Management of Life-Threatening

Electrolyte and Metabolic Disturbances

Introduction
Common in critically ill & injured patients Alter physiologic function & contribute to morbidity & mortality The most common electrolyte disturbance in critically ill patients are: disturbance in K, Na, Ca, Mg, P levels Metabolic disturbance accompany many systemic disease processes or result of altered endocrine function

Electrolyte Disturbances
Potassium: hypo- & hyperkalemia Sodium : hypo- & hypernatremia Others:

Calcium : hypo- & hypercalcemia Phosphate : hypo- & hyperphosphatemia Magnesium : hypomagnesemia

Potassium

Essential for maintenance of the electrical membrane potential Alteration of K primarily effect the CV, neuromuscular, and GI systems.

Hypokalemia
Plasma [K+] <3.5mEq/L (<3.5mmol/L) Can occur as a result from:
1. increased K loss (renal or extrarenal losses) 2. intercompartmental shift / transcellular shift of K 3. inadequate or decreased K intake

Causes of hypokalemia
Transcellular Shifts Alkalosis Hyperventilation Insulin -adrenergic agonists Renal Losses Diuresis Metabolic alkalos Renal tub defects Diabetic ketoacid Drugs (diuretics,
aminoglycosides, amphotericin B)

Extrarenal Losses Diarrhea Profuse sweating

Decreased Intake Malnutrition Alcoholism Anorexia nervosa

Hypomagnesemia Vomiting

Clinical manifestation:
Cardiac system:

(ventricular, & supraventricular, conduction delay, sinus bradycardia) ECG abnormalities (U waves, QT prolongation, flat or inverted T waves) Neuromuscular system: muscle weakness or paralysis, paresthesia, ileus, abdominal cramps, nausea, and vomiting

arrhythmias

Effect of hypokalemia
Cardiovaskular ECG changes/dysrhythmias Myocardial dysfunction Neuromuscular Skeletal muscle weakness Tetany Rhabdomyolisis Ileus Renal Polyuria (nephrogenic DI) Increased ammonia production Increased bicarbonate reabsorption Hormonal Decreased insulin secretion Decreased aldosteron secretion Metabolic Negative nitrogen balance Encephalopaty in patients with liver disease
Adapted from Schrier RE,ed: Renal and Electrolyte Disorders, 3rd ed. Little, Brown and Company, 1986.

Treatment (1)
Treatment is aimed: Correcting the underlying cause Administering potassium Stop offending drugs (if possible) Correct hypomagnesemia & other electrolyte disturbances Correct alkalosis

Treatment (2)
K <3 mEq/L (<3 mmol/L) & asymptomatic: K enterally (orally or NGT) (KCl 20-40 mEq every 4-6 hrs) K <2-2.5 mEq/L (<3 mEq/L if on digoxin) or if symptoms are present: K intravenously

Arrhythmias or paralysis: KCl 20-30 mEq via central venous catheter (sequential infusion: 10 mEq in 100 mL fluid over 20 mins, infusion rate can be slowed after symptoms resolve) Absence of life-threatening manifestation: KCl 10 mEq/hr IV

Treatment (3)

Acidemia is present, correct the potassium level before correcting pH (K shift intracellularly as the pH increases)

Monitoring
Continuous ECG monitoring is necessary (during parenteral administration of high concentration of KCl) Serum K levels must be monitored at frequent interval during repletion (every 1-2 hrs during initial replacement)

Hyperkalemia
Potassium >5.5 mEq/L (>5.5 mmol/L) Most often results from renal dysfunction Pseudohyperkalemia may result from a white blood cell count >100,000/mm3 or platelet count >600,000/mm3.

Causes of hyperkalemia
Renal dysfunction Acidemia Hypoaldosteronism Drugs (potassium-sparing diuretics,
ACE inhibitors, etc.)

Cell death

Rhabdomyolisis Tumor lysis Burns Hemolysis

Excessive intake

Clinical manifestation
Heart: arrhythmias (heart block, bradycardia, diminished conduction and contraction) ECG abnormalities (diffuse peaked T waves, PR prolongation, QRS widening, diminished P waves, sine waves) Muscle: muscle weakness, paralysis, paresthesias, and hypoactive reflexes

Treatment (1)

Recognition & treatment of underlying diseases Removal of offending drugs Limitation of potassium intake Correction of acidemia or eletrolyte abnormalities Any serum potassium level >6 mEq/L should be addressed, but the urgency of treatment depends on clinical manifestation The presence of ECG changes mandates immediate therapy

Treatment (2)
ECG abnormalities present: CaCl 5-10 mL of a 10% solution IV over 5-10 mins (the effect lasts only 30-60 mins & should be followed by additional treatment) Redistribution of K: Na bicarbonate 1 mEq/kg (1 mmol/kg) IV over 5-10 mins (beware of potential Na overload with Na bicarbonate) 50 g of 50% dextrose over 5-10 mins with 10 U of regular insulin IV Inhaled 2-agonists in high dose (albuterol 10-20 mg) Removal of K from body: Increase urine output with a loop diuretic Increase GI K loss with Na polystyrene sulfonate 25-50 g in sarbitol, enterally or by enema Dialysis

Monitoring

Should be monitored during evaluation & treatment: Repeat serum K levels Continuous cardiac monitoring and serial ECG tracings

Sodium
Primary functions: determinant of osmolality in the body involved in the regulation of extracellular volume Abnormalities in circulating Na primarily effect neuronal & neuromuscular function.

Hyponatremia
Sodium <135 mEq/L (>135 mmol/L) Most common cause: associated with a low serum osmolality is excess secretion of ADH (euvolemic hyponatremia) or associated with hypovolemic and hypervolemic conditions The presence of a nonsodium solute: glucose and mannitol (characterized by an elevated serum osmolality Pseudohyponatremia: occurs in the presence of severe hyperlipidemia, hyperproteinemia, or hyperglycemia

Causes of hyponatremia
Euvolemia
SIADH Psychogenic polydipsia Hypothyroidism Inappropriate water administration to infanst/children

Hypovolemia
Diuretic use Aldosterone deficiency Renal tubular dysfunction Vomiting Diarrhea Third-space fluid losses

Hypervolemia
CHF Cirrhosis Nephrosis

Clinical manifestation
CNS: disorientation, decreased mentation,

irritability, seizures, nausea and vomiting Muscle: weakness respiratory arrest

lethargy,

coma,

&

CNS-driven

Algorithm for treatment of hyponatremia

hyponatremia

water & Na+ loss

water loss

increased Na+ content

replace isotonic loss

replace water deficit

loop diuretic

replace water deficit

replace any water deficit

Treatment (1)
Treating the underlying disease Removing offending drugs Improving the circulating Na level

Hypovolemic hyponatremia: usually responds to IV volume repletion (with normal saline). Volume is replaced, ADH is suppressed & free water is excreted by the kidneys. Hypervolemic hyponatremia: usually not severe & improves with successful treatment of the underlying condition

Treatment (2)

Hyponatremia is acute or symptomatic: serum Na level should be increased

restricting free-water intake increasing free-water clearence with loop diuretics replacing IV volume with normal saline (154 mEq/L) or hypertonic 3% saline (513 mEq/L)

The goal of therapy: to remove free water & not Na

Hypernatremia
Sodium <145 mEq/L (>145 mmol/L) Indicates intracellular volume depletion with a loss of free water, which exceeds Na loss

Causes of hypernatremia
Water Loss Reduced Water Intake
Altered thirst Impaired access

Excessive Sodium Intake

Salt tablets Hypertonic saline Sodium bicarbonate

Diarrhea Vomiting Excessive sweating Diuresis Diabetes insipidus

Clinical manifestation
CNS:

altered mentation, lethargy, seizures, coma Muscle function: muscle weakness Polyuria: the presence of diabetes insipidus or excess salt and water intake

Treatment (1)
Centers on correcting the underlying cause of hypernatremia The vast majority of patients require freewater repletion The water deficit can be calculated using equation: water deficit (L)=0.6 x wt (kg) [(Na2/Na1)-1] Na1 = the normal sodium level Na2 = the measured sodium level

METABOLIC DISTURBANCES
Acute Adrenal Insufficiency Hyperglycemic Syndromes

Acute Adrenal Insufficiency

Lack of specific signs & symptoms makes early recognition of acute renal insufficiency difficult May result from: Failure of the adrenal glands (autoimmune disease, granulomatous disease, HIV infection, adrenal hemorrhage, meningococcemia, ketoconazole) Failure of the hypothalamic/pituitary axis (withdrawal from glucocorticoid therapy)

Clinical manifestation

Weakness Nausea/vomiting Abdominal pain Orthostatic hypotension Hypotension refractory to volume or vasopressor agents Fever Suggestive laboratory findings: Hyponatremia Hyperkalemia Acidosis Hypoglycemia Prerenal azotemia

Emergent treatment

Indicated in critically ill patients, even if the diagnosis is not established High-risk patients include: AIDS, disseminated tuberculosis, sepsis, acute anticoagulation, post CABG patients, patients from whom glucocorticoid therapy was withdrawn within the past 12 months If dexamethasone is used for emergent steroid replacement, a short adrenocorticotropic hormone stimulation test can be performed for diagnosis after resuscitative therapy is instituted

Short ACTH Stimulating Test

Blood for serum cortisol is drawn at baseline Synthetic 1-24 ACTH (cortrosyn, cosyntropin), 250 ug, is administered intravenously A serum cortisol level is drawn 60 mins after cosyntropin administration A cortisol level >20 ug/dL (>552 nmol/L) at 60 mins indicates adequate adrenal function Failure to attain adequate cortisol levels indicates the need for further testing and expert consultation Since cortisol level may not be reported quickly, corticosteroid should be administered, pending results, if the clinical situation is suggestive of acute adrenal insufficiency

Treatment

Obtain baseline blood samples for cortisol, electrolyte, etc Infuse D5 normal saline to support blood pressure Administer dexamethasone 4 mg IV, then 4 mg IV every 6 hrs Perform short adrenocorticotropic hormone stimulation test if needed for diagnosis If the diagnosis of adrenal failure is confirmed, hydrocortisone 100 mg IV, then 100 mg every 8 hrs, can be administered. Some physicians prefer administration of hydrocortisone as a continuous infusion, 300 mg over 24 hrs Treat precipitating conditions

Hyperglycemic Syndromes
Results from a relative or absolute lack insulin Characterized by: hyperglycemia, ketoacidosis, and osmotic diuresis-induced dehydration Life-threatening hyperglycemic syndromes: diabetic ketoacidocis (DKA) and hyperglycemic hyperosmolar nonketotic syndrome (HHNK)

Clinical manifestations

Result from hyperglycemia & excess ketone production

Hyperglycemia: Hyperosmolality Osmotic diuresis-induced Fluid & electrolyte loss Dehydration Volume depletion
Ketone (DKA): Acidosis Osmotic diuresis

dehydration

Clinical features

Weakness Dehydration Polyuria Polydipsia Altered mental status Coma Tachycardia Arrhythmias Hypotension

Anorexia Nausea/vomiting Ileus Abdominal pain Hyperpnea Fruity odor to the breath (DKA)

Laboratory investigation

Hyperglycemia Hyperosmolality (more common in HHNK) Glukosuria Ketonemia/Ketonuria (DKA) Anion gap metabolic acidosis (DKA) Hypokalemia Hypophosphatemia Hypomagnesemia Leukocytosis Azotemia Elevated amylase Creatine phosphokinase

Treatment (1)

The goal: to restore the fluid & electrolyte balance, provide insulin, & identify precipitating factors (infection, stroke, MI, pancreatitis) Volume deficits correlate with the severity of hyperglycemia & are usually greater in HHNK Normal saline: replenish IV volume & restore hemodynamic stability (1 L in the first hour, 250-500 mL/hr as needed)

Treatment (2)
After 1-2 L of NS, fluids with less Cl (0.5 saline) should be used to avoid hyperchloremic metabolic acidosis Urine output should be maintained at 1-3 mL/kg/hr (ensure adequate tissue perfusion & clearance of glucose) Invasive hemodynamic monitoring (arterial catheter, PA catheter): required in patients with underlying CV disease

Treatment (3)

DKA:

Loading dose: 5-10 U regular human insulin IV route is the most reliable & easiest to titrate Continuous infusion is necessary with serial monitoring of the blood glucose & electrolyte concentration

HHNK:

Smaller doses of adequate (1-2 U)

insulin

are

usually

Monitor glucose levels

Frequently Glucose decreases to >250 mg/dL (<13.8 mmol/L), switch to glucose-containing fluids to avoid hypoglycemia 10% dextrose may be necessary to maintain glucose levels >150 mg/dL (>8.3 mmol/L) while continuing insulin infusion Subcutaneous insulin (BS is controlled, ketonemia has cleared, the patient is stable)

Insulin & correction of acidosis shift potassium intracellularly & may lead to precipitous drops in K levels K deficit range from 3-10 mEq/kg K should be added to fluid therapy as soon as serum K is recognized or thought to be normal or low and urine output is documented K levels should be monitored frequently until levels stabilize & acidosis is resolved (DKA)

Priorities in initial resuscitation of DKA

Institute crystalloid resuscitation, initially with NS Institute insulin infusion at 0.1 U/kg/hr Consider bicarbonate if pH<7.0 Look for precipitating of DKA (infection, MI, GI bleed) Add KCl to fluid resuscitation when serum K is known or expected to be low or normal, and urine output is documented Add glucose to crystalloid infusion when serum glucose is <250 mg/dL. Do not decrease insulin infusion rate unless symptomatic hypoglycemia or precipitous drops in serum glucose. Administer 10% dextrose if necessary to maintain serum glucose >150 mg/dL Continue insulin infusion until ketosis is cleared (negative serum ketones with correction of increased anion gap).

References:

Fundamental Critical Care Support, Course Text, 3rd edition, Society of Critical Care Medicine Lange Clinical Anesthesiology, 3rd edition, Lange Medical Books/McGraw-Hill Medical Publishing Division Physiologic and Pharmacologic Bases of Anesthesia, 2nd edition, Williams and Wilkins Textbook of Critical Care, 3rd edition, W.B. Saunders Company