5 Versus 10 Units of Insulin in Hyperkalemia Management

5 Versus 10 Units of Insulin in Hyperkalemia Management: Multi-center, Prospective, Double-blind, Non-inferiority, Randomized Control Trial.

The goal of this study is to compare 5 units of intravenous Regular insulin to 10 units of intravenous regular insulin in the management of hyperkalemia. We will measure the efficacy of these 2 doses of insulin in reducing hyperkalemia at 2 hours from administration using the main laboratory serum values.

Study Overview

• Status: Recruiting
• Conditions: Hyperkalemia; Potassium Imbalance; Electrolyte Disturbance; Electrolyte Imbalance
• Intervention / Treatment: Drug: Insulin regular; Drug: Dextrose 50; Drug: salbutamol

Detailed Description

Introduction: Hyperkalaemia is a serum Potassium (K) level of more than 5.5 mEq/L. It is a common emergency medicine presentation and can be life-threatening. Because of the emergency in correcting hyperkalemia, different medications are used to reduce high potassium levels to normal as soon as possible. Salbutamol inhalers, Glucose solutions, and Insulin are the main medications for managing hyperkalemia. Insulin and Dextrose shift potassium ions into body cells by stimulating the sodium/potassium ATP pump. Its effect starts in less than fifteen minutes and can last up to sixty minutes. It usually reduces potassium up to 1.1 mEq/l. There are different recommendations for Insulin dose and rate of administration for patients with hyperkalemia.

Method: This will be a multi-center, prospective, double-blind, non-inferiority, randomized control trial. 336 hyperkalemia patients will be randomized to the intervention group 5 units of intravenous Regular insulin and 10 units of intravenous insulin groups with fifty ml of Dextrose Fifty percent. They will be enrolled once their potassium level is 5.5mEq/L or more. The attending physician and patient will be blinded about the dose of insulin that the patient received. Serum potassium will be measured at 0 and at 120 minutes from the start of the medications. Random blood glucose will be measured at 0, 60, and 120 minutes by Glucometer. The safety of our patients will be assessed by documentation of all adverse events, vital signs, and clinical assessment before and after drug administration. The study will end at 2 hours from insulin administration.

Aim: Our research idea aims to compare two recommended doses of Insulin (5 Units vs. 10 Units of Regular insulin given intravenously over thirty minutes) in the management of patients with hyperkalemia.

Primary objective: Mean reduction in serum potassium level using the main laboratory results at two hours from medication administration.

Secondary objectives: effect of initial (baseline) potassium level on the mean potassium reduction, and frequency of hypoglycemia between the 2 groups. Does the initial (baseline) blood glucose level will affect the function of insulin/dextrose in lowering potassium levels?

Patient Population: Adult patients (Aged 18 years and older) who present to the Emergency department at Sultan Qaboos University and Royal Hospital for evaluation and are found to have potassium levels of 5.5 mEq/L and above.

Intervention: Single dose of 5 units of intravenous insulin over 30 minutes with 50 ml of Dextrose 50%.

Clinical Measurement: Mean reduction of potassium level using the main laboratory results at 2 hours from insulin/dextrose administration. Hypoglycemia will be followed by a bedside glucometer.

Outcome: reduction of potassium level at 2 hours from medication administration and medication safety.

• Study Type: Interventional
• Enrollment (Estimated): 336
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Adnan Al-Ajmi, MD; Phone Number: +968 98880381; Email: r2124@resident.omsb.org
• Study Contact Backup: Name: Ibrahim Al-Hooti, MD; Phone Number: +968 92985424; Email: r2127@resident.omsb.org

Study Locations

• Oman
  • Muscat
    • Seeb, Muscat, Oman, 123
      • Recruiting
      • Sultan Qaboos University Hospital
      • Contact: Suad Al-Abri; Phone Number: +968 99878005; Email: ghammari@squ.edu.om
      • Contact: Saif Al-ghafri; Phone Number: +968 99814471; Email: saialghafri1@gmail.com
      • Sub-Investigator: Usama Al-Khallasi
      • Sub-Investigator: Ali Al-lawati
      • Sub-Investigator: abdullah Al-Reesi
      • Principal Investigator: Ibrahim Al - Hooti
      • Principal Investigator: Abulmonem Al-Farsi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hyperkalemia patients with lab potassium levels equal to or more than 5.5 mEq/L (≥ 5.5 mEq/L)+.
• Adult: age 18 years or more.

• Agreed to participate in the study.

  • If an investigator decides to start anti-hyperkalemia medications based on the VBG/ABG patient can be enrolled but if the main laboratory value is less than 5.5 mEq/L patients will be excluded

Exclusion Criteria:

• Cardiac arrest
• Hyperglycemia with random blood sugar 20 mmol/L (13) or with acute diabetic complications like Diabetic Ketoacidosis / Hyperosmolar Hyperglycemic State.
• Hypoglycemia with random blood sugar (RBS) ≤ 3.89 mmol/l in Diabetic patients and less than 3 mmol/l in non-diabetic patients.
• Allergies for any medication in the protocol.
• Pregnancy.
• Hemolyzed potassium level as reported by the main lab.
• Hemolysis, Tumor lysis syndrome, or Rhabdomyolysis due to the ongoing release of potassium.
• Acidosis with a pH less than 7.1 will require Sodium bicarbonate (NaHO3).
• A patient who will need urgent Furosemide (Lasix), and or dialysis during the study period of 2 hours.
• Refused to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5 units of intravenous R insulin; Will receive: IV Insulin Regular 5 units with Dextrose 50 % 50 ml over 30 minutes. Salbutamol 10 mg Nebulization over 15 minutes.	Drug: Insulin regular; Intravenous insulin; Drug: Dextrose 50; to be given to both arms; Drug: salbutamol; to be given to all patients
Active Comparator: 10 units of intravenous R insulin; Will Receive: IV Insulin Regular 10 units with Dextrose 50 % 50 ml over 30 minutes. Salbutamol 10 mg nebulization over 15 minutes.	Drug: Insulin regular; Intravenous insulin; Drug: Dextrose 50; to be given to both arms; Drug: salbutamol; to be given to all patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To study the efficacy of two intravenous insulin doses (5 units and 10 units) in reducing serum potassium level in patients receiving hyperkalemia treatment using the main laboratory measurements. (the aim of reduction of 0.6 mmol/l +/- 0.2 mmol/L) (1).	Once the baseline potassium identified 5.5 mmol/L or more patient will be enrolled after taken an informed consent. Blood sample will be collected and send to the main laboratory for analysis at two hours from medications administration. The efficacy of the 2 doses of insulin in reducing potassium level will be measured at 2 hours from administration of medications by comparing the amount of changes of potassium level at two hours from baseline level. - The main laboratory result will be used to measure and follow the patients. results will be reported in mmol/L.	At 2 hours from administration of medications

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study the mean difference of the response to the anti-hyperkalemic measures based on the level of initial potassium (serum potassium before given any medications - At baseline).	(The investigators will categorize potassium levels into groups mild (5.5-6 mmol/l), moderate (6-6.5 mmol/l), and severe (>6.5 mmol/l) and will see the mean difference in reduction in potassium level between the 2 doses).	2 hours from administration of medications
Association of mean potassium reduction with initial blood sugar level on potassium reduction	The investigators will categorize blood sugar into groups: Below 10mmol/L, 10.1-14.9 mmol/L, and 15 - 19.9mmol/L among each group the investigators will see the mean potassium reduction levels.	2 hours from administration of medications
Incidence of hypoglycemia (random blood sugar (RBS) ≤ 3.89 mmol/l in Diabetic patients and less than 3 mmol/l in non-diabetic patients) (12) and risk factor Characteristics of patients with a higher risk of developing hypoglycemia	The investigators will investigate which group of patients will have a high risk of hypoglycemia ((e.g.: initial Glucose level, initial creatinin/renal function, comorbidities, type of dialysis….	2 hours from administration of medications

Collaborators and Investigators

• Sponsor: Oman Medical Speciality Board
• Collaborators: Sultan Qaboos University
• Investigators: Principal Investigator: Suad Al-Abri, Sultan Qaboos University Hospital

Publications and helpful links

General Publications

• Verdier M, DeMott JM, Peksa GD. A comparison of insulin doses for treatment of hyperkalaemia in intensive care unit patients with renal insufficiency. Aust Crit Care. 2022 May;35(3):258-263. doi: 10.1016/j.aucc.2021.05.004. Epub 2021 Jun 21.
• Ron M. Walls, MD. Hyperkalemia. Rosen emergency medince Concepts and Clinical practice. 9th. Philadelphia : Elsevier, 2018, 117, pp. 1516 - 1519.
• Judith E. Tintinalli, MD, MS. Hyperkalemia. Tintinalli's Emergency Medicine a comprehensive study guide. 9th. s.l. : McGraw-Hill Education, 2020, 17, p. 89.
• McNicholas BA, Pham MH, Carli K, Chen CH, Colobong-Smith N, Anderson AE, Pham H. Treatment of Hyperkalemia With a Low-Dose Insulin Protocol Is Effective and Results in Reduced Hypoglycemia. Kidney Int Rep. 2017 Oct 24;3(2):328-336. doi: 10.1016/j.ekir.2017.10.009. eCollection 2018 Mar.
• Moussavi K, Nguyen LT, Hua H, Fitter S. Comparison of IV Insulin Dosing Strategies for Hyperkalemia in the Emergency Department. Crit Care Explor. 2020 Apr 29;2(4):e0092. doi: 10.1097/CCE.0000000000000092. eCollection 2020 Apr.
• LaRue HA, Peksa GD, Shah SC. A Comparison of Insulin Doses for the Treatment of Hyperkalemia in Patients with Renal Insufficiency. Pharmacotherapy. 2017 Dec;37(12):1516-1522. doi: 10.1002/phar.2038. Epub 2017 Nov 27.
• Moussavi K, Garcia J, Tellez-Corrales E, Fitter S. Reduced alternative insulin dosing in hyperkalemia: A meta-analysis of effects on hypoglycemia and potassium reduction. Pharmacotherapy. 2021 Jul;41(7):598-607. doi: 10.1002/phar.2596. Epub 2021 Jun 1.
• Harel Z, Kamel KS. Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review. PLoS One. 2016 May 5;11(5):e0154963. doi: 10.1371/journal.pone.0154963. eCollection 2016.
• Garcia J, Pintens M, Morris A, Takamoto P, Baumgartner L, Tasaka CL. Reduced Versus Conventional Dose Insulin for Hyperkalemia Treatment. J Pharm Pract. 2020 Jun;33(3):262-266. doi: 10.1177/0897190018799220. Epub 2018 Sep 6.

Helpful Links

• David B Mount, MD. Causes and evaluation of hyperkalemia in adults
• Treatment and prevention of hyperkalemia in adults
• Hyperkalemia Treatment & Management
• Hypoglycemia in adults without diabetes mellitus: Clinical manifestations, diagnosis, and causes
• Hyper K recognition and treatment of Hyperkalemia in the ED. American College of Emergency Physicians.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 10, 2023
• First Submitted That Met QC Criteria: September 11, 2023
• First Posted (Actual): September 14, 2023

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 1, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: insulin; hyperkalemia; electrolytes abnormalities; hypoglycmiea; anti-hyperkalemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Insulin; Insulin, Globin Zinc; Albuterol
• Other Study ID Numbers: MREC #2779

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No