Salbutamol Infusion Research Articles

Cardiac effects of salbutamol-induced hypokalaemia in the conscious dog.

1. Infusion of salbutamol (3.0 microgram/min after a bolus injection of 100 microgram) produced hypokalaemia in conscious dogs. 2. Measurement of arterial and coronary sinus potassium differences revealed no significant potassium loss from the heart with established hypokalaemia. 3. Shortly after the initial salbutamol bolus and before steady-state hypokalaemia had been achieved during salbutamol infusion, a prolongation of QTc occurred; this corresponded to a significant myocardial potassium of -0.12 mmol/l plasma. 4. Urinary electrolyte excretions indicated that the hypokalaemia was not due to urinary potassium loss. 5. It was deduced that potassium had moved intracellularly. No change in hydrogen ion status occurred to account for this. Pronounced rises in plasma insulin immunoreactivities during salbutamol infusions suggested this as one mechanism for potassium shifts.

Plasma steroid changes in pre-term labour in association with salbutamol infusion.

Serial measurements of peripheral plasma concentrations of progesterone and oestradiol-17beta were made in 23 women with singleton pregnancies who were given intravenous salbutamol in an attempt to inhibit pre-term labour. Mean levels of both hormones fell significantly during salbutamol infusion but returned to pre-treatment levels after therapy was stopped. Plasma human placental lactogen concentrations did not change during salbutamol infusion, suggesting that the fall in steroid hormone levels was unlikely to be an effect of altered uterine or placental blood flow.

Actions of salbutamol in late pregnancy: Plasma cyclic AMP, insulin and C-peptide, carbohydrate and lipid metabolites in diabetic and non-diabetic women

Salbutamol was administered intravenously in dose increasing from 3.75 to 22.5 microgram/min to 5 non-diabetic and 7 diabetic women in the last trimester of pregnancy. In diabetic as well as non-diabetic women the diastolic blood pressure fell progressively with increasing doses, and the systolic BP and heart rate increased at doses above 7.5 microgram/min. The effect of fetal heart rate was less pronounced than the effect on maternal heart rate. Cyclic AMP levels in plasma were similar in non-diabetic and diabetic women before salbutamol. Twenty min following 3.75 microgram/min a significant increase was seen in both groups. The peak increase (3-5 fold) was higher in the diabetic than in the non-diabetic women. Plasma insulin and C-peptide levels rose in a dose-dependent manner in the non-diabetic and four of the diabetic women. However, in three of the diabetic women the insulin level was unaffected by salbutamol and C-peptide was almost undetectable. Plasma concentrations of glucose, glycerol, NEFA and 3-HB were higher in the diabetics than in the non-diabetics before salbutamol and the elevations induced by salbutamol were also significantly larger in the diabetic women. The present data show that salbutamol in doses employed clinically may cause pronounced metabolic effects, especially in diabetic women, and it is suggested that when intravenous infusion of salbutamol is given to pregnant diabetic women not only cardiovascular but also some metabolic variable such as glucose should be carefully monitored.

Characterization of beta‐adrenoceptor subtype mediating the metabolic actions of salbutamol.

1. The following four intravenous treatments were administered in a balanced, randomized, Latin square design to four healthy volunteers: (1) saline injection (10 min); salbutamol infusion (0.15 microgram kg-1 min-1 for 60 min) (sS), (2) propranolol injection (0.3 mg kg-1 for 10 min); salbutamol infusion (pS), (3) practolol injection (2 mg kg-1 for 10 min); salbutamol infusion (PS) and (4) saline injection; saline infusion (ss). 2. Heart rate was recorded and venous blood taken for estimation of insulin, glucose and potassium before and after each injection (0 and 12-15 min) and at various times during the infusion (30,45,60 and 75 min). 3. The mean, peak % heart rate changes from baseline, control were +65.8%, +23.0%, -10.9% and -12.1%, the mean, peak % glucose changes, +61.0%, +7.1%, +3.6% and +6.9%, and the mean, peak % insulin changes, +298%, +28%, -28% and -43% during the infusions for sS, PS, ss and pS respectively. 4. The mean serum potassium levels before the injections and at the completion of the infusions were 3.98 and 3.08 4.03 and 3.63, 4.07 and 4.15, and 4.03 and 4.13 meq/l for sS, PS, ss and pS respectively. 5. Propanolol completely abolished the cardiac and metabolic responses of salbutamol. 6. Practolol produced only partial cardiac beta-adrenoceptor blockade, but completely inhibited the metabolic actions of salbutamol.

Antidiuresis induced by β1- and β2-adrenergic agonists in ethanol-anesthetized rats

The β 1- and β 2-adrenergic in antidiuresis and sodium retention induced by β-adrenergic agonists were analysed in ethanol-anesthetized, water-diuretic rats. Intravenous infusions of isoprenaline, salbutamol and carbuterol did not affect inulin clearance but all increased plasma renin concentration to the same extent. Propranolol completely blocked the decreases in urine volume (V) and urinary sodium excretion (U NaV) induced by isoprenaline; practolol ( β 1-blocker) inhibited only the decrease in U NaV and butaxamine ( β 2-blocker) inhibited only the decrease in V. The ratios of doses of β-agonists which decreased U NaV and V by 50% %ED 50 U NaV decrease/ED 50 V decrease) were 0.34, 0.68, 1.56 and 2.36 for isoprenaline, tretoquinol, salbutamol and carbuterol, respectively. This increasing order of the ratios coincided with the order reported for the preponderance of the β 2- over β 1-component of these agonists. These results indicate that the decrease in U NaV induced by β-antagonists is related to β 1, while the decrease in V is related to β 2 stimulation.

Gastric Acid Secretion after Chronic Administration of the Anti-Secretory Agent Salbutamol in the Dog

Salbutamol is known to be a potent inhibitor of pentagastrin stimulated gastric acid secretion in both man and dog. This study describes the results, in both acute and chronic experiments in the dog, of salbutamol administration on gastric acid output and plasma gastrin concentration in response to a standard food stimulus. In the acute experiments, salbutamol in fusion reduced both gastric acid output and peak plasma gastrin concentration. In contrast, during chronic oral administration, salbutanmol caused a significant increase in the acid secretory response to the food stimulus; 2 weeks after the drug was stopped acid output has returned to control values. Only small changes in plasma gastrin concentration were found in the chronic study and these changes could not explain the increase in acid output.

Peripheral platelet count in response to salbutamol before and after adrenergic beta-receptor blockade.

The effect of salbutamol (a comparatively selective adrenergic beta2-receptor agonist) on the peripheral platelet concentration was studied before and after the ingestion of either 50 mg metoprolol or 40 mg propranolol. The study was carried out on healthy males volunteers and autologous 51Cr-labelled platelets were employed at the experiments. Salbutamol was infused intravenously over a period of 6 min in a dose of 0.27 microgram.kg(-1). min(-1). Prior to metoprolol and propranolol administration a statistically significant lowering in platelet-bound radioactivity (PBR) was obtained in response to the salbutamol infusions. This salbutamol-induced fall in PBR was completely blocked by propranolol but was left unaffected by metoprolol. It is concluded that adrenergic beta2-receptor stimulation induces a transient lowering of the peripheral platelet count.

Metabolic effects of intravenous salbutamol in the course of acute severe asthma.

Peak expiratory flow rate and plasma free fatty acids, potassium, insulin, and glucose were measured in 10 patients admitted with acute severe asthma before and at frequent intervals for one hour after an infusion of salbutamol, 4 microgram/kg over 10 minutes. These studies were repeated during the recovery phase and again before discharge. Effective bronchodilatation seen after the infusion was similar in the acute and recovery phases. Baseline plasma free fatty acids were elevated but rose significantly after the infusion. There was also a significant fall in plasma potassium. These changes occurred in all individuals. There were no significant differences in mean baseline or peak changes of plasma free fatty acids, potassium or insulin on any of the study days. There was no evidence of beta receptor blockade in the acute phase in any patient.

Haemodynamic effects of salbutamol and nitroprusside after cardiac surgery.

The haemodynamic effects of a continuous intravenous infusion of salbutamol (15 to 30 microgram/min) and nitroprusside (50 to 100 microgram/min) were compared in 9 patients after cardiac surgical operations. The mean falls in left atrial pressure and systemic vascular resistance were similar with the two drugs but salbutamol caused a greater increase in heart rate, maximum acceleration of aortic blood flow, and maximum rate of change of left ventricular power. Because these differences would cause greater myocardial oxygen consumption with salbutamol and because the infusion of salbutamol is less easily controlled, nitroprusside is the preferred drug after cardiac operations.

Metabolic effects of salbutamol infusion during premature labour.

Plasma electrolytes, glucose and insulin concentrations were measured and serial electrocardiograms performed during the intravenous infusion of salbutamol to five women in premature labour. The plasma potassium (mean +/- standard error) fell from 3-5 +/- 0-1 to 2-7 +/- 0-1 mmol/l, and the glucose and insulin rose by 4-2 +/- 0-7 mmol/l (75 +/- 13 mg/100 ml) and 26 +/- 5 mU/l respectively. The maximum fall in potassium, and the rise in glucose and insulin occurred two hours after starting the infusion. No changes in other electrolytes were found. Electrocardiograms showed no signs of hypokalaemia. Highest pulse rates (148 +/- 4 beats per minute) occurred at two hours but no arrhythmias were observed.

Effects of salbutamol and isoxsuprine on uterine and umbilical blood flow in pregnant sheep

The effects of salbutamol and isoxsuprine upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) were investigated in near-term, nonlaboring chronic sheep preparations. During both intravenous salbutamol and isoxsuprine infusions to the ewe, UtBF and mean maternal arterial pressure decreased significantly. Also, dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred. There were no significant changes in UmBF, mean fetal arterial pressure, or fetal heart rate (FHR) during salbutamol infusions, but UmBF and FHR increased during isoxsuprine infusions. During the 120 minute postinfusion recovery period, UtBF rose significantly after the salbutamol infusions but not after the isoxsuprine infusions. The effects and structure-activity relationship of these two drugs are comparable to those of ritodrine and fenoterol, two other β-adrenergic agonists.

The effect of intravenous salbutamol upon plasma and urinary potassium during premature labour.

Plasma potassium and urinary potassium excretion were measured in eight patients in premature labour treated with salbutamol, and in ten patients at full term in spontaneous labour. There was a significant fall in plasma potassium concentration following salbutamol infusion, but no change during labour in the control groups. Urinary potassium excretion was similar in both groups.

The effect of beta-receptor-stimulating agents on the utero-placental blood flow.

The influence of salbutamol, a beta-2-receptor-stimulating agent, on the blood flow through the utero-placental unit was evaluated in the human. Serial placenta scintigrams were analysed quantitatively, after injection of 0.5 mCi Indium-113m, by means of a gamma-camera connected on line to a computer. The examinations were performed in the third trimester of pregnancy. No sedation was used. Uterine contractions were not present. Salbutamol caused an increase in activity over the placental region, corresponding to a 15% increase in blood volume. The rise time of the initial phase of isotope accumulation (calculated from 5 to 95% of final activity) was prolonged by 100% during salbutamol infusion. As the rise time is proportional to the volume/flow ratio of blood in the uteroplacental region, our data indicate that salbutamol infusion causes a decrease in blood flow in the absence of uterine contractions.

The immediate effect of a beta-adrenergic agonist (salbutamol) on carbohydrate and lipid metabolism during the third trimester of pregnancy.

The responses of plasma insulin and the C-peptide of proinsulin, glucose, lactate, free fatty acids (FFA), glycerol, D-beta-hydroxybutyrate and alanine to a beta2-adrenergic agonist (salbutamol) were determined in 5 patients during the last trimester of pregnancy before labor. Salbutamol was given as an infusion in the same dosage as is used to inhibit uterine contractions in cases of premature labor and in obstetric emergencies. The influsion of salbutamol was given for 45 min, accompanied by repeated sampling of arterial blood. All patients developed moderate tachycardia and exhibited metabolic effects following salbutamol infusion, implying marked increases in plasma levels of insulin, C-peptide, glucose and lactate. An increased rate of lipolysis was evident from the rises of FFA, glycerol and D-beta-hydroxybutyrate. Plasma levels of alanine declined, possibly due to stimulation of gluconeogenesis. It is unlikely that these acute maternal metabolic changes would have significant adverse effects on the fetus.

The Nature of the β-Adrenoreceptor Controlling Plasma Renin Activity in Man

1. Seven healthy sodium-replete male volunteer subjects remained supine during and for at least 1 h before the study. Heart rate and blood pressure were recorded continuously, and peripheral venous blood samples were taken every 15 min for determinations of plasma renin activity. 2. All subjects were studied twice: after 3 days of oral practolol (100 mg, three times daily) and after a similar period on placebo. Each study consisted of an intravenous infusion of isoprenaline in graded doses (0-20 microng/min in the placebo phase; 0-16 microng/min in the practolol phase), followed after rest for 2 h by an intravenous infusion of salbutamol (0-20 microng/min after placebo; 0-80 microng/min after practolol). 3. Both salbutamol and isoprenaline produced dose-related increases in systolic blood pressure, heart rate and plasma renin activity and decreases in diastolic pressure. 4. The increases in heart rate and plasma renin activity induced by either agonist were competitively blocked by practolol, as was the fall in diastolic blood pressure induced by isoprenaline; the salbutamol-induced fall of diastolic blood pressure was unaffected by practolol. 5. Comparison of dose ratio--1 estimates confirmed that practolol selectively blocked increases in heart rate and plasma renin activity due to salbutamol; no selective blockade against isoprenaline-induced changes was shown. 6. Selective blockade of salbutamol-induced changes indicate that a beta1-adrenoreceptor mediates changes in plasma renin activity.

Intravenous infusion of salbutamol in the treatment of asthma.

The effects of i.v. infusion of increasing rates of salbutamol for up to 4 h were documented in ten convalescent asthmatic patients. 2 The major bronchodilator effect was seen at 4.16 mug/minute. A small further improvement occurred at infusion rates up to 25.0 mug/min but was not significantly better than that seen at the lower infusion rate. 3 Cardiovascular effects were minimal after 60 min at the lower rate and even at 25.0 mug/min mean heart rate rose by only 17.1 beats/minute. All patients tolerated the 4 h infusion well. 4 It is concluded that i.v. infusion of salbutamol may be a useful addition to the treatment of the patient with a severe attack of asthma.

The Effect of Intravenous Infusion of Salbutamol on Heart Rate, Plasma Potassium and the Ventilatory Response to Carbon Dioxide and Hypoxia in Normal Man

The Effect of Intravenous Infusion of Salbutamol on Heart Rate, Plasma Potassium and the Ventilatory Response to Carbon Dioxide and Hypoxia in Normal Man

The uterine and cardiovascular effects of salbutamol and practolol during labour.

Intravenous salbutamol, a beta-adrenoceptor stimulant, given to nine patients in normal labour, with continous monitoring of uterine activity and of the maternal and fetal cardiovascular systems, was shown to decrease uterine activity significantly; maternal and fetal heart rates were significantly increased, and maternal systolic and diastolic arterial pressures were significantly decreased during the infusion, although no treatment had to be discontinued because of these effects. Apart from worsening of low back pain during the infusion in one patients, subjective side-effects were trival. With the salbutamol infusion continued at an effective maintenance rate, the carioselective beta-adrenoceptor blocking drug, practolol, given intravenously, reduced the maternal heart rate (although not significantly) but it did not alter the fetal heart rate; it also appeared to interfere transiently with the inhibiting action of salbutamol on uterine activity, but cerevical dilatation was arrested until the salbutamol infusion was discontinued. At least in five patients, labour remained suppressed until oxytoxin was infused intravenously.

Metabolic and cardiovascular effects of isoprenaline and salbutamol in the dog.

1 The intravenous infusion of isoprenaline and salbutamol into the greyhound increased heart rate and levels of free fatty acids, lactic acid and glucose. 2 On terminating the infusions of isoprenaline the changes produced declined rapidly but the effects produced by salbutamol were more persistent. When high doses of salbutamol had been infused, glucose and lactic acid levels in fact increased during the 20 min following the infusions. 3 These results support suggestions that, in the dog, lipolysis is mediated by beta1-adrenoceptors and liver glycogenolysis by beta2-adrenoceptors. The beta-adrenoceptors mediating muscle glycogenolysis could not be assigned inequivocally to either subtype. 4 The differences in the behaviour of isoprenaline and salbutamol in the period following the infusions are considered to be due partly to slower removal of salbutamol. Increases in lactic acid levels after infusion of large amounts of salbutamol may be secondary to the persistence of high glucose levels.

A COMPARISON OF THE EFFECTS OF PROSTAGLANDIN E2 AND SALBUTAMOL BY INTRAVENOUS INFUSION ON THE AIRWAYS OBSTRUCTION OF PATIENTS WITH ASTHMA

1 The effects of intravenous infusion of prostaglandin E(2) (PGE(2)) on forced expiratory volume in 1 second (FEV(1)) were studied in ten asthmatic patients and compared with the effects of intravenous salbutamol. 2 PGE(2) at infusion rates of 5, 10 and 20 μg/min for three 15 min periods resulted in a small bronchodilator effect in four patients, bronchoconstriction in four, and had no measurable effect on FEV(1) in two patients; side effects were frequent and it was concluded that PGE(2) was unsuitable for use in the management of attacks of asthma. 3 In the same subjects bronchodilatation occurred during infusion of salbutamol at flow rates of 5, 10 and 20 μg/min (six patients), 10, 20 and 40 μg/min (two patients) and 20, 40 and 80 μg/min (two patients). Serious cardiovascular effects were not encountered at flow rates of less than 20 μg/minute.