Levalbuterol Compared to Albuterol Regarding Cardiac Side Effects and Potassium Lowering Effects.

Study Overview
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Brief Summary
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Hyperkalemia is a common life-threatening electrolyte disturbance which may impair cardiac and many other organs' functions. Unfortunately, a well-established guideline for the treatment of hyperkalemia in the emergency setting is still missing. However, the last Kidney Disease: Improving Global Outcomes (KDIGO) conference proposed a treatment protocol for hyperkalemia and addressed controversies in this matter. Beta2-agonists were one of the main lines in the approach towards managing a patient with hyperkalemia. However, this evidence was only available for racemic albuterol. Levalbuterol is the isolated R-enantiomer of racemic albuterol which is comprised of S- and R-enantiomers. Several lab and clinical studies have assessed the effect, affinity, and selectivity of each of the enantiomers. Few studies in medical literature have compared the difference between these two drugs regarding cardiac effects with inconclusive results, and even fewer studies have compared the efficacies of these two drugs regarding potassium lowering effect. To the investigators' knowledge, no study to date has compared the efficacy and safety of albuterol compared to levalbuterol in hyperkalemic patients with the properly adjusted dosing. So, in clinical practice, the investigators wanted to know based on evidence if levalbuterol can be an effective substitute for albuterol in lowering potassium levels in hyperkalemia patients while yielding fewer cardiac side effects. To answer this question, the investigators designed a single-centered controlled clinical trial that includes adult hyperkalemia patients in Aleppo University Hospital.

Official Title
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Is Levalbuterol an Effective Treatment With Less Cardiac Side Effects Than Albuterol in Hyperkalemia Patients: A Randomized-controlled Clinical Trial Protocol.

Conditions
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Hyperkalemia

Intervention / Treatment
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* Drug: Levalbuterol
* Drug: Albuterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients serum potassium level >5.9 mEq/L Exclusion Criteria: Pseudohyperkalemia: Hemolysis of blood sample Thrombocytosis > 10*6 /mm3 Hyperleukocytosis > 10*5/mm3 Mechanical Trauma during Venipuncture Fist clenching during blood drawing Tourniquet time > 1 minute Diabetes acute complications DKA Hyperosmolar Hyperglycemic Syndrome Insulin-dependent diabetes mellitus ( if insulin is taken recently) Pregnant women Hyperthyroidism Hemodynamic instability Pacemakers if providing impulses (demand pacemakers that are not firing right now are included) Atrial fibrillation or any other arrhythmia Baseline tachycardia >120 bpm Acute exacerbations of HF Patients expected to require emergency intubation and ventilation Patients expected to require dialysis within the first 60 minutes Patients with hypersensitivity to the medication Patients with Acute Coronary Syndrome Patients on beta-blockers / beta-agonists or anti-arrhythmic drugs Patients with severe dyspnea or hypoxia SpO2 <90%

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levalbuterol Arm<br> | Drug: Levalbuterol<br>* Levalbuterol nebulizer solution 1.25mg/3ml with a total dose of 5 mg (12ml) for each patient.<br>|
| Active Comparator: Albuterol Arm<br> | Drug: Albuterol<br>* Albuterol nebulizer solution 2.5 mg/3ml with a total dose of 0 mg (12ml) for each patient.<br>* Other names: salbutamol, racemic albuterol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate changes | Heart rate changes over time measured as beats per minute | Heart rate is measured at baseline before drug administration and at 15, 30, 45, 60, 90, 120 minutes after treatment. | 
| Serum potassium level changes | Serum potassium level changes after treatment measured as mEq/L | Serum potassium levels are measured at baseline and 90 minutes after treatment administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ECG changes | ECG Changes at presentation with hyperkalemia (Depressed ST segment, Diphasic T wave, Prominent U wave, Peaked T wave, Wide PR interval, Wide QRS duration, Peaked T wave, Loss of P wave, Sinusoidal wave, Others) and after treatment | ECG changes detected at baseline and at 90 minutes after therapy | 
| Blood Pressure (BP) changes | BP changes over time measured as mmHg | BP changes measured at baseline and at 30, 60, and 90 minutes after therapy | 
| Frequency of reported symptoms at presentation | Symptoms at presentation (Muscle weakness, Paresthesia, Paralysis, flushing, Nausea/Vomiting, Chest pain, Dyspnea, Fasciculation, Palpitations, Others). | Symptoms reported only at the presentation of the patient | 
| Frequency of Adverse effects | Adverse effects following treatment (Fever, Palpitations, Hypoglycemia, Hypokalemia, Headache, Tremor, Nervousness, Nausea/vomiting, Lightheadedness) | Adverse effects after treatment detected during the first two hours following treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperkalemia, Albuterol, Levalbuterol, Heart rate