Randomised controlled trialindependent cross-checkabstract checked★ key study I-INS-110 in-depth review
How fast to give drip fluids to children with ketoacidosis
Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.
Overview
Kuppermann N et al.. N Engl J Med 2018 · PMID 29897851 · DOI 10.1056/NEJMoa1716816
Faster or slower fluids, with more or less salt, gave the same brain outcomes; brain injury was rare (0.9%).
Does the study support the specific claim? No · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Test fluid rates and types in childhood DKA.
- How was the study done?
Randomised trial, 13 hospitals.
- How many people, animals or samples were studied?
1,389 DKA episodes.
- What was actually found?
No differences between fluid strategies.
- How large was the observed effect?
Brain injury 0.9% overall.
- What do the results mean in everyday life?
Drip fluids, given with insulin, are a safe part of DKA treatment.
- What are the study's limitations?
Did not compare against no fluids.
- What does it say about Elawady's specific claim?
Contradicts 'no IV fluids' in DKA.
- Do the results apply to Germany and Europe?
Applicable to Europe.
- What can explicitly not be concluded from this study?
Cannot say anything about steroid treatment.
Scientific in-depth review
1. Full reference
- Authors
- Kuppermann N et al.
- Journal
- N Engl J Med
- Year
- 2018
- Identifier
- PMID 29897851 DOI 10.1056/NEJMoa1716816
- Verification
- verified – PubMed efetch 2026-10-26; Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
NICHD and HRSA funding; no relevant conflicts (record).
2. Research question
Do rate and sodium content of IV fluids affect neurological outcomes in paediatric DKA?
3. Study design and population
- Study design
- Randomised controlled trial – 13-centre 2x2 factorial randomised controlled trial (PECARN FLUID)
- Population
Children with DKA
- Country
USA
- Period
Trial NCT00629707
- Sample size
1,389 episodes in 1,255 children
- Inclusion and exclusion criteria
Children with DKA at 13 centres
4. Methods and endpoints
- Exposure / intervention
0.9% vs 0.45% saline; rapid vs slow rate (all received IV fluids and insulin)
- Comparator
Other fluid arms
- Endpoints
Decline in GCS <14; brain injury; memory; IQ
- Statistical methods
Factorial analysis
5. Actual results
- Results
GCS fell below 14 in 48 episodes (3.5%) and clinically apparent brain injury occurred in 12 (0.9%); no significant differences between fluid groups for any neurological outcome; serious adverse events rare and similar across groups.
- Absolute risks
Brain injury 0.9% across all arms
- Authors' conclusion
Neither rate nor sodium chloride content of IV fluids significantly influenced neurological outcomes.
6. Strengths
- Large RCT
- Neurological outcomes
- Low risk of bias
7. Weaknesses
- No 'no fluid' arm (would be unethical)
- Children only
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Randomised factorial design.
9. Assessment of the statistical interpretation
Wilson 95% CI brain injury 0.5-1.5% (stats/C-INS-08_insulin_omission_and_fluids.py).
10. Relevance to the specific claim
Shows IV fluids within a wide range of rates are safe in DKA; contradicts fear of fluids. Does not test withholding fluids, which is unethical because DKA involves severe dehydration.
11. Independent contrary findings
12. Transferability to Germany and Europe
Directly applicable; same biology and clinical standards in Europe.
13. Overall methodological judgement
High-quality trial supporting guideline fluid therapy.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | unknown |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |