CASE 46-1
A 68-year-old woman with a history of diabetes mellitus (DM) type II, sick sinus syndrome (SSS), and pacemaker placement is admitted to hospital after new-onset dysarthria and left hemiparesis. Her home medications are metformin, glyburide, and lisinopril. Her admission blood glucose is 243 mg/dL. The patient is made NPO on admission until a formal speech evaluation is completed the next day and a CT angiogram with contrast is ordered as part of her stroke workup.
Factors to consider:
Stress of illness, abrupt changes in caloric intake, and physical activity will change her metabolic state and insulin requirements
Need for NPO status for procedures or tests
Interactions between some oral hypoglycemic agents and intravenous contrast on kidney function
Neurological conditions that will affect nutrition (dysphagia)
National guidelines recommend blood glucose between 140 and 180 mg/dL in critically ill patients and pre-meal glucose of less than 140 mg/dL and random glucose of <180 mg/dL in noncritically ill patients.1
Oral hypoglycemic agents are often temporarily discontinued during hospitalization because of contraindications (renal failure, need for contrast, NPO status, heart failure). These agents could be restarted at discharge if metabolic status returns to previous baseline.
The majority of hospitalized patients with DM will require some form of insulin coverage during their admission. The goal for hospitalized patients requiring insulin is to provide a baseline minimum insulin coverage throughout the day to combine with additional doses to match the nutritional needs.
Sliding scale insulin (SSI) are protocols adopted that provide predetermined amount of subcutaneous regular insulin based on glucose levels checked after meals or every 6 hours for patients on NPO status or on continuous enteral feeds. Relying on SSI alone is not enough, as it addresses hyperglycemia only after it occurs and has been associated with excessive hyperglycemia in hospitalized patients when used alone.2 It can be used initially to estimate insulin coverage for patients who are insulin naïve, newly diagnosed with DM, or cannot continue oral hypoglycemic agents. A sliding scale order could accompany a basal bolus regimen to temporarily correct any increase in demand during neurological illness (insulin correction).
Basal bolus correction. This strategy consists in the administration of an intermediate or long-acting dose insulin (NPH, glargine, detemir) and a short-acting dose insulin (lispro, aspart, and glulisine) provided before meals (or soon after if food intake is uncertain) to mitigate the hyperglycemic response. Calculation of the dose is based on AM glucose and previous insulin requirements (Figure 46-1).
CASE 46-2
A 38-year-old man presenting with acute-onset headaches, emesis, and fever is diagnosed with bacterial meningitis. He has a history of DM and ran out of insulin 2 days ago. Vital signs on admission are: BP 106/67 mmHg, heart rate 123 beats per minute, respiratory rate 32 breaths per minute, and temperature 98.8°F. Initial laboratory data are: blood glucose 450 mg/dL, arterial pH 7.24, pCO2 25 mmHg, bicarbonate 12 mEq/L, WBC count 18,500/µL, sodium 128 mEq/L, potassium 5.2 mEq/L, chloride 97 mEq/L, BUN 32 mg/dL, creatinine 1.7 mg/dL, and serum ketones positive.
Diabetic ketoacidosis (DKA) is characterized by hyperglycemia (glucose > 250 mg/dL) and acidemia (pH < 7.30) with elevated anion gap caused by the production of ketoacids. It occurs more frequently in patients with type 1 DM. Patients can have nonspecific symptoms of fatigue, abdominal pain, nausea, and vomiting. Metabolic acidosis can cause compensatory rapid deep breathing (Kussmaul). Severe acidemia and hyperosmolarity can lead to coma.
Hyperosmolar hyperglycemic state (HHS). Patients with type 2 DM are more likely to develop severe hyperglycemia (glucose levels > 600 mg/mL) associated with osmotic diuresis, dehydration, and alteration of consciousness without significant acidemia or ketosis.
Notably, these conditions could overlap in about one third of patients presenting with severe hyperglycemia. (Table 46-1)
Treatment is aimed to correct:
Hypovolemia and hyperosmolarity
Sodium and potassium imbalance
Acidosis
Insulin requirements
Fluid replacement is initially started with 0.9% normal saline at 15–20 mL/kg/hour over the first hour. Depending on the degree of dehydration and corrected sodium level, fluid rate can be decreased and solution can be changed to half-normal saline (NS). In case of hypovolemic shock intravenous fluid (IVF), bolus might be required to establish hemodynamic stability.
Insulin infusion is started at 0.1 units/kg/hour. Some protocols suggest an initial bolus of 0.1/units/kg. Finger-sticks blood glucose should be checked every hour, as glucose levels might fall precipitously after treatment. Once glucose is <250 mg/dL, dextrose solutions need to be added so that insulin infusion can be continued, usually at lower rates. Insulin is continued until the acidosis has resolved (resolution of anion gap or drop in beta-hydroxybutyrate <3 mmol/L) or until the electrolytes derangements are corrected. After the hyperglycemic crisis is resolved and patient tolerates PO intake, a basal bolus subcutaneous insulin regimen should be initiated, 1–2 hours before insulin infusion is discontinued.
Potassium depletion occurs as a consequence of hyperglycemic osmotic diuresis and urinary ketones secretions, regardless of the serum potassium level that could be relatively normal or elevated due to lack of insulin. Potassium level needs to be monitored every 2–4 hours initially. Treatment with fluids and insulin will lower serum potassium rapidly, and replacement should be started as it reaches normal ranges, if renal function is normal.
Metabolic acidosis can impair myocardial contractility, delivery of oxygen to the tissues, and contribute to organ dysfunction. Volume repletion and insulin therapy are usually sufficient to correct the metabolic acidosis that presents in DKA. The use of bicarbonate infusion is suggested only if pH drops below 6.9. As pH is corrected, potassium levels might decrease further and more might be required. As the DKA resolves a nonanion gap, metabolic acidosis can occur due to the chloride content of normal saline solutions administered. This is usually self-limited.
Cerebral edema is a rare and dangerous consequence of DKA in children and young adults. It usually manifests after treatment is initiated and remains subclinical in the majority of cases. Clinical identification is challenged by the nonspecificity of symptoms commonly caused by DKA itself, such as nausea, vomiting, headaches, and impaired sensorium. New focal neurological findings are usually signs of severe elevation of intracranial pressure (ICP). Hyperosmolar state with accumulation of intracellular osms, ischemia/hypoxia, and rapid correction of osmotic gradient are some of the hypothesized mechanisms responsible. Treatment should focus on strategies aimed to reduce intracranial pressure and counteract edema formation:
Head of bed elevation
Decrease rate of isotonic fluids to slow down correction of osmotic gradient
Discontinuation of any hypotonic solutions (D5W, half NS, Ringer lactate)
Hyperosmolar therapy
Both mannitol (0.25 mg to 1 g /kg infusion) and hypertonic saline solutions (3% NaCl 5–10 ml/kg bolus infusion) are indicated as hyperosmolar agents to treat cerebral edema. Both agents raise plasma osmolality and improve serum viscosity, resulting in improved cerebral blood flow and osmotic movement of water out of the brain, with subsequent reduction in cerebral edema. The osmotic diuresis resulting from mannitol may require adjusting fluid status. Hypertonic saline will raise serum Na, which might be indicated depending on the level of hypovolemic hyponatremia present.
Hyperventilation
Hyperventilation in DKA-related cerebral edema—as for all forms of cerebral edema—is not indicated, unless as brief rescue treatment for cases of impending cerebral herniation. Hyperventilation will reduce CO2 and decrease cerebral blood flow, worsening ischemia. These patients are often already tachypneic (Kussmaul respirations) due to the underlying metabolic acidosis, and reducing PCO2 further could be detrimental.
KEY CONCEPT 1 HYPERGLYCEMIA-INDUCED HYPONATREMIA
Dilutional hyponatremia or “pseudo-hyponatremia” occurs because of shift of water from the intracellular to the extracellular compartment secondary to osmotic gradient induced by hyperglycemia. The true serum sodium should be determined by the following formula:
Effective serum sodium = measured sodium + 1.6 × [serum glucose – 100)/100]
CASE 46-3
A 67-year-old woman with a history of DM type 2 was admitted for evaluation of a right internal capsule infarct. She returns from a brain MRI around 11.30 and is found to be sleepy and confused. She can still follow some commands but has developed upper-limb tremor. Her vital signs are: RR = 20, HR = 94, BP = 134/98, and sats = 94%. She received Lantus 25 units the night before but missed breakfast because of her test. Her fingerstick blood glucose (FSBG) is 52 mg/dL.
Hypoglycemia is often present as a result of erroneous insulin administration, decrease in oral intake, or steroids dose adjustment. Diagnosis is made on the basis of both clinical presentation and glucose level, as the threshold for symptomatic hypoglycemia varies among individuals. Glucose levels from 45 and 70 mg/dL can cause symptoms. Increased risk is associated with concomitant use of beta blockers, as can they can blunt the sympathetic response to hypoglycemia. Neurologic patients are also at increased risk because symptoms of hypoglycemia can be masked by the primary neurologic disorder (encephalopathy, post ictal state) (Table 46-2).
Every insulin order or protocol ordered in the hospital setting should be accompanied by a hypoglycemia order set that can be immediately used in case of symptomatic hypoglycemia. Several algorithms for hypoglycemia managed in hospitalized patients are available.
Severe symptomatic hypoglycemia. Patient is hypoglycemic and altered, unconscious, and not able to swallow. Administer 50 mL of 50% dextrose intravenously or start a 5% dextrose infusion at 100 mL/hour. If no IV access is available, administer 1 mg glucagon IM or subcutaneously. Glucose levels should be rechecked in 10–15 minutes. Additional glucose infusion might be needed. Glucagon infusion may be followed by nausea or vomiting.
Symptomatic hypoglycemia. Patient has hypoglycemic symptoms but is usually able to swallow. Glucose (15 g) sublingual or 4 oz. apple or orange juice or 3 Graham crackers. Recheck glucose in 15 minutes.3,4
KEY CONCEPT 2 HYPOGLICEMIA UNAWARENESS
Some DM patients may not manifest typical clinical symptoms even in the setting of life-threatening hypoglycemia due to failure of the adreno-medullary and sympathetic responses. For these individuals, the level that triggers the response is below the glucose level associated with neuroglycopenia. The first sign of hypoglycemia is confusion and alteration of consciousness that could confound diagnosis and delay treatment, if not properly identified.
Excessive extra cellular potassium (K >5.5 mEq/L) is often encountered due to conditions or medications that interfere with its renal excretion, cause extracellular shift, or inhibit the renin-angiotensin aldosterone system. Untreated hyperkalemia can cause muscle weakness and cardiac conduction abnormalities that can lead to arrhythmias, bradycardia, conduction blocks, and ultimately cardiac arrest (Table 46-3 and Figure 46-2).
Causes of Hyperkalemia
| Intracellular Shift | Decreased Renal Losses |
|---|---|
|
|
Figure 46-2
Progression of EKG changes in Hyperkalemia. Tall, “peaked” T waves (most evident in the precordial leads), shortened QT interval, loss of P waves, and widening of the QRS complex culminating in a “sine wave” morphology. Reproduced with permission from Butterworth JF, Mackey DC, Wasnick JD: Morgan & Mikhail’s Clinical Anesthesiology, 5th ed. New York: McGraw-Hill Companies; 2013.
Rapid treatment is indicated when EKG changes are present, K > 6.5–7 mEq/L, or hyperkalemia is rapidly increasing. Treatment strategies, besides addressing reversible causes, aim to stabilize the cardiac membrane and remove excessive extracellular potassium.
Calcium
Calcium stabilizes the cardiac membrane, and its effect starts within minutes but lasts only 30–60 minutes. Both calcium chloride and calcium gluconate infusion can be used, but calcium chloride contains 3 times the amount of calcium compared to calcium gluconate and is preferred in unstable conditions.
Insulin and glucose
Insulin drives potassium into cells through the Na-K pump present on muscular tissues and needs to be followed by administration of glucose to prevent hypoglycemia (10–20 units insulin IV, combined with 50 mL of dextrose 50% if the serum glucose is less than 250 mg/dL). The effect starts 20 minutes after the infusion and lasts for 4–6 hours. Glucose level should be monitored about one hour after the infusion.
β 2 agonists
Albuterol can provide transient intracellular shift of potassium through the same mechanism of insulin and can be given as adjunct to insulin to potentiate its effects. Effective dose is about 4 times the one used for bronchodilation and maximum effect is seen within 90 minutes. At this dose, tachycardia can be a notable side effect and presence of cardiac disease needs to be considered prior to use.
Sodium polystyrene sulfonate (kayexalate)
Cation exchange resins exchange sodium for excreted potassium in the colon cells and are given orally or rectally combined with a laxative to avoid constipation. The onset of action is variable (2–6 hours). Its slow effects and severe side effects reported (colon ischemia) make this therapy a distant choice for nonurgent treatment of chronic hyperkalemia, in cases when dialysis is not feasible.
Loop diuretics + intravenous fluids infusions
Intravenous fluids (NS or sodium bicarbonate) can be used to improve potassium excretion at the nephron level. This effect can be potentiated by the use of loop diuretics, but euvolemia needs to be preserved to assure adequate nephron perfusion (Table 46-4).
Management of Hyperkalemia
| Hyperkalemia | Action |
|---|---|
| EKG changes or K > 7 | Calcium gluconate 1000 mg IV (10 mL of 10% solution). Can repeat every 5 minutes if cardiac abnormalities persist |
| EKG changes + hemodynamic instability AV block | Calcium chloride 500–1000 mg IV + Insulin 10 units + 50 mL of D 50 + Albuterol 10–20 mg in 4 mL of nebulizer over 10 minutes |
| Nonacute phase | Use cation exchange resins with caution (15 mg–30 mg sodium polystyrene sulfonate orally) |
| No EKG changes | Loop diuretics: Lasix 20–40 mg. Fluid losses need to be replaced |
| Refractory severe hyperkalemia | Dialysis |
| Renal failure | |
| Extensive tissue breakdown |
