Page 1402 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 101: Hyperglycemic Crisis and Hypoglycemia 975

TABLE 101-1 Signs and Symptoms of Hyperglycemic Crisis
• Fluid volume restoration, insulin, and electrolyte management are key.
Symptoms Signs
• Regular electrolyte and glycemic assessment is needed.
• DKA is more commonly seen in younger patients with type 1 DM. Polyuria Dry mucous membrane
Polydipsia Increased skin turgor
• Patients presenting with HHS are often older with type 2 DM. Weight loss Tachycardia
• Precipitating causes should be sought. Orthostatic dizziness Postural hypotension
Lethargy Neurological compromise
Malaise Signs of precipitating illness
■ PATHOPHYSIOLOGY Nausea Seizures a
Vomiting
Acetone breath
Serum glucose is a continuum and there is a spectrum of hyperglyce- Abdominal pain a Kussmaul respiration a
mia. DKA and HHS represent the extremes of hyperglycemia and are Symptom of precipitating illness
regarded as medical emergencies. Hyperglycemia is caused by a relative a Associated with DKA.
insulin insufficiency. This may be caused by any combination of
a) Decreased insulin production
b) Increased insulin requirements hyperglycemia. Hyperglycemia itself is a β-cell toxic state and insulin
secretion is reduced. This cycle of hyperglycemia, falling insulin secre-
9
c) Increased counterregulatory hormones tion, and dehydration through glucose-mediated osmotic diuresis can
d) Decreased peripheral glucose utilization result in HHS, particularly if unmatched by increased oral increased
free water intake. Peripheral insulin sensitivity, peripheral glucose uti-
In type 1 diabetes mellitus (DM), autoimmune-mediated β-cell death lization, and endogenous insulin production, all increase after HHS is
leads to a dramatic fall, and eventually a complete cessation, of insulin treated. When euglycemia is restored, endogenous insulin production
production. This can lead to hyperglycemia over a very short period of may be sufficient to prevent recurrence of uncontrolled hyperglycemia if
time. In type 2 DM, there is lowered insulin sensitivity, increased hepatic combined with dietary changes and oral hypoglycemic agents.
gluconeogenesis, and a more gradual reduction in insulin secretion over Initially, rising serum glucose draws free water into the intravascular
years. Traditionally DKA was seen almost exclusively in patients with space. While transiently maintaining intravascular volume, this process
type 1 DM, while HHS was a rare complication of elderly patients with can lead to a dilutional hyponatremia. Over time, intravascular volume
type 2 DM. HHS has supplanted the older terms hyperglycemic hyper- contraction occurs if water loss through hyperglycemia associated
osmolar nonketotic coma and hyperglycemic hyperosmolar nonketotic osmotic diuresis is not met by an increase in oral free water intake.
state. This change reflects that patients with HHS may have detectable Serum sodium, urea, and glucose rise gradually and thus serum osmo-
ketonemia and need not have an altered sensorium or present with coma. lality climbs. Hypertriglyceridemia, secondary to hyperglycemia, can
Profound insulin deficiency leads to conversion of excess fatty also result in lowering of serum sodium concentration. 10
acid to acetyl coenzyme A (ACA) via β-oxidation. Ordinarily ACA
would be further oxidized via the TCA cycle. In the absence of ■ PRESENTATION
insulin, excess amounts of ACA form ketone bodies (acetone, aceto-
acetate, and B-hydroxybutyrate) via acetoacyl-CoA and β-hydroxy- There is huge variation in the presentation patterns of patients with
β-methylglutaryl-CoA. Ketone bodies are produced in small hyperglycemia emergencies. The typical signs, symptoms, and biochem-
physiologically acceptable amounts (<0.5 mM) in the fasting state when ical profiles are represented in Tables 101-1 and 101-2. DKA develops
carbohydrate is unavailable or inaccessible for short periods of time. over a short period of time, often less than 24 hours, while HHS tends to
However, hyperketonemia (>1 mM, usually >3.0 mM in ketoacidosis) be a more insidious process. Patients with hyperglycemia can range from
can result in a raised anion gap metabolic acidosis, ketonuria, dehydra- being relatively asymptomatic to unresponsive and obtunded. Patient
tion, and electrolyte imbalance. 1 factors including age, access to water, ability to communicate thirst,
Ketonemia and ketoacidosis are classically seen in patients with type and pre-existing medical conditions affect the mode of presentation.
1 DM leading to DKA. However, DKA can be seen in any form of DM Biochemical factors such as degree of acidosis and hyperglycemia also
with significant insulin deficiency, usually during times of physiological influence both the severity of the illness and the mode of presentation.
stress (eg, sepsis, cardiovascular event, or trauma). Increasingly, DKA is Elderly patients with reduced mobility and an inability to access
being described as the presenting illness of African American patients sufficient fluids to counter the hyperglycemic diuresis are particu-
with type 2 DM. Initially these patients may require high doses of larly vulnerable. Equally infants may have quite nonspecific signs
2
insulin but often remain off insulin therapy for many years after their and become profoundly dehydrated prior to contact with medical
original presentation. Glucotoxicity and lipotoxicity are postulated services. Significant neurological compromise is rare in the absence of
3,4
causes for this transient β-cell dysfunction but the etiology is uncertain.
5
These patients are typically negative for both anti-islet antibodies and
mutations in genes known to be associated with maturity onset diabetes TABLE 101-2 Hyperglycemic Crisis Biochemical Profiles
of youth (MODY). 6
In response to significant hyperglycemia, a cascade of counter- Laboratory Values DKA HHS
regulatory hormones is released. Glucagon, catecholamines, cortisol, Glucose mmol/L >11.0 >33.0
and growth hormone all stimulate gluconeogenesis and lipolysis, have pH <7.3 >7.3
anti-insulin effects, and reduce glucose utilization in the peripheral
−
tissues. In patients with type 2 DM, high insulin resistance coupled with this HCO mmol/L <18.0 >18.0
3
increase in anti-insulin hormones can lead to a relative insulin deficiency. Anion gap Raised Variable
This combination can result in profound hyperglycemia without ketosis as Serum ketones mmol/L >2.0 <2.0
there is sufficient circulating insulin to prevent significant ketonemia. 7
Once the renal threshold for reabsorption of glucose is breached Serum osmolality mmol/kg <320 mmol/kg >320
(∼10.0 mmol/L or 180 mg/dL), glycosuria occurs. The resultant osmotic Serum osmolality = 2(Na) + serum urea + glucose
8
diuresis gives rise to many of the symptoms and signs associated with Anion gap = (Na) – (Cl + HCO )
−
3

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