Salbutamol Infusion Research Articles

Effective treatment of acute hyperkalaemia in childhood by short-term infusion of salbutamol.

Hyperkalaemia is a life-threatening emergency and infusion of glucose with insulin has so far been regarded as the standard treatment of choice. Recently the beta-2 stimulatory drug salbutamol has been shown to be an effective agent to treat hyperkalaemia by inducing a shift of potassium into the intracellular compartment. We treated 15 children aged 0.1-14 (mean 5.2) years suffering from acute hyperkalaemia (mean level 6.6 +/- 0.54, range 5.9-7.7 mmol/l) with a single infusion of salbutamol (5 micrograms/kg over 15 min). Serum potassium concentrations decreased significantly within 30 min to levels of 5.74 +/- 0.53 and 4.92 +/- 0.53 mmol/l after 120 min (P < 0.001, respectively). No side-effects occurred other than a light increase in heart rate in 3 patients. A single intravenous infusion of salbutamol at a dose of 5 micrograms/kg is a highly effective treatment for hyperkalaemia with minimal clinical side-effects. The effect lasts for at least 120 min and may reverse hyperkalaemia in some patients without further interventions so that salbutamol seems justified as the first choice treatment for this condition in childhood.

Lack of effect of TNF antibodies on the cardiovascular sequelae of lipopolysaccharide infusion in conscious rats

1. The aims of the present study were to determine the profile of tumour necrosis factor (TNF) release, and the effect of monoclonal antibodies to TNF, on the changes in regional haemodynamics and the responses to vasodilator and vasoconstrictor challenges, during a continuous 24 h low dose infusion of lipopolysaccharide (LPS) in conscious rats. 2. Male Long Evans rats were chronically instrumented for measurement of regional haemodynamics (renal, superior mesenteric and hindquarters) and were challenged with 3 min infusions of acetylcholine (22 nmol min-1), methoxamine (120 nmol min-1), salbutamol (0.83 nmol min-1) and bradykinin (14.4 nmol min-1). The rats were given either saline, or the TNF antibodies, TN3g1 or TN3g2a, 1 h before the start of a continuous infusion of LPS (150 micrograms kg-1 h-1) and were subsequently re-tested with the vasodilator and vasoconstrictor challenges 2, 6 and 24 h after the start of the LPS infusion. 3. Prior to infusion of LPS, TNF was not detectable in the plasma. During continuous infusion of LPS there was a transient elevation in plasma TNF levels, reaching a maximum (approximately 2300 pg ml-1) after approximately 1 h, and returning to undetectable levels after approximately 3 h of LPS infusion. 4. In the saline pretreated group, after 1-2 h of LPS infusion, there was a small hypotension and a marked renal vasodilation; 6 h after the start of LPS infusion there was a minor elevation in MAP above control levels, renal vasodilatation was maintained and a hindquarters vasoconstriction occurred; after 24 h of LPS infusion, there was a hypotension and renal and hindquarters vasodilatation. There were significant reductions in the tachycardic and renal vasodilator responses and an enhanced depressor response to acetylcholine after 24 h of LPS infusion. LPS infusion also caused a generalized hyporesponsiveness to the cardiovascular effects of methoxamine and salbutamol. The major changes in response to bradykinin were reduced tachycardic and enhanced depressor responses throughout the LPS infusion, a biphasic decrease and increase in renal conductance and enhanced hindquarters vasodilatation at 24 h. 5. Pretreatment with either TN3g1 or TN3g2a antibodies had no major effects on the changes in resting haemodynamics, or on the changes in response to methoxamine, salbutamol or bradykinin challenges during LPS infusion. However, the tachycardic responses to acetylcholine were generally preserved, and its hypotensive effect after 24 h of LPS infusion was not enhanced after TN3g1 or TN3g2a pretreatment. Thus, despite substantial, but transient, elevation of plasma TNF levels during continuous LPS infusion, it appears that the majority of cardiovascular changes were dependent on factors other than plasma TNF.

Resting cardiovascular status and vasodilator function in a vasopressin-deficient, hypertensive strain of rat

To assess resting haemodynamic status and vasodilator responses in normotensive vasopressin-deficient (DI/N) and hypertensive vasopressin-deficient (DI/H) rats. DI/N and DI/H rats were chronically instrumented with pulsed Doppler probes and intravascular catheters and were given 3-min infusions of acetylcholine (56 nmol/kg per min), bradykinin (36 nmol/kg per min) or salbutamol (2.1 nmol/kg per min) in the absence and presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 183 nmol/kg per min) or vasopressin (5 pmol/kg per min), to control for the pressor effects of L-NAME. The DI/H rats had a higher mean arterial blood pressure, lower hindquarters flow and lower vascular conductance than the DI/N rats. In the two strains of rat the haemodynamic responses to L-NAME, as well as to acetylcholine, bradykinin and salbutamol, in the absence or presence of L-NAME, were similar. In both strains of rat the acetylcholine-induced renal vasodilation was blocked by L-NAME, but bradykinin-induced mesenteric and salbutamol-induced hindquarters vasodilation involved L-NAME-sensitive and L-NAME-insensitive components. There is vasoconstriction in the hindquarters but not in renal and mesenteric vascular beds of DI/H rats. Vasodilator function is not necessarily impaired in congenital hypertension.

Regional haemodynamic responses to acetylcholine, methoxamine, salbutamol and bradykinin during lipopolysaccharide infusion in conscious rats.

1. The aim of the study was to assess the regional haemodynamic responsiveness to vasoconstrictor and vasodilator challenges during continuous 24 h infusion of lipopolysaccharide (LPS) in conscious Long Evans rats. 2. Rats were chronically instrumented for the measurement of regional haemodynamics (either internal and common carotid or renal, superior mesenteric and hindquarters) and received 3 min of infusions of acetylcholine (22 nmol min-1), methoxamine (120 nmol min-1), salbutamol (0.83 nmol min-1) and bradykinin (14.4 nmol min-1) at 2, 6 and 24 h after the start of saline or LPS (150 micrograms kg-1 h-1) infusion (rats with carotid probes received only acetylcholine and methoxamine). 3. During infusion of LPS there was a changing haemodynamic profile. After 2 h, there was a modest hypotension and vasodilatation in the internal carotid, renal and hindquarters vascular beds. After 6 h, arterial blood pressure had returned to baseline, there was still vasodilatation in the renal vascular bed but vasoconstriction in the internal and common carotids and the hindquarters. After 24 h, there was hypotension, tachycardia and generalized vasodilatation. 4. Acetylcholine caused a fall in blood pressure, tachycardia and hyperaemic vasodilatation in the carotid and renal vascular beds. Throughout the infusion of LPS, the carotid vasodilator response was enhanced after 2 h, reduced after 6 h and enhanced again after 24 h, whereas the renal vasodilator response to acetylcholine was either reduced (6 h) or absent (2 and 24 h); at this juncture the hypotensive response to acetylcholine was also enhanced and the tachycardia was reduced. 5. Methoxamine caused a rise in blood pressure, a fall in heart rate, and vasoconstriction in all the vascular beds monitored. During infusion of LPS, the pressor response to methoxamine was consistently reduced as were the vasoconstrictor responses in the carotid and mesenteric vascular beds, whereas the renal and hindquarters vasoconstrictor responses to methoxamine were only significantly reduced at some time points (renal 6 h, hindquarters 2 and 6 h).6. Salbutamol caused hypotension, tachycardia and hyperaemic vasodilatation, particularly in the hindquarters vascular bed. Throughout the infusion of LPS, the cardiovascular responses to salbutamol were substantially attenuated.7. Bradykinin caused hypotension, tachycardia and hyperaemic vasodilatation in the renal, mesenteric and hindquarters vascular beds. During the infusion of LPS, the hypotensive response to bradykinin was consistently augmented, and the tachycardia was consistently reduced, but the regional haemodynamic profile changed with time. Thus, after 2 h, the mesenteric vasodilator response was augmented and the hindquarters vasodilator response was reduced; after 6 h, the mesenteric vasodilator response appeared normal, but the renal and hindquarters vasodilator responses were reduced; after 24 h, the hindquarters vasodilator response was markedly augmented and the renal response had changed to a vasoconstriction.8. The present findings indicate marked regional variations in response to acetylcholine, methoxamine,salbutamol and bradykinin with time during LPS infusion. The changes observed are likely to reflect the interplay of a number of endogenous vasodilator and vasoconstrictor systems; further investigations will be required to clarify the mechanisms involved.

Ketotifen inhibits exacerbation of allergic airway hyperreactivity by racemic salbutamol in the guinea pig

In passively sensitized anesthetized guinea pigs, intravenous infusion of low doses of antigen ovalbumin induced a marked increased responsivity of the airways to intravenous injection of leukotriene C 4. Sustained infusion of racemic salbutamol intensified responses to leukotriene C 4 both before and after infusion of ovalbumin. Hyperreactivity as a result of infusion of ovalbumin was inhibited by intraduodenal injection of either hydrocortisone or ketotifen at doses that did not diminish responses to leukotriene C 4 in animals not exposed to antigen. Ketotifen, but not hydrocortisone, inhibited the enhanced hyperreactivity associated with infusion of racemic salbutamol.

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

In guinea pigs passively sensitized to ovalbumin, sustained (6 days) subcutaneous infusion of (+/-)salbutamol (1 mg/kg/day) induced significant airway obstruction and heightened responsivity to airway spasmogens. Of these animals, a substantial proportion (78/235) were too responsive to injected spasmogens to permit infusion of ovalbumin or died following infusion of ovalbumin; yet there were few deaths (2/166) amongst the sensitized animals not exposed to (+/-)salbutamol. In comparison to the animals not exposed to (+/-)salbutamol, infusion of ovalbumin led to exaggerated responsivity of the airways to leukotriene C4, leukotriene E4, histamine, serotonin and acetylcholine, but not to prostaglandin F2 alpha or bradykinin. The capacity of sustained exposure to high doses of (+/-)salbutamol to induce airway hyperreactivity to allergic mediators may account for an association between asthma death and regular, excessive use of sympathomimetics.

Respiratory mechanics and bronchodilator responsiveness in patients with the adult respiratory distress syndrome.

To study the effects of salbutamol (a selective beta 2-adrenergic receptor agonist) on respiratory mechanics in patients with the adult respiratory distress syndrome (ARDS). Prospective study. ICU in a university hospital. Seven mechanically ventilated, paralyzed ARDS patients. Measurements of respiratory system compliance, maximum, and minimum inspiratory resistance (by the end-inspiratory occlusion method during constant flow inflation) were performed at 0, 5, 10 cm H2O positive end-expiratory pressure, both before and at least 30 mins after the start of a continuous iv infusion of salbutamol (15 micrograms/min). Minimum inspiratory resistance represents the ohmic air flow resistance, while maximum inspiratory resistance includes minimum inspiratory resistance plus the effective additional resistance due to stress adaptation and to time constant inhomogeneities. Air flow was measured at the airway connector and tracheal pressure near the central end of the artificial airway. Maximum inspiratory resistance, minimum inspiratory resistance, and additional resistance were higher than the values reported for normal anesthetized subjects. On average, salbutamol caused a decrease in maximum and minimum inspiratory resistances (from 6.48 +/- 2.56 to 4.67 +/- 1.74 and from 4.06 +/- 2.12 to 2.07 +/- 0.95 cm H2O/L/sec, respectively). Positive end-expiratory pressure increased additional resistance, whereas it decreased minimum inspiratory resistance. No interaction was found between positive end-expiratory pressure and salbutamol. Respiratory system compliance was not significantly affected by salbutamol nor by positive end-expiratory pressure. In ARDS patients, salbutamol decreases the abnormally high airway resistance, by reducing minimum resistance, but has no effect on the effective additional resistance.

Interaction of sepsis and sepsis plus sympathomimetics on myocardial oxygen availability.

The ability to regulate myocardial blood flows (Q) in accord with changing myocardial O2 needs may be depressed in sepsis. This could be an important concern when sympathomimetics are used to augment systemic oxygen delivery (QO2) in this syndrome as increased myocardial O2 needs may accompany an infusion of this class of drugs. Therefore after measuring the effect of sepsis on myocardial O2 metabolism, we then infused various sympathomimetics to evaluate the sepsis+sympathomimetic interaction on myocardial QO2. We measured Q to the left (LV) and right (RV) ventricles by the radioactive microsphere technique in 36 unanesthetized mature sheep, before and during the infusion of dopamine, dobutamine, dopexamine, norepinephrine, salbutamol, or placebo. Randomly selected for infusion, these drugs were titrated to augment the thermodilution-derived cardiac index (CI) by greater than 20%. This study was repeated 24-48 h after cecal ligation and perforation had resulted in a hyperdynamic septic state [change (delta) in CI = sepsis - baseline = +54%; P less than 0.01]. During the septic study, both Q-LV (delta = +80%; P less than 0.01) and Q-RV (delta = +84%; P less than 0.01) were increased above baseline values; the augmented Q to both LV and RV was directly correlated with the arterial perfusion pressure (PA) x CI product and the mean pulmonary artery pressure (PPA) x CI product, respectively. Only 23% of study animals demonstrated net transmyocardial lactate production during the septic study. When the infusion of sympathomimetics was accompanied by an increase in the PPA x CI and PA x CI products, a further increase in both Q-RV and Q-LV, respectively, occurred. Also, neither the ventricular endocardial-to-epicardial flow ratios nor transmyocardial lactate extraction were modified by the sympathomimetics infusion. We conclude that the septic response to infection in this animal model was not accompanied by significant abnormalities in the metabolic regulation of myocardial QO2 (R. E. Cunnion, G. L. Scher, and M. M. Parker, Circulation 73: 637-644, 1986).

Changes in plasma glucose and lactate evoked by alpha and beta 2-adrenoceptor stimulation in conscious fasted rabbits.

In conscious fasted rabbits, the iv infusion of salbutamol (3 micrograms/kg per min) and clonidine (2 micrograms/kg per min) induced a blood glucose increase amenable to blockade, respectively by ICI 118551 (1 micrograms/kg per min) and idazoxan (20 micrograms/kg per min). Amidephrine (10 micrograms/kg per min) and salbutamol mediated an increase in plasma lactate which was attenuated by prazosin (50 micrograms/kg, sc) and ICI 118551 respectively. Clonidine did not alter basal plasma lactate. The iv infusion of adrenaline (0.3 micrograms/kg per min) evoked an increase in plasma lactate more sensitive to blockade by ICI 118551 than by prazosin. ICI 118551 also shortened the hyperglycaemic response to adrenaline, 3-Mercaptopicolinic acid (25 mg/kg) reduced salbutamol- and adrenaline-mediated hyperglycaemia and increased at the same time the lactate/glucose ratio. Our data show that plasma lactate levels may be regulated by alpha 1- and beta 2-excitatory adrenoceptor stimulation. However, only the increase in blood lactate derived from beta 2-adrenergic stimulation seems to contribute to the overall catecholamine-mediated hyperglycaemia.

Effects of dobutamine and salbutamol on haemodynamics and atrial natriuretic factor in patients with severe congestive heart failure

The influence of two cardiac inotropic drugs, dobutamine and salbutamol, on plasma atrial natriuretic factor (ANF) was investigated in 20 patients with congestive heart failure. All were in New York Heart Association class-III or IV. The patients underwent right heart catheterization with determination of central pressures, cardiac output, and pulmonary arterial plasma ANF during incremental infusions with dobutamine or salbutamol. Fourteen patients completed the study. Both drugs induced comparable increases in cardiac index and decreases in total systemic vascular resistance (P less than 0.01) without significant changes in central pressures. Heart rate rose after salbutamol (P less than 0.05), but not after dobutamine. No changes in plasma ANF were observed after either of the drug infusions. ANF secretion rate was calculated from simultaneous measurements of ANF in right atrial and pulmonary arterial plasma before and after salbutamol infusion, and median values rose more than seven-fold (P less than 0.05). The results demonstrate that ANF secretion rate is augmented after beta-adrenergic agents, possibly by a direct beta 2-adrenergic stimulation, in patients with severe congestive heart failure, and that changes in plasma ANF are an insufficient measure of ANF release when patient samples are small.

Treatment of hyperkalaemia with intravenous salbutamol.

Thirteen children with hyperkalaemia were treated by intravenous infusions of salbutamol, 4 micrograms/kg over 20 minutes. Reductions in the mean (SD) plasma potassium concentrations, of 1.48 (0.5) and 1.64 (0.5) mmol/l were obtained at 40 and 120 minutes, respectively, after completion of the infusions. No side effects were noted.

Dermatite de contact par cathéter intraveineux périphérique à embase métallique

A case is reported of a 26-year-old woman who developed contact dermatitis due to a peripheral venous catheter. This catheter had a metal connector, made of nickel-brass. The patient had been admitted for uterine contractions and was to receive an infusion of salbutamol. Twelve hours after the catheter had been set up, she developed at the puncture site an acute inflammatory reaction, with oedema and bullae. She later admitted to having had a few “spots” when wearing a cheap metal bracelet. Skin tests with nickel (5 % solution of nickel sulphate) confirmed the diagnosis. This case underlines the importance of looking for an allergic history in patients.

Acute hemodynamic and arrhy thmogenic effects of high‐dose intravenous salbutamol in patients with chronic left ventricular dysfunction

The short-term hemodynamic and possible arrhythmogenic effects of intravenous salbutamol at a dose of 30 or 60 micrograms/min were evaluated in 14 patients with severe chronic left ventricular dysfunction using equilibrium radionuclide angiocardiography and electrocardiographic monitoring. Salbutamol infusions at a dose of 30 micrograms/min did not cause significant hemodynamic changes; however, at a dose of 60 micrograms/min there was a significant increase in stroke volume, cardiac output, and left ventricular ejection fraction. Heart rate increased significantly while systemic peripheral resistance decreased significantly. Two patients developed ventricular premature beats and another two supraventricular tachycardia, but none were associated with adverse consequences. Thus, high-dose intravenous salbutamol is effective and safe, and may be used in the acute management of patients with poor left ventricular function.

Ambulatory long-term subcutaneous salbutamol infusion in chronic severe asthma

Although most patients with asthma improve with currently available drugs, there appears to be a subset of patients with asthma resistant to intensive treatment, including large doses of systemic corticosteroids. In 10 patients with asthma difficult to treat, a double-blind, placebo-controlled, crossover study was performed to evaluate whether long-term, continuous subcutaneous infusion of large doses of salbutamol, in addition to steroids, could improve pulmonary function, compared with intermittent nebulization of salbutamol. Four weeks of administration of large doses (>14 mg/day) of β 2-agonists were well tolerated, elicited a significant decrease of corticosteroid consumption ( p < 0.01), and were associated with an improvement in pulmonary function ( p < 0.01), compared with run in or the placebo administration period. Mean morning and evening peak expiratory flow rates were similar during all periods, and the variability between morning and evening peak expiratory flow rates was only slightly and nonsignificantly reduced during the period when salbutamol was administered subcutaneously. Both nebulized and subcutaneous salbutamol elicited similar metabolic and muscular side effects, but these untoward reactions never caused any patient to stop the treatment. Local infection at the injection site was observed in two of 10 patients with continuous subcutaneous infusion. Tachyphylaxis to β 2-agonist, as measured by the reversibility of FEV 1 to inhaled salbutamol 12 hours after the end of each period, did not occur. In conclusion, large doses of β 2-agonist administered to patients with severe, chronic, and steroid-dependent asthma were able to improve respiratory function and to decrease corticosteroids requirements.

Ventilation-perfusion mismatching in acute severe asthma: effects of salbutamol and 100% oxygen.

Ventilation-perfusion (VA/Q) relationships and gas exchange were studied by the multiple inert gas technique in 19 patients admitted to hospital with acute severe asthma (FEV1 41% predicted) before and during the administration of intravenous salbutamol, inhaled salbutamol, or 100% oxygen. Eight patients received a continuous intravenous infusion of salbutamol (4 micrograms/min, total dose 360 micrograms) and were studied before treatment, after 60 and 90 minutes of treatment, and one hour after treatment had been discontinued. Six patients had measurements before and 15 minutes after inhaling 300 micrograms salbutamol from a metered dose inhaler on two occasions (total dose 600 micrograms) and one hour after the last dose. Measurements were also made in five patients before and while they breathed 100% oxygen for 20 minutes. At baseline (fractional inspired oxygen (FiO2) 21%) all patients showed a broad unimodal (n = 10) or bimodal (n = 9) distribution of blood flow with respect to VA/Q. A mean of 10.5% of the blood flow was associated with low VA/Q units without any appreciable shunt. One of the best descriptors of VA/Q inequality, the second moment of the perfusion distribution on a log scale (log SD Q), was moderately high with a mean of 1.18 (SEM 0.08) (normal less than 0.6). Measures of VA/Q inequality correlated poorly with spirometric findings. After salbutamol the increase in airflow rates was similar regardless of the route of administration. Intravenous salbutamol, however, caused a significant increase in heart rate, cardiac output, and oxygen consumption (VO2); in addition, both perfusion to low VA/Q areas and log SD Q increased significantly. Inhaled salbutamol caused only minor changes in heart rate, cardiac output, VO2, and VA/Q inequality. Arterial oxygen tension (PaO2) remained unchanged during salbutamol administration, irrespective of the route of administration. During 100% oxygen breathing there was a significant increase in log SD Q (from 1.11 to 1.44). It is concluded that patients with acute severe asthma show considerable VA/Q inequality with a high level of pulmonary vascular reactivity. Despite similar bronchodilator effects from inhaled and intravenous salbutamol, VA/Q relationships worsened only during intravenous infusion. PaO2 remained unchanged, however, because the change in VA/Q relationships was associated with an increase in metabolic rate and cardiac output.

Pharmacokinetics of intravenous salbutamol in renal insufficiency and its biological effects.

Salbutamol was administered intravenously to 5 patients with renal function impairment for estimation its pharmacokinetic parameters. The mean terminal half-life was 256 min, similar to previously reported values in healthy adults. The mean clearance (167 ml/min) and the mean volume of distribution (551) were decreased. These parameters were not correlated with the creatinine clearance. A slight but significant decrease was observed in the plasma potassium level up to 125 min after the salbutamol infusion. The heart rate was significantly increased, and the increase in 3 patients was correlated with the salbutamol concentration. The biological effects of the drug were less marked than expected.

How Does Salbutamol Improve the Ventricular Performance in Patients with Chronic Obstructive Pulmonary Disease?

To evaluate the influence of beta 2 mimetics on ventricular contractility and pump function, radionuclide ventriculography and right heart catheterization were simultaneously performed in 10 patients with severe chronic obstructive pulmonary disease. After a 60 min constant infusion of 17 micrograms/min salbutamol, cardiac index increased by 60%, heart rate by 39%, and stroke volume index by 14%. Mean pulmonary artery pressure remained unchanged and mean arterial pressure decreased slightly but not significantly. Right ventricular (RV) function improved as attested to by an increase of RV ejection fraction (+8%), a decrease of RV end-diastolic pressure (-5 mm Hg), and RV end-systolic volume index (-18%). Simultaneously, the pulmonary vascular resistance index decreased by 33% and RV contractility, appreciated by RV dP/dtmax, RV (dP/dtmax)/P, and RV end-systolic pressure/volume ratio, increased by 44, 77, and 27%, respectively. Left ventricular (LV) function also improved. The LV ejection fraction increased by 18% and LV end-systolic volume decreased by 34%. Concomitantly, the systemic vascular resistance index decreased by 40% and the LV end-systolic pressure/volume ratio increased by 50%. Our results suggest that the infusion of salbutamol improves ventricular performance by a decrease of ventricular afterload and by a positive inotropic effect.

Nécrose myocardique électrique asymptomatique lors d'une perfusion de bêta-mimétiques au cours d'un état de mal asthmatique

A case is reported of a 56 year old woman admitted for status asthmaticus. She had no known history of cardiovascular disease. During the infusion of salbutamol, there appeared signs of myocardial infarction on the ECG trace. The patient did not complain of any symptoms suggestive of myocardial infarction. Closer cardiac examination and ultrasound revealed features of hypertrophic cardiomyopathy. The first ECG carried out on admission was in fact in favour of this diagnosis. The pathogenesis of this myocardial infarction is discussed : the long lasting hypoxaemia and the tachycardia induced by the salbutamol simulated hard exercise, poorly tolerated by patients suffering from hypertrophic cardiomyopathy. Also, this type of cardiomyopathy is known to be associated with impaired myocardial vasodilator reserve and small vessel coronary artery disease.

Improved Cardiac Performance by Salbutamol, a Selective β2-Agonist, in Chronic Cor Pulmonale

The effects of salbutamol, a relative specific beta 2-agonist, on hemodynamics and arterial blood oxygenation, were studied in 12 patients with chronic cor pulmonale. The studies were done during heart catheterization at rest (n = 12) and during arm bicycle exercise (n = 7) before and during salbutamol infusion of 0.2 microgram/kg/min. At rest, salbutamol significantly increased cardiac index on average by 31%, stroke volume index by 11%, and heart rate by 12 beats/min. Mean pulmonary artery pressure was not changed by salbutamol, whereas a small reduction in mean arterial pressure was observed. The vascular resistance was reduced by 15% in pulmonary and 24% in systemic circulation. Similar hemodynamic changes by salbutamol were observed during exercise. Arterial oxygen tension and saturation were not changed by salbutamol, but a significant rise in mixed venous oxygen saturation and oxygen delivery were observed both at rest and during exercise. Thus, salbutamol infusion improves the cardiac performance in patients with chronic cor pulmonale through a chronotropic effect combined with vasodilation in both the systemic and pulmonary circulation and thereby increased stroke volume. No deleterious effects on arterial blood oxygenation by salbutamol infusion were observed.

Infused salbutamol accentuates acid-induced lung injury in the rat.

The effect in the rat of salbutamol infusion (1 microgram min-1 kg-1) on acid-induced lung injury has been determined. Severity of lung injury was assessed by two techniques: the pulmonary clearance of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and the lung wet/dry weight ratio, giving indices of alveolar epithelial permeability and transendothelial water filtration respectively. Mean half-time of clearance of 99mTc-DTPA was increased significantly in rats who had intratracheal acid-induced injury and control (saline) intravenous infusion (19.4 +/- 2.6 min) compared with non-acid-treated rats (98.1 +/- 7.2) (P less than 0.0001). However, those animals who had intratracheal acid injury and subsequent salbutamol intravenous infusion had significantly faster clearance (11.5 +/- 1.9) than the acid and control infusion group (P less than 0.05). Gravimetric lung water in the acid-only rats (expressed as wet/dry weight ratio) was increased significantly (6.4 +/- 0.3) compared with the non-acid-treated controls (5.4 +/- 0.2) (P less than 0.01). Acid-treated rats who had salbutamol infused had dramatically increased lung water (10.0 +/- 0.6) (P less than 0.001 vs acid and control infusion). Intravenous salbutamol infusion itself produced no significant difference in the results for both techniques, compared with the non-acid-treated time-course controls. Infused salbutamol accentuates acid-induced lung injury in the rat. Possible factors responsible for these findings include beta 2-adrenergic agonist mediated inhibition of hypoxic pulmonary vasoconstriction (HPV) and a predominant beta 1-adrenergic agonist inotropic effect of salbutamol with resultant rise in pulmonary artery pressure.