0.9% Saline Versus Balanced Solutions in Severe Diabetic Ketoacidosis

0.9% Sodium Chloride Versus Ringer's Lactate in the Treatment of Severe Diabetic Ketoacidosis: a Randomized Trial

Severe diabetic ketoacidosis (DKA) is a potentially serious complication of diabetes mellitus. The treatment regimen is based on insulin and rehydration. The choice of rehydration solution is a question that remains open. We sought to compare the effect of sodium chloride 0.9% (SC) versus ringer lactate (RL) in the resolution of severe DKA as well as on the variation of electrolytes.

Study Overview

• Status: Completed
• Conditions: Metabolic Ketoacidosis; Ketoacidemia; Acetonemia; Acetonuria
• Intervention / Treatment: Drug: Sodium chloride 0.9% (SC); Drug: Ringer lactate (RL)

Detailed Description

We design an open randomized trial in adult patients admitted to our ICU for severe DKA. The insulin therapy protocol was identical and the randomization concerned the rehydration solution either by SC or RL. The primary endpoint was resolution of DKA at H48 defined by a composite endpoint (glycemia <11 mmol/l, bicarbonates > 15 mmol/l or pH>7.30 and anion gap <16). The secondary endpoints were resolution of DKA at H24, change in base excess to ≥ -3 meq/L at 48 h and H24 and change in electrolytes, insulin requirements, length of stay and mortality. Blood gases, ionogram with chloride and lactate were performed at baseline, H6, H12, H24 and H48.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tunisia
  • Tunis, Tunisia, 1007
    • Ahlem Trifi

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- All patients aged 16 and over hospitalized in intensive care for severe ketoacidosis defined as arterial pH ≤ 7.25 (or serum bicarbonate ≤ 15 mmol/L) and blood glucose ≥ 14 mmol/L and need for ICU.

Exclusion Criteria:

• < 16 Y

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium chloride 0.9% (SC) arm; The SC arm receives insulin therapy via an electric syringe (Actrapid HM ®, Novorapide®) (1 ml = 100 IU) - take 0.5 ml (= 40 IU) and complete to 50 ml with SC to obtain a solution of 1 ml = 1 IU. -Infusion rate = 0.1 IU/kg/h. In parallel, and on an insulin-independent route, 0.9% chloride saline is started on the basis of 3 L/ 24 hours per day if capillary glyceamia>2,5 g/l . Blood samples were taken for glycemia, arterial Blood gas, electrolytes, lactate at baseline, 6, 12, 24 and 48 hours later.	Drug: Sodium chloride 0.9% (SC); This trial looks specifically at the type of hydratation liquid. The patients included will receive SC. The volume, frequency of fluid administration and other severe DKA therapies, such as insulin therapy and electrolytes, are prescribed similarly. The intervention will continue for 48 hours from admission to the ICU with a blood gas control (including base excess) + Blood glucose + ionogram (Na, K, chlorine) + lactates on admission (or H0), H6, H12, H24 and H48.; Other Names: Hydration solution
Active Comparator: Ringer lactate (RL) arm; The SC arm receives insulin therapy via an electric syringe (Actrapid HM ®, Novorapide®) (1 ml = 100 IU) - take 0.5 ml (= 40 IU) and complete to 50 ml with SC to obtain a solution of 1 ml = 1 IU. -Infusion rate = 0.1 IU/kg/h. In parallel, and on an insulin-independent route, Ringer lactate is started on the basis of 3 L/ 24 hours per day if capillary glyceamia>2,5 g/l . Blood samples were taken for glycemia, arterial Blood gas, electrolytes, lactate at baseline, 6, 12, 24 and 48 hours later.	Drug: Ringer lactate (RL); The intervention will continue for 48 hours from admission to the ICU with a blood gas control (including base excess) + Blood glucose + ionogram (Na, K, chlorine) + lactates on admission (or H0), H6, H12, H24 and H48.; Other Names: Hydration solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with composite endpoint achievement	composite endpoint (glycemia <11 mmol/l, bicarbonates >15 mmol/l or pH >7.30 and anion gap <16).	48 hours from inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in base excess to ≥ -3 meq/L	to ≥ -3 meq/L	at 48 hours and at 24 hours from inclusion
Number of participants with hyperchloremia	chlore level > 105 mmol/L	at 48 hours from inclusion
Total insulin dose received	insulin dose prescribed during treatment	through study completion, an average of 9 months

Collaborators and Investigators

• Sponsor: Tunis University
• Investigators: Principal Investigator: Ahlem Trifi, Rabta

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Actual): December 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Base excess; Severe diabetic ketoacidosis,; Sodium chloride 0.9%; Ringer lactate
• Additional Relevant MeSH Terms: Metabolic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Acid-Base Imbalance; Acidosis; Ketosis; Diabetic Ketoacidosis; Pharmaceutical Solutions
• Other Study ID Numbers: Rabta-ICU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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