The Karl Heusner Memorial Hospital

1. Emergencies
in Diabetes
1
Ivan De Paz, MD, MSc
Chapter 11
OBJECTIVES
Considering the importance of acute care management in a busy emergen-
cy room, the objective of this chapter is to present the emergency physician
with sequential and organized guidelines. This chapter offers a practical ap-
proach for the diagnosis and treatment of the acute complications of diabetes
mellitus.
The information provided here should be used as adjunct material and not
as the only reading material for the treatment of patients. Clinical judgement
should always guide the physician in the selection, dosing, and duration of
treatment for individual patients.
INTRODUCTION
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS)
are potentially fatal complications of diabetes mellitus. Currently, their mor-
tality rate is of 1-5% for DKA(1, 2)
and 10-17% for HHS.(3, 4)
DKA and HHS
differ clinically according to the presence of ketoacidosis and the degree of
hyperglycemia.(2, 5, 6)
However, there’s significant overlap between DKA and
HHS in more than one third of patients (Tables 1 and 2).(7)

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Table 1. Diagnostic criteria
Criterion Mild Moderate Severe
Plasma glucose >250 >250 >250
Arterial pH 7.25-7.30 7.00-7.24 <7
Bicarbonate 15-18 10 - <15 <10
Urine ketones + + +
Serum ketones + + +
Anion Gap >10 >12 >12
Mental obtundation Alert Alert/drowsy Stupor/coma
*
Copyright © 2006 American Diabetes Association. From: Diabetes Care. Vol 29, Issue 12, 2006.
Information updated from: Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic
crises in adult patients with diabetes. Diabetes Care. 2009;32:1335. Reprinted with permission
from the American Diabetes Association.
Table 2. Diagnostic criteria *
Plasma glucose > 600
Effective serum osmolality 320 mOsm per kg
Arterial pH 7.30
Bicarbonate 18 mEq
Urine ketones Small
Serum ketones Small
Anion Gap Variable
Mental obtundation Stupor/coma
Mortality in hyperglycemic crisis is primarily due to the underlying pre-
cipitating illness. It becomes substantially worse at extremes ages. Hence,
the importance of starting an adequate and urgent therapy for the metabolic
derangements, along with a meticulous search of the precipitating condition
(Table 3).

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CHAPTER 11 | EMERGENCIES IN DIABETES
Table 3. Precipitating factors DKA
Infections Pneumonia, urinary tract infection
New onset diabetes type 1
Inadequate insulin therapy Non-adherence to insulin treatment plans
Financial problems
Insulin pump failure
Drugs that affect carbohydrate
metabolism
Antipsychotic agents (olanzapine,(9) risper-
idone(10)) cocaine,(11) alcohol, cortico-
steroids, glucagon, thiazide diuretics,(2)
dobutamine(2)
Acute major illnesses Arterial thrombosis,(12) cerebrovascular
accident, myocardial infarction, pancreati-
tis,(12) trauma,(13) sepsis
No apparent cause
DIABETIC KETOACIDOSIS
Diagnosis
Clinical features:
Symptoms evolve rapidly (over 24 hours). Patients may present with nausea,
vomiting, abdominal pain (that may be related to the severity of metabolic
acidosis).(8)
Neurologicsymptomsmayoccurwhensevereacidosisispresent.
On physical examination, the patient may present a fruity odor, and deep
respirations that reflect compensatory hyperventilation. Signs of volume
depletion are common and include decreased skin turgor, dry oral mucosa,
tachycardia and if severe DKA, hypotension.
HYPEROSMOLAR HYPERGYCEMIC STATE
Diagnosis
Clinical features:
Typically,patientspresentingwithHHSareolderandhaveundiagnoseddiabe-
tes or type 2 diabetes. Their symptoms, usually, develop more insidiously with
polyuria, polydipsia, and weight loss, often persisting for several days before
hospital admission. These patients, usually, present weakness, visual distur-
bance or leg cramps.(14, 15)
Neurological symptoms are most common in HHS.
Some patients may have focal neurologic signs (hemiparesis, seizures).(16-20)

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THE KHMH MANUAL
The most frequent gastrointestinal complaints of patients are loss of appetite
and constipation, Nausea and vomiting may occur but are much less frequent
than in patients with DKA. Abdominal pain is unusual in HHS.(8)
On physical examination there are signs of volume depletion, including
decreased skin turgor, sunken eyeballs, dry oral mucosa, absent sweating,
cool extremities, rapid pulse and in severe cases hypotension. Abdominal
distention may occur because of gastroparesis induced by hypertonici-
ty,(21)
but resolves quickly after an adequate hydration. Abdominal dis-
tention that persists after rehydration may be related to other underlying
causes (Table 4).
Table 4. Precipitating factors in HHS
Infections Pneumonia, urinary tract infections,
sepsis, cholecystitis
Non-compliance with
diabetes treatment
Drugs that affect
carbohydrate metabolism
Calcium channel blockers, Loop diuretics,
olanzapine, thiazide diuretics, phenytoin,
chemotherapeutic agents, beta blockers,
steroids, total parenteral nutrition
Comorbidities cerebrovascular accident, myocardial infarction,
pancreatitis, trauma, mesenteric thrombosis,
severe burns, intestinal obstruction, trauma,
peritoneal dialysis, thyrotoxicosis
Undiagnosed type 2 diabetes
No apparent cause
MANAGEMENT
The initial evaluation of patients with hyperglycemic crises should include an
assessment of cardiorespiratory status, volume status and mental status. The
complete initial and rapid physical examination should focus on:
■■ ABC
■■ Vital signs
■■ Mental status
■■ Precipitating events
■■ Volume status
■■ Comorbidities

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CHAPTER 11 | EMERGENCIES IN DIABETES
Theinitiallaboratoryevaluationofapatientwithhyperglycemiccrisesshould
include the determination of:
■■ Serum glucose
■■ Complete chemistry (electrolytes, BUN, Creatinine)
■■ Complete blood count with differential
■■ Urine test and urine ketones
■■ Plasma osmolality
■■ Arterial blood gas measurement
■■ Electrocardiogram
■■ Chest radiography
If clinically indicated:
■■ Serum lipase
■■ Serum cpk and troponins
■■ Serum liver function tests
■■ Urine and blood cultures
General Measures:
■■ Oxygen by nasal cannula if oxygen saturation is less than 90%.
■■ Obtain large bore peripheral IV access.
■■ Elderly patients, cardiac, renal or hemodynamically unstable patients, will
need central venous catheterization and a cardiac monitor.
■■ Monitor serum glucose hourly.
■■ Nasogastric tube may be needed in patients with altered mental status, ab-
dominal distention, and pancreatitis.
■■ Constant monitoring of intake and output.
■■ Serum glucose should be monitored hourly until stable, serum electro-
lytes, creatinine; venous pH should be measured every 2-4 hours, depend-
ing upon disease severity and the clinical response.
TREATMENT
The treatment of DKA and HHS is similar; it includes the correction of
the fluid and electrolyte abnormalities present with the administration of
insulin.(2, 21-24)
The first step in the treatment of DKA or HHS is the infusion of isotonic
saline to expand extracellular volume and stabilize cardiovascular status. This

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THE KHMH MANUAL
also increases insulin responsiveness by lowering plasma osmolality, reduc-
ing vasoconstriction and improving perfusion, and reducing stress hormone
levels.(25, 26)
Fluid replacement:
Initiate with isotonic saline 0.9% at a rate of 15-20 mL/kg/hr (if the cardiac
reserve of the patient allows it) for the first 2 hours. After the first 2 hours,
the choice of fluid replacement depends upon the state of hydration, serum
electrolytes, and urine output. Obtain the corrected sodium, and if it is less
than 135 mEq/L, then isotonic saline should be continued at a rate of 250-
500 mL/hour.(2)
Once the corrected sodium is normal or high (greater than
135 mEq/L), the solution can be changed to saline 0.45%. Dextrose is added
to the saline solution, when the serum glucose reaches 200 mg/dL in DKA
or 250 mg/dL in HHS. The goal is to correct the estimated deficits within the
first 24 hours.
Insulin:
Insulin is required to correct the metabolic derangement and reverse the ac-
idosis and ketone production. A level ≥3.3 mEq/L of serum potassium is re-
quired to start insulin therapy. In patients with less than 3.3 mEq/L of serum
potassium, insulin will worsen hypokalemia by driving potassium into the
cells. Insulin therapy should be delayed until the serum potassium is ≥3.3
mEq/L to avoid arrhythmias, cardiac arrest, and respiratory muscle weak-
ness.(2, 27, 28)
Treatment is initiated with an IV bolus of regular insulin (0.1 U/
kg body weight) followed by a continuous infusion of regular insulin or 0.1
U/kg/hr.(23, 29-32)
When the serum glucose reaches 200 mg/dL in DKA or 250
mg/dL in HHS, the IV fluids are changed to dextrose in saline and it may be
possible to decrease the insulin infusion to 0.02 to 0.05 U/kg/hr. The insulin
infusion could be prepared by adding 100 units of regular insulin into 100 mL
of normal saline.
Potassium:
Although potassium (K) is profoundly depleted in persons with DKA, de-
creased insulin levels, acidosis, and volume depletion cause elevated extra-
cellular concentrations. Improved renal perfusion will increase K excretion,
insulin therapy and correction of acidosis will cause cellular uptake of K.
If the serum K concentration is initially greater than 5.3 mEq/L, then K re-
placement should be delayed until its concentration has fallen below this level.

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CHAPTER 11 | EMERGENCIES IN DIABETES
If the serum K is between 3.3 and 5.3 mEq/L and the urinary output is ad-
equate, replacement is initiated immediately with potassium chloride (KCL)
20-30 mEq on each liter of IV replacement fluid and continued until serum K
has increased to the 4-5 mEq/L range.
If the initial serum K is below 3.3 mEq/L IV KCL 20-40 mEq/L should be
given. Repletion is most urgent in patients with massive potassium deficits
who are hypokalemic prior to therapy. Such patients require aggressive K re-
placement with KCL at 40 mEq/hr.
Bicarbonate:
Bicarbonate is administered when the arterial pH is less than 6.90; the dose
is 100 mEq of sodium bicarbonate diluted in 400 mL of sterile water with 20
mEq of KCL if the serum K is less than 5.3 mEq/L administered over two
hours. The venous pH and the bicarbonate should be monitored every two
hours and bicarbonate doses can be repeated until the pH rises above 7.
At an arterial pH above 7, most experts agree that bicarbonate therapy is
not necessary.
Phosphate:
Twenty to thirty mEq of sodium phosphate can be added to 1 liter of IV fluid
when the phosphate level is below 1 mg/dL, or if the patient is having cardiac
dysfunction, rhabdomyolysis haemolytic anemia or respiratory failure.(2)
RESOLUTION OF HYPERGLYCEMIC CRISIS
The hyperglycemic crisis is considered resolved when the treatment goals are
reached (Table 5).
Table 5.
Diabetic Ketoacidosis Hyperglycemic Hyperosmolar state
Serum glucose <200 Serum glucose below 250 mg/dL
Serum bicarbonate ≥15 mEq/L Plasma osmolality below 315
Serum anion Gap <12 mEq/L Patient is mentally alert
Venous pH >7.30 The patient can eat
The patient is able to eat

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THE KHMH MANUAL
CONVERTING TO SUBCUTANEOUS INSULIN
The insulin infusion should be continued for one to two hours after initiating
the SQ insulin; abrupt discontinuation of IV insulin reduces insulin levels
and may result in recurrence of hyperglycemia.
CALCULATIONS FOR THE EVALUATION
OF HYPERGLYCEMIC CRISES
■■ Anion gap
■■ Serum osmolality
■■ Serum sodium correction
KEYPOINTS
■■ DKA typically occurs in lean, younger patients with type 1 diabetes
mellitus; increasingly seen in type 2; may be the initial presentation.
■■ HHS is less frequent than DKA and is mostly a disease of elderly
patients.
■■ Abdominal pain in the absence of severe acidosis, or persistent pain in
a patient in whom ketoacidosis has resolved, requires that other causes
of abdominal pain be sought, like pancreatitis.
■■ Abdominal pain in the HHS patient should alert the physician to per-
form a detailed abdominal exam, and perform further studies to find
the causes of the abdominal pain.
■■ Normal temperature of patients with a hyperglycemic crisis does not
rule out infection accurately.
■■ The lack of ketosis in HHS may delay presentation resulting in an on-
going osmotic diuresis, which results in more severe volume depletion.
■■ The majority of patients with hyperglycemic crises present with
leucocytosis, a band count greater than 10% increases suspicion for
infection.
■■ Repeat arterial blood gases are unnecessary during the treatment of
DKA. Venous pH that is about 0.03 units lower is adequate to assess
the response to therapy.
■■ Pain and phlebitis can occur during parenteral infusion of potassium
into a peripheral vein. This primarily occurs at rates above 10 mEq/hr.
■■ Rates above 20 mEq/hr are highly irritating to peripheral veins. When
such high rates are given, they should be infused into a large central vein.

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CHAPTER 11 | EMERGENCIES IN DIABETES
■■ A hyperchloremic non-gap metabolic acidosis is a common manifes-
tation of the later treatment phase of diabetic ketoacidosis and takes
longer to resolve than the gap ketoacidosis as its correction depends
on the kidney’s ability to regenerate bicarbonate.
■■ If nitroprusside testing for ketones is used, ketonemia and ketonuria
may persist for more than 36 hours due to the slow elimination of ac-
etone. Because acetone is not an acid, it does not cause metabolic ac-
idosis, and a persistent ketone test due to acetone does not indicate
ketoacidosis. Enzymatic measurement of beta-hydroxybutyrate obvi-
ates this issue.
SUGGESTED READINGS
■■ Charfen MA, Fernández-Frackelton M. Diabetic ketoacidosis. Emerg
Med Clin North Am. 2005;23(3):609-28.
■■ De Fronzo RA, Ferrannini E, Keen H, Zimmet P. International Textbook
of Diabetes Mellitus. 3rd
edition. England: John Wiley & Sons, Ltd; 2004.
■■ Jara Albarran A. Endocrinology. 2nd
edition. Editorial Médica
Panamericana; 2010.
■■ Kahn CR, Weir GC, King GL, Jacobson AM, Moses AC, Smith RJ.
Joslin’s Diabetes mellitus. 14th
edition. Boston: Lippincott Williams &
Wilkins; 2005.
■■ Kitabchi AE, Nyenwe EA. Hyperglycemic crises in diabetes mellitus:
diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol
Metab Clin North Am. 2006;35(4):725-51.
■■ Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic
crises in adult patients with diabetes: a consensus statement from the
American Diabetes Association. Diabetes Care. 2006;29(12):2739-48.
■■ Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J. Harrison’s
Principles of Internal Medicine. 18th
edition. United States: McGraw-
Hill; 2012.
■■ Marx J, Hockberger R, Walls R. Rosen’s Emergency Medicine - Concepts
and Clinical Practice. 8th
edition. Philadelphia: Elsevier Saunders; 2014.
■■ Melmed S, Polonsky K, Larsen R, Kronenberg HM. Williams Textbook
of Endocrinology. 12th
edition. Philadelphia: Elsevier; 2011.
■■ Zubiran S. Manual de terapéutica médica y procedimientos de urgencia.
6th
edition. España: McGraw-Hill Professional Publishing; 1999.

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SUGGESTED WEBSITES
■■ http://medcalc3000.com/qc-idx.htm
■■ http://www.aafp.org/afp/2013/0301/p337.html
■■ http://www.aafp.org/afp/2005/0501/p1723.html
■■ http://care.diabetesjournals.org/content/32/6/1119.full.pdf
■■ http://care.diabetesjournals.org/content/35/Supplement_1/S11.full
■■ http://www.who.int/hinari/en/
■■ http://www.nejm.org/doi/pdf/10.1056/NEJMra1208627
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