Resident Version
Diabetic Ketoacidosis and Nonketotic Hyperglycemia
created by Erik Kraai, M.D.
Objectives:
1. Understand the basic pathophysiology of DKA and NKH.
2. Recognize the signs, symptoms, and predisposing conditions of DKA/NKH.
3. Know the keys to successful treatment and follow-up of DKA/NKH.
References:
Mohsen S. et al. Overview of the Diagnosis and Management of Diabetic Ketoacidosis.
The American Journal of the Medical Sciences. 2006;331(5):243-251.
Nugent, BW. Hyperosmolar Hyperglycemic State. Emergency Medicine Clinics of
North America 23 (2005) 629-648.
Magee, F, et al. Endocrine and Metabolic Dysfunction Syndromes in the Critically Ill.
Management of Decompensated Diabetes, Diabetic Ketoacidosis and Hyperglycemic
Hyperosmolar Syndrome. Critical Care Clinics Vol 17 Number 1. January 2001
Case Presentation #1:
You are called to the ER to evaluate a 68-year old male that was brought in by EMS after his wife found
him unresponsive. She states that he has been increasingly confused over the past several days and has had
decreased PO intake.
PMHx: Diabetes, HTN, CAD
Meds: Metformin, Lisinopril, Atenolol, ASA
SocHx: Lives with his wife in Abq, no e/t/d.
ROS: + for recent f/c, wt loss, cough, and nocturia for 1 week. All others negative.
PE: T38.2 BP 92/60 HR 115 RR 20 91%RA
GEN: Somnolent, groaning male. Not able to follow commands.
HEENT: MM dry
NECK: Supple, No LAD
CV: Tachycardic, regular, no m/r/g.
LUNGS: CTAB
ABD: soft, NT, ND, +BS, no HSM
EXT: no c/c/e
NEURO: PERRL, moves all extremities, DTRs 2+ and symmetric.
SKIN: decreased turgor, +tenting, no rash.
LABS: WBC 12, HCT 46, PLT 285
NA 142, K+ 4.5, CL 110, HCO3 20, BUN 41, CR 2.3, GLU 1340
ABG: 7.38/38/80/20
OSM: 336
U/A: +glu, trace protein, trace ketones, no LCE/NIT, no RBC/WBC.
CXR: No acute cardiopulmonary disease.
Questions:
1.
What is your differential diagnosis and how is it narrowed?
2.
Is this DKA or NKH? Why?
3.
What is the initial management?
4.
What labs should be followed and when should electrolytes be replaced?
Case Presentation #2
A 24 yo male with type I diabetes is brought from jail because he has had high CBGs, abdominal pain, and
is difficult to arouse. He was brought to jail several days ago and it is unclear how much insulin he
normally uses. The jail has been using a sliding scale.
PMHx: Type I Diabetes
Meds: Lantus 70 qhs, Humalog with meals.
SocHx: Lives in abq with mother, +h/o IVDA, occ etoh, no tobacco.
ROS: + for abd pain, shortness of breath, blurred vision, and polyuria/polydipsia.
PE: T 36 BP 100/60 HR 110 RR 28 O2 98%RA
GEN: Ill-appearing male in mild respiratory distress
HEENT: MM dry
NECK: supple, no lad
CV: Tachycardic, no murmurs
LUNGS: CTAB
ABD: diffuse TTP, no rebound, hypoactive BS
EXT: no c/c/e
SKIN: decreased turgor, no rashes
NEURO: CN 2-12 intact, +DTRs, 4/5 strength throughout, normal sensation
LABS:
WBC 8.5 (70%N)
HCT 42
PLT 169
Na 122
K+ 5.5
Cl 98
BICARB 6
BUN 39
Cr 1.6
GLU
642
ABG 7.1/23/85/6
Serum Ketones: negative
U/A: + glucose, +ketones, -LCE/NIT
Questions:
1.
What is the initial management?
2.
Should he be intubated?
3.
Is his mentation altered because of his hyponatremia? What is the corrected sodium?
4.
His next electrolytes show his potassium is 3.9, now what?
5.
How/When do we change back to his SQ regimen?
Outline for Discussion:
I.
Normal Glucose/Insulin Regulation:
A. Role of Insulin: Insulin is synthesized in the pancreatic islet cells as preproinsulin, then
cleaved to proinsulin and eventually secreted as insulin and C-peptide by fusion of
secretory granules to the cell membrane. It is secreted in a pulsatile manner about every
10 minutes. It also responds primarily to increases in plasma glucose (as well as other
secretogogues such as arginine) with a “first-phase” response that peaks in 3-4 minutes
and then continues to be secreted if glucose levels remain high in a “second-phase”.
Insulin acts primarily by reducing hepatic gluconeogenesis and glyocgenolysis, and
increasing skeletal muscle and adipose uptake of glucose.
B. Role of Glucagon: Also secreted in the pancreas, glucagon primarily acts as a
counterbalance to insulin. It stimulates hepatic gluconeogenesis and glyocgenolysis. It is
normally inhibited by the presence of insulin and therefore, insulin absence leads to
increased glucose production. Glucagon also stimulates lipogenesis and inhibits lipolysis
leading to increased circulating free fatty acids (FFAs).
C. Other counterregulatory hormones: Epinephrine, cortisol, growth hormone, and proinflammatory cytokines. A relative or absolute deficiency of insulin also leads to an
excess in these other hormones which can contribute to the excess glucose production
and increased FFAs.
II.
Diabetic Ketoacidosis
A. Hallmark is triad of hyperglycemia, acidosis, and ketosis. Usually seen in type I
diabetes.
B. Insulin deficiency and high levels of counterregulatory hormones leads to marked
hyperglycemia and increased FFAs.
1. FFAs are taken up by liver and oxidized to ketone bodies (betahydroxybutyrate
and acetoacetate).
2. Ketone bodies are relatively strong acids that dissociate at physiologic pH and
produce high hydrogen load leading to metabolic acidosis (with high anion gap).
C. Volume and Electrolyte Depletion
1. Hyperglycemia raises extracellular fluid osmolality and shift of water from
intracellular to extracellular compartment.
2. Causes dehydration of cells and shift of electrolytes out of cells.
3. Glucosuria leads to osmotic diuresis and hypovolemia.
D. Precipitating factors
1. Infection (30-40% of cases) - should always be sought (blood cxs, urine cxs,
CXR).
2. Omission of insulin (20-50% of cases)
3. Other (e.g. MI, pancreatitis, CVA).
E. Clinical Presentation
1. Polyuria, polydipsia, polyphagia, wt loss, abdominal pain, weakness, shortness
of breath, neurological changes (usually short duration ~1-2 days).
2. +/- Symptoms of precipitating illness (fever, chest pain, SOB, dysuria, etc.)
3. Physical signs: dehydration, dry mucous membranes, tachycardia, decreased
skin turgor, Kussmaul respirations, acetone breath, hypotension, shock, coma.
4. Laboratory Findings: Initial labs should include plasma glucose, electrolytes,
serum/urine ketones, ABG, osmolality, CBC, U/A. If infection suspected, then
blood and urine cultures, CXR. To diagnose DKA, should have CBG > 250,
urine or serum ketones, and acidosis (bicarb < 18). Anion gap usually elevated.
Elevated WBC common. Serum sodium should be corrected for elevated
glucose (increase by 1.6 for every 100 over normal). Serum K+ is usually
elevated due to shift out of cells but there is total body K+ depletion (see
management).
F. Management:
1. Fluid: IVFs should be initiated immediately with normal saline. Total body
water deficit can be calculated (0.6 x weight x [1-140/serum sodium]) and is
usually 5-8 liters. Goal is to replace 50% in first 8 hours and completely within
24 hours. Change to D5 ½ NS when glucose level falls below ~250-300.
Pediatric patients require more careful and frequent assessment to avoid possible
cerebral edema.
2. Electrolytes: Frequent monitoring is critical (initially q2hrs). Typically sodium,
potassium, phosphorous, and chloride are all depleted though hyperkalemia is
often present at presentation. Insulin can further lower potassium and so
hypokalemia should be corrected simultaneously. K+ supplementation should
begin when serum K+ falls below 5.0 either by increments, addition to IVFs, or
both. Phosphorous should be replaced only if it falls below 1.0 as replacement
can lead to severe hypocalcemia.
3. Insulin: Start with IV bolus of regular insulin at 0.10-0.15 U/kg followed by 0.1
U/kg/hour. Measure plasma glucose level hourly and if not decreasing by 50-75
mg/dl, double the insulin rate. Add dextrose to IVFs when CBG falls below
250. Insulin infusion should not be dc’d until ketoacidosis resolves. Once
resolved and patient is eating may start long and short acting regimen but IV
insulin should be continued for ~ ½ hour to ensure adequate blood levels.
4. Prevention: Prevention of recurrent admissions requires the assistance of
patient, family members, diabetic educators, and good out-patient primary care
follow-up.
III.
Nonketotic Hyperglycemia: More typically seen in elderly patients with type II diabetes.
Generally thought not to be a separate disorder from DKA but part of a continuum of
hyperglycemia with little or no ketoacid accumulation.
A. Absence of ketones: Not completely understood but may be related to differential
sensitivities of fat and glucose to effects of insulin, lower levels of counterregulatory
hormones, and relative inhibition of lipolysis. This is the reason for generally mild or no
acidosis found in NKH.
B. Higher glucose levels in NKH: Patients with NKH typically have higher CBGs at
presentation (usu > 1000). This may be due to:
1. Pts with DKA present earlier (due to abd pain, SOB, etc), rather than later due to
severe dehydration in NKH.
2. Pts with DKA are generally younger and have higher GFR so excrete more
glucose leading to less hyperglycemia.
C. More severe dehydration: Symptoms have generally developed over a longer period (12 weeks) by the time of presentation and altered mental status from dehydration is often
the reason for seeking medical care. Water deficit is usually 8-12 liters.
D. Clinical Presentation: Most commonly include fatigue, blurred vision, polydipsia,
polyuria, and wt loss developing over days to weeks. As volume depletion worsens,
hypotension, tachycardia, and shock develop. Altered mental status correlates with the
degree of hyperosmolality. 20-25% present with coma. Similar to DKA, underlying
predisposing factors like infection should be sought.
E. Laboratory Findings: CBG usually higher, Osm often >320-340, bicarb > 15, and
sodium usually higher than in DKA. K+, Mg, and Phos are usually elevated at
presentation but decline with treatment.
F. Treatment:
1. Fluids: Cornerstone of therapy. Usually need 8-12 liters. If osm <320, 2-3 L
NS over first 2 hours, then decrease to 500 cc/hr. If osm >340, consider initial
use of 1/2NS at 1.5 L for 1st hour, then 1L/hr for 2 hours, then 500 cc/hr for 3rd
and 4th hours. Change to NS when effective osm <320. If hypotension not
responding to crystalloids, may try colloids. Add dextrose when CBG < 250.
2. Insulin: Begin with low-dose insulin (0.5U/kg/hr) because CBG will decrease
dramatically with IVFs alone. If CBG not decreasing after 2-4 hours with
appropriate fluid hydration and blood pressure and UOP stable, double rate of
insulin.
3. Electrolytes: Similar to DKA. Frequent monitoring and early repletion of
potassium.
G. Complications: Include thromboembolism and DIC (due to severe dehydration and
vasoocclusive disease) and Rhabdomyolysis.
Board Question:
A 42-year old man with long-standing type I diabetes presents with gastroenteritis that has been worsening
for 5 days. His serum biochemistry values are consistent with DKA; his BP is 90/55, his HR is 135 bpm.
Other laboratory findings are as follows: blood glucose 656 mg/dl; sodium 127 meq/L, potassium, 4.2
meq/l; HCO3, 14 meq/l; anion gap, 25; and pH, 7.05.
Which of the following would not be an appropriate step in the immediate management of this
patient?
A.
B.
C.
D.
E.
IV administration of 0.9% saline
Admission to the ICU
IV administration of potassium chloride
IV administration of insulin
IV administration of sodium bicarbonate
Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to
Dr. Wendy Gerstein, Department of Medicine, VAMC (111).
1) Topic of module:__________________________
2) On a scale of 1-5, how effective was this module for learning this topic? _________
(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment
below:
________________________________________________________________________
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________________________________________________________________________
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4) Was the attending involved in the teaching of this module? Yes/no (please circle).
5) Please provide any further comments/feedback about this module, or the inpatient
curriculum in general:
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