Diabetic Ketoacidosis (DKA):

Pitfalls Not to be Missed

June 2022

Misdiagnosis of New-onset DKA

Clinical features resemble other conditions
Drowsiness: encephalitis, meningitis, sepsis
Hyperpnea:: hyperventilation syndrome, pneumonia
Polyuria: psychogenic polydipsia, renal disease (salt
wasting)
Weight loss: malnutrition
Nausea/vomiting: gastroenteritis
Abdominal pain: gastritis, appendicitis, pancreatitis
 Overlooked Precipitating Causes of DKA
What should we look for?
Infection: viral, bacterial, TB
Site: lungs, GI, GU, systemic, CNS
Co-existing
existing disease: thyrotoxicosis, obesity (insulin
resistance)
Drugs: glucocorticoid, SGLT2, missing insulin

Misdiagnosis of New-onset T1DM

Retrospective study in 223 T1DM in Malaysia (Yr 2010-19)
Misdiagnosis 39%
Most common symptoms: polyuria / polydipsia (44%),
weight loss (33%), vomiting (33%)
Most common erroneous diagnosis: respiratory (37%),
GI (35%), other ID (11%), renal (9%)
Significant risk factor: age <5 yr
Unawareness of T1DM among healthcare professionals

Mavinkurve M, et al. Front Endocrinol 2021;12:606018

 Management of DKA: Beginning
What would you find the abnormalities? Look holistically!
Integrate all pathophysiologic changes!
How to correct all abnormal findings simultaneously?
Act fast! Understand and normalize the deranged
pathophysiologc changes rather than just normalize labs
What would you expect to see in the next 2, 4, 6..., 12 h?
(look forwards and forecast the next labs, not just correct
the labs)

Pathophysiology of DKA
Chronic cellular starvation ketosis, acidosis
Total volume deficit ( ICF, ECF) dehydration
Hyperosmolality from hyperglycemia cellular tonicity
(major concern: neuronal cells)
Initial: cerebral ischemic hypoperfusion
Later: reperfusion injury
Key: Gradual reduce BS (osmolality)
Optimal IV fluid rate for rehydration
Optimal glucose and insulin infusion
 Pitfalls in Hydration Status Assessment
DKA: always dehydration
Frequently underestimate degree of dehydration .why?
Good urine output (osmotic diuresis)
Polydipsia and frequent voids
(misinterpretation adequate renal blood flow)
Contracted ICF > ECF, relatively adequate intravascular
volume (looked not dehydrated) due to osmolality
Frequent voids and unconcentrated urine do not mean
well hydrated

Pitfalls in Fluid Therapy (1)

Initial resuscitation
Type of fluid?
Isotonic: Normal saline (convenient and low cost)
Balanced salt solution (BSS) (RLS, plasmalyte)
plasmalyte
(not usually available and high cost)
No studies show that BSS is better than NS (few small
RCT)
Pitfalls: hypotonic for young infants not recommended

Agwu JC, et al. Diabet Med 2021;38:e14595

 Pitfalls in Fluid Therapy (2)
Initial resuscitation
Amount of fluid?
If shock (rare), give NS 20 mL/kg in 15' for correcting
shock (can be repeated if still shock)
If not shock (majority), give NS 10-20
10 mL/kg in 1-2
1 2 hr
Pitfalls:
No fluid resuscitation because of good urine output
Obese child too much fluid (limit: max 1-1.5 L in 1st hr)
Use weight for age not enough fluid
Replace urine output not recommended
Agwu JC, et al. Diabet Med 2021;38:e14595

Pitfalls in Fluid Therapy (3)

Subsequent fluid (maintenance + deficit)
Subtract initial resuscitation fluid?
If not shock, fluid deficit initial resuscitation fluid
If shock, fluid deficit initial resuscitation fluid
(but not subtract fluid for correcting shock)
Pitfalls:
No subtraction of initial resuscitation fluid fluid overload
Subtract fluid for correcting shock inadequate rehydration
NICE guideline NG18, 2020
British Society for Paediatric Society Guideline. Arch Dis Child Educ Pract Ed 2021;106:220-2
 Pediatric DKA: AKI vs Non-AKI
Definition of AKI: eGFR >50% (pRIFLE criteria)
eGFR = [height (cm)/SCr (mg/dL)] x 0.55 mL/min (Schwartz)
Microalbuminuria:: ACR >30 mg albumin/g of Cr
Hyperchloremia cutoff >112 mmol/L (before treatment)
discriminate AKI from non-AKI
AKI associated with hyperchoremia and ACR and
prolonged acidosis (cause-effect relationship?)
Thus, balanced crystalloids may be better in children with
high risk for AKI
Ahmed HM, et al. Pediatr Nephrol 2021

Fluid Volume Estimates in Obesity:

Actual weight (AW) vs Ideal Body weight (IDW)
Height 150 cm, weight 100 kg, IDW 42 kg, SA 2.1 m 2
Maintenance fluid = 3,100 mL/day
AW IDW
Initial load (10 mL/kg) 1,000 mL 420 mL
10% deficit 10,000 mL 4,200 mL
1st 12 hr (M/2)+(deficit/2)-load
(M/2)+(deficit/2) load 1,550+5,000
1,550+5,000-1,000
1,000 1,550+2,100-1,000
1,550+2,100
2nd 12 hr (M/2)+(deficit/4) 1,550+2,500 1,550+1,050
Total 24 hr 9,600 5,250
(Max./24 hr: 2.5 M = 7,750 mL or 4,000 mL/m2 = 8,400 mL)
AW overestimated; IDW underestimated
 Total Body Water (TBW) vs Obesity
Hydration (water) fraction

Obesity: TBW = 60 x [IDW + (AW IDW)/3]

Weight (for calculation) = IDW + (AW IDW)/3

Chamney PW, et al. Am J Clin Nutr 2007;85:80-9

(AW = actual weight, IDW = ideal body weight) Mattoo TK, et al. PLOS ONE 2020;15:e0239212

Pitfalls in Insulin Adjustment (1)

Initial RI bolus not recommended
Start RI too soon 1st h RI drip (not recommended)
Hydration 1
1-2
2 h before RI IV drip
Reason:
Reduction of BS following volume expansion (without
insulin) e.g. NS 1st h, BS >100 NS 2nd h (not give RI)
 Pitfalls in Insulin Adjustment (2)
Reduce/stop RI when BS <100-150 mg/dL but still
ketosis/acidosis
Goals: Keep BS 150-250
150 250 mg/dL,
mg/ , if BS <250, add glucose
in IV fluid (not RI dose)
Usual RI dose 0.1 U/kg/h used fixed dose
Goals: Decrement of BS 50-100 mg/dL/h (gradual Osm)
If BS reduction rate <50/h, RI dose (0.1-0.15 U/kg/h)
If the rate >100/h, RI dose (0.05-0.1 U/kg/h)

Pitfalls in Insulin Adjustment (3)

Use rapid-acting insulin instead of RI: not recommended
Reducing RI after resolving DKA because maintaining BS
100-200 mg/dL and keep only maintenance IV fluid
(5%D/NS) with inadequate oral intake
Goals:
DKA state of cellular starvation for days weeks
Restore energy intake during recovery phase of DKA

(not optimal insulin for optimal BS)

 Pitfalls in K Supplement (1)
No K in initial fluid resuscitation (The must)
DKA usually has high-normal to high K (5-7 mmol/L)
(despite total K deficit) (Fact)
Thus, often administered inadequate K i.e. 20 mmol/L
Remember! Correction of acidosis in DKA cause K shift
into ICF (K pools: ICF 140 mmol/L, ECF 4 mmol/L)
Therefore, if void + K <5.5 mmol/L, IV K >40 mmol/L
(always)

Agwu JC, et al. Diabet Med 2021;38:e14595

Pitfalls in K Supplement (2)

If K <4 mmol/L, IV K should be >40-80 mmol/L (max 0.5
mmol/kg/h, need ECG monitoring)
If no ECG monitoring, IV K 40 mmol/L + oral KCI 2-4
mmol/kg/day (7.5% KCI: K 1 mmol/mL) safe and easy
If K <3.3 mmol/L,
/L, give K before insulin
If hyperchloremia (serum Cl >75% of Na) or ongoing NS
infusion, change KCI to K2HPO4 (8.7%) (K 1 mmol/mL) IV
or PO
 HCO3 for DKA Therapy
Acute severe metabolic acidosis may compromise CVS
function hemodynamic failure
Treatment: reduce acidity with HCO3
DKA: subacute / chronic metabolic acidosis (due to
ketoacids and lactic acid) rarely impair CVS function
Thus, HCO3 is rarely needed for DKA therapy
HCO3 Rx is associated with cerebral edema
Recommended Rx: severe acidosis (pH<6.9 or CO 2 <5
mM) with impaired CVS function

Take Home Messages

Early recognition and treatment immediately
More severe = more acidosis and more dehydration
Restore volume and cellular energy simultaneously
Rapid initial hydration correct cerebral and kidney
ischemic hypoperfusion
Gradual reduction of BS slow reduction of osmolality
Restore energy: feed the cell with glucose (by IV insulin)
Beware rapid correction of dehydration CNS
reperfusion injury
Adequate K supplement
Avoid HCO3 therapy