DKA and HHS

In depth

The one-page summary above is what the PDF prints. These sections go further.

Insulin deficiency, counter-regulation and ketones

DKA begins when insulin is too low to restrain liver and fat while glucagon, catecholamines, cortisol and growth hormone rise (2024 consensus). The liver makes glucose from glycogen, amino acids, lactate and glycerol while muscle and fat take up less. Above the renal threshold (about 180–200 mg/dL) osmotic diuresis drains water, sodium, potassium, phosphate and magnesium; as GFR falls, glucose and ketones are no longer excreted and stress hormones climb further.

Ketogenesis needs both missing insulin and excess glucagon. Unopposed lipolysis floods the liver with fatty acids; glucagon lowers malonyl-CoA, which releases the brake on carnitine palmitoyltransferase-1, so the fatty acids enter mitochondria for beta-oxidation. Surplus acetyl-CoA becomes acetoacetate (AcAc), which is reduced to beta-hydroxybutyrate (BOHB) or loses CO₂ to form acetone, while insulin deficiency also slows ketone use by muscle and heart.

Both ketoacids have a pKa below 5, so at body pH each gives up its hydrogen ion: bicarbonate falls and the ketoanion widens the anion gap. Ketoanions excreted in urine take sodium and potassium with them and are bicarbonate that insulin can no longer regenerate; with the chloride in saline, that explains the normal-gap acidosis of recovery (2024 consensus).

HHS differs in degree. In the 2009 consensus data C-peptide was 1.14 nmol/L in HHS versus 0.21 in DKA: enough insulin to block lipolysis, too little for glucose uptake. Days to weeks of diuresis in older adults with blunted thirst leave water deficits of about 7–12 L, against 5–7 L in DKA (Chiasson 2003). Both crises are inflammatory and procoagulant (TNF-α, IL-6, CRP, PAI-1) for about the first 24 h of treatment (2009 consensus).

Diagnosis, severity and euglycemic DKA

The 2024 consensus ranks blood BOHB above urine ketones: BOHB ≥3.0 mmol/L has more than 90% sensitivity and specificity for DKA, while nitroprusside misses BOHB, underreads early, overreads in recovery and is falsely positive with captopril or valproate. Point-of-care meters lose accuracy above about 5 mmol/L (ISPAD 2022). The anion gap left the criteria because a third of patients have mixed disorders, such as a vomiting alkalosis that pulls pH toward normal. A venous gas suffices; venous pH runs about 0.03 below arterial (Brandenburg 1998).

First tests: glucose, electrolytes, BUN, creatinine, venous gas, BOHB, CBC, osmolality, lactate and an ECG, with cultures, lipase or troponin as the history directs. Leukocytosis of 10,000–15,000/mm³ is expected; above 25,000 suggests infection, and amylase is raised in 21–79% with little link to pancreatitis (2009 consensus). Starvation (bicarbonate rarely below 18), alcohol and pregnancy cause ketoacidosis without much hyperglycemia.

Euglycemic DKA is now mostly an SGLT2 inhibitor effect: glycosuria keeps glucose low, insulin doses get cut, glucagon rises and ketogenesis follows. On these drugs DKA occurs in about 4% of people with T1D and in 0.6–4.9 per 1,000 patient-years in T2D; in two series 35% presented below 200 mg/dL and 71% at 250 or less (2024 consensus). Triggers are surgery, fasting or very-low-carbohydrate diets, dehydration, alcohol, acute illness and insulin dose cuts.

• After urgent surgery in an SGLT2 inhibitor user, watch for DKA at any glucose (ADA 2026)
• In hospital: the consensus says do not start or continue them; ADA 2026 allows them in T2D with heart failure after recovery from the acute illness, but not with ketonemia, severe illness or fasting
• Pregnancy: DKA complicates up to 2% of pregnancies with pregestational diabetes, can be euglycemic and needs obstetrics at once (2024 consensus)

Fluids: choice and rate

Fluid restores perfusion and GFR, lowers counter-regulatory hormones and improves insulin sensitivity; alone it lowers glucose about 50–70 mg/dL per hour (2024 consensus). After 500–1,000 mL/h for 2–4 h (about 1 L/h in severe hypovolemia), the rate follows blood pressure, heart rate, urine output and sodium, replacing half the deficit in 8–12 h and the rest by 24–48 h (2024 consensus and Fig. 4). The 2009 consensus then switched to 0.45% saline at 250–500 mL/h if corrected sodium was normal or high.

The chloride in saline produces a normal-gap acidosis that can hold the drip after ketones clear. Balanced crystalloids (lactated Ringer's, Plasma-Lyte) resolved DKA faster in the SMART/SALT-ED subgroup and a meta-analysis, and earlier in SCOPE-DKA, whose 48 h primary outcome was not significant (see Evidence); the acetate in Plasma-Lyte did not raise ketones. The 2024 consensus accepts either fluid, and the 4–5 mEq/L of potassium in balanced solutions is no reason to avoid them. For HHS, JBDS keeps 0.9% saline as the main fluid because it is hypotonic relative to the patient's serum.

Insulin protocols and the two-bag system

• Drip: regular insulin 1 unit/mL in 0.9% saline. Prime about 20 mL through new tubing; unprimed lines delivered about 16% less because insulin binds plastic (Goldberg 2006)
• Bolus 0.1 unit/kg (IV or IM) only if the infusion will be delayed (2024 consensus)
• Variable-rate nurse-driven protocols aim for a glucose fall of 50–75 mg/dL per hour (2009 consensus) and should not go below 1 unit/h while acidosis persists (ADA 2026)
• Not falling: check pump, line, concentration and fluids first. JBDS adds 1 unit/h hourly until BOHB falls ≥0.5 mmol/L/h or bicarbonate rises ≥3 mmol/L/h
• Uncomplicated mild DKA (the consensus text also allows moderate) by SC rapid-acting analog: 0.1 unit/kg, then 0.1 unit/kg hourly or 0.2 every 2 h, halved below 250 mg/dL (2024 Fig. 4); not for severe DKA or HHS
• Basal insulin: continue home basal through the drip (JBDS, 2024 consensus); 0.15–0.3 unit/kg given early shortened the drip without more hypoglycemia, though some avoid it for hypoglycemia or hypokalemia risk

The two-bag system hangs two bags with identical electrolytes, one plain and one with 10% dextrose, on separate channels. The total rate stays fixed while the nurse shifts the ratio by glucose (equal rates give 5% dextrose), so the dextrose changes in minutes instead of waiting for pharmacy. Introduced in children (Grimberg 1999), it was linked in adult before-and-after studies to faster gap closure and less hypoglycemia (Munir 2017, Nahle 2025); one found no difference (Cho 2021).

Potassium, bicarbonate and phosphate

Total-body potassium is 3–6 mmol/kg short from diuresis, vomiting, hyperaldosteronism and ketoanion loss, yet most patients arrive normal or high because insulin deficiency, acidosis and hypertonicity hold it outside cells (2009 and 2024 consensus). Insulin through Na⁺/K⁺-ATPase, correction of acidosis, dilution and ongoing urine losses then lower it 1–2 mmol/L within 48 h. About 5–10% arrive below 3.5; during treatment 16% of DKA and 9% of HHS patients fall below 2.5.

Bicarbonate: the case for it below pH 7.0 is depressed contractility and vascular tone (2024: 100 mmol of 8.4% in 400 mL sterile water every 2 h until pH >7.0). The case against: fluid and insulin regenerate bicarbonate from ketoanions anyway, while infused bicarbonate lowers potassium and tissue oxygen uptake, can transiently worsen ketosis, makes CO₂ that enters cerebrospinal fluid faster than bicarbonate (paradoxical CNS acidosis) and in children tracked with cerebral edema. No trial included pH below 6.85 (Chua 2011).

Phosphate: losses reach about 1.0 mmol/kg, but replacement has not improved outcomes and fast infusion lowers calcium. The 2009 consensus replaced below 1.0 mg/dL or with cardiac dysfunction, anemia or respiratory depression (20–30 mEq/L potassium phosphate in fluids, at most 4.5 mmol/h). The 2024 text prints <1.0 mmol/L, about 3.1 mg/dL, which looks like a unit slip. Severe deficiency causes weakness, respiratory failure, hemolysis and low 2,3-DPG.

Resolution and the switch to subcutaneous insulin

Glucose usually falls below 250 mg/dL within 4–8 h, long before the ketoacidosis clears (2024 consensus), and JBDS expects resolution within 24 h; when it lags, look for too little fluid, a faulty insulin infusion or an untreated infection (ISPAD 2022). Judge by BOHB with pH or bicarbonate, never the anion gap or urine ketones. Low bicarbonate with BOHB under 0.6 and a normal gap is hyperchloremic acidosis, not a reason to keep the drip.

1. Can the patient eat? If not, continue the drip with dextrose (2009) or give basal plus correction insulin every 4–6 h (2024 Fig. 5)
2. Give SC basal 1–2 h before stopping the drip (2024 consensus; ADA 2026 says 2–4 h), because IV insulin is gone within minutes. JBDS gives rapid-acting insulin with a meal and stops the drip 1 h later
3. Dose: the home regimen if it worked; insulin-naive 0.5–0.6 unit/kg/day, about 0.3 if frail or with kidney failure; 40–60% as basal, the rest over three meals
4. Prefer basal-bolus analogs to NPH and regular: less hypoglycemia after DKA (Umpierrez 2009)

Before discharge: sick-day rules (never stop basal insulin; check ketones when ill or glucose is high), injection technique, enough insulin and supplies, CGM, screening for depression (PHQ-9) and cost-related rationing (up to 20% of insulin users), and follow-up within 2–4 weeks. Readmission runs 10–20%, often for recurrent DKA within 2 weeks (2024 consensus).

HHS and cerebral edema: pacing the osmolality

HHS mortality is 5–10 times that of DKA (2024 consensus), and treatment risk lies in moving water too fast. Brain cells adapt to days of hypertonicity by making intracellular osmoles; if serum osmolality falls faster than these clear, water enters the brain, and fast sodium shifts risk osmotic demyelination. Mental impairment is more common above 330 mOsm/kg (JBDS 2023); stupor with effective osmolality below 320 calls for another explanation (2009 consensus).

JBDS checks osmolality hourly at first, plots it with sodium and glucose, and corrects sodium by 2.4 mEq/L per 100 mg/dL (Hillier 1999) rather than the consensus 1.6. Use 0.45% saline only when osmolality stops falling despite a positive balance and adequate insulin. Insulin given before the volume is replaced can collapse the circulation. Check feet daily and protect heels.

Cerebral edema is mainly a pediatric DKA problem: clinically overt injury occurs in 0.5–0.9% of episodes with 21–24% mortality, usually within 12 h of starting treatment but sometimes before it or 24–48 h later (ISPAD 2022). Risk rises with young age, new-onset diabetes, low PaCO₂, high BUN, severe acidosis and bicarbonate. Hypoperfusion and neuroinflammation now look more important than fluid choice (ISPAD 2022; PECARN FLUID).

• Diagnostic (any one): abnormal motor or verbal response to pain, decorticate or decerebrate posture, cranial nerve palsy, abnormal neurogenic breathing
• Major: altered or fluctuating consciousness, heart rate drop over 20/min not explained by volume or sleep, age-inappropriate incontinence
• Minor: vomiting, headache, lethargy, diastolic BP over 90 mm Hg, age under 5

One diagnostic, two major, or one major plus two minor criteria give 92% sensitivity with 4% false positives (Muir 2004). Treat on suspicion, before imaging: mannitol 0.5–1 g/kg IV over 10–15 min, repeatable after 30 min, or 3% saline 2.5–5 mL/kg over 10–15 min; trim fluid but keep blood pressure normal; intubate only for respiratory failure and match PaCO₂ to the acidosis (ISPAD 2022). In adults it is rare and may be visible only on imaging (2024 consensus).

Monitoring, flowsheet and common errors

Chart one row per hour: time, glucose and its change, insulin units/h, dextrose concentration and rate, other fluids, potassium added, intake, urine output, running balance, GCS, and labs as they return with calculated effective osmolality and corrected sodium. One page (the ISPAD hourly flow chart; JBDS plots for HHS) makes a stalled BOHB fall or a too-fast osmolality drop visible early. For transport, keep insulin and dextrose on pumps, carry a meter and the latest K⁺, and keep checking glucose hourly.

• Stopping insulin when glucose normalizes, or titrating below 1 unit/h, while ketones persist
• Starting insulin before a potassium result, or with K⁺ below 3.5
• Too little dextrose: hypoglycemia occurs in 16–28% of treated DKA, and below 40 mg/dL carried 4.8 times the odds of death (Pasquel 2020)
• Unprimed tubing, a wrong concentration, or an infusion not reaching the vein (clamp, infiltration)
• Calling resolution by anion gap, bicarbonate alone or urine ketones; keeping the drip for hyperchloremia
• Stopping the drip with no SC basal on board, then rebound DKA
• In HHS: insulin before fluid, glucose falling faster than 90–120 mg/dL/h, no VTE prophylaxis
• Missing the trigger: MI, sepsis, pancreatitis, or abdominal pain that outlasts the acidosis

Evidence and controversies

These studies moved practice to low-dose insulin without a routine bolus, SC analogs for mild DKA, basal-bolus analogs and early basal insulin at transition, no routine bicarbonate or phosphate, and balanced fluids as an accepted first choice. Still unsettled (2024 consensus research priorities): whether balanced crystalloids should replace saline, pending a large trial; the best potassium regimen, since about half of patients still fall below 3.5 on protocol; when to start insulin in HHS and how to treat mixed DKA–HHS; bicarbonate below pH 6.9, never randomized; the phosphate threshold; ultra-long-acting basal insulin at transition; and inpatient ketone and glucose sensors.

Exam pearls

• Order: fluids, potassium result, then insulin; hold insulin if K⁺ is below 3.5 (older books: 3.3)
• Serum K⁺ is often high on arrival while total-body K⁺ is depleted; it falls once insulin starts
• Add dextrose below 250 mg/dL and keep insulin until ketoacidosis resolves; glucose is not the endpoint
• Glucose under 200 does not exclude DKA, especially with an SGLT2 inhibitor
• Nitroprusside detects acetoacetate, not BOHB; urine ketones can rise as the patient improves
• Resolution: BOHB <0.6 with pH ≥7.3 or HCO₃⁻ ≥18; overlap SC basal 1–2 h (ADA 2026: 2–4 h)
• HHS: older, T2D, glucose ≥600, effective osmolality >300, little ketosis; correct slowly, insulin 0.05 unit/kg/h, VTE prophylaxis
• Bicarbonate only below pH 7.0 (2009: 6.9); phosphate only when severely low with weakness
• Pediatric cerebral edema: headache, falling GCS, bradycardia, hypertension, usually within 12 h; mannitol or 3% saline at once