Actions of amiodarone on mitochondrial ATPase and lactate dehydrogenase activities in guinea pig heart preparations

The effects of amiodarone on mitochondrial ATPase (EC 3.6.1.3) and lactate dehydrogenase (LDH: EC 1.1.1.27) activities were studied in guinea pig mitochondrial preparations in order to test the hypothesis that amiodarone exerts some of its effects as a result of multiple actions on membrane-bound enzymes and receptors. Amiodarone inhibited the ATPase activity in the range of 10 pM to 10 mM (n = 10) with IC50 values of 56.4 +/- 7.2 microM. However, although the inhibitory action was very significant (P < 0.0001, compared to the control) in the concentration range of 100 pM to 10 microM, the differences in individual enzyme responses showed very weak correlation with drug concentration. In this region, the inhibitory effects were almost constant at approximately 37%. Below 100 pM and above this range however, the concentration-response relationships were steep, reaching total inhibition at approximately 2.5 mM. Amiodarone also exerted concentration-dependent inhibitory effects on lactate dehydrogenase activity. However, over the effective inhibitory concentration range (5-95%) of 7.5 microM to 2.5 mM (n = 8) and IC50 value of 108 +/- 6 microM, its inhibitory potency was twofold weaker than that of its ATPase inhibition. We propose that these actions contribute, at least in part, to the mechanism(s) of some of the pharmacological actions of amiodarone.     

Clinical predictors of implantable cardioverter-defibrillator shocks (results of the CASCADE trial). Cardiac Arrest in Seattle, Conventional versus Amiodarone Drug Evaluation

The Cardiac Arrest in Seattle, Conventional Versus Amiodarone Drug Evaluation (CASCADE) study evaluated antiarrhythmic drug therapy in high-risk survivors of out-of-hospital ventricular fibrillation. Antiarrhythmic drug therapy for 228 patients was randomized to amiodarone or conventional antiarrhythmic drugs. Additional therapy with an implantable cardioverter-defibrillator was provided to 105 of these patients. Clinical predictors of shocks were evaluated for the 88 patients with coronary artery disease (amiodarone 46, conventional 42), treated with an implantable cardioverter-defibrillator. Survival free of all shocks at 2 years was 77% for patients taking amiodarone and 42% for those receiving conventional therapy (p = 0.014). Two-year survival free of syncopal shocks was 98% for amiodarone-treated patients and 81% for those receiving conventional agents (p = 0.01). Multiple clinical factors were evaluated by Cox analysis for potential clinical predictors of shocks. The independent clinical predictors of shocks were low ejection fraction (p = 0.002), female gender (p = 0.007) and conventional antiarrhythmic drug therapy (p = 0.015). The only independent predictor of a shock associated with syncope was conventional antiarrhythmic drug therapy (p = 0.035). Patients treated with amiodarone receive fewer shocks than patients treated with conventional drug therapy.     

The role of intravenous amiodarone in the management of cardiac arrhythmias

PURPOSE: To review the electropharmacology, clinical applications, side effects, and hemodynamic profile of intravenous amiodarone. DATA SOURCES: The MEDLINE database was searched for English-language material, including reports of clinical trials and in vivo studies, review articles, and abstracts presented at national symposia, that was published between 1985 and 1996. Bibliographies of textbooks and articles were also examined. STUDY SELECTION: Studies that reported on the efficacy, toxicity, and hemodynamic profile of intravenous amiodarone and studies that examined the pharmacologic behavior of intravenous amiodarone in laboratory models were reviewed. DATA EXTRACTION: Study design and quality and relevant data on efficacy of suppression and treatment of arrhythmias with oral and intravenous amiodarone therapy, the reported mechanisms of antiarrhythmic effect, and hemodynamic changes seen with therapy were analyzed. DATA SYNTHESIS: Amiodarone is a unique antiarrhythmic agent that is now available in oral and intravenous forms in the United States. The use of intravenous amiodarone in the short-term treatment of life-threatening or hemodynamically unstable rhythm disturbances has generated much interest. Amiodarone has many electropharmacologic actions, some of which differ between the oral and intravenous forms. The wide clinical application of amiodarone includes treatment and prevention of supraventricular and ventricular arrhythmias and arrhythmias related to myocardial infarction. Intravenous amiodarone is effective for supraventricular and ventricular arrhythmias that are resistant to other antiarrhythmic agents. The effectiveness of intravenous amiodarone as short-term treatment also suggests that the drug has an important role in protocols of advanced cardiac life support. Intravenous amiodarone seems to have an overall favorable hemodynamic profile and does not produce many of the unwanted long-term side effects associated with oral therapy. CONCLUSION: Intravenous amiodarone shows much promise for the short-term treatment of unstable arrhythmias. Its favorable hemodynamic effects and minimal short-term side effects make it an attractive option in the management of cardiac arrhythmias.     

The diagnostic value of symptoms and signs in childhood abdominal pain

Amiodarone is a benzofuran derivative with a chemical structure similar to thyroxine. Originally introduced to treat angina pectoris, amiodarone was found to have antiarrhythmic properties, and in 1985, was approved in the United States for treatment of life-threatening ventricular arrhythmias. It is now used for various ventricular and supraventricular arrhythmias refractory to conventional first-line medications, and as a result, side effects have been observed with increased frequency. The most severe and potentially life-threatening of these side effects is the development of pulmonary toxicity. Typically, amiodarone pulmonary toxicity (APT) is manifested by acute pneumonitis and chronic fibrosis. Amiodarone-associated hemoptysis (AAH) is a rare occurrence. The authors describe a case of AAH successfully treated with cessation of drug and steroid therapy.     

Amiodarone causes endothelium-dependent vasodilation in human hand veins in vivo

OBJECTIVE: Amiodarone, a class III antiarrhythmic agent, is a potent coronary vasodilator. However, direct evidence for its vasodilatory effects in human vasculature in vivo is not available. The aim of the study was to investigate the short-term effects of amiodarone in preconstricted human hand veins and to explore the underlying mechanisms. METHODS: Thirty-one healthy male volunteers were studied with the use of the dorsal hand vein compliance technique. The hand veins of the subjects were preconstricted with the alpha 1-adrenergic receptor agonist phenylephrine, and amiodarone, inhibitors of nitric oxide formation (NG-monomethyl-L-arginine, L-NMMA), and adenosine triphosphate-dependent potassium channels (glyburide [INN, glibenclamide]) were infused in the presence or absence of a cyclooxygenase inhibitor (acetylsalicylic acid), and the venodilator effect was measured. Furthermore, amiodarone was infused in prostaglandin F2 alpha (dinoprost)-preconstricted hand veins. RESULTS: Amiodarone produced dose-dependent venodilation (51% +/- 3% maximum). Maximum amiodarone-induced venodilation was lower in dinoprost compared with phenylephrine-preconstricted veins. Pretreatment with acetylsalicylic acid reduced the amiodarone-induced venodilation by 40% +/- 6%. L-NMMA reduced the amiodarone-induced venodilation after pretreatment with acetylsalicylic acid by 72% +/- 3%. Glyburide decreased the venodilatory response of amiodarone by 31% +/- 11%, whereas only a slight but not statistically significant additional reduction in venodilation was detected after pretreatment with acetylsalicylic acid. Infusion of the solvents of commercially available amiodarone (polysorbate 80 and benzyl alcohol) did not cause vasodilation in phenylephrine-preconstricted veins. CONCLUSIONS: Amiodarone dilates preconstricted human hand veins in vivo and acts as a venodilator through the cyclooxygenase pathway, activation of nitric oxide synthase, and blockade of alpha adrenergic mechanisms.     

Rehospitalization in surviving patients of out-of-hospital ventricular fibrillation (the CASCADE Study). Cardiac Arrest in Seattle: Conventional Amiodarone Drug Evaluation

Surviving patients of out-of-hospital ventricular fibrillation (VF) often need rehospitalization after initial hospital discharge, but little is known regarding the frequency of or reasons for rehospitalization. Rehospitalization was examined in 224 patients enrolled in the Cardiac Arrest in Seattle: Conventional Amiodarone Drug Evaluation (CASCADE) study, a randomized clinical trial comparing amiodarone with other antiarrhythmic drug therapy in survivors of out-of-hospital VF. The annual rate of rehospitalization was 79/100 patients/year; 168 of 224 patients (75%) were hospitalized at least once before censoring or cardiac mortality. Baseline left ventricular ejection fraction was significantly lower in patients who were rehospitalized. Rehospitalization rates were lower in patients randomized to amiodarone therapy and in those with the automatic implantable cardioverter-defibrillator, although neither difference was statistically significant. However, length of stay for the first rehospitalization was shorter for patients with automatic implantable cardioverter-defibrillators (p = 0.005). More than 50% of patients were rehospitalized in the first year after enrollment; 65% with ejection fractions < or = 0.3 were rehospitalized in the first year. Rehospitalization was a frequent occurrence for surviving patients of out-of-hospital VF, particularly in those with low ejection fractions.     

Clinical tolerance of oral loading with elevated doses of amiodarone in a group of patients with heart failure

Amiodarone is a choice drug for the treatment of patients suffering from life-threatening hyperkinetic ventricular arrhythmias and depressed ventricular function. The drug is characterized by a remarkably long halflife and a delayed initial activity after oral administration of the usual loading levels. The aim of this study was to establish: -the clinical tolerance to elevated doses in patients with heart failure presenting complex, hyperkinetic ventricular arrhythmias; -the possibility to shorten hospitalization as a result of the oral loading; -whether this administration route would take less time to be efficacious. For this purpose, 30 patients with heart failure and complex, hyperkinetic ventricular arrhythmias were treated with 0.50 mg/kg body weight of amiodarone for three days and with 0.30 mg/kg on the 4th and 5th days, followed by a maintenance period of treatment with 200-400 mg daily. All patients underwent a 24-h Holter test before and after administration and an echocardiographic examination showing an average ejection fraction of approximately 30%. Amiodarone was clinically well tolerated; only 2 patients required discontinuation of therapy whereas, among the the remaining 28 patients, 2 cases of transient hypotension and 3 cases of gastroenteric disorders were observed. It was concluded that elevated doses of amiodarone were well tolerated, which allowed to reduce the loading period and, therefore, hospitalization.     

Comparison of S(-)-bupivacaine with racemic (RS)-bupivacaine in supraclavicular brachial plexus block

Control of heart rate in critically ill patients who develop atrial fibrillation or atrial flutter can be difficult. Amiodarone may be an alternative agent for heart rate control if conventional measures are ineffective. We retrospectively studied intensive care unit patients (n = 38) who received intravenous amiodarone for heart rate control in the setting of hemodynamically destabilizing atrial tachyarrhythmias resistant to conventional heart rate control measures. Atrial fibrillation was present in 33 patients and atrial flutter in 5 patients. Onset of rapid heart rate (mean 149 +/- 13 beats/min) was associated with a decrease in systolic blood pressure of 20 +/- 5 mm Hg (p <0.05). Intravenous diltiazem (n = 34), esmolol (n = 4), or digoxin (n = 24) had no effect on heart rate, while reducing systolic blood pressure by 6 +/- 4 mm Hg (p <0.05). The infusion of amiodarone (242 +/- 137 mg over 1 hour) was associated with a decrease in heart rate by 37 +/- 8 beats/min and an increase in systolic blood pressure of 24 +/- 6 mm Hg. Both of these changes were significantly improved (p <0.05) from onset of rapid heart rate or during conventional therapy. Beneficial changes were also noted in pulmonary artery occlusive pressure and cardiac output. There were no adverse effects secondary to amiodarone therapy. Intravenous amiodarone is efficacious and hemodynamically well tolerated in the acute control of heart rote in critically ill patients who develop atrial tachyarrhythmias with rapid ventricular response refractory to conventional treatment. Cardiac electrophysiologic consultation should be obtained before using intravenous amiodarone for this purpose.     

Preoperative therapy with amiodarone and the incidence of acute organ dysfunction after cardiac surgery

We examined the influence of preoperative therapy with amiodarone on the incidence of acute organ dysfunction after cardiac surgery in a matched case-control study. There were 220 case-control pairs matched by day of surgery, source of admission, demographic characteristics, placement of intraaortic balloon pump before surgery, repeat operations, emergency surgery, thoracic aorta surgery and other surgical procedures. History of congestive heart failure was more prevalent in the amiodarone group than in the control group before surgery (60% vs 38%, P < 0.0001). The incidence of acute organ dysfunction, duration of mechanical ventilation, and death was similar in both groups after surgery. The requirement for inotropes (26% vs 17%, P = 0.03) and vasopressors (66% vs 55%, P = 0.02) and the incidence of postoperative nosocomial infections (12% vs 6%, P = 0.04) was greater in the amiodarone group. However, the difference was not significant after adjustment for congestive heart failure (Cochran-Mantel-Haenszel test P = 0.15, P = 0.25, P = 0.16, respectively). Amiodarone did not increase the incidence of acute organ dysfunction or death after cardiac surgery. The requirement for inotropes and vasopressors and the incidence of nosocomial infections were related to the severity of the underlying cardiac disease. The practice of discontinuing amiodarone treatment before surgery to reduce the incidence of postoperative organ dysfunction should be critically reevaluated. IMPLICATIONS: Amiodarone is often used for the treatment of life-threatening rhythm disorder. Amiodarone has been blamed for causing organ injury after cardiac surgery. In a study of 220 patients, amiodarone did not increase the risk of organ injury or death after cardiac surgery when compared with control patients. There was no evidence to support the practice of stopping amiodarone before cardiac surgery to avoid serious complications.     

Amiodarone N-deethylation in human liver microsomes: involvement of cytochrome P450 3A enzymes (first report)

Experiments were conducted on three different human liver samples to identify the cytochrome P450 isozyme which is involved in the biotransformation of the class III antiarrhythmic agent, amiodarone, into its major metabolite, desethylamiodarone (DEA). The classic P450 inhibitors, SKF 525A, metyrapone, and carbon monoxide provided a significant reduction in the in vitro formation of DEA by human hepatic microsomes. Amiodarone N-deethylase activities expressed by intrinsic clearance values were similar in all the livers used, although two livers were genotyped as extensive and one as a poor metabolizer for the cytochrome P450 CYP2D6 gene. DEA production was strongly inhibited (more than 80%) by the anti-P450 3A4 antibody, but not by anti-LKM1-positive serum. It seems therefore that the P450 3A subfamily is certainly implicated in human hepatic amiodarone N-deethylation.     

Amiodarone-associated proarrhythmic effects. A review with special reference to torsade de pointes tachycardia

PURPOSE: To assess the incidence of amiodarone-mediated aggravation of ventricular tachyarrhythmias or the development of new arrhythmias, such as torsade de pointes, in patients with cardiac disease. DATA SOURCES AND STUDY SELECTION: A MEDLINE literature search was done to identify articles published during the last 20 years that presented data on amiodarone-associated proarrhythmic events. The articles were divided into three categories: case reports, uncontrolled retrospective studies, and prospective controlled trials. In addition, articles were identified that examined the effects of amiodarone in patients with previously documented drug-induced torsade de pointes. RESULTS: 65 English-language case reports dealing with torsade de pointes during amiodarone therapy were found in the literature. In many of these cases, other predisposing factors for the development of torsade de pointes were reported. Seventeen studies each reported data from at least 50 patients who were treated with amiodarone for at least 6 months. Of 2878 patients included in these trials, 57 were reported to have a proarrhythmic event while exposed to the drug (an overall incidence of 2%). Torsade de pointes was observed in one third of these patients (an overall incidence of 0.7%). In seven placebo-controlled trials in which the drug was given as monotherapy, amiodarone was not associated with the development of a proarrhythmic event in any patient. Finally, in three reports, 31 patients with previous drug-mediated torsade de pointes were exposed to amiodarone during short- and long-term therapy. In none of these patients did a recurrent episode of torsade de pointes develop, despite the amiodarone-induced prolongation of the QTc interval, which was equivalent to that observed at the time of torsade de pointes during exposure to previous drugs. CONCLUSIONS: Amiodarone appears to be associated with a remarkably low frequency of proarrhythmic events and an incidence of torsade de pointes of less than 1.0%. This low arrhythmogenicity and the negligible negative inotropic effect of the compound constitute properties that make amiodarone particularly useful in treating high-risk patients prone to sudden cardiac death. Its potential to reduce this risk is currently being evaluated in several large prospective trials.     

Amiodarone-induced pulmonary toxicity in Fischer rats: release of tumor necrosis factor alpha and transforming growth factor beta by pulmonary alveolar macrophages

Amiodarone is an antiarrhythmic drug with numerous side effects, the most serious being the development of pulmonary toxicity. We have previously reported that a single intratracheal instillation of amiodarone to Fischer 344 rats results in pulmonary fibrosis within 6 wk of treatment. Presently, the mechanism of amiodarone-induced pulmonary toxicity is unknown. Cytokines that stimulate fibroblast proliferation and/or collagen production may play a role in amiodarone-induced pulmonary toxicity. To investigate this possibility, female rats were given a single intratracheal instillation of amiodarone (6.25 mg/kg), its metabolite desethylamiodarone (5 mg/kg), or vehicle (sterile water). At 1, 2, 3, or 6 wk after treatment the lungs were lavaged and the recovered cells were counted and identified. The alveolar macrophages were isolated by attachment to plastic petri dishes, cultured overnight, and the spent media collected for tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) analyses. Desethylamiodarone treatment resulted in a neutrophilic alveolitis, but the levels of TNF-alpha and TGF-beta were not significantly different from control animals. In contrast, amiodarone treatment resulted in a lymphocytic alveolitis and significantly higher amounts of TNF-alpha were observed at 3 and 6 wk after treatment. A trend toward higher levels of TGF-beta was also noted in the amiodarone-treated group at wk 1-3 but the values were not significantly different from those of controls. In conclusion, the release of TNF-alpha may play a role in the development of amiodarone-induced pulmonary toxicity.     

Effects of triiodothyronine and amiodarone on the promoter of the human LDL receptor gene

Treatment of patients with amiodarone, a potent anti arrhythmic drug, increases plasma LDL cholesterol levels, similar to that seen during hypothyroidism. This increase is the result of a decreased expression of the hepatic LDL receptor gene. We investigated the effects of thyroid hormone, amiodarone and desethylamiodarone on the first 687 bp upstream of the first ATG of the human LDL receptor gene by co-transfection with TRbeta1 into HepG2 cells. Promoter activity showed a dose-dependent increase upon addition of thyroid hormone up to a maximum of 600% at 10(-6) M T3. Using 5'-deletions it was found that a functional TRE(s) is present between -687 bp and -160 bp upstream of the ATG of the LDL receptor gene. Amiodarone and desethylamiodarone at 10(-6) M reduced basal LDL receptor promoter activity further then with the TRbeta1 alone (to 30% vs. 50% respectively, p<0.01) but interestingly in combination with T3 these compunds show a synergistic effect on promoter activity (to 225% T3 alone vs. 380% respectively, p<0.01).     

Amiodarone induced pulmonary fibrosis in infancy

We report a case of pulmonary fibrosis in an infant receiving amiodarone for treatment of intractable atrioventricular reentrant tachycardia secondary to Wolff-Parkinson-White syndrome. At 9 months, a screening chest radiograph showed a diffuse interstitial infiltrate in an asymptomatic, thriving infant. Amiodarone was discontinued and the pulmonary fibrosis resolved gradually over 6 months. This case documents the first report of amiodarone induced pulmonary fibrosis in the pediatric age group. We speculate that as amiodarone is used more frequently to manage pediatric arrhythmias, pulmonary fibrosis, a known complication of this antiarrhythmia in adults may be seen with increasing frequency in children.     

Surface reaction controlled oxygen absorption in a Ta-8 W-2 Hf alloy: kinetics and concentration gradients

It is known that the rate of oxygen absorption in several bcc metals and alloys under conditions of low oxygen pressure and high temperature is controlled by the absorption rate of oxygen at the gas-metal interface, but the relationships between absorption rate, oxygen concentration gradient, and average oxygen concentration have not been studied in detail. In this paper these relationships are examined using several different solutions of the diffusion equation to represent the absorption process, and the relations derived are compared to oxygen absorption measurements for a Ta-8 W-2 Hf alloy under the appropriate experimental conditions. It was found that the absorption rate and oxygen gradient were accurately described by a solution of the diffusion equation using a constant oxygen flux into the specimen as the external boundary condition. The rate limiting step in the process is the oxygen absorption rate at the gas-metal interface. This phenomenological model should also properly describe the oxygen absorption behavior of pure metals under the same conditions when the process is controlled by the absorption rate at the gas-metal interface, provided the sticking coefficient does not change during absorption.     

Can amiodarone pulmonary toxicity be predicted in patients undergoing implantable cardioverter defibrillator implantation?

Implantable cardioverter defibrillator (ICD) implantation is rapidly becoming accepted as primary therapy for malignant ventricular arrhythmias. Many patients undergoing ICD implantation are on concomitant antiarrhythmic drugs to decrease shock frequency, slow tachycardia rate, and suppress supraventricular arrhythmias. Amiodarone is a potent antiarrhythmic agent that is also frequently used in the treatment of patients with refractory ventricular arrhythmias. Ten to forty percent of patients undergoing ICD implantation will also be taking amiodarone. It has been reported to cause pulmonary toxicity in about 5% of patients per year. Acute amiodarone toxicity presenting as adult respiratory distress syndrome has been reported much less frequently. Although perioperative morbidity due to amiodarone has been described, the risk, predictability, and consequences of acute pulmonary toxicity from amiodarone in patients undergoing ICD implantation have not been previously described. We reviewed the records of 99 consecutive patients undergoing ICD implantation at our institution from October 1987 to April 1992. Thirty-nine patients were taking 480 +/- 230 mg of amiodarone (median 400 mg, lower 20th percentile 400 mg, upper 80th percentile 800 mg) for 291 +/- 554 days prior to ICD implantation. Ten patients taking amiodarone developed acute pulmonary toxicity clinically manifesting as diffuse pulmonary infiltrates on chest radiography and adult respiratory distress syndrome with hypoxia (arterial pO2 < 60 mmHg) without evidence of pneumonia or elevated pulmonary capillary wedge pressure (PCW < or = 15 mmHg). Of the 60 patients not taking amiodarone none developed adult respiratory distress syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympatholytic action of intravenous amiodarone in the rat heart

BACKGROUND: Amiodarone is a commonly used antiarrhythmic agent with complex pharmacological effects. Although ventricular arrhythmias can be suppressed soon after intravenous amiodarone, the mechanisms responsible for this action are unclear. We studied the effects of acute treatment with amiodarone on the metabolism and release of norepinephrine (NE) in intact rats and in perfused rat hearts. METHODS AND RESULTS: Experiments were performed in anesthetized rats and in perfused, innervated hearts with amiodarone administered intravascularly. NE release was induced by electrical stimulation of the sympathetic ganglion. Concentrations of NE and its intraneuronal metabolite dihydroxyphenylglycol (DHPG) in hearts, plasma, and coronary venous effluent were measured by high-performance liquid chromatography. Acute administration of amiodarone induced dose-dependent increases in DHPG concentrations in plasma (5 mg/kg, +48%; 15 mg/kg, +84%; and 50 mg/kg, +467%) and in coronary venous effluent (1 mumol/L, +37%; 3 mumol/L, +510%; and 10 mumol/L, +1100%) together with an unchanged basal overflow of NE. In perfused hearts, NE release evoked by nerve stimulation was inhibited by infusion of amiodarone (1 mumol/L, -16%; 3 mumol/L, -24%; and 10 mumol/L, -64%) or by intravenous amiodarone (50 mg/kg) given 1 hour before heart perfusion (-70%), and the extent of this suppression correlated well with levels of DHPG overflow present immediately before nerve stimulation. When given in vitro and in vivo, amiodarone also significantly reduced NE and increased DHPG content in the heart, leading to a raised DHPG/NE ratio. All these effects of amiodarone were similar to those found with reserpine but less potent. In contrast, oral amiodarone produced none of these effects. CONCLUSIONS: Acute administration of amiodarone in perfused hearts or intact rats induces partial NE depletion in the heart by interfering with vesicular NE storage and enhancing intraneuronal NE metabolism, effects associated with an impaired NE release during sympathetic activation. Oral dosing with amiodarone has no such effect. Further study is required to test whether this novel sympatholytic effect of amiodarone contributes to its antiarrhythmic action after intravenous administration.     

Limitations in the use of gamma-glutamyl transferase estimations in alcohol-dependent subjects

OBJECTIVE: To investigate any relationship between the pathological features of amiodarone-induced pulmonary toxicity (APT) and clinical use of amiodarone in patients dying from acute respiratory distress syndrome (ARDS). DESIGN: Retrospective study. Review of clinical and pathological findings of patients dying from ARDS. SETTING: Intensive Care Unit (ICU) and Pathology Department of University hospital. SUBJECTS: Ten patients with clinical diagnosis of ARDS, who died in ICU and underwent post mortem examination. INTERVENTIONS: Case note review of clinical details; independent review of histological specimens. MEASUREMENT AND RESULTS: Over a 3-year period, ten patients underwent post mortem examination, of whom seven had received amiodarone. Three patients who received longer than 48 h of amiodarone had histological changes of widespread lipoid pneumonia, a recognised pattern of APT. CONCLUSIONS: Acute amiodarone pulmonary toxicity is a definite pathological entity in ICU patients. High oxygen concentrations may be a risk factor, while pre-existing pathology, e. g. ARDS, may mask its development. Amiodarone should be used with caution in this group of patients.