Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis. A Swedish multi-center study.

A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpasture's syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpasture's syndrome) whereas 70% of them could leave the dialysis program.

Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects.

AIMS: The present study was undertaken to see whether the difference in plasma cortisol suppression between single and repeated dosing of fluticasone propionate (FP) can be explained by systemic accumulation. METHODS: Twelve healthy subjects (six women) were given, in a crossover fashion, a single dose inhalation (1000 micrograms) of FP via Diskhaler and repeated inhalations (1000 micrograms twice daily) every 12 h during 7 days. There was a washout period of 2 weeks between the treatments. An intravenous dose of 20 micrograms FP was given as a reference. Plasma concentrations of FP for each treatment were determined by liquid chromatography plus tandem mass spectrometry. Plasma cortisol after the inhaled doses was determined using an immunoassay and was compared with baseline values. RESULTS: The average plasma concentration of FP was about 1.7 times higher after multiple inhalations than after a single dose. Systemic availability, mainly attributable to pulmonary deposition, was 15.6 [13.6-18.0]% of the nominal dose. Daytime plasma cortisol suppression vs baseline was 47 [20-65]% and 95 [93-97]% for the single and repeated doses, respectivley. CONCLUSIONS: To conclude, a slow elimination of FP leads to accumulation during repeated dosing. This accumulation may explain the marked decrease in plasma cortisol seen during treatment with fluticasone propionate within the clinical dose range.

Terbutaline in COPD comparison between Turbuhaler and chlorofluorocarbon (CFC) inhaler.

Patients with chronic obstructive pulmonary disease (COPD) often subjectively benefit from inhaled beta 2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second (FEV1.0). A comparison between the effects of terbutaline administered via a dry powder inhaler (Turbuhaler) and via a chlorofluorocarbon (CFC) inhaler in conjunction with a spacer device (Nebuhaler) was performed in patients with regard to FEV1.0, forced expiratory capacity (FVC), residual volume (RV), and specific conductance (s-Gaw). Fifteen hospitalised patients (11 male) with COPD were studied, each of whom had a diurnal variation in peak expiratory flow (PEF) not exceeding 15% and with a demonstrated volume response to inhaled beta 2-agonists in FVC and/or RV of at least 15%. Patients were administered each of the following five treatments on a single occasion in a randomized order (latin square) in intervals of at least 2 days: placebo, terbutaline via Turbuhaler (1.0 and 2.5 mg) and terbutaline via a CFC inhaler (1.0 mg without and 2.5 mg with Nebuhaler). Inhalation of terbutaline in different doses and from different devices induced a decrease in RV, an increase in FVC, and s-Gaw and a less pronounced increase in FEV1.0. No statistically significant differences between the four terbutaline treatments were seen, but all were significantly different from the placebo. These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation, the choice of inhalation device seems to be of little importance for its efficacy.

Bambuterol and terbutaline in human cerebrospinal fluid and plasma.

Concentrations in cerebrospinal fluid (CSF) and plasma of bambuterol and its active metabolite, the beta 2-adrenoceptor agonist terbutaline, were measured in man after four once-daily doses of 30 mg bambuterol hydrochloride (Bambec). Nine patients scheduled for orthopaedic surgery under spinal anaesthesia completed the study. The concentrations of both substances were much lower in CSF than in plasma, the ratio CSF/plasma being 0.09 for bambuterol and 0.19 for terbutaline, at apparent steady state. While the rank order of the ratios was expected from the fractions of unbound bambuterol and terbutaline in plasma, their absolute values were only about 1/6 (bambuterol) and 1/4 (terbutaline) of those predicted from diffusion equilibria between plasma and CSF. Thus, the rates of transport of bambuterol and terbutaline from plasma into the central nervous system appear to be slow relative to transport out of the system, e.g. by outflow of CSF. The findings are in agreement with animal experiments and suggest that bambuterol and terbutaline are less likely than lipophilic beta 2-adrenoceptor agonists to interact with central receptors.

Bricanyl Turbuhaler and Ventolin Rotahaler in exercise-induced asthma in children.

Bricanyl Turbuhaler (0.5 mg terbutaline sulphate) and Ventolin Rotahaler (0.4 mg salbutamol) were compared in a randomized double-blind placebo controlled study on exercise-induced asthma in 19 children (14 boys) aged 7-14 years. The study was carried out on 3 separate days. Asthmatic attacks were provoked by free range running. Peak expiratory flow (PEF) was measured before and after exercise. If PEF decreased by greater than 20%, one inhalation from each of the inhalers was given under supervision of the investigator. Only one of the inhalers (none on the placebo day) delivered active drug. PEF was measured again 5 and 10 min after treatment. Already 5 min after treatment PEF had returned to baseline after active treatment. There was no statistically significant difference between the two active treatments. After placebo treatment, PEF did not return to baseline even at the 10 min post-exercise measurement. Ten children needed extra medication after the last PEF measurement on the placebo day, whereas no child needed extra medication after any of the active treatments. No adverse events were reported in this study. In conclusion, Bricanyl Turbuhaler (0.5 mg) and Ventolin Rotahaler (0.4 mg) were equally efficacious in the treatment of exercise-induced asthma in children.

The effect of bambuterol (carbamylated terbutaline) on plasma cholinesterase activity and suxamethonium-induced neuromuscular blockade in genotypically normal patients.

Bambuterol (the bisdimethylcarbamate prodrug of terbutaline) is a new bronchodilator with a prolonged duration of action due to its inhibition of plasma cholinesterase during metabolism. The effect of bambuterol on suxamethonium-induced neuromuscular blockade was studied in 10 patients undergoing elective laparotomy. Thirty mg of bambuterol was given 2 h before anaesthesia, which was performed with thiopentone, fentanyl, halothane and nitrous oxide in oxygen. Neuromuscular function was monitored using supramaximal train-of-four stimulation of the ulnar nerve and a force displacement transducer. Suxamethonium 1 mg.kg-1 was given i.v. for endotracheal intubation. Plasma cholinesterase activity was measured before and after intake of bambuterol and during anaesthesia. The results from the 10 patients were compared with those of 41 patients not given bambuterol but otherwise studied during the same conditions. Following bambuterol, all patients had a significant decrease of plasma cholinesterase activity (P less than 0.001) and the suxamethonium-induced blockade was 3-4 times prolonged compared to patients not given bambuterol (P less than 0.001). Five patients with very low plasma cholinesterase activity developed a long-lasting phase II block.

The effect of bambuterol on plasma cholinesterase activity and suxamethonium-induced neuromuscular blockade in subjects heterozygous for abnormal plasma cholinesterase.

Bambuterol is a new bronchodilator which is also a reversible inhibitor of plasma cholinesterase. In patients with normal plasma cholinesterase genotype, bambuterol prolongs suxamethonium-induced neuromuscular blockade. In the present study, we investigated the interaction of bambuterol and suxamethonium in nine patients heterozygous for abnormal plasma cholinesterase during anaesthesia with fentanyl, thiopentone, halothane and nitrous oxide in oxygen. The patients (seven E1uE1a and two E1uE1s) were given 20 mg of bambuterol orally 2 h before anaesthesia. Suxamethonium 1 mg.kg-1 was given for tracheal intubation. The neuromuscular function was monitored using train-of-four (TOF) stimulation of the ulnar nerve and a force displacement transducer. Plasma cholinesterase activity decreased in all patients following bambuterol (P less than 0.001). In patients with genotype E1uE1a, median time to 90% recovery of twitch height and TOF ratio greater than or equal to 0.7 (37.5 min) was prolonged compared to 28 E1uE1a patients not treated with bambuterol (14.0 min) (P less than 0.001). Four of these patients developed a phase II block apparently not correlated to plasma cholinesterase activity. In the E1uE1s; patients, full recovery was seen after 22.0 and 31.4 min, respectively. It is concluded that in patients heterozygous for abnormal plasma cholinesterase, bambuterol 20 mg taken 2 h before anaesthesia causes a 2-3 times prolongation of the neuromuscular blockade following suxamethonium 1 mg.kg-1 and in some patients a phase II block.

The influence of 10 mg and 20 mg of bambuterol on the duration of succinylcholine-induced neuromuscular blockade.

Bambuterol is an inactive prodrug which is enzymatically cleaved by plasma cholinesterase to yield the active compound, terbutaline. This catalytic process is accompanied by a selective inhibition of plasma-cholinesterase, the enzyme also necessary for the break-down of succinylcholine. We therefore studied the possible effect of bambuterol on succinylcholine-induced neuromuscular blockade in a double-blind fashion in patients undergoing surgery under general anaesthesia. Of the 39 patients studied, 13 patients had 10 mg of bambuterol, 12 had 20 mg and 14 were given placebo 10-16 h prior to anaesthesia. Succinylcholine 1 mg.kg-1 bw was administered after induction of anaesthesia. Following supramaximal train-of-four stimulation of the ulnar nerve, the tension developed in the adductor pollicis muscle was measured. Onset time and the durations of action (times to 10%, 25%, 75% and 90% recovery of the first twitch of the train-of four response) were recorded. The mean recovery times were prolonged 30-50% in patients who had received 10 or 20 mg of bambuterol as compared with placebo. It is concluded that a prolonged duration of action of succinylcholine can be expected in patients being treated with bambuterol.

Comparison of Bricanyl Turbuhaler and Berotec dry powder inhaler.

Terbutaline (Bricanyl) 0.5 mg t.i.d. administered via Turbuhaler was compared with fenoterol (Berotec) 0.2 mg t.i.d. administered via Inhalator Ingelheim in 36 asthmatic children aged 7-12 years. The study was of an open crossover design with two randomly allocated treatment periods, each lasting 2 weeks. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured at clinic visits before study start and at the end of each treatment period. The patients recorded peak expiratory flow (PEF) before and after inhaler use, morning and evening. They also recorded asthma symptoms and number of extra inhalations. At the end of the study, children and parents were asked for inhaler preference. No differences between the treatments were found concerning the results of the lung function measurements at the clinic or at the PEF measurements at home. No differences were found between the treatments as regards asthma symptoms or number of extra inhalations. Two patients experienced mild side effects during fenoterol treatment, none during terbutaline treatment. Treatment with terbutaline in Turbuhaler was preferred by a majority of children and parents. In conclusion, in this group of asthmatic children, treatment with terbutaline administered via Turbuhaler was as efficacious as treatment with fenoterol administered via Inhalator Ingelheim. There was a clear preference in favour of the Turbuhaler.

The bronchodilator response from increasing doses of terbutaline inhaled from a multi-dose powder inhaler (Turbuhaler).

Twelve adult asthmatics inhaled single doses of 0.5, 2.0 or 4.0 mg of terbutaline, respectively, via Turbuhaler, on three separate days. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and pulse rate were measured 15, 30, 45 and 60 min after inhalation from the inhaler and then hourly up to 8 h. The results showed that a more rapid onset of action, a greater maximal response and a longer duration of action can be achieved by exceeding the standard dose of terbutaline of 0.5 mg. The incidence of adverse effects was very low even at the highest dose, 4 mg. This study emphasizes the need for individual dosing of inhaled bronchodilators.

The bronchodilator response from inhaled terbutaline is influenced by the mass of small particles: a study on a dry powder inhaler (Turbuhaler).

This study was carried out to investigate if particles approximately less than 5 microns are optimal when delivered from a dry powder inhaler. It was performed as a cumulative dose response study of twelve asthmatic adults. Three different versions of a dry powder inhaler, Bricanyl Turbuhaler, were studied. Each inhaler delivered 0.5 mg of pure terbutaline sulphate with each dose. Out of this 0.5 mg, they delivered 90 micrograms, 40 micrograms and 5 micrograms, respectively, of particles approximately less than 5 microns with each dose at an inspiratory flow rate of 28 l.min-1. Terbutaline 0.5 mg, 0.5 mg, 1.0 mg and 2.0 mg was inhaled with a 30 min interval between the doses. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured 5 and 20 min after each dose. The bronchodilator response was greater with the inhaler delivering 90 micrograms of small particles with each dose than with the inhaler delivering 5 micrograms, thus confirming the importance of small (approximately less than 5 microns) particles.

Respiratory complications following surgery. Improved prediction with preoperative spirometry.

Patients who are old, overweight, who smoke and/or have symptoms of respiratory disease have an increased risk of atelectases and/or arterial hypoxemia in conjunction with surgery. The present study in 53 middle-aged men, operated on for gallbladder or peptic ulcer disease, illustrates how spirometry can be used to improve the prediction of respiratory complications. The relative risk of atelectases was greater in patients with functional residual capacity-closing capacity (FRC-CC) below -0.11 and the risk prediction based on age, body weight, smoking habits and respiratory symptoms was improved by adding information on FRC-CC. Arterial hypoxemia was more common in patients with wash-out volumes (WOV) above than below 35 l. The preoperative identification in high-risk patients of arterial hypoxemia based on the above-mentioned risk factors, was improved by adding information on WOV.

Pre- and postoperative lung function in sitting and supine position related to postoperative chest X-ray abnormalities and arterial hypoxaemia.

Spirometry in both sitting and supine position was performed before and 3-5 days after elective upper abdominal surgery in 53 men, aged 41-72 years. The results were related to postoperative respiratory complications as defined by chest radiography and to measurements of the arterial oxygen tension. Preoperative total lung capacity (TLC), functional residual capacity (FRC) and wash-out volume (WOV) were lower in both positions among patients who were to develop major chest X-ray abnormalities than among patients with normal chest radiographs postoperatively. All patients who developed major chest X-ray abnormalities had a negative value for FRC - closing capacity (CC) in the supine position preoperatively, indicating 'airway closure' during tidal breathing. Preoperative WOV and lung clearance index (LCI) were higher in both sitting and supine positions in patients who developed postoperative hypoxaemia than in patients who did not. The postoperative decrease in TLC, FRC and WOV in the sitting position was greater among patients with major X-ray abnormalities and/or arterial hypoxemia postoperatively than among patients without these complications. According to our results, conventional spirometry in the supine position is not superior to conventional spirometry in the sitting position as part of pre- or post-operative assessment of patients. On the other hand, both preoperative 'airway closure' and arterial oxygen tension, measured in the supine position, showed a correlation with postoperative chest X-ray abnormalities.

Risk factors for postoperative respiratory complications and their predictive value. A study in 40-75 year-old men undergoing elective surgery for peptic ulcer or gallbladder disease.

Age, body weight, smoking, chronic bronchitis and duration of anaesthesia were assessed as risk factors for respiratory complications following surgery for peptic ulcer or gallbladder disease. The studies were made on 53 men aged 40-75 years. All variables were associated with increased postoperative risk of chest X-ray abnormality or arterial hypoxaemia or clinically overt respiratory complications. In the statistical analysis, however, none of the factors proved to be useful as a predictor of postoperative respiratory complications. The observed high frequencies of X-ray abnormalities (54%) and arterial hypoxaemia (43%) after operation indicate potential dangers. They may be reduced by cessation of smoking before the operation and reduction of weight.

The clinical significance of postoperative chest X-ray abnormalities, arterial hypoxemia and clinically recorded respiratory complications.

The clinical consequences of postoperative complications as defined by signs and symptoms, chest radiography and measurements of the arterial oxygen tension were studied in 53 men, aged 40-75, who were electively operated for peptic ulcer or gallbladder disease. Clinical signs of a respiratory complication were detected in 4 patients. Of the 28 patients with chest X-ray abnormalities and 23 with arterial hypoxemia only 2 had clinical signs of a disordered pulmonary function. None of the remaining patients with arterial hypoxemia and/or chest X-ray abnormalities required any specific treatment. Hospital stay was not prolonged in patients with respiratory complications. Arterial hypoxemia and chest X-ray abnormalities in patients without clinical signs of a disordered pulmonary function had no influence on postoperative course or rehabilitation and were in all cases reversible without treatment.

Respiratory complications after upper abdominal surgery. The incidence of chest X-ray abnormalities, arterial hypoxemia and clinically recorded pulmonary complications.

The incidence of postoperative chest X-ray abnormalities, arterial hypoxemia and clinically recorded pulmonary complications was studied in fifty-two 40-75-year-old men admitted for elective surgery for peptic ulcer or gallbladder disease. Twenty-eight (54%) patients had an abnormal chest X-ray and twenty-three (43%) arterial hypoxemia, whereas only four patients (8%) were identified with clinical signs and symptoms of respiratory complications. Forty-one patients (79%) were found with pulmonary complications by at least one of the three methods. Twelve patients had both an abnormal chest X-ray and arterial hypoxemia. Only two of these were identified with clinical signs indicating pulmonary complications. The great discrepancy between results based on clinical signs and symptoms noted in the patients' records and results based on postoperative chest X-ray and measurements of the arterial oxygen tension, respectively, should be of great importance when comparing the incidence of pulmonary complications after different forms of surgery and when assessing risk factors and clinical consequences of respiratory complications.