The "Two Bag" System for Treatment of Adults With Diabetic Ketoacidosis: a Prospective Randomized Study
Phase: NA
Conditions: Diabetic Ketoacidosis
Sponsor: MetroHealth Medical Center

 
 
 
The “two bag” system for treatment of adults with 
diabetic ketoacidosis: a prospective randomized trial 
Protocol Number: 18-00025 
National Clinical Trial (NCT) Identified Number:  NCT03660189 
Principal Investigator: Dr. Vidya Krishnan 
9 October 2018 
 
 

Two Bag System for DKA 
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Protocol 18-00025 
<19 July 2018> 
 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
The “two bag” system for treatment of adults with diabetic ketoacidosis: a 
prospective randomized study 
Study Description: 
Patients with diabetic ketoacidosis (DKA) will be randomized to the “two 
bag” system group or the usual care group using the one bag system. 
Patients treated with the two bag system of intravenous (IV) fluids for DKA 
will have a significantly shorter time to anion gap closure when compared 
to the traditional one bag system. 
Objectives: 
 
This is a prospective randomized controlled trial to determine whether the 
“two bag” system of administering IV fluids for the treatment of adults 
with DKA results in decreased time to anion gap closure and decreased 
length of stay in the hospital, when compared to usual care with a “one 
bag” system of IV fluids.  
 
 
 
 
Endpoints: 
The primary endpoint is time to anion gap closure. Secondary endpoints 
include hypoglycemic episodes, clinical signs of dyspnea, pulmonary 
edema, hypoxemia events, chest pain with EKG changes, hyponatremia 
events, hypokalemia events, ICU/hospital length of stay, and total volume 
of intravenous fluids administered. 
Study Population: 
Sample size of 150 patients, between the age of 18-85, admitted for 
diabetic ketoacidosis. 
Phase: 
N/A 
Description of 
Sites/Facilities Enrolling 
Participants: 
The study will be performed at a single center, at MetroHealth Medical 
Center in Cleveland, Ohio. 
Description of Study 
Intervention: 
The two bag system of IV fluids for DKA management. 
Study Duration: 
12 months 
Participant Duration: 
Subjects will participate in the study for the duration of their 
hospitalization while in the intensive care unit or the stepdown unit. On 
average this may range from 1-5 days.  
 
 
1.2 
SCHEMA 
 
 
 
 

Two Bag System for DKA 
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Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
Admission 
To CP4 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
Transfer out of CP 4 
Or Discharge 
 
 
Obtain informed consent. Screen potential participants by inclusion and exclusion criteria; 
obtain history, document. 
Perform baseline assessments. 
Baseline vital signs, blood glucose, BMP, magnesium, phosphorus, beta-hydroxybutyrate, 
urinalysis, hepatic panel, lactate, troponin, lipase 
Follow-up assessments of study endpoints and safety 
Pulmonary edema, oxygen desaturations, chest pain, EKG changes, hypo/hypernatremia, 
hypo/hyperkalemia 
Accuchecks every 1 hour 
BMP every 4 hours until anion gap closed x 2 
Continuous pulse oximetry 
Neuro-checks and CAM-ICU every 4 hours 
Final Assessments 
Anion gap closed x2 
Insulin infusion converted to 
subcutaneous insulin 
2 Bag System 
N = 47 
Usual care 
N = 47 
Fluid resuscitation and initiation of insulin infusion at 0.1 U/kg/hr 
Randomize 

Two Bag System for DKA 
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2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
 
The “two bag” system of IV fluids for management of DKA is used widely in the pediatric intensive care 
unit. The benefits of the two bag system from the pediatric literature include: decreased response time 
to IV fluid changes, decreased time to correction of bicarbonate and ketones, and decreased total IV 
fluid volume administered. There was one retrospective study of the two bag system in adults, which 
showed decreased time to anion gap closure and decreased hypoglycemic events. To this date, there are 
no prospective randomized trials to evaluate the efficacy of the two bag system in adults.  
 
2.2 
BACKGROUND  
 
Diabetic ketoacidosis (DKA) remains an ongoing problem in the United States, with up to 500,000 
hospitalizations per year (1). The incidence of this life threatening disorder has been increasing over the 
last several years. Most patients with DKA have Type 1 diabetes, but up to one third of DKA cases are 
seen in adults with Type 2 diabetes. Dehydration resulting in hypovolemia and electrolyte abnormalities 
are significant causes of morbidity and mortality in this patient population.  
 
The management of DKA requires frequent monitoring of the patient’s blood glucose, fluid status, and 
electrolytes which usually requires intensive care level of monitoring. The recommendations for DKA 
management are based on the American Diabetes Association (ADA) Consensus Statement guidelines 
from 2009 (1), which uses a one bag system. The ADA guidelines recommend an insulin infusion to be 
initiated at 0.1 units/kg/hour. The initial bag of fluid is either 0.9% saline or 0.45% saline depending on 
the patient’s corrected sodium level. Once the blood sugar decreases to 200 mg/dl, the insulin infusion 
is decreased to 0.02 to 0.05 U/kg/hr and 5% dextrose is added to the fluid bag being administered. The 
rate of the fluids is determined by the patient’s estimated level of dehydration. One of the challenges 
with the one bag system is that there is an intrinsic delay in changes to IV fluids since the new fluid bag 
must be prepared by the pharmacy prior to administration, which may lead to hypoglycemia while 
waiting for the new fluid bag containing dextrose to arrive. It is also more likely to waste IV fluid bags, if 
a new fluid bag is started prior to the completion of the current fluid bag, and multiple changes may be 
necessary throughout their hospital stay depending on the patient’s electrolyte levels.  
 
The “two bag” system involves two bags of identical fluids with electrolytes, except one bag has 0% 
dextrose and the other has 10% dextrose. The two fluid bags run simultaneously into a Y-connector and 
into a single IV catheter. The rates of the two fluid bags are adjusted depending on the patient’s blood 
sugar. For example, if the blood sugar is greater than 500 mg/dl, the 0% dextrose bag will run at the full 
rate of 200 ml/hr (determined by the patient’s degree of dehydration) and the 10% dextrose bag will run 
at 0 ml/hr. As the blood sugar falls, the rate of the 10% dextrose bag increases according to pre-
determined rates, while the rate of the 0% dextrose bag decreases to keep the total fluid rate constant. 
Since the hyperglycemia in DKA typically corrects before the ketosis, this provides a more efficient 
method of titrating the dextrose concentration based on the patient’s needs, while continuing to infuse 
the insulin drip at a constant rate to prevent further ketogenesis. The two bag system has been studied 
in pediatric patients with Type 1 diabetes and used frequently in pediatric intensive care units for the 
treatment of DKA.  

Two Bag System for DKA 
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The two bag system was first studied in the pediatric population when Grimberg, et al performed a 
retrospective chart review in 1999. This study concluded that when compared to the traditional one bag 
system, the two bag system used a significantly less amount of total IV fluids (from 8.6 L to 4.5 L) which 
resulted in decreased hospital costs (2). There was also a shorter response time for IV fluid changes and 
the protocol was well liked by the nursing and house staff. Another retrospective chart review in 
pediatrics (by So, et al in 2009) revealed that the two bag system had a faster rate of serum bicarbonate 
and ketone correction which was statistically significant (3). However, the rate of pH and blood glucose 
correction was no different in the two groups. In contrast, a prospective study in pediatrics from 2004 
showed no significant differences in serum bicarbonate correction, glucose correction, or total number 
of IV fluid bags used (4). Nevertheless, there was a significant decrease in time to make changes to the 
IV fluids, as seen in previous studies. Although the overall results of these pediatric studies together 
were somewhat inconclusive, all of them were limited by small sample sizes of around 30 patients and 
no randomized controlled trials have been performed.  
 
There is one study in the literature that introduced the two bag system into the care of adult patients 
with diabetic ketoacidosis. Munir, et al performed a retrospective cohort study in 2015 involving adult 
patients who were treated with the two bag system compared to conventional treatment with the one 
bag system (a retrospective before/after study) with a larger sample size of 383 patients. They found the 
two bag system to be beneficial, with decreased time to anion gap closure (from 13.56 hours to 10.94 
hours), decreased hypoglycemic events, and faster time to blood glucose normalization to less than 250 
mg/dl (5).  There was no difference in improvement in serum bicarbonate or hospital length of stay. The 
two groups were similar in severity of DKA and Charlson Comorbidity Index.  
 
To this date, there are no prospective studies to evaluate the potential benefits of the two bag system in 
adult patients with DKA.  
 
2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
 
• 
Shortness of breath – uncommon  
• 
Pulmonary edema due to fluid overload – uncommon  
• 
Desaturations to less than 89% or new oxygen requirement – uncommon 
• 
Chest pain with acute EKG changes not on admission EKG – rare  
• 
Hypo/hypernatremia - uncommon 
• 
Hypo/hyperkalemia - uncommon 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
The literature demonstrates that when using the set protocol of the two bag system for IV fluid 
administration during the treatment of DKA, there is the potential for faster time to resolution of DKA. 
Resolution of DKA is defined as normalized blood glucose with the cessation of ongoing ketogenesis, 
which is marked by the closure of the anion gap on two sequential blood tests. Using the two bag 
system may lead to decreased ICU stay and potentially decreased hospital length of stay. In addition, 
with a set protocol of IV fluids, there may be less confusion between physicians and nurses regarding 

Two Bag System for DKA 
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fluid management based on each hourly blood glucose value. For society in general, there is potential 
benefit of decreased hospitalization costs for patients admitted with DKA.  
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The main risks of the two bag system is concern for developing fluid overload or electrolyte 
abnormalities while on a continuous infusion of IV fluids. However, the same risks are present in the 
“usual care” group and during the aggressive fluid resuscitation phase.  
 
The potential benefits outweight the risks, which can be minimized. In order to minimize the patient’s 
exposure to these risks, the patients will be monitored continuously by pulse oximetry to watch for 
developing hypoxemia which may result from pulmonary edema (this is usual care for all DKA patients). 
The electrolytes will be monitored every 4 hours to ensure that any abnormalities are treated in a timely 
manner, and the concentration of electrolytes will be repleted as needed. Confidentiality of patient data 
will be emphasized to all research staff during regular research meetings. Patient data will be de-
identified using a numbering system in RedCap.  
 
3 
OBJECTIVES AND ENDPOINTS 
 
This is a prospective randomized controlled trial to determine whether the “two bag” system of 
administering intravenous (IV) fluids for the treatment of adults with diabetic ketoacidosis (DKA) results 
in decreased time to anion gap closure and decreased length of stay in the hospital, when compared to 
usual care with a “one bag” system of IV fluids. 
 
The primary endpoint is time to anion gap closure. Secondary endpoints include hypoglycemic episodes, 
clinical signs of dyspnea, pulmonary edema, hypoxemia events, chest pain with EKG changes, 
hyponatremia events, hypokalemia events, ICU/hospital length of stay, and total volume of intravenous 
fluids administered. 
 
4 
STUDY DESIGN  
 
 
4.1 
OVERALL DESIGN 
 
This study will be performed at a single center, at MetroHealth Medical Center in Cleveland, OH.  
This a prospective, randomized trial comparing the “two bag” system for DKA compared to the 
traditional “one bag” system. The duration of participation will vary, as it will be based on the time the 
patient requires treatment with the insulin infusion.  
 
• 
The on-call fellow physician (a co-investigator of the study) will screen all patients admitted with 
DKA to CP4 West and CP4 East and determine if they qualify for enrollment by the inclusion and 
exclusion criteria.  
• 
Informed consent will be obtained by the fellow from either the patient, healthcare power of 
attorney, next of kin, or legal guardian depending on the patient’s mental status and 
competency   
• 
Subjects will be fluid resuscitated with IV fluids based on usual care 

Two Bag System for DKA 
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• 
Insulin infusion will be ordered at 0.1 U/kg/hr for all subjects 
• 
Home diabetic medications will be held until DKA is resolved 
• 
Neurologic checks and CAM-ICU scores will be performed every 4 hours 
• 
Laboratory orders:  
o Basic metabolic panel STAT every 4 hours.  
o Admission EKG, troponin, lipase, magnesium, phosphorus, and hepatic function panel 
(to calculate the expected anion gap based on the albumin).  
o Finger stick blood glucose every 1 hour  
• 
Subjects will be randomized into two groups of “usual care” and “two bag system” for IV fluids 
• 
The randomization process will be performed by assigning patients to a random number after 
enrolling in the study, using an online “random number generator.” Patients with odd numbers 
will be assigned to the control group and patients with even numbers will be assigned to the 
experimental group. The randomization will be performed on a 1:1 basis for the two groups.  
• 
The “usual care” group is the control group  
o This group will be treated with one bag of IV fluid at a time, and the algorithm is based 
on the American Diabetes Association Consensus Statement guidelines from 2009 (1).  
o The initial bag of fluid is usually either 0.9% saline or 0.45% saline depending on the 
patient’s corrected sodium level 
o Once the blood sugar reaches 200 mg/dl, the insulin infusion is decreased to 0.02 to 
0.05 U/kg/hr and 5% dextrose is added to the fluid bag being used  
o The rate of the fluids is determined by the patient’s estimated dehydration 
• 
The “two bag system” group is the experimental group 
• 
One bag will be saline (either normal saline (NS) or half normal saline depending on 
patient’s sodium level) and the second bag will be normal saline with 10% dextrose (D10) 
• 
The protocol is as follows: 
o If blood sugar is > 300, run D10 solution at 0 ml/hr and saline solution at 200 ml/hr 
o If blood sugar is 250-299, run D10 solution at 50 ml/hr and saline solution at 150 
ml/hr 
o If blood sugar is 200-249, run D10 solution at 100 ml/hr and saline solution at 100 
ml/hr 
o If blood sugar is 150-199, run D10 solution at 150 ml/hr and saline solution at 50 
ml/hr 
o If blood sugar is < 150, run D10 solution at 200 ml/hr and saline solution at 0 ml/hr 
• 
Normal saline infusion will be used if corrected Na is low 
• 
Half normal saline infusion may be used if corrected sodium is normal or high 
• 
Other fluids (such as lactated ringers) may be used depending on patient’s hydration status 
and electrolytes 
• 
Potassium chloride (20 mEq/1 L fluid) will be added to the fluids if renal function is within 
normal limits and potassium is less than 5.2.  
• 
Potassium phosphate (20 mEq/1 L fluid) will be added to the fluids if phosphate is less than 
1.0. 
• 
The primary team should replete the magnesium  as needed for levels less than 2.0 mg/dl  
• 
The insulin infusion rate will not be adjusted until the anion gap has closed on 2 
occurrences, unless patient develops hypoglycemia despite maximum D10 rate.  
• 
Transition to subcutaneous insulin when anion gap is closed on two occurrences.  
• 
The anion gap will be calculated by the equation: 
o Anion gap = Na – Cl – HCO3 

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o The expected anion will be adjusted for low albumin by a calculation of 1g/dl 
decrease in albumin correlates with +2.5 points in the anion gap 
• 
 The investigators performing the data collection will be blinded to the treatment groups 
• 
For patients in the experimental group, if the subject develops hypo/hypernatremia, 
hypo/hyperkalemia, shortness of breath, pulmonary edema, oxygen desaturations < 89%, or 
chest pain with new EKG changes, the provider/house staff may temporarily suspend the 
two bag system protocol in order to treat the complication appropriately. It will remain up 
to the primary team whether or not it is appropriate to restart the protocol. All protocol 
deviations will be documented and measured.  
 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
A randomized prospective trial has not yet been performed to evaluate efficacy of the two bag system in 
adults.  
 
 
4.3 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all phases of the 
study. This occurs when the anion gap is closed and the patient is transitioned to subcutaneous insulin.  
 
5 
STUDY POPULATION 
 
 
5.1 
INCLUSION CRITERIA 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Provision of signed and dated informed consent form 
2. Stated willingness to comply with all study procedures and availability for the duration of the 
study  
3. Male or female, aged 18-85 
4. Diagnosis of diabetic ketoacidosis defined as: 
a. Blood sugar greater than 250 mg/dl 
b. Venous pH less than 7.25 
c. Bicarbonate less than 18 
d. Evidence of ketone formation with either positive urine ketones or elevated beta-
hydroxybutyrate > 3 
e. Anion gap greater than 10 +/ - 2 (or higher than expected anion gap corrected for 
albumin) 
 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Pregnancy 
2. Hyperglycemic hyperosmolar state  

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3. Ketosis from other etiology such as starvation or alcoholic ketosis 
4. Acute exacerbation of congestive heart failure  
5. Acute coronary syndrome or non-ST elevation MI 
6. Pulmonary edema from other cause such as decompensated liver failure or acute renal failure 
7. Renal failure requiring renal replacement therapy (hemodialysis) 
8. Septic shock 
 
 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
All patients admitted to CP4 with a diagnosis of DKA will be screened for participation in the study. No 
other forms of recruitment will be performed.   
 
6 
STUDY INTERVENTION 
 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 
The “two bag system” group is the experimental group 
• 
One bag will be saline (either normal saline (NS) or half normal saline depending on 
patient’s sodium level) and the second bag will be normal saline with 10% dextrose (D10) 
• 
The protocol is as follows: 
o If blood sugar is > 300, run D10 solution at 0 ml/hr and saline solution at 200 ml/hr 
o If blood sugar is 250-299, run D10 solution at 50 ml/hr and saline solution at 150 
ml/hr 
o If blood sugar is 200-249, run D10 solution at 100 ml/hr and saline solution at 100 
ml/hr 
o If blood sugar is 150-199, run D10 solution at 150 ml/hr and saline solution at 50 
ml/hr 
o If blood sugar is < 150, run D10 solution at 200 ml/hr and saline solution at 0 ml/hr 
• 
Potassium will be added to the fluids if the patient has normal renal function and potassium 
value is less than 5.2.  
• 
The insulin infusion rate will not be adjusted until the anion gap has closed on 2 
occurrences, unless patient develops hypoglycemia despite maximum D10 rate.  
 
6.2 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
The subjects will be randomized into the two groups using a random number generator. Odd numbers 
will be assigned to the control group and even numbers will be assigned to the experimental group. 
Randomization will be performed on a 1:1 basis for the two groups. The providers/house officers are not 
able to be blinded, since they will be responsible for the IV fluid orders for the patients. The patients and 
the investigators will be blinded.  
 
 

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7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
If the subject develops any of the potential risks, the patient will still be included in the study. The 
complication will be treated appropriately. If necessary, protocol deviations will be allowed in order to 
treat the complication. Protocol deviations will be documented.  
 
The patient may also withdraw from the study if they decide they no longer want to participate.  
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Will allow if patient withdraws from the study. 
 
8 
STATISTICAL CONSIDERATIONS  
 
8.1 
SAMPLE SIZE DETERMINATION 
 
We are planning a study of a continuous response variable from independent control and experimental 
subjects with 1 control per experimental subject.  In a previous study the response within each subject 
group was normally distributed with standard deviation 1.6.  If the true difference in the experimental 
and control means is 1.082, we will need to study 47 experimental subjects and 47 control subjects to be 
able to reject the null hypothesis that the population means of the experimental and control groups are 
equal with probability (power) 0.9.   The Type I error probability associated with this test of this null 
hypothesis is 0.05. 
 
8.2 
POPULATIONS FOR ANALYSES 
Data will be analyzed using the intention to treat method.  
 
 
 
8.3 
STATISTICAL ANALYSES 
 
 
8.3.1 GENERAL APPROACH 
 
Patient characteristics will be compared using Student’s t-test or chi-squared tests, as appropriate. The 
time to anion gap closure between the traditional one bag system and the two bag system will be 
compared by the Student’s t-test to determine if there is a statistically significant difference between 
the two groups. Secondary outcomes will be evaluated using chi-squared tests, bivariate and 
multivariable logistic regressions. The two group’s time to anion gap closure can be compared 
graphically using a Kaplan Meier curve. The difference in time to anion gap closure between the two 
groups can be further analyzed using a multivariable Cox regression analysis to control for confounding 

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factors. All analyses will be performed using STATA 11.0 software. A p-value of <0.05 will be considered 
statistically significant.  
 
 
9 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
9.1 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
 
9.1.1 INFORMED CONSENT PROCESS 
 
9.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention. 
 
 
9.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
If the patient has altered mental status and is unable to consent, the next of kin or power of attorney 
will be approached for consent.  
 
 
9.1.1.3 STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 4 years after the last approval of a marketing 
application in an International Conference on Harminosation (ICH) region and until there are no pending 

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or contemplated marketing applications in an ICH region or until at least 4 years have elapsed since the 
formal discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. 
 
 
9.1.2 CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  The study 
leadership in conjunction with the MetroHealth IRB has established policies and procedures for all study 
group members to disclose all conflicts of interest and will establish a mechanism for the management 
of all reported dualities of interest. 
 
REFERENCES  
 
1. Kitabchi, A. et al. “Hyperglycemic Crises in Adult Patients with Diabetes.” Diabetes Care. 2009 
July; 32(7): 1335-1343.  
2. Grimberg, A. et al. “The ‘two bag system’ for variable intravenous dextrose and fluid 
administration: Benefits in diabetic ketoacidosis management.” The Journal of Pediatrics. 1999 
March; 134(3): 376-8.  
3. So, YT. et al. “Evaluation of the Two-Bag System for Fluid Management in Pediatric Patients with 
Diabetic Ketoacidosis.” The Journal of Pediatric Pharmacology and Therapeutics. 2009 April; 
14(2): 100-5. 
4. Poirier, M. et al. “A Prospective Study of the ‘Two-Bag System’ in Diabetic Ketoacidosis 
Management.” Clinical Pediatrics. 2004 Nov-Dec; 43(9): 809-13. 
5. Munir, I. et al. “Comparison of a ‘two-bag system’ versus conventional treatment protocol (‘one-
bag system’) in the management of diabetic ketoacidosis.” BMJ Open Diabetes Research & Care. 
2017 Aug 11; 5(1):e000395.