Treatment of hyperkalaemia by altering the transcellular gradient in patients with renal failure: effect of various therapeutic approaches. Treatment of hyperkalaemia using intravenous and nebulised salbutamol. Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe? Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Comparison of IV salbutamol with IV aminophylline in the treatment of severe, acute asthma in childhood. Comparison of aminophylline and insulin-dextrose infusions in acute therapy of hyperkalemia in end-stage renal disease patients. Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma. Randomised trial of intravenous salbutamol in early management of acute severe asthma in children. Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy. The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. Effect of adding aminophylline infusion to nebulised salbutamol in severe acute asthma. Nebulized versus intravenous albuterol in hypercapnic acute asthma. A multicenter, double-blind, randomized study.
Ten patients with acute and 60 with chronic renal failure (both groups having hyperkalaemia), were managed at Kenyatta National Hospital in the medical wards and Renal Unit between August, 1995 and January, 1996. They were divided into seven different treatment groups, each consisting of ten patients. Treatment A glucose 25g i.v. with insulin 10 units i.v., treatment B 50 mmol of 8.4% sodium bicarbonate infusion, treatment C 0.5mg of salbutamol i.v. in 50mls 5% dextrose, treatment D was a combination of treatments A and B, treatment E was a combination of treatment B and C, treatment F was a combination of treatments A and C while treatment G was a combination of treatments A and B and C. Serum potassium was measured, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours after treatment. Plasma glucose concentration was measured before treatment was given and 1 hour after in all patients. Electrocardiography was done before treatment on all patients and repeated 30 minutes and 1 hour after treatment for the patients with hyperkalaemic changes on the initial recording. All treatment modalities had satisfactory potassium lowering effects. Of the single therapeutic approaches, treatment A and C were equieffective, but better than treatment B (P < 0.001). Amongst the two regimen combinations, treatment D and F were more efficacious than treatment E and all the single therapeutic approaches (P < 0.001). Treatment G was the most efficacious in lowering serum potassium in this study. All treatment modalities had maximum serum potassium lowering effect at 1-2 hours. A fall in plasma glucose concentration was a notable feature of treatments A and D, but significant hypoglycaemia occurred in 20% of patients receiving treatment A and in none on treatment D. The ECG changes of hyperkalaemia did not correlate with serum potassium levels. The normalisation of hyperkalaemic ECG alteration occurred within the first 30 minutes after treatment. In conclusion, combination therapies for hyperkalaemia appear to be more efficacious than single therapeutic approaches. Inclusion of salbutamol seems to protect against insulin induced hypoglycaemia. The maximum potassium lowering effect is observed 1-2 hours of administration of either agents. The potassium reducing effect remains significant compared to baseline values even after 8 hours. If dialysis cannot be instituted early enough it seems reasonable to repeat treatment every 4-6 hours to sustain the effect. Repeated administration of glucose with insulin may not be safe because of the hypoglycaemic effect. Other single and combination therapies can theoretically be repeated regularly until dialysis is initiated although this requires further clinical evaluation. In 11 children (aged 5-18 years) with end stage chronic renal failure, the effect on plasma potassium of two doses of salbutamol (separated by two hours) given intravenously (4 micrograms/kg) and on a separate date, of salbutamol administered by nebuliser (2.5 mg if the child weighed below 25 kg, 5 mg if above) was observed. Within 30 minutes of the first dose, the mean plasma potassium concentration fell significantly by 0.87 and 0.61 mmol/l after intravenous and nebulised administration respectively. Sixty minutes after the second dose the plasma potassium was significantly reduced by a further 0.28 and 0.53 mmol/l respectively. There was a significant difference between the two methods of administration at 300 minutes after the first dose favouring nebulisation. No major side effects were observed. Nebulised salbutamol should be the first choice emergency treatment of hyperkalaemia. To determine the efficacy of inhaled salbutamol (rapidly delivered, using a metered-dose inhaler with a spacer device [MDI-S]) in lowering the serum potassium levels in patients with hyperkalemia.
                A randomized, double-blind, placebo-controlled trial.
                Seventeen chronic renal failure patients referred to the Nephrology Unit between October 1, 1997 and March 31, 1998 for hemodialysis were randomized.
                Group 1 received salbutamol followed by a placebo. Group 2 received a placebo followed by salbutamol. Each patient inhaled 1,200 microg salbutamol or a placebo through an MDI-S within 2 min. Blood samples were obtained repeatedly before inhalation and after 1, 3, 5, 10, and 60 min. The pulse rate and blood pressure were repeatedly measured. Insulin levels were examined in a subset of patients (n = 10) before, and 1 and 5 min following inhalation. Salbutamol's known side effects, palpitation, tachycardia tremor, and headache, were recorded. Potassium levels rose after 1 min following the completion of treatment and then decreased steadily thereafter. A rise of > or = 0.1 mEq/L was seen in 10 of 17 patients (59%) during the treatment period and there was no change (0%) seen during the placebo period (p < 0.0001). Within 3 min after inhalation of salbutamol, potassium levels declined as a function of time. Potassium levels in those patients taking the placebo did not change as a function of time (p < 0.001). The difference between the placebo and the salbutamol-treated periods reached significance after 5 min (p < 0.05). The serum glucose levels rose following inhalation of salbutamol, with a significant rise after 3 min. The heart rate rose significantly within the first 5 min following inhalation. Serum insulin levels remained unchanged 1 min after inhalation; however, after 5 min, a significant elevation was detected.
                Salbutamol inhalation of 1,200 microg, using an MDI-S, has a relatively rapid onset of action that induces a consistent reduction in serum potassium levels, starting 3 to 5 min following delivery. Unexpectedly, a paradoxical elevation was detected in serum potassium levels in the first minutes following inhalation. This effect, although minor (0.15 mEq/L above baseline), may cast some doubt on the role of salbutamol inhalation as the first treatment for excessive hyperkalemia. We evaluated in maintenance hemodialysis patients the potassium lowering effects of intravenous insulin with glucose, nebulized albuterol, and a regimen combining both modalities. There was a similar decrease in plasma potassium following either insulin with glucose (0.65 +/- 0.09 mmol/liter) or albuterol (0.66 +/- 0.12 mmol/liter), and a substantially greater fall with the combined regimen (1.21 +/- 0.19 mmol/liter, P less than 0.02 vs. either drug alone). Baseline plasma glucose concentrations were similar (about 4.8 mmol/liter) prior to all three treatments. Following insulin with glucose, plasma glucose increased transiently. but then fell to 2.8 +/- 0.3 mmol/liter at one hour, with concentrations below 3 mmol/liter in 9 of 12 patients. None of the patients had symptoms of hypoglycemia. Plasma glucose increased to 6.8 +/- 0.5 mmol/liter with albuterol. After the combined drug regimen plasma glucose rose transiently and was back to baseline (4.7 +/- 0.7 mmol/liter) at one hour. Treatment with insulin or albuterol produced trivial increases in heart rate, whereas the combined drug regimen was associated with a significant rise (15.1 +/- 6.0 min-1). These observations suggest that albuterol and insulin with glucose are equally efficacious in lowering plasma potassium in uremic patients, and that the hypokalemic effects of the two drugs is additive. The hypoglycemic effect of insulin is attenuated by coadministration albuterol. Combined therapy with insulin, glucose and albuterol is efficacious and safe for the acute treatment of hyperkalemia in hemodialysis patients. A double-blind test to compare IV aminophylline with salbutamol in the treatment of acute, uncontrolled asthma showed that both drugs were equally effective during the first 24 hours. Salbutamol caused a relative tachycardia. Hydrocortisone was given after 2 hours, but did not appear to affect the rate of recovery. This study was performed to compare the efficacy of aminophylline and insulin-dextrose infusion as acute treatment modality of hyperkalemia in patients with end-stage renal disease (ESRD).
                This study was conducted on 30 ESRD patients with serum potassium > 6.0 mEq/L. These patients were divided in two groups of 15 each. Group A patients were treated with aminophylline infusion, whereas group B patients were treated with insulin-dextrose infusion. Serum potassium and other biochemical parameters such as blood sugar were measured at beginning of treatment followed by at 60 minutes, 180 minutes, and 360 minutes after treatment.
                Intervenous infusion of aminophylline lowered plasma potassium from 6.48 +/- 0.39 mEq/L to 5.92 +/- 0.40 mEq/L at 180 minutes (p < 0.001 Vs basal) and 6.05 +/- 0.53 mEq/L at 360 minutes (p < 0.01 Vs basal). Whereas, intravenous infusion of insulin-dextrose decreased plasma potassium from 6.59 +/- 0.31 mEq/L to 5.76 +/- 0.32 mEq/L (p < 0.001 Vs basal) and 5.84 +/- 0.21 mEq/L (p < 0.001 Vs basal). Thus in both groups, plasma potassium levels were significantly less than basal levels throughout the study. The decrease in plasma potassium was significantly more in group B patients (p value is < 0.001 after 60 minutes, < 0.05 after 180 minutes and < 0.05 after 360 minutes) when compared to group A patients. There was one episode of hypoglycemia (blood sugar < 60 mg%) in insulin-dextrose infusion group. No other side effects were observed throughout the study.
                Aminophylline is an effective modality for acute treatment of hyperkalemia, though it is less effective than insulin-dextrose infusion. However, more studies are required to confirm these results. Twenty-one patients admitted to hospital with acute severe asthma were allocated in a random, single-blind manner to receive intravenous infusions for 24 hours or either aminophylline or salbutamol or a combination of the two drugs. Infusions were administered by a slow infusion pump with an initial loading dose given over 15 minutes, followed by a continuous lower dose of the drug 24 hours as follows: 1. Aminophylline 0.285 mg/kg/min for 15 min followed by 0.014 mg/kg/min (20 mg/min. followed by 1 mg/min for a 70 kg subject). 2. Salbutamol 0.285 microgram/kg/min for 15 min followed by 0.057 microgram/kg/min (20 microgram/min followed by 4 microgram/min for a 70 kg subject). 3. Combined regimen of the above infusions. In addition each patient received intravenous hydrocortisone (4 g) and potassium chloride (4 g) in 2 litres of 5% dextrose infused over 24 hours amd 35% oxygen given via a Ventimask. Peak expiratory flow rates showed a significant improvement after 15 minutes treatment with aminophylline and the combined infusion, but this was not seen until 60 minutes with the salbutamol infusion. No synergistic bronchodilator effect was seen with the combined infusion. The results show that intravenous aminophylline is superior to intravenous salbutamol in the doses given in the initial treatment of acute asthma and that the combination when given intravenously is not better than aminophylline alone. The mainstay of treatment for acute asthma in children is nebulised beta 2-adrenergic agents such as salbutamol, given with corticosteroids. However, penetration of the drug to the small airways is impeded by obstruction so intravenous salbutamol may be more effective. We assessed the use of intravenous salbutamol in the management of children with acute severe asthma in a double-blind randomised study.
                Children who presented to the Emergency Department of Westmead Hospital, Sydney, Australia with asthma were assessed with a clinical assessment scale, and those with severe acute asthma were given nebulised salbutamol at a dose of 2.5 mg (age < or = 2 years) or 5.0 mg (age > 2 years), made up to 4 mL with saline. Children who did not improve were eligible to enter phase one of the study. In this phase (0 h-2 h) treatment was by a standard protocol: nebulised salbutamol at the above dose: 4 L/min or 6 L/min continuous oxygen until oxygen saturation reached 93% in room air for at least 30 min; a bolus of intravenous hydrocortisone 5 mg/kg given over 3 min; and then 15 micrograms/kg intravenous salbutamol or saline, depending on randomised allocation. In phase two (2 h-24 h) the children were given nebulised salbutamol continuously then at 30 min, 1 h, 2 h, 3 h, and 4 h, according to need. All children were transferred to the ward once they were ready to start hourly nebulisation. All patients were followed up until discharge. The primary endpoints were recovery time (no longer requiring inhaled salbutamol) and persistent moderate to severe asthma 2 h after randomisation. Analyses were by intention-to-treat although no withdrawals occurred.
                The recovery time (time to cessation of nebulised salbutamol every 30 min) was 4 h in the 14 children allocated intravenous salbutamol compared with 11.5 h for the 15 children in the control group. 2 (14%) of the intravenous salbutamol group compared with 8 (53%) of the control group needed oxygen to maintain oxygen saturation at 93% room air. The intravenous salbutamol group were ready for discharge from the emergency department 9.7 h earlier than the control group. No clinically significant side-effects were found in either group.
                Addition of a 10 min infusion of salbutamol in the early treatment of children with acute severe asthma has the potential to curtail the clinical progression of asthma, reduce demand placed on hospital resources, and improve the quality of health care provided to the acutely sick child with asthma. To evaluate the effectiveness of early administration of intravenous Magnesium sulfate (i.v. MgSO4) in children with acute severe asthma not responding to conventional therapy.
                Randomized double-blind, placebo-controlled trial.
                Pediatric emergency service of a large teaching hospital.
                47 children aged between 1-12 years with acute severe asthma showing inadequate or poor response to 3 doses of nebulized salbutamol given at an interval of 20 min each.
                The MgSO4 group received 0.2 ml/kg of 50% MgSO4 as intravenous (i.v.) infusion over 35 minutes and the placebo group received normal saline infusion in the same dose and at the same rate. MgSO4 solution and normal saline were coded and dispensed in identical containers. Decoding was done at the completion of the study. All the patients received oxygen, nebulized salbutamol, i.v. aminophylline and corticosteroids.
                MgSO4 group showed early and significant improvement as compared to placebo group in PEFR and SaO2 at 30 min and 1, 2, 3 and 7 hours after stopping the infusion (p ranging from < 0.05 to < 0.01). The clinical asthma score also showed significant improvement in the MgSO4 group 1, 2, 3 and 11 hours after stopping the infusion (p < 0.01).
                Addition of MgSO4 to conventional therapy helps in achieving earlier improvement in clinical signs and symptoms of asthma and PEFR in patients not responding to conventional therapy alone. The aim of this study was to compare the efficacy and safety of salmeterol/fluticasone propionate combination product (SFC) with fluticasone propionate (FP) plus oral montelukast (M) over 12 weeks in symptomatic asthma patients. The study was a multinational, randomised, double-blind, double-dummy, parallel-group design in patients aged > or = 15 years. After a 4-week run-in during which all patients received FP 100 microg twice daily, patients were randomised to inhaled SFC (50/100 microg) twice daily or inhaled FP 100 microg twice daily and oral M 10 mg once daily. Patients kept daily records of their peak expiratory flow (PEF) symptom scores and use of rescue medication. Over the 12-week treatment period, the adjusted increase in mean morning PEF was significantly greater in the SFC group (36 l/min) than the FP/M group (19 l/min; P < 0.001). The improvement in FEV1 was also significantly greater in the SFC group (mean treatment difference 0.11 l; P < 0.001). SFC provided significantly better control of daytime and night-time symptoms and there were fewer exacerbations. Patients in the SFC group were also significantly more likely to have a rescue-free day. Both treatments were equally well tolerated. Combination therapy with FP plus salmeterol (SFC) produced significantly greater improvements in lung function and asthma control than the addition of montelukastto FP. The benefit of adding theophylline to beta 2 agonists in acute asthmatic attacks has been debated frequently.
                In an open randomised study 25 patients with severe acute asthma who presented to the emergency department were treated with either a combined nebulised salbutamol (5 mg/dose) and aminophylline infusion (0.6-0.9 mg/kg/hour), or nebulised salbutamol alone.
                The responses to treatment as measured by peak expiratory flow (PEF) and the time taken to achieve maximum PEF were similar in both groups. Side effects were observed more commonly in patients receiving the combined treatment.
                Nebulised salbutamol is equally efficacious in acute asthma when given alone or in combination with aminophylline. In a multicenter, randomized, double-blind study, we compared the effects of nebulized (5 mg x 2) and intravenous (0.5 mg) albuterol (salbutamol) over 1 h in 47 patients admitted to hospital with severe acute asthma defined as a peak expiratory flow (PEF) below 150 L/min and hypercapnia (Pa(CO2) > or = 40 mm Hg). Additional treatment included nasal oxygen and hydrocortisone succinate. The efficacy was assessed after 1 h. In the group treated by nebulization (NEB group, n = 22) 19 (86%) patients (95% confidence interval: 65 to 97%) had been treated successfully according to predefined criteria, versus 12 (48%) patients (95% confidence interval: 28 to 69%) in the intravenously treated group (i.v. group, n = 25), p = 0.006. The mean increase in PEF was greater in the NEB group than in the i.v. group (+107 +/- 94 L/min versus +42 +/- 66 L/min, p = 0.01) as well as the decrease in Pa(CO2) values (-10 +/- 5 mm Hg versus -2 +/- 12 mm Hg, p < 0.01). Beta agonist-induced hypokalemia was more pronounced in the i.v. group than in the NEB group. We conclude that, in hypercapnic acute asthma, the nebulized route has a greater efficacy and fewer side effects than the intravenous route.
Nebulised or inhaled salbutamol, or IV insulin-and-glucose are the first-line therapies for the management of emergency hyperkalaemia that are best supported by the evidence. Their combination may be more effective than either alone, and should be considered when hyperkalaemia is severe. When arrhythmias are present, a wealth of anecdotal and animal data suggests that IV calcium is effective in treating arrhythmia. Further studies of the optimal use of combination treatments and of the adverse effects of treatments are needed.