Diagnosis and management

of hyperglycemic emergencies

Tasya Sylvia Nursofa

4151161511
Introduction
• Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS)
are life-threatening manifestations of decompensated diabetes mellitus.
Clinically, they differ by the severity of dehydration and whether or not ketosis
Hyperglycemic emergencies 251 and metabolic acidosis are present. Excess
secretion of glucagon, catecholamines, cortisol and growth hormone promotes
gluconeogenesis, glycogenolysis and lipolysis, resulting in DKA through a
relative (type 2 diabetes) or absolute (type 1 diabetes) deficiency of insulin
effect. These occur under stress, serious infection, trauma and cardiovascular
emergencies. Characterized by severe hyperglycemia, hyperosmolarity and
dehydration (but without apparent ketoacidosis), HHS is typically seen in
elderly type 2 diabetic patients and carries a higher mortality rate (5-20%)
compared to DKA (<2%).
 Diagnosis
• The symptoms of DKA begin rapidly, i.e. within hours of a precipitating
event, while HHS develops insidiously over days or weeks. Hyperglycemia-
associated symptoms common to both include polyuria, polydipsia, weight
loss, increasing malaise, orthostatic dizziness and dry mucous membranes.
Kussmaul respirations, acetone-scented breath, nausea, vomiting and
abdominal pain (due to ketosis itself and correlating with the severity of
acidosis) may occur in DKA. Late symptoms in severe cases of either
disorder include confusion or stupor, which can progress to mental
obtundation and coma.
 Precipitating Factors
• The most common illnesses precipitating DKA or HHS are infections, including
viral syndromes, urinary tract infections, pelvic inflammatory disease, pneumonia,
mucormycosis, malignant otitis externa (with pseudomonas aeruginosa), periodontal
abscess and dental infection. Fever is frequently absent even with active infection;
conversely, leukocytosis (≥20,000/mm3 ) and even leukemoid reactions may be
present in the absence of infection. The possibility of meningitis should be
considered in patients with nuchal rigidity, photophobia and headache or when a
depressed level of consciousness does not improve promptly with hydration and
blood sugar reduction.
 Precipitating Factors
• Drugs affecting carbohydrate metabolism (e.g. corticosteroids, second
generation antipsychotic agents) can precipitate either emergency. Cocaine
abuse causes recurrent DKA via several mechanisms, including therapeutic
noncompliance, stimulation of adrenal release of epinephrine and
norepinephrine and increased release of other counter regulatory hormones.
 Differential Diagnosis
• Other causes of metabolic acidosis and ketosis must be differentiated from
DKA. Acute renal failure accounts for ~5-7% of all adult
hospitalizations.30,31 It shares the common feature of an elevated anion gap
metabolic acidosis, but can be easily differentiated from DKA by the absence
of hyperglycemia or ketonemia. Conversely, severe cases of DKA or HHS
can lead to prerenal azotemia and secondary acute kidney injury. Uremia
typically develops when creatinine clearance falls to and ethylene glycol will
also cause a serum osmolal gap.
• Measuring suspected drug/toxin concentrations when the index of suspicion is high
can confirm the diagnosis of acute intoxication. Non-anion gap metabolic acidosis
is characterized by a low serum bicarbonate concentration (via gastrointestinal or
renal losses) with subsequent chloride retention. Diarrhea and renal tubular acidosis
are frequent causes of this condition, which can also occur with carbonic anhydrase
inhibitor therapy. Rapid dilution of plasma bicarbonate by infused saline can result
in a non-anion gap metabolic acidosis as well. Diabetic ketoacidosis can be easily
differentiated from this condition by the presence of an increased anion gap and
hyperglycemia.
 Treatment
• Treatment Treatment of both DKA and HHS focuses on replacing volume deficits,
correcting electrolytes, reversing the acid-base imbalance, normalizing blood glucose
and treating precipitating factors to prevent recurrence and hasten recovery.
Successful treatment of either condition requires frequent monitoring of clinical
and laboratory parameters. A flow sheet recording laboratory results, vital signs and
fluid balance is helpful in monitoring progress and adjusting therapy. A systematic
approach to treatment should achieve clinical stability within 12-36 hours. A sample
protocol for managing adult patients with hyperglycemic emergencies is summarized
in Figure 1. Additionally, endocrinology/diabetes team consultations may result in
shorter hospital stays, fewer medical procedures and lower medical costs and should
be considered for most patients
 Monitoring
• General recommendations for ongoing laboratory monitoring include hourly blood glucose levels
for the first 4-6 hours, and at 2 hour intervals subsequently; electrolyte and CO2 content (every 2-
4 hours) and blood urea nitrogen and creatinine levels (every 4 hours) should also be monitored
until stable. Fluid intake and output should be accurately recorded.3 Since serum bicarbonate and
anion gap are good indices of therapeutic response, repeated assessments of arterial blood gases
or serum or urine ketones are usually unnecessary. As β-hydroxybutyrate converts to acetoacetate,
and conventional (nitroprusside) testing detects only acetoacetate and acetone, standard ketone
levels during therapy may appear unchanged or erroneously high even when treatment has
successfully arrested ketogenesis.32 When acidosis begins to resolve, the anion gap falls to near
normal and the response to glycemic therapy becomes predictable, it is reasonable to reduce
laboratory test frequency.32 Persistent acidosis that does not respond to treatment may be caused
by sepsis, concomitant illness or inadequate insulin dosing and mandates further evaluation and
intervention.3,32
 Complications of Therapy
• Hypoglycemia and hypokalemia are the two most common complications seen
during treatment of DKA.
• Cerebral edema occurs in 0.3-1% of children with DKA but is very rare in
adults7,77 and its mechanism is debated.
• 7,77-83 Other reported life-threatening complications include adult respiratory
distress syndrome, hydrostatic pulmonary edema, bronchial mucous plugging,
ischemic intestinal necrosis and arterial and venous thromboses; 32,84-88 standard
low-dose unfractionated heparin or low molecular weight heparin prophylaxis is
reasonable adjunctive therapy when no contra-indications are present.32,87
 Prevention of recurrences
• Hyperglycemic emergencies are usually preventable. Infection and medical noncompliance
are the two most common causes of DKA and HHS. Established patients should be
educated on how to manage their diabetes during stress or infection; this “sick-day
management” includes never omitting insulin, preventing dehydration and hypoglycemia,
monitoring blood glucose frequently, testing for ketosis, administering supplemental rapid-
acting insulin doses according to prescribed guidelines, treating underlying triggers early and
aggressively and having frequent contact with their diabetes health care team to evaluate
their acute condition.32,89 Patient education and 24-hour access to care are cornerstones of
preventive therapy. Educating caregivers to recognize signs and symptoms of worsening
hyperglycemia and dehydration can reduce the incidence and severity of HHS. For patients
who live alone, family or friends should check daily to assess for changes in mental status or
signs of dehydration.
 Summary
• Though the hyperglycemic emergencies DKA and HHS are life-threatening,
with mortality rates up to 20% (for HHS), they are largely preventable
conditions. A diligent search for precipitating causes contributes to better
outcomes and fewer recurrences, while an organized, methodical and
aggressive approach to treatment can achieve clinical stability in 12- 36 hours.
Patient education and easy access to health care resources are essential to
prevent recurrences. No conflict of interest or financial support declared.