Management of Life-Threatening

Electrolyte and Metabolic Disturbances

Introduction

Common in critically ill & injured patientsAlter physiologic function & contribute to

morbidity & mortalityThe most common electrolyte disturban-

ce 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- & hyperkalemiaSodium : hypo- & hypernatremiaOthers: 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 Renal Losses Extrarenal Losses

Decreased Intake

Alkalosis

Hyperventilation

Insulin

β-adrenergic agonists

Hypomagnesemia

Vomiting

Diuresis

Metabolic alkalos

Renal tub defects

Diabetic ketoacid

Drugs (diuretics, aminoglycosides, amphotericin B)

Diarrhea

Profuse sweating

Malnutrition

Alcoholism

Anorexia nervosa

Clinical manifestation:

Cardiac system: arrhythmias (ventricular, & supraventricular,

conduction delay, sinus bradycardia) ECG abnormalities (U waves, QT prolo- ngation, flat or inverted T waves) Neuromuscular system: muscle weakness

or paralysis, paresthesia, ileus, abdominal cramps, nausea, and vomiting

Effect of hypokalemiaCardiovaskular ECG changes/dysrhythmias Myocardial dysfunctionNeuromuscular Skeletal muscle weakness Tetany Rhabdomyolisis IleusRenal Polyuria (nephrogenic DI) Increased ammonia production Increased bicarbonate reabsorptionHormonal Decreased insulin secretion Decreased aldosteron secretionMetabolic Negative nitrogen balance Encephalopaty in patients with liver disease

Adapted from Schrier RE,ed: Renal and Electrolyte Disorders, 3 rd ed. Little, Brown and Company, 1986.

Treatment (1)

Stop offending drugs (if possible)Correct hypomagnesemia & other

electrolyte disturbancesCorrect alkalosis

Treatment is aimed:Correcting the underlying causeAdministering potassium

Treatment (2)

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

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

Treatment (3)

Acedemia 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 dysfunctionPseudohyperkalemia may result from a

white blood cell count >100,000/mm3 or platelet count >600,000/mm3.

Causes of hyperkalemia

Renal dysfunction

Acidemia

HypoaldosteronismDrugs (potassium-sparing diuretics, ACE inhibitors, etc.)

Excessive intake

Cell death Rhabdomyolisis Tumor lysis Burns Hemolysis

Clinical manifestation

Heart: arrhythmias (heart block, bradycardia, dimi- nished conduction and contraction) ECG abnormalities (diffuse peaked T waves, PR prolongation, QRS widening, diminished P waves, sine waves) Muscle: muscle weakness, paralysis, pares-

thesias, and hypoactive reflexes

Treatment (1)

Recognition & treatment of underlying diseases Removal of offending drugs Limitation of potassium intake Correction of acidemia or eletrolyte abnorma-

lities 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 β2-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 volumeAbnormalities 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 Hypovolemia Hypervolemia

SIADH

Psychogenic polydipsia

Hypothyroidism

Inappropriate water admi- nistration to infanst/chil- dren

Diuretic use

Aldosterone deficiency

Renal tubular dysfunction

Vomiting

Diarrhea

Third-space fluid losses

CHF

Cirrhosis

Nephrosis

Clinical manifestation

CNS: disorientation, decreased mentation, irritability, seizures, lethargy, coma, nausea and vomiting

Muscle: weakness & CNS-driven respiratory arrest

Algorithm for treatment of hypernatremia

hypernatremia

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 diseaseRemoving offending drugsImproving 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 increasedrestricting free-water intakeincreasing free-water clearence with loop

diureticsreplacing 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

The amount of NaCl necessary to raise plasma [Na+] to the desired value, the Na+ deficit, can be estimated by the following formula:

Na+ deficit=TBW x (desired [Na+]-present [Na+] )

Example:

An 80-kg woman is lethargic and found to have a plasma [Na+] of 118 mEq/L. How much NaCl must be given to raise her plasma [Na+] to 130 mEq/L?

[Na+] deficit = TBW x (130-118)

TBW is approximately 50% of body weight in females:

[Na+] deficit=80x0.5x(130-118)

=480 mEq

Normal (isotonic) saline contains 154 mEq/L, the patient should receive 480 mEq : 154 mEq/L = 3.12 L of normal saline.

For correction rate of 0.5 mEq/L/hour, this amount of saline should be given over 24 hours (130 mL/hour)

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

Excessive Sodium Intake

Diarrhea

Vomiting

Excessive sweating

Diuresis

Diabetes insipidus

Altered thirst

Impaired access

Salt tablets

Hypertonic saline

Sodium bicarbonate

Clinical manifestation

CNS: altered mentation, lethargy, seizures, coma

Muscle function: muscle weaknessPolyuria: 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 free-water 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

Example:

A 70-kg man is found to have a plasma [Na+] of 160 mEq/L. What is his water deficit?

If one assumes that the hypernatremia if from water loss only, then total body osmoles are unchanged. Thus, assuming he had a normal [Na+] 140 mEq/L and a TBW content that is 60% of body weight:

Normal TBW x 140 = present TBW x [Na+]plasma

(70 x 0.6) x 140 = present TBW x 160 present TBW = 36.7 ltr Water deficit = normal TBW – present TBW = (70 x 0.6)- 36.7 = 5.3 L

To replace this deficit over 48 hours, one would give 5% Dextrose in water intrave-nously, 5.300 mL over 48 hours, or 110 mL/hour

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, meningococ- cemia, 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, keto-acidosis, and osmotic diuresis-induced dehydration

Life-threatening hyperglycemic syndromes: diabetic ketoacidocis (DKA) and hyper-glycemic hyperosmolar nonketotic syndro-me (HHNK)

Clinical manifestations

Result from hyperglycemia & excess ketone productionHyperglycemia:

HyperosmolalityOsmotic diuresis-induced dehydrationFluid & electrolyte lossDehydrationVolume depletion

Ketone (DKA):AcidosisOsmotic diuresis

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 insulin are usually adequate

(1-2 U)

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