Salbutamol Metered-Dose Inhaler With Spacer for Hyperkalemia: How Fast? How Safe?

doi:10.1378/chest.115.3.617

Chest

Volume 115, Issue 3, March 1999, Pages 617-622

https://doi.org/10.1378/chest.115.3.617 Get rights and content

Objective

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.

Design

A randomized, double-blind, placebo-controlled trial.

Patients

Seventeen chronic renal failure patients referred to the Nephrology Unit between October 1, 1997 and March 31, 1998 for hemodialysis were randomized.

Intervention and results

Group 1 received salbutamol followed by a placebo. Group 2 received a placebo followed by salbutamol. Each patient inhaled 1,200 μg 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 ≥ 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.

Conclusion

Salbutamol inhalation of 1,200μ g, 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.

Section snippets

Patients

The patients were studied with the approval of our institution's ethics committee. They were personally interviewed by the investigator, and each patient gave informed and signed consent to participate in the study.

Inclusion criteria: Patients with severe renal failure and elevated serum potassium levels (> 5 mEq/L) who were undergoing hemodialysis were included in the study.

Exclusion criteria: Patients in the study were excluded from participating if they had active ischemic heart disease

Results

It was shown that serum potassium levels rise initially for 1 min following salbutamol inhalation but steadily decline thereafter; with placebo therapy, no change was observed (Fig 1, top and bottom). After 1 min, a significant difference (p < 0.001) was detected between the declining trend of the curve following salbutamol inhalation and the lack of change with placebo therapy (general linear model), as a function of time.¹⁸ In 10 patients (59%) receiving salbutamol, a rise of 0.1 mEq/L or

Discussion

Sixty-four years ago, it was found that adrenaline (a nonselectiveα - and β-stimulant), may lower serum potassium levels.¹⁹ Nevertheless, this drug was not accepted as a clinical remedy for hyperkalemia, perhaps due to its potentially overwhelming side effects. Recently, several publications have addressed the issue of lowering serum potassium levels usingβ ₂-agonist receptor agents.⁴⁵⁶⁷⁸⁹¹⁰¹¹¹²¹³¹⁴¹⁵¹⁶¹⁷²⁰²¹²² Our study indicates a significant and consistent lowering of the serum potassium

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Aerosolized salbutamol has been associated with hypokalemia in horses undergoing colic surgery. The objective of this study was to evaluate the effect of aerosolized salbutamol on arterial potassium concentration ([K +]) in healthy anaesthetized horses undergoing elective surgery.
Anesthetic records were reviewed from healthy adult horses undergoing elective surgery over a 3-year period with two complete sets of arterial electrolyte (sodium [Na +], potassium [K +], chloride [Cl -], calcium [Ca 2+]) concentration measurements. Records were excluded if intra-operative electrolyte supplementation, antimicrobial administration or noncrystalloid fluid administration were documented or if salbutamol was administered prior to electrolyte measurement. Sixty records which fulfilled inclusion criteria were divided into two groups depending on whether or not aerosolized salbutamol (2μg kg -1) (to treat hypoxemia) was administered after baseline electrolyte measurement and before the second electrolyte measurement. Aerosolized salbutamol was administered (Group S) in 22 horses and not administered (group NS) in 38 horses. There was a significant reduction in [K +] and [Ca 2+] between baseline and the second electrolyte measurement in both groups (P< .001). The reduction in [K +] between baseline and the second electrolyte measurement was significantly greater in group S (12.3%) compared to group NS (6.9%) (P= .017) and was significantly associated with salbutamol administration (P= .04). The results of this study indicate that monitoring [K +] is important in anaesthetized horses, particularly after aerosolized salbutamol administration.
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Fluid and electrolyte disturbances are common among children and fluid management is critical to the successful care of a wide range of pediatric conditions. This chapter outlines the basic anatomy and physiology of fluid compartments, their developmental maturation, and a general approach to fluid administration. Clinical assessment of hydration states, perioperative fluid management, and the care of common pathophysiologic states are discussed in detail. Specific attention is given to acid–base balance and to disorders of sodium, potassium, and water homeostasis.
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Nebulized albuterol administered to patients with ESRD demonstrates an ability to cause a decrease of serum K+, with decreases of 0.6 mmol/L within 30 min after a 10-mg inhaled dose and of 1.0 mmol/L 1 h after administration of a dose of 20 mg (8,69,82,97,105). The latter decrease seems to be sustained for at least 2 h (8,69,82,97,99,105). The albuterol nebulized dose is higher than typically used for obstructive airway disease, but it can be safely given and can result in a decrease of 0.4–1.0 mmol/L at 1 h (99,106).
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Potassium (K+) plays a key role in determining the transmembrane potentials of “excitable membranes” present in nerve and muscle cells. K+ is the predominant intracellular cation, and clinical deterioration typically ensues when patients develop sufficiently marked elevation in extracellular fluid concentrations of K+ (hyperkalemia). Hyperkalemia is usually detected via serum clinical laboratory measurement. The most severe effect of hyperkalemia includes various cardiac dysrhythmias, which may result in cardiac arrest and death. Treatment includes measures to “stabilize” cardiac membranes, to shift K+ from extracellular to intracellular stores, and to promote K+ excretion. Calcium gluconate 10% dosed 10 mL intravenously should be provided for membrane stabilization, unless the patient is in cardiac arrest, in which case 10 mL calcium chloride is warranted. Beta-agonists and intravenous insulin should be given, and some experts recommend the use of synthetic short-acting insulins rather than regular insulin. Dextrose should also be administered, as indicated by initial and serial serum glucose measurements. Dialysis is the most efficient means to enable removal of excess K+. Loop and thiazide diuretics can also be useful. Sodium polystyrene sulfonate is not efficacious. New medications to promote gastrointestinal K+ excretion, which include patiromer and sodium zirconium cyclosilicate, hold promise.
Hyperkalemia can be deadly, and treatment requires specific measures including membrane stabilization, cellular shift, and excretion.
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2018, A Practice of Anesthesia for Infants and Children
Fluid and electrolyte disturbances are common among children and fluid management is critical to the successful care of a wide range of pediatric conditions. This chapter outlines the basic anatomy and physiology of fluid compartments, their developmental maturation, and a general approach to fluid administration. Clinical assessment of hydration states, perioperative fluid management, and the care of common pathophysiologic states are discussed in detail. Specific attention is given to acid–base balance and to disorders of sodium, potassium, and water homeostasis.
Factors Regulating the External Balance of Potassium
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Chest

Clinical InvestigationsBronchodilatorsSalbutamol Metered-Dose Inhaler With Spacer for Hyperkalemia: How Fast? How Safe?

Objective

Design

Patients

Intervention and results

Conclusion

Section snippets

Patients

Results

Discussion

Am J Kidney Dis

Chest

Chest

Chest

Lancet

Lancet

Kidney Int

Kidney Int

Disorders of potassium homeostasis

Pediatric Clin North Am

Clinical features and management of poisoning due to potassium chloride

Med Toxicol Adverse Drug Exp

Adrenergic modulation of extrarenal potassium disposal

N Engl J Med

The effect of adrenergic blockade on potassium concentration in different condition

Acta Med Scand

Adregenic control of Na-K-homeostasis

Acta Med Scand

Treatment of hyperkalemia using intravenous and nebulized salbutamol

Arch Dis Child

Potassium-lowering effect of albuterol for hyperkalemia in renal failure

Arch Intern Med

Hyperkalemia: therapeutic options in acute and chronic renal failure

Clin Nephrol

Clinical Investigations
Bronchodilators
Salbutamol Metered-Dose Inhaler With Spacer for Hyperkalemia: How Fast? How Safe?