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Metabolic and Endocrine Emergencies 

Metabolic and Endocrine Emergencies
Chapter:
Metabolic and Endocrine Emergencies
Author(s):

Greta L. Piper

and Adrian A. Maung

DOI:
10.1093/med/9780199377275.003.0006
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date: 24 October 2020

Acidosis

Definition

Blood pH <7.36 (normal 7.36–7.45). Acidosis can include respiratory acidosis (PaCO2 > 45 mm Hg), metabolic acidosis (plasma bicarbonate <22 mEq/L or arterial base excess < –3 mEq/L) or mixed.

Presentation

  • Laboratory result on arterial or venous blood gas analysis

  • Mild acidosis is often asymptomatic.

  • Severe cases can cause vasodilation, shock, hypotension resistant to catecholamines, myocardial depression, and cardiac arrhythmias.

  • Respiratory acidosis can include signs of CO2 retention and respiratory failure such as hypoxemia, narcosis, and cyanosis.

  • Metabolic acidosis can be associated with compensatory hyperventilation (Kussmaul breathing).

Pathophysiology

Metabolic acidosis is caused by increased acid generation (e.g., lactic acidosis), loss of bicarbonate (e.g., severe diarrhea), decreased renal acid excretion or dilution (volume expansion with hyperchloremic fluids [e.g., 0.9% saline]). Respiratory acidosis is caused by an increase in PaCO2; most commonly from inability to eliminate CO2 caused either by respiratory failure or by increased CO2 production (e.g., malignant hyperthermia).

Differential Diagnosis

  • Laboratory error

Immediate Management

  • Establish IV access

  • Mild cases of acidosis may not need urgent treatment.

  • Intubate the trachea and begin mechanical ventilation in the setting of severe acidosis (pH <7.2), especially respiratory acidosis, or in cases of respiratory distress, respiratory failure, or hypoxemia.

  • In ventilated patients, adjust minute ventilation to decrease PaCO2 (10 mm Hg decrease in PaCO2 increases pH by approximately 0.08).

  • Severe metabolic acidosis (pH <7.2) can be treated with sodium bicarbonate (NaHCO3). NaHCO3 (mEq) = 0.5 × weight (kg) × (24-HCO3 [mEq/L]). Administer half of the calculated dose and repeat the ABG in 30 minutes to determine the need for additional therapy.

  • Restore normal circulating blood volume. Lactated Ringer’s solution is preferred to normal saline because it has a lower chloride content and reduces the risk of hyperchloremic acidosis.

Diagnostic Studies

  • Basic metabolic panel

  • Arterial blood gas analysis

  • Calculation of anion gap

A([Na+[K+]) - ([Cl-] - [HCO3-])

Subsequent Management

  • Diagnose and treat the underlying etiology of the acidosis.

  • Respiratory acidosis due to respiratory failure should be treated by supporting ventilation, with either noninvasive or invasive means and by treating the underlying cause.

  • Metabolic acidosis can be categorized as either high anion gap or normal (hyperchloremic) anion gap. Therapy should be directed to the cause(s) of the increased acid generation, loss of bicarbonate, or the diminished renal acid excretion.

  • Renal replacement therapy may be indicated in patients with kidney failure and severe metabolic acidosis or in patients with severe acidosis due to toxin ingestion.

Risk Factors

  • Respiratory failure

  • Acute illness

  • Acute blood loss

  • Shock (hypoperfusion)

  • Hypermetabolic states (e.g., thyrotoxicosis)

  • Massive resuscitation with hyperchloremic fluids

  • Hyperthermia

  • Hypothermia

  • Severe diarrhea

  • Diabetic ketoacidosis

Prevention

No specific prevention except for treatment of the underlying condition.

Special Considerations

  • Monitor patients with acid base disorders closely and adjust treatment for a change in clinical status (e.g., adjust minute ventilation as metabolic acidosis improves to prevent rebound alkalosis).

  • Do not reduce PaCO2 to <25 mm Hg, as this may produce hypocarbia-induced vasoconstriction and ischemia.

  • Resuscitation with normal saline in shock states can worsen metabolic acidosis.

  • Respiratory acidosis can be corrected by decreasing PaCO2. Metabolic acidosis can be buffered acutely by inducing a respiratory alkalosis.

Further Reading

Fidkowski C, Helstrom J. Diagnosing metabolic acidosis in the critically ill: bridging the anion gap, Stewart, and base excess methods. Can J Anaesth. 2009; 56(3): 247–256.Find this resource:

Kraut JA, Madias NE. Treatment of acute metabolic acidosis: a pathophysiologic approach. Nat Rev Nephrol. 2012; 8(10): 589–601.Find this resource:

Neligan PJ, Deutschman CS. Perioperative acid-base balance. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1557–1572.Find this resource:

Acute Adrenal Insufficiency

Definition

Failure of the hypothalamic-pituitary adrenal axis to produce sufficient glucocorticoids and/or mineralocorticoids.

Presentation

  • Nausea, vomiting

  • Fever

  • Acute dehydration

  • Tachycardia

  • Hypotension/shock, often refractory to fluids and/or vasopressors

  • Hyponatremia

  • Hypokalemia

  • Hypoglycemia

Pathophysiology

Corticotrophin-releasing hormone (CRH) is released from the hypothalamus and stimulates the pituitary to release adrenocorticotropic hormone (ACTH). Adrenocorticotropic hormone then causes the adrenal glands to release cortisol. Cortisol provides negative feedback, inhibiting the release of CRH and ACTH. Adrenal insufficiency (AI) can be caused by destruction of the adrenal cortex, pituitary disease, or exogenous steroids. Primary AI is caused by destruction of the cortex, most commonly due to autoimmune reaction, hemorrhage, or infection. It is associated with both cortisol and mineralocorticoid deficiency. Secondary AI is caused by pituitary lesions; tertiary AI is caused by dysfunction of the hypothalamus. Both are associated only with cortisol deficiency. Suppression of adrenal function by exogenous glucocorticoids administration can also cause AI. Relative or functional AI is defined as a decreased level of glucocorticoids that may be adequate under normal situations but is insufficient under physiologic stress.

Differential Diagnosis

  • Septic shock

  • Acute abdomen

Immediate Management

  • Administer steroids (hydrocortisone 100 mg IV or dexamethasone 4 mg IV). Hydrocortisone is preferred in primary AI with hyperkalemia because of its mineralocorticoid activity, but dexamethasone may be used because it does not affect serum cortisol assays.

  • Restore intravascular volume with isotonic (normal saline or LR) fluids. Hypotonic saline may worsen hyponatremia.

  • Correct hypoglycemia with a dextrose infusion (25 g dextrose in 50 mL of water).

  • Support blood pressure with vasopressors. (Consider a norepinephrine infusion, but hypotension in AI may be resistant to catecholamines. Vasopressin infusion is an alternative.)

Diagnostic Studies

  • Plasma electrolytes and glucose

  • Baseline cortisol, renin, and ACTH levels. (If possible, draw labs before steroid administration but do not delay therapy for blood draws.)

  • Consider an ACTH stimulation test.

Subsequent Management

  • Evaluate the patient for the precipitating cause of AI.

  • Stress dose steroids can be tapered to maintenance doses over the course of several days depending on the course of the underlying illness.

  • Although the initial doses of steroids have sufficient mineralocorticoid activity, mineralocorticoid replacement may be eventually required in patients with primary adrenal insufficiency in order to prevent sodium loss and associated volume depletion and hyperkalemia.

  • Consider consulting an endocrinologist.

Risk Factors

  • Known chronic adrenal insufficiency

  • Corticosteroid use (more than prednisone 20 mg/day or equivalent) for >4 weeks within the preceding year

  • Abrupt discontinuation of exogenous corticosteroids.

  • Severe sepsis

Prevention

A careful history and physical examination may elicit steroid use or signs of chronic AI. Patients at risk should receive perioperative stress dose steroids. For major surgical stress, administer hydrocortisone 100 mg before induction of anesthesia followed by 50 mg every 8 hours for 24 hours and then taper over several days to baseline dose.

Special Considerations

  • Patients with septic shock may develop relative adrenal insufficiency without a previous history of steroid use or other risk factors. Adrenal insufficiency should be suspected in patients with hypotension that is unresponsive to vasopressor or fluid therapy. Although the data are conflicting, low-dose steroids (200–300 mg/day hydrocortisone) appear to reduce the time to reversal of septic shock but have no clear benefit on overall mortality.

Further Reading

Batzofin BM, Sprung CL, Weiss YG. The use of steroids in the treatment of severe sepsis and septic shock. Best Pract. Res. Clin. Endocrinol. Metab. 2011; 25(5):735–743.Find this resource:

Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014; 383(9935): 2152–2167.Find this resource:

Alkalosis

Definition

Blood pH >7.45 (normal 7.36–7.45) caused by either hypocarbia, metabolic effects (i.e., increased plasma HCO3), or both.

Presentation

  • Mild alkalosis is often asymptomatic.

  • Laboratory results on arterial or venous blood gas analysis

  • Respiratory alkalosis symptoms include paresthesias, carpopedal spasm, and lightheadedness.

  • Metabolic alkalosis symptoms are usually related to the underlying etiology (e.g., hypovolemia) and/or the associated electrolyte abnormalities (e.g., hypokalemia).

Pathophysiology

Alkalosis is caused by loss of acid from the extracellular space (e.g., hypochloremia), excessive HCO3 loads (e.g., administration of sodium bicarbonate to treat lactic acidosis) or hyperventilation that acutely reduces PaCO2. Compensation may be prevented by inability to excrete the excess HCO3 in urine due to intravascular volume depletion (caused by hypovolemia or factors such as heart failure or cirrhosis), renal insufficiency, chloride depletion, or hypokalemia.

Differential Diagnosis

  • Laboratory error

Immediate Management

  • Establish IV access.

  • Mild cases of alkalosis do not necessarily need urgent treatment.

  • If the patient is mechanically ventilated, adjust minute ventilation to increase PaCO2 while ensuring adequate oxygenation (10 mm Hg increase in PaCO2 produces approximately 0.08 decrease in pH).

  • Correct the effective volume deficit for true volume deficit, replete with isotonic or hypertonic saline.

  • In patients who are edematous (e.g., cirrhosis, heart failure), alkalosis may be caused by diuretic induced hypokalemia. If this is suspected, administer potassium chloride.

  • Administer potassium chloride for patients with potassium and chloride depletion.

Diagnostic Studies

  • Basic metabolic panel

  • Arterial blood gas analysis

  • Urinary chloride

Subsequent Management

  • Diagnose and treat the underlying cause.

  • Potassium sparing diuretics (e.g., spironolactone 25–200 mg/day) may be helpful in patients with metabolic alkalosis and edematous states that require further diuresis.

  • Acetazolamide is a carbonic anhydrase inhibitor and can increase urinary bicarbonate excretion; the effect may take several hours.

  • Renal replacement therapy may infrequently be indicated in patients with kidney failure and severe metabolic alkalosis.

  • Patients with severe metabolic alkalosis (pH >7.55) who cannot be dialyzed may rarely be treated with hydrochloric acid infusion (1 liter of 0.1 N solution of HCL over 12–24 hours).

Risk Factors

  • Second most common acid-base disorder in hospitalized adults

  • Loop diuretic administration

  • Severe hypoproteinemia

  • Hypocarbia

  • Volume contraction

  • Hypochloremia

    • Vomiting

    • Proximal enteric fistula

  • Iatrogenic causes

    • Hyperventilation

    • Administration of weak ions (acetate, citrate). This occurs most commonly in patients who receive total parenteral nutrition.

Prevention

Avoid inadvertent hyperventilation in mechanically ventilated patients. Monitor acid-base status in patients who are receiving diuretics.

Special Considerations

  • Regardless of the specific etiology, alkalosis generally responds to either PaCO2 regulation or chloride administration.

Further Reading

Khanna A, Kurtzman NA. Metabolic alkalosis. J Nephrol. 2006; 19(Suppl 9): S86–S96.Find this resource:

Laski ME, Sabatini S. Metabolic alkalosis, bedside and bench. Semin Nephrol. 2006; 26(6): 404–421.Find this resource:

Neligan PJ, Deutschman CS. Perioperative acid-base balance. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1557–1572.Find this resource:

Anaphylaxis

Definition

An acute, severe allergic or hypersensitivity reaction that is caused by release of inflammatory mediators and cytokines from mast cells and basophils.

Presentation

  • Respiratory compromise (dyspnea, bronchospasm, hypoxemia)

  • Hypotension

  • Tachycardia

  • Urticaria

  • Angioedema

  • Gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain)

Pathophysiology

Massive release of leukotrienes, histamine, and prostaglandins in response to release of IgE from mast cells triggered by an allergen such as food, medication, or insect bite. Anaphylaxis can be associated with potentially life-threatening vasodilation, myocardial suppression, bronchoconstriction, and tissue edema.

Differential Diagnosis

  • Shock (e.g., sepsis, hypovolemia, cardiogenic shock)

  • Nonimmunologic drug reaction

    • Red man syndrome caused by rapid administration of vancomycin

    • Morphine-induced histamine release

  • Drug overdose

  • Malignant hyperthermia

  • Acute asthma exacerbation

  • Nonallergic angioedema

  • Acute generalized urticaria

Immediate Management

  • Evaluate the patient’s airway and consider endotracheal intubation

  • Administer supplemental O2 as needed to treat hypoxia

  • Establish large-bore IV access

  • Treat bronchospasm (inhaled albuterol 4–8 metered doses)

  • Anaphylaxis without pulmonary/cardiovascular compromise

    • Adminster hydrocortisone 100 mg IV

    • Administer diphenhydramine 50 mg IV (H1 antagonist). Note: This will not relieve airway obstruction, hypotension, or shock.

  • Anaphylaxis with cardiovascular compromise

    • Preceding interventions plus

      • Consider intubation and mechanical ventilation

      • Arterial blood gas to evaluate acid-base status, hypoxia, hypoventilation

      • Administer isotonic crystalloid or colloid solutions to replace intravascular volume

      • Epinephrine—Titrate to symptom severity and clinical response. No absolute contraindications to its use in anaphylaxis.

      • Epinephrine 0.15–0.3 mg IM (auto-injector)

      • Epinephrine 1 mg IV bolus for cardiac arrest

      • Epinephrine infusion (start at 2–10 mcg/min, titrate to effect)

  • For anaphylaxis resistant to epinephrine, use

    • Norepinephrine infusion (initial dose 0.05–0.1 mcg/kg/min)

    • Glucagon for patients on beta-blockers (initial dose 1–5 mg over 5 minutes followed by infusion 5–15 mcg/min)

    • Vasopressin (0.04 U/min)

  • Search for and discontinue the triggering agent. Perform a careful evaluation of all agents administered immediately prior to the anaphylactic event, including antibiotics, latex, and neuromuscular blocking agents.

  • Inform the surgical team and consider terminating the procedure if possible.

Diagnostic Studies

  • Predominantly a clinical diagnosis.

  • Histamine levels peak almost immediately after the reaction and if measured should be drawn within an hour of the reaction.

  • A tryptase level can be drawn 15 minutes to 3 hours after the onset of symptoms. Note: A normal level does not exclude an allergic reaction.

Subsequent Management

  • Document the event and the trigger to avoid future exposure.

  • If the trigger is unknown, consider further evaluation by an allergy specialist for skin testing and/or measurement of specific IgE.

Risk Factors

  • Prior history of allergic reactions

  • Allergic rhinitis

  • Asthma

Prevention

  • Review carefully each patient’s record for known allergies and previous reactions.

  • Limit availability and exposure to latex products.

Special Considerations

  • Although anaphylaxis may occur at any time during the operation, most reactions occur around the time of induction.

  • Neuromuscular agents are the most common trigger in the perioperative period followed by latex and antibiotics. Local anesthetics have been implicated in anaphylactic reactions, but local anesthetic toxicity should be ruled out first. Any agent or medication may cause anaphylaxis.

Further Reading

Mertes PM, et al. Perioperative anaphylaxis. Med Clin North Am. 2010; 94(4): 761–789.Find this resource:

Nel L, Eren E. Peri-operative anaphylaxis Br J Clin Pharmacol. 2011; 71(5): 647–658.Find this resource:

Diabetes Insipidus

Definition

Disorder of water metabolism leading to polyuria (>3 L/day in adults) due to either deficient secretion of antidiuretic hormone (ADH) (central diabetes insipidus [DI]) or renal resistance to ADH (nephrogenic DI).

Presentation

  • Polyuria (>200 mL/h)

  • Nocturia

  • Polydipsia

  • Hypernatremia

  • Low urine osmolality (<150 mOsm/kg)

  • Hypovolemia

  • Hypotension

Pathophysiology

Antidiuretic hormone, also known as vasopressin, increases water absorption in the kidney collecting ducts, concentrating urine and decreasing its volume. A precursor of ADH is synthesized in the hypothalamus. Antidiuretic hormone is stored and released from the posterior pituitary in response to reduced plasma volume. Central or neurogenic DI results from lack of ADH secondary to injury to the posterior pituitary gland, pituitary stalk, or the anterior hypothalamus. Most common causes include pituitary surgery, traumatic brain injury, intracranial hypertension, brain death, tumors, and infections. Nephrogenic DI in adults is typically associated with chronic lithium use or hypercalcemia.

Differential Diagnosis

  • Psychogenic polydipsia

  • Osmotic (including hyperglycemia) diuresis

  • Diuretic use

  • Fluid overload

  • Fluid mobilization

Immediate Management

  • Establish adequate IV access

  • Correct the free water deficit [deficit (L) = weight (kg) × 0.6 × (Na–140)/Na].

  • Control polyuria with vasopressin or desmopressin acetate (DDAVP). DDAVP can be given intranasally 10–20 mcg and repeated every 30–60 minutes until urine output is <100 mL/hour. If intranasal route is not feasible, administer DDAVP 2 mcg IV over 2 minutes every 12 hours.

Diagnostic Studies

  • Plasma sodium

  • Plasma osmolality

  • Urine osmolality

  • Urine specific gravity

Subsequent Management

  • Continue replacing free water deficit either with enteral water or dextrose 5% in water as guided by laboratory studies.

  • Replace urine losses hourly.

  • Monitor electrolytes and glucose every 4 to 6 hours.

  • Redose DDAVP when urine output increases to above 200 mL/hour.

  • If patient condition permits, allow unrestricted access to free water.

Risk Factors

  • Traumatic brain injury

  • Pituitary surgery

  • Chronic lithium use

  • Brain death

Prevention

Monitor urine output in patients at risk for developing diabetes insipidus.

Special Considerations

  • Nephrogenic DI is less commonly seen in acute settings. It is treated with low sodium and low protein diet, thiazide diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit prostaglandin synthesis.

  • Patients with free access to water may be able to drink sufficient amounts to compensate for urinary loss.

Further Reading

Devin JK. Hypopituitarism and central diabetes insipidus: perioperative diagnosis and management. Neurosurg Clin North Am. 2012; 23(4): 679–689.Find this resource:

Diabetic Ketoacidosis and Hyperosmolar Hyperglycemia

Definition

Diabetic ketoacidosis (DKA) is characterized by hyperglycemia, anion gap metabolic acidosis, ketosis, and severe volume deficit. Serum glucose is typically >500 mg/dL. In hyperosmolar hyperglycemia (HHS) there is no (or very little) ketoacidosis, elevation of serum osmolality, and serum glucose is frequently >1000 mg/dL. These are two of the most serious acute complications of diabetes.

Presentation

  • DKA usually evolves rapidly over a 24-hour period. Hyperosmolar hyperglycemia typically has a slower onset that may take several days.

  • Polyuria

  • Polydipsia

  • Weight loss

  • Neurologic symptoms (lethargy, obtundation, coma)

  • Hyperventilation (DKA)

  • Abdominal pain (DKA)

  • Hyperglycemia

  • Acidosis (DKA)

Pathophysiology

Diabetic ketoacidosis and hyperosmolar hyperglycemia are caused by either a relative or absolute lack of insulin in combination with a precipitating factor (most commonly an infection). Fluid, electrolyte, and acid-base balance are all affected. Hyperglycemia causes osmotic diuresis with subsequent fluid and electrolyte deficits. In DKA, unopposed glucagon leads to increased lipolysis and the formation of ketones. Severe acidosis increases the required minute ventilation for pH buffering.

Differential Diagnosis

  • Lactic acidosis

  • Renal failure

  • Alcoholic ketoacidosis

  • Fasting ketoacidosis

  • Sepsis

  • Aspirin overdose

  • Other conditions that can cause metabolic acidosis

Immediate Management

  • Assess airway, breathing, circulation, and mental status.

  • Establish IV access.

  • Assess fluid status.

    • Hypotensive patients should be given isotonic fluids (0.9% NaCl) as quickly as possible to restore volume and blood pressure.

    • Normotensive patients with mild volume deficits can be given fluids at 2–3 times the maintenance rate (250–500 mL/h). Use 0.9% saline in patients with low serum sodium and 0.45% saline for high or normal serum sodium.

    • Check electrolytes hourly.

  • Assess acid-base status

    • If pH is <7.0, consider bicarbonate (100 mmol in 400 mL H2O with 20 mEq KCl over 2 hours) especially in patients with decreased cardiac contractility and vasodilation.

  • Insulin deficiency

    • Start continuous regular insulin infusion (suggested initial dose 0.1 U/kg bolus followed by a 0.1 U/kg/h infusion).

    • Double the dose if serum glucose does not fall 50–70 mg/dL in the first hour.

  • Assess electrolytes

    • Replete serum potassium to 3.3 mEq/L

Diagnostic Studies

  • Electrolytes and glucose

  • Plasma osmolality

  • Urine and serum ketones

  • Arterial blood gas

  • Complete blood count

  • Additional workup directed to possible inciting etiologies

Subsequent Management

  • Add 5% dextrose to the intravenous fluids when serum glucose reaches 200 mg/dL.

  • Decrease the insulin infusion and begin transition to subcutaneous insulin sliding scale once glucose is <200 mg/dL.

  • Postpone elective surgery and if feasible delay urgent surgery while the patient is resuscitated and electrolytes, pH, and perfusion normalize.

  • Identify and treat the inciting cause.

Risk Factors

  • Diabetes mellitus

  • Discontinuation of insulin in a diabetic patient

  • Acute illness or emergency surgery in a diabetic patient

Prevention

Early detection and treatment of hyperglycemia and diabetes mellitus.

Special Considerations

  • Treatment of acidosis in DKA with bicarbonate remains controversial.

  • Avoid subcutaneous insulin administration in DKA and HHS due to variable absorption.

  • Hyperglycemia and dehydration may induce hypernatremia that is often artifactual and not clinically significant.

  • K+ and Mg2+ are cotransported with glucose and should be simultaneously repleted to prevent life-threatening dysrhythmias.

Further Reading

Gouveia CF, Chowdhury TA. Managing hyperglycaemic emergencies: an illustrative case and review of recent British guidelines. Clin Med. 2013; 13(2): 160–162.Find this resource:

Russo N. Perioperative glycemic control. Anesthesiol Clin. 2012; 30(3): 445–466.Find this resource:

Sebranek JJ, Lugli AK, Coursin DB. Glycaemic control in the perioperative period. Br J Anaesth. 2013; 111(Suppl 1): 18–34.Find this resource:

Hypercalcemia

Definition

Calcium (Ca2+) level >10.5 mg/dL (normal, 8.5–10.5 mg/dL)

Presentation

  • Incidental laboratory finding

  • Mental status changes

  • Hyperreflexia

  • Hypertension

  • Bradycardia

  • Cardiac arrest

  • Nausea/vomiting

  • Polyuria

  • Renal calculi

  • Oliguric renal failure

Pathophysiology

The most common causes of hypercalcemia are metastatic disease, paraneoplastic syndrome, secondary hyperparathyroidism, lithium or thiazide toxicity, and immobility.

Differential Diagnosis

  • Laboratory error

Immediate Management

  • Evaluate airway, breathing, and circulation.

  • Administer 0.9% normal saline solution.

  • Administer furosemide 40 mg IV in patients with normal renal function in order to increase urinary calcium excretion.

  • Begin hemodialysis in patients with renal failure.

  • Discontinue pharmacologic agents associated with hypercalcemia (e.g., thiazides, calcium carbonate, lithium, theophylline).

Diagnostic Studies

  • Basic metabolic panel including Ca2+, Mg2+, and phosphorus levels

  • Liver function tests

  • Parathyroid hormone (PTH) level

  • Amylase level

  • 12-Lead electrocardiogram

Subsequent Management

  • Bisphosphonate therapy

  • Calcimimetic agents (e.g., cinacalcet)

  • Calcitonin therapy

  • Investigate underlying cause if unknown.

  • Workup for malignancy

  • Follow amylase levels until Ca2+ returns to normal.

Risk Factors

  • Malignancy (especially breast, lung, kidney, multiple myeloma, lymphoma)

  • Hyperparathyroidism

  • Kidney failure

  • Granulomatous diseases: tuberculosis, sarcoidosis

Prevention

Maintain adequate hydration and urine output with sodium-containing fluids in patients at risk for hypercalcemia. Avoid prolonged bed rest in patients.

Special Considerations

  • Avoid salt restriction and thiazide diuretics in patients at risk for hypercalcemia.

  • Consider using reduced doses of neuromuscular blocking agents in patients with muscle weakness.

  • Hypercalcemia can cause pancreatitis.

Further Reading

Chang WT, Radin B, McCurdy MT. Calcium, magnesium, and phosphate abnormalities in the emergency department. Emerg Med Clin North Am. 2014; 32(2): 349–366.Find this resource:

Kaye AD, Riopelle JM. Intravascular fluid and electrolyte physiology. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1711–1712.Find this resource:

Hypocalcemia

Definition

  • Calcium (Ca2+) level <85 mg/dL (normal, 8.5–10.5 mg/dL)

  • Ionized calcium level <2.0 meq/L (normal, 2.0–2.5 meq/L)

Presentation

  • Incidental laboratory finding

  • Mental status changes

  • Tetany

  • Chvostek sign (momentary contraction of the facial muscles in response to tapping the facial nerve)

  • Trousseau sign (flexion of the wrist and metacarpophalangeal joints, extension of the DIP and PIP joints, and finger adduction in response to an inflated blood pressure cuff)

  • Perioral numbness or tingling

  • Laryngospasm

  • Hypotension

  • Prolongation of Q–T interval or heart block

  • Seizures

Pathophysiology

The most common cause of low total serum calcium is hypoalbuminemia secondary to cirrhosis, nephrosis, malnutrition, burns, chronic illness, or sepsis. This may not accurately represent the physiologically important ionized calcium concentration. Other causes include hypoparathyroidism, pseudohypoparathyroidism, hypomagnesemia, vitamin D deficiency, and chronic kidney disease.

Differential Diagnosis

  • Laboratory error

Immediate Management

  • Administer CaCl2 1 g IV over 5 minutes

  • Repeat as needed to return ionized Ca2+ levels to normal or until symptom resolution.

Diagnostic Studies

  • Basic metabolic panel including Ca2+, Mg2+, phosphorus levels

  • Ionized calcium

  • If ionized calcium level is not available, calculate the corrected total calcium:

Corrected Ca2+ = (measured total Ca2+) + 0.8 * (4.1 – patient’s albumin)

  • Liver function tests, including albumin

  • Parathyroid hormone level

  • 12-Lead ECG

Subsequent Management

  • Investigate the cause of hypocalcemia if unknown.

  • Maintain normocalcemia with calcium gluconate via IV bolus or continuous infusion (less irritating to veins).

Risk Factors

  • Low albumin level

  • Acute renal failure or chronic kidney disease

  • Rapid transfusion of citrated blood products (1.5 mL/kg/min)

  • Acute hyperventilation

  • Hyperparathyroidism

  • Sepsis

  • Thyroidectomy or parathyroidectomy

  • Acute panhypopituitarism

  • Hypomagnesemia

Prevention

  • Consider administration of 500 mg CaCl2 for every 8–10 units of packed red blood cells (PRBC) during rapid transfusion.

  • Alternatively, measure ionized Ca2+ every 5 units and treat as necessary.

Special Considerations

  • CaCl2 provides immediately available calcium. Calcium gluconate requires degluconation by the liver before the calcium is biologically available. Hepatic dysfunction may limit the timely availability of calcium gluconate.

  • Hypocalcemia may be accompanied by hypomagnesemia in the setting of large-volume resuscitation with isotonic saline.

Further Reading

Chang WT, Radin B, McCurdy MT. Calcium, magnesium, and phosphate abnormalities in the emergency department. Emerg Med Clin North Am. 2014; 32(2): 349–366.Find this resource:

Kaye AD, Riopelle JM. Intravascular fluid and electrolyte physiology. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1711–1712.Find this resource:

Hyperkalemia

Definition

Elevated serum potassium (normal typically 3.5–5.0 mEq/L).

Presentation

  • Incidental laboratory finding

  • Nausea, vomiting

  • Muscle weakness, paresthesias, paralysis

  • Cardiac conduction abnormalities and cardiac arrhythmias. Peaked T waves with shortened QT interval are typically the first findings. In more severe cases, there is progressive PR interval and QRS prolongation leading to a sine wave pattern on ECG and cardiac arrest. Electrocardiogram changes do not always correlate with the serum potassium concentration and also depend on the acuteness of the potassium elevation.

Pathophysiology

High plasma concentration of potassium impairs myocardial conduction and may potentially result in cardiac arrest.

Differential Diagnosis

  • Laboratory error

  • Improper sample handling or mechanical trauma during venipuncture (cell lysis)

  • Severe leukocytosis or thrombocytosis can cause artificial potassium elevation

Immediate Management

  • Establish IV access.

  • Obtain a 12-lead ECG and establish continuous ECG monitoring.

  • If ECG changes are significant, administer 500–1000 mg calcium chloride to stabilize cardiac membranes. Can be repeated after 5 minutes if ECG changes persist.

  • Administer 10 units of regular insulin IV along with 50 mL of D50W IV to temporarily shift potassium into cells.

Diagnostic Studies

  • Plasma electrolytes, blood urea nitrogen (BUN), creatinine

  • Electrocardiogram

Subsequent Management

  • Treat the underlying cause(s).

  • Reduce excess potassium from the body.

    • Loop and thiazide diuretics combined with normal saline hydration increase potassium loss in urine.

    • Administration of a cation exchange resin (e.g., sodium polystyrene sulfonate without sorbitol [15–30 g orally every 4–6 hours]) can lower serum potassium but is not effective in the acute phase and should be used with extreme caution, especially in patients with suspected ileus or bowel obstruction.

    • Hemodialysis, especially in patients with severe hyperkalemia, renal failure, or severe tissue breakdown (e.g., crush injury)

Risk Factors

  • Acute and chronic renal failure

  • Metabolic acidosis

  • Insulin deficiency (diabetic ketoacidosis, hyperosmolality)

  • Increased tissue catabolism

  • Tissue or cell destruction: tissue necrosis, hemolysis, skeletal muscle crush injury

  • Strenuous exercise

  • Use of depolarizing neuromuscular blockers in patients with severe burn injury or upper motor neuron disorders (e.g., cerebral pathology, spinal cord injury)

  • Iatrogenic (massive transfusion, inadvertent overdose)

Prevention

Avoid iatrogenic causes. Monitor potassium levels closely in patients with risk factors.

Special Considerations

  • Therapy for hyperkalemia addresses three major aims: (1) supporting myocardial polarization and depolarization; (2) relocating potassium from the plasma space to the intracellular space; and (3) reducing the total body potassium load.

Further Reading

Kaye AD, Riopelle JM. Intravascular fluid and electrolyte physiology. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1710.Find this resource:

Hypokalemia

Definition

Low serum potassium (normal 3.5–5.0 mEq/L, mild 3.0–3.5 mEq/L, moderate 2.5–3.0 mEq/L, and severe <2.5 mEq/L).

Presentation

  • Incidental laboratory finding

  • Severe muscle weakness. Typically begins in lower extremities and progresses to trunk and the upper extremities.

  • Respiratory failure due to respiratory muscle weakness

  • Rhabdomyolisis

  • Cardiac arrhythmias—premature atrial and ventricular beats, bradycardia, paroxysmal atrial or junction tachycardias, atrioventricular block, ventricular tachycardia, or fibrillation.

  • Electrocardiogram abnormalities—ST segment depression, inverted T waves and U waves.

Pathophysiology

Most cases of hypokalemia results from loss of potassium from gastrointestinal or urinary tracks that are not appropriately repleted. The severity of symptoms is dependent on the degree and duration of the hypokalemia.

Differential Diagnosis

  • Laboratory error

  • Hypomagnesemia

  • Hypocalcemia

  • Cushing syndrome

Immediate Management

  • Establish IV access.

  • Initiate ECG monitoring.

  • Slowly administer potassium chloride 20 mEq IV for life-threatening hypokalemia.

  • Limit infusion to 20 mEq/hour except in the setting of life-threatening dysrhythmias with careful ECG monitoring.

Diagnostic Studies

  • Plasma electrolytes, including magnesium, BUN, creatinine

  • 12-Lead ECG

Subsequent Management

  • Consider administration through a central venous catheter because potassium chloride infusions are extremely irritating to peripheral veins.

  • Treat or reverse underlying etiology of potassium loss (e.g., hold potassium-wasting diuretics, gastrointestinal [GI] losses).

  • Correct coexisting hypomagnesemia.

  • If appropriate, additional oral potassium replacement can be administered.

  • Continue telemetry monitoring postoperatively.

Risk Factors

  • Diuretic administration

  • Large volume resuscitation

  • Alkalosis (including respiratory alkalosis due to hyperventilation)

  • Gastrointestinal losses (diarrhea, vomiting, ileal conduit)

  • Uncontrolled diabetes (DKA, HHS)

  • Salt-wasting nephropathies

  • Primary aldosteronism

  • Beta-agonist use

Prevention

Monitor plasma electrolytes in patients at risk for hypokalemia.

Special Considerations

  • Mild or moderate hypokalemia rarely requires emergency treatment.

  • Potassium is principally an intracellular cation. Low plasma levels imply that the intracellular stores are depleted. Severe hypokalemia may require as much as 200–300 mEq of potassium to restore normal plasma and intracellular levels and may require several days of intravenous therapy to correct.

  • In DKA and HHS, the insulin deficiency favors movement of potassium out of cells. The patient may therefore have a total body potassium deficit despite a normal or slightly low serum potassium level. Insulin therapy to treat the hyperglycemia may worsen hypokalemia.

Further Reading

Kaye AD, Riopelle JM. Intravascular fluid and electrolyte physiology. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1710.Find this resource:

Hypermagnesemia

Definition

Magnesium (Mg2+) level >2.5 mEq/L (normal 1.5–2.0 mEq/L).

Presentation

  • Incidental laboratory finding

  • Neuromuscular effects (in order of increasing Mg levels)

    • Diminished deep tendon reflexes (first sign)

    • Headache, lethargy, drowsiness

    • Muscle weakness

    • Somnolence, loss of deep tendon reflexes, muscle paralysis

    • Flaccid quadriplegia

    • Fixed and dilated pupils mimicking brain stem herniation

  • Cardiovascular (in order of increasing Mg levels)

    • Bradycardia, hypotension

    • PR, QRS prolongation

    • Increase in Q-T interval

    • Complete heart block

    • Cardiac arrest

  • Hypocalcemia

Pathophysiology

Most commonly caused by excessive intake of Mg2+ (especially laxatives) or in patients with renal impairment. High magnesium levels decrease impulse transmission across the neuromuscular junction.

Differential Diagnosis

  • Laboratory error

Immediate Management

  • Assess airway, ventilation, and mental status. Intubate the trachea and initiate mechanical ventilation as necessary.

  • Control the underlying cause (e.g., stop the infusion).

  • Administer calcium chloride 1 g IV over 5 minutes in severe hypermagnesemia.

  • Intravenous isotonic fluid therapy (normal saline or lactated Ringer’s) plus loop diuretics can increase renal excretion of magnesium.

Diagnostic Studies

  • Electrolytes including magnesium, calcium, and phosphate

  • BUN, creatinine

  • 12-Lead ECG

Subsequent Management

  • Cessation of magnesium therapy should be enough to reduce the magnesium level in patients with normal renal function.

  • Hemodialysis may be necessary in patients with severe symptoms and acute or chronic renal failure.

Risk Factors

  • Aggressive treatment of pre-eclampsia

  • Use of Mg2+ containing antacids or laxatives

  • Renal failure

Prevention

Monitor Mg levels when using it therapeutically especially in patients with renal insufficiency.

Special Considerations

  • Magnesium and calcium antagonize each other’s effects.

  • Mg2+ will produce profound muscle weakness in patients with myasthenia gravis or Lambert-Eaton syndrome.

  • Mg2+ prolongs the action of neuromuscular blocking agents.

Further Reading

Herroeder S, Schonherr M et al. Magnesium—essentials for anesthesiologists. Anesthesiology. 2011; 114(4): 971–993.Find this resource:

Kaye AD, Riopelle JM. Intravascular fluid and electrolyte physiology. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1713–1714.Find this resource:

Hypomagnesemia

Definition

Magnesium (Mg2+) level <1.5 mEq/L (normal 1.5–2.0 mEq/L).

Presentation

  • Incidental laboratory finding

  • Neuromuscular: tremor, involuntary movements, tetany, weakness, altered mental status, seizures, delirium, coma

  • Cardiovascular: QRS widening, peak T waves with moderate hypomagnesemia. More severe deficits can lead to widening of PR interval, decreased T waves, and atrial and ventricular arrhythmias including torsades des pointes.

  • Hypocalcemia, hypoparathyroidism, PTH resistance

  • Hypokalemia

Pathophysiology

Most commonly occurs due to gastrointestinal (diarrhea) or renal losses. It is also associated with hypokalemia and hypocalcemia.

Differential Diagnosis

  • Laboratory error

Immediate Management

  • Establish IV access and ECG monitoring.

  • In hemodynamically unstable patients, given 1–2 g of magnesium sulfate over 2–15 minutes.

  • In hemodynamically stable patients, the amount of replacement can be estimated from the plasma level:

Mg level

Replacement dose (IV)

2.0–2.25

2.0 g

1.75–1.9

4.0 g

1.5–1.74

6.0 g

1.25–1.49

8.0 g

1.0–1.24

10.0 g

Diagnostic Studies

  • Electrolytes including magnesium, calcium, and phosphate

  • Blood urea nitrogen, creatinine

  • 12-Lead ECG

Subsequent Management

  • Serial serum Mg levels

  • Patients with minimal or no symptoms can receive oral replacement. This may cause diarrhea and other GI symptoms.

Risk Factors

  • Chronic diarrhea

  • Proton pump inhibitor therapy

  • Alcohol abuse

  • Diuretic use

  • Large volume fluid resuscitation

  • Very common in critically ill patients

Prevention

Careful monitoring of magnesium levels in high-risk patients.

Special Considerations

  • Hypomagnesemia is associated with an increased risk of perioperative arrhythmias and bronchospasm.

  • Serum Mg level should be monitored during administration in patients with acute or chronic renal insufficiency.

Further Reading

Herroeder S, Schonherr M, et al. Magnesium—essentials for anesthesiologists. Anesthesiology. 2011; 114(4): 971–993.Find this resource:

Kaye AD, Riopelle JM. Intravascular fluid and electrolyte physiology. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1713–1714.Find this resource:

Hypernatremia

Definition

Sodium level >145 mEq/L (normal sodium, 135–145 mEq/L).

Presentation

  • Incidental laboratory finding

  • Severe dehydration (hypotension, oliguria, decreased skin turgor)

  • Mental status changes

  • Seizures

Pathophysiology

Excessive free water loss is the most common cause. Excessive sodium administration may also result in hypernatremia.

Differential Diagnosis

  • Laboratory error

Immediate Management

  • Hypovolemic hypernatremia:

    • Administer fluids to correct hypovolemia

    • Hypotonic fluid: 0.45% saline or D5W (free water) to correct Na+

  • Normovolemic hypernatremia:

    • Hypotonic fluid: 0.45% saline or D5W to correct Na+

    • Correct underlying cause (e.g., administer DDAVP for diabetes insipidus)

  • Hypervolemic hypernatremia:

    • Discontinue Na+ containing solutions

    • Consider furosemide (20 mg IV as a starting dose) if appropriate for the patient’s renal function

Diagnostic Studies

  • Basic metabolic panel, including Ca2+, Mg2+, and phosphorus

  • Serum osmolality

  • Urine electrolytes and creatinine

  • Urine osmolality

  • 24-Hour urine volume

Subsequent Management

  • Monitor fluid and electrolyte intake carefully.

  • Monitor urine output carefully.

  • Follow serial sodium trends in order to control the rate of sodium correction.

  • Determine the cause of hypernatremia and treat appropriately.

Risk Factors

  • Advanced age

  • Hospitalization: tube feeding, mechanical ventilation, hypertonic infusions

  • Hypovolemic patients: open wounds, GI losses, insufficient ACTH, mannitol or lactulose administration, loop diuretic use in conjunction with a salt-restricted diet

  • Euvolemic patients: diabetes insipidus (nephrogenic or central), lithium toxicity

  • Hypervolemic patients: iatrogenic (NaHCO3 or hypertonic saline administration)

Prevention

Follow plasma electrolyte levels closely in patients receiving large quantities of sodium-containing fluids, as well as those with large-volume losses from diuretics, lactulose, or other sources.

Special Considerations

  • Acute onset is <24 hours; chronic onset is >24 hours.

  • In acute hypernatremia, correct the serum sodium at a rate of 2–3 mEq/L/h (maximum 12 mEq/L/day).

  • For chronic hypernatremia, correct the serum sodium at a rate not exceeding 0.5 mEq/L/h.

  • Free water deficit may be calculated using the following equation:

    Free H2o deficit=Body water (L/kg) × weight (kg)                                 ×((serum Na+/140) 1)

  • Estimate body water as 0.6 L/kg in males and 0.5 L/kg in females.

Further Reading

Bagshaw SM, Townsend DR, McDermid RC. Disorders of sodium and water balance in hospitalized patients. Can J Anaesth. 2009; 56(2): 151–167.Find this resource:

Kaye AD, Riopelle JM. Intravascular fluid and electrolyte physiology. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1706–1709.Find this resource:

Lindner G, Funk GC. Hypernatremia in critically ill patients. J Crit Care. 2013; 28(2): 216, e11–e20.Find this resource:

Hyponatremia

Definition

Sodium level <135 mEq/L (normal sodium is 135–145 mEq/L).

Presentation

  • Incidental laboratory finding

  • Nausea

  • Mental status changes

  • Seizures

  • Cerebral edema leading to tentorial herniation and death

Pathophysiology

Many patients have dilutional hyponatremia and not a true total body Na+ deficiency. Dilutional hyponatremia is characterized by low Na+ but nearly normal Cl. accompanied by dilute urine and a normal to high urine Na+.

Hypovolemic hyponatremia occurs with a decrease in total body water and a greater decrease in total body sodium.

Differential Diagnosis

  • Laboratory error

  • Sample dilution (drawing from the same arm as an IV running hyponatremic fluid)

  • Hyperglycemia

Immediate Management

  • Establish IV access.

  • Monitor ECG or hemodynamics as indicated.

  • In patients with dilutional hyponatremia:

    • Restrict tree water intake

    • Administer furosemide 20–40 mg IV if patient is hypervolemic and renal function is appropriate.

  • In hypovolemic patients: Administer 0.9% saline.

  • In severe (Na+ < 125 mEq/L) or symptomatic hyponatremia, consider intravenous 3% hypertonic saline

  • Calculate sodium deficit using the formula:

    Sodium deficit (mEq)=0.6×body weight (kg)                                          ×(pts Na+desired Na+)

Diagnostic Studies

  • Basic metabolic panel

  • Serum osmolality

  • Urine osmolality

  • Urine sodium

Subsequent Management

  • Acute hyponatremia is <48 hours; chronic hyponatremia is >48 hours.

  • For acute hyponatremia, correction of serum sodium should occur at a rate of 1–2 mEq/L/h until serum sodium is 125 mEq/L and symptoms subside.

  • In chronic hyponatremia, the rate of serum sodium correction should not exceed 0.5 – 1 mEq/L/h or 12 mEq/L/day.

Caution: Rapid correction may lead to central pontine myelinolysis, an irreversible demyelinating disorder that causes permanent neurologic injury.

Risk Factors

  • Excess free water or hypotonic fluid administration.

  • Comorbidities including congestive heart failure, liver cirrhosis, and renal failure.

  • Absorption of irrigation fluid containing large amounts of free water (during transurethral prostate resection or endoscopic genitourinary or gynecological procedures)

  • Thiazide diuretic administration

  • Adrenocortical insufficiency

  • Hypothyroidism

  • Syndrome of inappropriate antidiuretic hormone (SIADH)

  • Alcoholism

Prevention

Measure serum electrolyte levels in patients with risk factors.

Special Considerations

  • Estimate body water as 0.6 L/kg in males and 0.5 L/kg in females.

  • Although ADH antagonist therapy (i.e., aquaretics) is not yet readily available in the United States, these agents will likely replace furosemide, because ADH antagonists induce free water loss with minimal changes in solute excretion.

Further Reading

Bagshaw SM, Townsend DR, McDermid RC. Disorders of sodium and water balance in hospitalized patients. Can J Anaesth. 2009; 56(2): 151–167.Find this resource:

Kaye AD, Riopelle JM. Intravascular fluid and electrolyte physiology. In: Miller RD, ed. Miller’s anesthesia. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010:1706–1709.Find this resource:

Hypothermia

Definition

  • Body temperature <35° C (normal body temperature is 36.5–37.5° C)

  • Mild hypothermia: 32–35° C

  • Moderate hypothermia: 28–32° C

  • Severe hypothermia: <28° C

Presentation

  • Mild hypothermia:

    • Shivering

    • Lethargy and confusion

    • Weakness

  • Moderate hypothermia:

    • Shivering ceases

    • Myocardial depression

    • Dysrhythmias

    • Metabolic acidosis

    • Hyperkalemia

    • Coagulopathy

  • Severe hypothermia:

    • Unconsciousness

    • Electrically silent EEG (if <18° C)

    • Ventricular fibrillation or cardiac arrest

Pathophysiology

Hypothermia may be due to increased heat loss from environmental exposure or decreased heat production from thermal dysregulation. During surgery, heat is transferred from the core to the periphery due to anesthesia-induced vasodilation. Heat is also lost during surgery through radiation, evaporation, and convection. Cold-induced diuresis may lead to profound intravascular volume depletion. Impaired thermal regulation (e.g., after injury or drug overdose) results from failure of the hypothalamus to regulate core body temperature. Patients may also present after prolonged exposure to extreme cold (e.g., after a traumatic injury in the winter or after immersion in cold water).

Differential Diagnosis

  • Myxedematous coma (hypothyroidism)

Immediate Management

  • Assessment of airway, breathing, circulation.

  • Establish an airway and ventilate with 100% O2.

  • If necessary, begin resuscitation according to ACLS guidelines. (Note: A normal cardiac rhythm may not reappear until the patient’s core temperature reaches 30° C.)

  • Consider administration of Mg2+ (2 g of magnesium sulfate IV) for dysrhythmias.

  • Rewarm the patient:

  • Mild to moderate hypothermia:

    • Warm IV fluids

    • Warming blankets

    • Forced-air warmers

  • Severe hypothermia:

    • In addition to the preceding:

    • Gastrointestinal lavage via nasogastric tube

    • During surgery, consider body cavity lavage (in particular bladder, and on occasion abdomen or chest) with warm fluid

    • Consider cardiopulmonary bypass support and rewarming (best option) in patients with life-threatening hypothermia.

Diagnostic Studies

  • Monitor core temperature.

  • Thyroid function tests if hypothyroidism is suspected.

Subsequent Management

  • Caution: Warming-induced peripheral vasodilation in the setting of hypovolemia may lead to significant hypotension requiring hemodynamic support and fluid resuscitation.

  • It may be necessary to buffer “washout acidosis” with sodium bicarbonate during rewarming.

  • Consider limiting intraoperative time to <2 hours in patients who arrive with or develop hypothermia.

Risk Factors

  • Prolonged exposure to cold ambient environment.

  • Immersion in cold water.

  • Impaired level of consciousness.

  • Failure to actively warm the patient during surgery (especially trauma, craniofacial procedures, extensive body cavity surgery)

  • Acute alcohol intoxication

  • Tranquilizer use (many classes suppress shivering)

Prevention

  • Use active warming devices in the operating room (OR) and preoperative holding area.

  • Warm the OR.

  • Cover the patient to the extent possible.

  • Place warming pads on the OR bed.

  • Use a forced air warming device during the surgical procedure.

  • Use active warming devices for fluids.

Special Considerations

  • Patients who are hypothermic on arrival in the OR may be suffering from sepsis, environmental exposure, or injury with acute hemorrhage. Take precautions to prevent further heat loss.

  • Shivering, a common sign of core hypothermia is not typically seen in the OR because anesthetics and neuromuscular blocking agents blunt the response to hypothermia.

  • Temperature monitoring is recommended as part of the ASA Guidelines on Intraoperative Monitoring.

Further Reading

Horosz B, Malec-Milewska M. Inadvertent intraoperative hypothermia. Anaesthesiol Intensive Ther. 2013; 45(1): 38–43.Find this resource:

Insler SR, Sessler DI. Perioperative thermoregulation and temperature monitoring. Anesthesiol Clin. 2006; 24(4): 823–837.Find this resource:

Malignant Hyperthermia

Definition

Malignant hyperthermia (MH) is a relatively rare inherited disorder of skeletal muscle that causes a hypermetabolic response to a triggering anesthetic agent. Characterized by hyperthermia, body rigidity, and increased CO2 production, it may be accompanied by cardiovascular collapse or hypertension.

Presentation

  • May occur in the operating room or in the early postoperative period

  • Increased end-tidal CO2 production is the first sign

  • Tachycardia

  • Hypertension

  • Muscular rigidity (especially masseter muscle spasm)

  • Hyperthermia is a late sign.

  • Rhabdomyolysis

Pathophysiology

Malignant hyperthermia is the result of an inborn error of calcium metabolism in skeletal muscle. It is inherited as an autosomal dominant trait.

Differential Diagnosis

  • Light anesthesia (hypertension and tachycardia without CO2 production)

  • Thyrotoxicosis

  • Equipment malfunction, increased carbon dioxide, rebreathing, soda lime exhaustion

  • Neuroleptic malignant syndrome

Immediate Management

  • Call for help and notify the surgeon!

  • Immediately discontinue triggering anesthetic agent(s): succinylcholine and potent volatile anesthetics. Propofol, narcotics, and N2O are safe.

  • Increase FiO2 to 100%.

  • Hyperventilate the patient with a new anesthesia circuit to treat hypercarbia and respiratory acidosis.

  • Establish large-bore IV access.

  • Insert an intra-arterial catheter (blood pressure monitoring and frequent blood gas measurements for acid-base status).

  • Administer sodium dantrolene (2.5 mg/kg IV until signs and symptoms are controlled or to a maximum of 10 mg/kg). Note: Dantrolene is difficult and may require several minutes to reconstitute. If possible, one member of the team should be assigned to this task.

  • Expand plasma volume with 15 cc/kg bolus × 3 using cool fluids.

  • Treat hyperkalemia early.

  • Cool the patient aggressively with cold IV solutions. Ask the surgeon to lavage any open body cavity/wound surface with cold irrigating solution. Insert a nasogastric tube and irrigate with ice-cold solution.

  • Terminate the surgical procedure as quickly as possible using total intravenous anesthesia.

Diagnostic Studies

  • Frequent arterial blood gas and serum electrolyte measurements

  • Muscle biopsy for caffeine halothane contracture testing (CHCT) or genetic testing at a separate setting to confirm diagnosis.

Subsequent Management

  • Admit patient to the intensive care unit.

  • Contact the MHAUS Consultant Hotline (800-644-9737) as soon as possible.

  • Maintain urine output at least 2 mL/kg to minimize risk of renal tubular injury from rhabdomyolysis.

  • Severe metabolic acidosis may require management with sodium bicarbonate.

  • Continue to monitor and correct hyperkalemia.

  • Continue dantrolene 1 mg/kg every 4–6 hours for 36 hours after the episode, because the recurrence rate is 25%.

  • Discuss the episode with the patient’s family and add the patient to the MH national database maintained by the Malignant Hyperthermia Association of the United States (www.mhaus.org).

Risk Factors

  • Use of triggering agents (succinylcholine, potent volatile anesthetics) in a patient with a known history of MH.

  • Family history, especially an unexplained death of a relative during an anesthetic.

  • Malignant hyperthermia may occur despite prior uneventful exposure to triggering agents.

Prevention

Avoid the use of triggering agents in patients with a known history of MH or a suggestive family history.

Special Considerations

  • Do not administer calcium channel blockers. In the presence of dantrolene, hyperkalemia and cardiac arrest may result.

  • If there is a question as to MH susceptibility, the patient should be managed as if he or she is known to have MH. Because MH is an inherited disorder, consider testing family members for susceptibility.

Further Reading

Benca J, Hogan K. Malignant hyperthermia, coexisting disorders, and enzymopathies: risks and management options. Anesth Analg. 2009; 109(4): 1049–1053.Find this resource:

Hopkins PM. Malignant hyperthermia: pharmacology of triggering. Br J Anaesth. 2011; 107(1): 48–56.Find this resource:

Myxedema Coma

Definition

An uncommon, life-threatening form of untreated, decompensated hypothyroidism that is precipitated by a secondary insult, such as infection, hypothermia, or medication.

Presentation

  • Lethargy, delirium, coma

  • Hypothermia

  • Bradycardia

  • Hypoventilation

  • Hyponatremia

  • History of generalized fatigue, cold intolerance, constipation, dry skin

Pathophysiology

Physiologic adaptations to long-standing, untreated hypothyroidism include reduced metabolic rate, decreased oxygen consumption, peripheral vasoconstriction, and decreased number of beta-adrenergic receptors. Myxedema coma occurs when these adaptations are not sufficient to compensate for an extreme physiologic stress.

Differential Diagnosis

  • Hypothermia

  • Hypoventilation syndrome

  • Septic shock

Immediate Management

  • Assess airway, breathing, and circulation.

  • Intubate the trachea and initiate mechanical ventilation if needed.

  • Immediately administer of levothyroxine 500 mcg IV while awaiting results of thyroid function studies, even if diagnosis is only suspected.

  • Passively rewarm the patients with blankets and a warm room (rapid warming is contraindicated).

  • Pan-culture the patient and start empiric broad spectrum antibiotics.

  • Send a cortisol level and then start stress dose steroids while awaiting results.

Diagnostic Studies

  • Thyroid function tests including T3, T4, and TSH levels

  • Basic metabolic panel

  • Complete blood count with differential

  • Arterial blood gas

  • Pan-culture

  • 12-Lead ECG

  • Chest X-ray

Subsequent Management

  • Admit to the intensive care unit.

  • Administer levothyroxine 50–100 mcg IV daily.

  • Administer gentle volume resuscitation for management of hypotension.

  • Follow up all labs and cultures. Discontinue steroids if no adrenal insufficiency. Narrow antibiotic coverage as appropriate as culture data becomes available.

  • Serial serum electrolytes with corrections as indicated.

Risk Factor

  • Hypothyroidism

Prevention

Evaluate and treat hypothyroidism when it becomes symptomatic.

Special Considerations

  • Controversy exists regarding the added benefit of administering T3 in addition to levothyroxine.

  • Most cases of myxedema coma occur during the winter in women >60 years old.

Further Reading

Wartofsky L. Myxedema coma. Endocrinol Metab Clin North Am. 2006; 35(4): 687–698.Find this resource:

Pheochromocytoma

Definition

A catecholamine-secreting chromaffin cell tumor usually found in the adrenal medulla.

Presentation

  • Sustained or paroxysmal hypertension, tachycardia, and tachydysrhythmias that worsen and become more frequent with time

  • History of headaches, chest pain, palpitations, and diaphoresis

  • Myocardial ischemia

  • Acute crisis may occur during induction of anesthesia or surgical manipulation of the tumor.

Pathophysiology

Excessive catecholamines secreted by a chromaffin cell tumor cause tachycardia and vasoconstriction. Cardiac manifestations may be caused by increased myocardial oxygen demand or catecholamine-induced myocarditis.

Differential Diagnosis

  • Light anesthesia

  • Malignant hyperthermia (fever, mixed respiratory and metabolic acidosis)

  • Malignant hypertension

  • Alcohol withdrawal

  • Illegal drug use: cocaine, amphetamines, PCP, LSD

  • Pharmacologic agents: Monoamine oxidase inhibitors, decongestants, sympathomimetics

  • Thyrotoxicosis (fever, acidosis, tachycardia)

Immediate Management

  • If the patient is anesthetized, administer additional opioids or potent volatile anesthetics to decrease the blood pressure via vasodilation and myocardial depression.

  • Return the blood pressure to a safe level:

    • Insert an intra-arterial catheter to monitor blood pressure.

    • Infuse sodium nitroprusside (starting dose is 1 mcg/kg/min), fenoldopam infusion (0.2–0.8 mg/kg/min), or nicardipine infusion (start at 5 mg/h).

    • Administer labetalol (20–40 mg IV every 10 minutes), or esmolol (500 mcg/kg IV, then 50 mcg/kg/min titrated to heart rate). Use beta-blocking agents to control heart rate only after blood pressure is adequately controlled. Betablockade combined with unopposed alpha-adrenergic activity may lead to severe hypertension and vasoconstriction.

    • Titrate medications to return the blood pressure to the patient’s baseline.

  • Administer intravenous fluids as necessary.

  • Discontinue surgery as soon as practical.

  • If myocardial ischemia refractory to beta-blockade is suspected, nitroglycerine should be used with caution.

Diagnostic Studies

  • Plasma-free metanephrine and urinary fractionated metanephrine (highest sensitivity)

  • Urinary vanillylmandelic acid (highest specificity)

  • Computed tomography scan or MRI to evaluate to visualize adrenal mass

  • Toxicology screening to rule out cocaine or other compounds

Subsequent Management

  • Careful postoperative blood pressure monitoring (consider transfer to the intensive care unit)

  • Consider Mg2+ (40–60 mg/kg bolus), then infusion 2 g/h. (Magnesium inhibits catecholamine release and has antiarrhythmic and vasodilator effects.)

  • Consult endocrinology to confirm the diagnosis.

  • Obtain a 24-hour urine collection to measure free catecholamines.

Risk Factors

  • Associated with multiple endocrine neoplasia (MEN) type 2 (pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism), von Hippel-Lindau syndrome, or neurofibromatosis type 1.

Prevention

  • Careful preoperative workup in patients with unexplained symptoms that are suggestive of pheochromocytoma.

  • Careful manipulation of the adrenal glands in patients who have a known pheochromocytoma.

Special Considerations

  • Hydralazine causes reflex tachycardia and should not be used as a sole antihypertensive.

  • Labetalol is a vasodilator in addition to its cardiac effects and is preferred over metoprolol or other cardio-specific beta-blockers.

  • Reducing preload with venodilation or attempted diuresis may be ineffective in pheochromocytoma patients. These patients generally have reduced intravascular volume due to renal excretion of both salt and water.

Further Reading

Connery LE, Coursin DB. Assessment and therapy of selected endocrine disorders. Anesthesiol Clin North Am. 2004; 22(1): 93–123.Find this resource:

Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007; 92(11): 4069–4079.Find this resource:

Porphyria

Definition

A family of related enzyme disorders of heme pathway intermediates that cause pathologic accumulation of porphyrins or porphyrin precursors. The disorders are classified as erythropoietic (bone marrow) or hepatic (liver) depending on where the accumulation occurs. The three most common types are porphyria cutanea tarda, erythropoietic porphyria, and acute intermittent porphyria (AIP). Acute intermittent porphyria is most likely to cause complications in the perioperative period.

Presentation

  • Porphyria cutanea tarda: skin blistering related to sun exposure.

  • Erythropoietic porphyria: skin lesions, occasional hemolysis, and rarely liver failure.

  • Acute intermittent porphyria:

    • Abdominal pain (possibly related to autonomic neuropathy)

    • Sympathetic hyperactivity with hypertension and tachycardia

    • Central nervous system (CNS) symptoms, including confusion, hallucinations, seizures, and autonomic neuropathy

    • Progressive motor neuropathy that may lead to acute postoperative respiratory failure and reintubation. A patient who has received neuromuscular blocking drugs may fail to regain motor function after a long procedure.

    • Reddish-colored urine that darkens after exposure to light occurs during an acute attack.

Pathophysiology

The heme precursors are believed to be neurotoxic; delta- aminolevulinic acid and porphobilinogen are two characteristic intermediates in the heme biosynthetic pathway that are increased during acute attacks of porphyria.

Differential Diagnosis

  • Acute abdomen

  • Guillain-Barré syndrome

Immediate Management

  • Withdraw any triggering agents, including barbiturates and ketamine.

  • Begin aggressive hydration with dextrose-containing fluids.

    • Administer a bolus of D50W. Begin D10W at 1 mL/kg/h to deliver at least 3 L per day.

  • Anticipate cardiovascular instability.

    • Consider beta-blockade (treats hypertension and tachycardia and may decrease ALA synthetase activity).

  • Control pain with opiates.

  • Treat nausea/emesis with phenothiazines.

Diagnostic Studies

  • Urine porphobilinogen (diagnostic of an acute attack).

  • Follow serum Na+, K+, and Mg2+ levels during acute attack.

  • Measure porphyrin precursors and porphyrins in red blood cells, plasma, and/or urine will help to make the diagnosis in the OR or in the postanesthesia care unit.

Subsequent Management

  • Admit patients with acute porphyria.

  • Administer hemin (Panhemin, Lundbeck, Inc., Deerfield, IL) 3–4 mg/kg delivered as a single daily dose. Large-bore peripheral or central IV administration is preferred.

  • Genetic testing is helpful for diagnosis confirmation and family analysis, but is not useful in the acute setting.

  • A hematology consultation is strongly recommended for acute diagnosis and management.

Risk Factors

  • Potential triggers (not a complete list): Alcohol, angiotensin converting enzyme inhibitors, anticonvulsants except gabapentin, barbiturates, calcium channel blockers (especially nifedipine), ergots, etomidate, progesterone, sulfonamide antibiotics

  • Reduced caloric intake (especially carbohydrates)

  • Dehydration

Prevention

  • Avoid use of known triggering agents. A porphyria drug database is available at http://www.porphyriafoundation.com/drug-database.

  • Patients with a family history of porphyria should undergo plasma volume expansion prior to elective procedures.

  • Consider regional anesthesia if feasible and after evaluating the patient’s neurological status. There is no evidence to suggest that local anesthetics can trigger an acute attack.

Special Considerations

  • Propofol and benzodiazepines are probably safe.

  • Inhaled anesthetics, including N2O, are considered safe.

  • Neuromuscular blocking agents (including succinylcholine) are widely considered to be safe but should be used with caution.

  • Morphine, fentanyl, and sufentanil are safe.

  • In general, a single exposure to even potent inducers may be tolerated, but repeat exposure or use during an acute attack is considered to be unsafe.

  • Acute blood loss does not seem to provoke a porphyric attack.

  • An attack may last for days, but is generally followed by complete recovery.

  • A missed diagnosis of porphyria may lead to a nontherapeutic laparoscopy or laparotomy, although frank peritonitis is quite rare.

  • Anhematin restores normal hepatic heme levels and suppresses aminolevulinic acid (ALA) synthetase activity.

Further Reading

James MF, Hift RJ. Porphyrias. Br J Anaesth. 2000; 85(1): 143–153.Find this resource:

Thyroid Storm

Definition

An acute, life-threatening, hypermetabolic state characterized by high levels of circulating catecholamines that is driven by excessive release of thyroid hormones.

Presentation

  • Hyperthermia

  • Tachycardia

  • Hypertension

  • Tremors

  • Anxiety

  • Delirium

  • High fever (as high as 40–41° C)

  • Diaphoresis

Pathophysiology

Thyroid storm is a state of severe sympathetic overactivity in the setting of clinical hyperthyroidism, generally precipitated by physiologic stress such as surgery or infection.

Differential Diagnosis

  • Malignant hyperthermia (mixed metabolic and respiratory acidosis, creatine kinase is elevated in MH)

  • Pheochromocytoma (no fever)

Immediate Management

  • Establish large-bore peripheral or central venous access.

  • Begin fluid resuscitation.

  • Administer beta-blockers: labetalol 20–40 mg IV every 10 minutes, metoprolol 5 mg IV every 10 minutes, or esmolol 80 mg over 5 minutes, then 150 mcg/kg/min infusion.

  • Administer glucocorticoids (possibility of adrenal insufficiency; glucocorticoids block conversion of T3 to T4): dexamethasone 4 mg IV every 6 hours or hydrocortisone 100 mg IV every 6 hours.

  • Supplement Mg2+ as needed.

  • Administer acetaminophen or NSAIDs to decrease fever.

Diagnostic Studies

  • Thyroid function studies including T3, free T4, TSH

  • Serum electrolytes

  • Electrocardiogram

Subsequent Management

  • If the patient is already intubated, consider continuing mechanical ventilation into the postoperative period.

  • Administer a loading dose of antithyroid medication: propylthiouracil (PTU) [200 mg every 4 hours] or methimazole [20 mg every 6 hours]. (Both are oral preparations.)

  • Begin administration of elemental iodine after starting the antithyroid medication.

  • Consult the endocrinology service to guide subsequent management.

Risk Factors

  • Recent iodine therapy (radioiodine or iodine-containing contrast agents)

  • Cessation of antithyroid medications

  • Infection or serious illness (e.g., myocardial infarction) in a patient with pre-existing hyperthyroidism

  • Trauma

  • Pre-eclampsia

  • Excessive thyroid hormone replacement

  • Excessive manipulation of a hypertrophic thyroid gland during surgery

Prevention

Establish an adequate depth of anesthesia in a patient with hyperthyroidism who is undergoing surgery in order to avoid an excessive sympathetic response.

Special Considerations

  • Emergency therapy consists of circulatory support and blockade of the end-organ effects of the excess thyroid hormone.

  • Intraoperative hypotension should be treated with a direct-acting vasoconstrictor (e.g., phenylephrine).

Further Reading

Connery LE, Coursin DB. Assessment and therapy of selected endocrine disorders. Anesthesiol Clin North Am. 2004; 22(1): 93–123.Find this resource:

Transurethral Resection of the Prostate Syndrome

Definition

Systemic absorption of fluids used for bladder distention during a transurethral resection of a prostate mass (TURP). Occurs in approximately 2% of patients undergoing this procedure.

Presentation

  • Hyponatremia

  • Central nervous system manifestations:

    • Mental status changes

    • Diplopia

    • Nausea and vomiting

  • Cardiovascular symptoms:

    • Hypertension

    • Bradycardia

    • Myocardial ischemia and dysrhythmia

Pathophysiology

Nonionic irrigating solution (mannitol, glycine, or sorbitol) enters the circulation through open venous sinuses. Excessive absorption of irrigating solution leads to hyponatremia, circulatory overload, or neurotoxicity (if glycine-containing solution is used).

Differential Diagnosis

  • Congestive heart failure

  • Hyponatremia

Immediate Management

  • Discontinue administration of irrigation fluid.

  • Send blood for serum electrolyte levels (Na+).

  • Administer furosemide (20 mg IV); adjust dose for preoperative creatinine.

  • The TURP syndrome is usually time-limited (generally resolves within 6 hours after surgery).

  • Terminate the procedure as soon as practical.

Diagnostic Studies

  • Complete blood count

  • Basic metabolic panel

Subsequent Management

  • Continue monitoring into the postoperative period until symptoms abate. The patient may be monitored in the postanesthesia care unit or the intensive care unit.

  • Consider administration of hypertonic (3%) saline in patients with severe hyponatremia (<120 mEq/L, or those with neurologic symptoms).

Risk Factors

  • Prolonged operative time (approximately 1 liter of fluid is absorbed per 40 minutes operating time)

  • High irrigating pressure (determined by the height of the bag above the patient)

  • Large prostate, extensive resection

  • Glycine-containing solution (may cause transient blindness)

Prevention

  • Consider use of regional anesthesia (permits early detection of CNS changes).

  • The patient should be kept horizontal, because using the Trendelenburg position reduces the intravesical pressure required to initiate absorption, thus increasing the risk of irrigation fluid absorption.

  • Avoid glycine-containing solutions if able.

  • The height of the irrigating fluid bag should be approximately 60 cm above the patient.

Special Considerations

  • There are no definite criteria to diagnose TURP syndrome. The clinician must have a high index of suspicion.

  • Use of glycine-containing solution may cause transient blindness.

Further Reading

Malhotra V. Transurethral resection of the prostate. Anesthesiol Clin North Am. 2000; 18(4): 883–897.Find this resource: