose-related improvement in PaO2/FIO2 ratio (p = 0.003) and P(A-a)O2 (p = 0.01). Systemic prostacyclin metabolite levels increased significantly in response to delivered IAP (p = 0.001). There was no significant dose effect on systemic or pulmonary arterial pressures, or on platelet function, as determined by platelet aggregation in response to challenge with adenosine diphosphate.
Conclusions: IAP is an efficacious SPV, with marked dose-related improvement in oxygenation and with no demonstrable effect on systemic arterial pressures over the dose range 0 to 50 ng/kg/min. Despite significant systemic levels of prostacyclin metabolite, there was no demonstrable platelet function defect.
(C) 2000Elsevier, Inc.
|
Author Keywords: | aerosolized prostacylin; ARDS.
|
References: | 1 Bernard GR, Artigas A, Brigham KL, et al. Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination. Intensive Care Med 1994; 20:225-232
2 Vallance P, Collie J. Biology and clinical relevance of nitric oxide. BMJ 1994; 309:453-457
3 Zapol WM. Nitric oxide inhalation in acute respiratory distress syndrome: it works, but can we prove it? Crit Care Med 1998; 26:2-3
4 Walmrath D, Schneider T, Pilch J, et al. Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet 1993; 342:961-962
5 Wetzel RC. Aerosolized prostacyclin: in search of the ideal pulmonary vasodilator. Anesthesiology 1995; 82:1315-1317
6 Walmrath D, Schneider T, Pilch J, et al. Effects of aerosolized prostacyclin in severe pneumonia: impact of fibrosis. Am J Respir Crit Care Med 1995; 151:724-730
7 van Heerden PV, Power BM, Leonard RC. Delivery of inhaled aerosolised prostacyclin (IAP). Anaesth Intensive Care 1998; 24:624-625
8 van Heerden PV, Webb SAR, Hee G, et al. Inhaled aerosolized prostacyclin as a selective pulmonary vasodilator for the treatment of severe hypoxaemia. Anaesth Intensive Care 1996; 24:87-90
9 Webb SAR, Stott S, van Heerden PV. The use of inhaled aerosolized prostacyclin (IAP) in the treatment of pulmonary hypertension secondary to pulmonary embolism. Intensive Care Med 1996; 22:353-355
10 Bein T, Mctz C, Keyl C, et al. Cardiovascular and pulmonary effects of aerosolized prostacyclin administration in severe respiratory failure using a ventilator nebulizing system. J Cardiovasc Pharmacol 1996; 27:583-586
11 Scheeren T, Radermacher P. Prostacyclin (PGI2): new aspects of an old substance in the treatment of critically ill patients. Intensive Care Med 1997; 23:146-158
12 Soditt V, Aring C, Groneck P. Improvement of oxygenation induced by aerosolized prostacyclin in a preterm infant with persistent pulmonary hypertension of the newborn. Intensive Care Med 1997; 23:1275-1278
13 Silvester W. Prostacyclin in review: its physiology and role in intensive care. Intensive Care World 1997; 15:22-39
14 Turanlahti MI, Laitinen PO, Sarna SJ, et al. Nitric oxide, oxygen, and prostacyclin in children with pulmonary hypertension. Heart 1998; 79:169-174
15 Haraldsson A, Kieler-Jensen N, Nathorst-Westfelt U, et al. Comparison of inhaled nitric oxide and inhaled aerosolized prostacyclin in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance. Chest 1998; 114:780-786
16 Zobel G, Dacar D, Rodl S, et al. Inhaled nitric oxide versus inhaled prostacyclin and intravenous versus inhaled prostacyclin in acute respiratory failure with pulmonary hypertension in piglets. Pediatr Res 1995; 38:198-204
17 Haraldsson A, Kieler-Jensen N, Nathorst-Westfelt U, et al. Inhaled prostacyclin compared to inhaled nitric oxide in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance [abstract]. Br J Anaesth 1996; 76(suppl 1):14
18 Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13:818-829
19 Murray JF, Matthay MA, Luce JM, et al. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988; 138:720-723
20 Zwissler B, Kemming G, Habler O, et al. Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome. Am J Respir Crit Care Med 1996; 154:1671-1677
21 Machleidt C, Forsteman U, Anhut H, et al. Formation and elimination of prostacyclin metabolites in the cat in vivo as determined by radioimmunoassay of unextracted plasma. Eur J Pharmacol 1981; 74:19-26
22 Machin SJ, Chamone DA, Defreyn G, et al. The effect of clinical prostacyclin infusions in advanced arterial disease on platelet function and plasma 6-keto PGF1 alpha levels. Br J Haematol 1981; 47:413-422
23 Berry CN, Hoult JR. 6-keto-prostaglandin E1: its formulation by platelets from prostacyclin and resistance to pulmonary degradation. Pharmacology 1983; 26:324-330
24 Rosenkranz B, Fischer C, Weimer KE, et al. Metabolism of prostacyclin and 6-keto-prostaglandin F1 alpha in man. J Biol Chem 1980; 255:194-198
25 Belch JJ, Greer I, McLaren M, et al. Measurement of prostacyclin metabolites [letter]. Lancet 1983; 2:1504
26 Wong WK, Lachenbruch PA. Tutorial in biostatistics: designing studies for dose response. Stat Med 1996; 15:343-359
27 Burghuber OC, Silberbauer K, Haber P, et al. Pulmonary and antiaggregatory effects on prostacyclin after inhalation and intravenous infusion. Respiration 1984; 45:450-454
28 van Heerden PV, Gibbs NM, Michalopoulos N. The effect of low concentrations of prostacyclin on platelet function in vitro. Anaesth Intensive Care 1997; 24:343-346
29 Kollef MH, Schuster DP. The acute respiratory distress syndrome. N Engl J Med 1995; 332:27-37
30 Modig J. Adult respiratory distress syndrome: pathogenesis and treatment. Acta Chir Scand 1986; 152:241-249
31 Meduri GU, Kohler G, Headley S, et al. Inflammatory cytokines in the BAL of patients with ARDS. Chest 1995; 108:1303-1314
32 Knaus WA. The ongoing mystery of ARDS. Intensive Care Med 1996; 22:517-518
33 Jenkinson SG. Oxygen toxicity. New Horiz 1993; 1:504-511
34 Kleen M, Habler O, Hofstetter C, et al. Efficacy of inhaled prostanoids in experimental pulmonary hypertension. Crit Care Med 1998; 26:1103-1109
35 Royston D. Inhalation agents for pulmonary hypertension. Lancet 1993; 342:941-942
36 Ichinose F, Adrie C, Hurford WE, et al. Selective pulmonary vascdilation induced by aerosolized zaprinast. Anesthesiology 1998; 88:410-416
|
Language: | English.
|
Document Type: | Clinical Investigations in Critical Care.
|
Journal Subset: | Clinical Medicine.
|
ISSN: | 0012-3692
|
NLM Journal Code: | 0231335, d1c
|
Annotation(s) | |
|
|