0.9% Saline Versus Balanced Solutions in Severe Diabetic Ketoacidosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Metabolic Ketoacidosis, Ketoacidemia, Acetonemia, Acetonuria

Intervention / Treatment
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* Drug: Sodium chloride 0.9% (SC)
* Drug: Ringer lactate (RL)


Participation Criteria
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Eligibility Criteria
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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

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
Interventional Model Description: Independant groups included by randomisation
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sodium chloride 0.9% (SC) arm<br>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)<br>* 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.<br>* Other names: Hydration solution;|
| Active Comparator: Ringer lactate (RL) arm<br>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)<br>* 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.<br>* Other names: Hydration solution;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe diabetic ketoacidosis,, Sodium chloride 0.9%, Ringer lactate, Base excess