Urine Alkalinization

Passawat Na Nakorn, MD.

R3 Emergency Medicine

H+ secretion

HCO3- reabsorption

Mechanism • Alkalinization of the urine increases urinary excretion

of weak acids different forms of the acid have different lipid solubility

• Alkalinisation - reducing the concentration of free

H+, more the ionised form to maintain an equilibrium less lipid soluble

• Ionised form has low lipid and high water solubility 'trapped' in the renal tubules and is excreted in the urine

Ion Trapping

Applicable drugs

• Drugs must have the following characteristics for this

process to effectively increase total clearance 1. Weak acid (pKa 3.0 – 7.5)

2. Low protein binding & primarily extracellular fluid

3. Renal excretion is a substantial part of total excretion

4. Clinically significant toxicity

• salicylate, chlorpropamide, phenobarbital, fluoride

chlorphenoxy herbicides, diflunisal, methotrexate

Applicable drugs

• Dimercaprol therapy o Dimercaprol-metal complex dissociates faster in acidic urine

o The released metal can damage the kidney

• Rhabdomyolysis o Alkalinization of the urine has been postulated to minimize the breakdown

of myoglobin into its nephrotoxic metabolites & to reduce crystallization of

uric acid

o Some authorities believe that aggressive hydration sufficiently causes a

solute diuresis that alkalizes the urine

o Evidence for urine alkalinization mostly from animal studies and

retrospective adult studies

Forced Diuresis • Urine volumes of 200 – 300 mL/hour inhibited solute

tubular reabsorption o dilute urine prevented a favorable concentration gradient for passive

reabsorption in the distal tubule

• Increased urine volume through forced diuresis did not significantly enhance drug elimination when combined with urinary alkalinization

• Complication of force diuresis: volume overload, pulmonary edema, cerebral edema, electrolyte disorders

Method (Olson) • 50 – 100 mEq in 1 L of 5% dextrose in 0.25% NSS

or

• 100 – 150 mEq in 1 L of 5% dextrose at 2 – 3 mL/kg/h

(adults: 150 – 200 mL/h)

• Check urine pH and adjust flow rate hourly to

maintain urine pH level at 7 – 8.5 o Keep blood pH < 7.55 and prevent hypernatremia

• Add 20 – 40 mEq of K to each 1 L unless renal failure

Method (Brenner & Rectors)

• 50 mEq IV bolus of sodium bicarbonate

follow by

• 100 – 150 mEq in 1 L of 5% dextrose at 250 mL/h o Rate of infusion based on volume status

o Goal of urine output: 2 – 3 mL/kg/h

• Monitored electrolyte and urine pH q2-3h o Target urine pH: 7.5 – 8.5

• Carbonic anhydrase inhibitors not recommended o Systemic metabolic acidosis, hypokalemia

Contraindications

• Significant metabolic or respiratory alkalemia or

hypernatremia

• Severe pulmonary edema associated with volume

overload

• Intolerance to sodium load (renal failure, CHF)

Adverese effects • Excessive alkalemia

o Impaired O2 release from Hb

o Paradoxical intracellular acidosis

o Hypocalcemic tetany

o Hypokalemia

• Hypernatremia and hyperosmolality

• Aggravation of CHF and pulmonary edema

• Extravasation -> tissue inflammation & necrosis

Salicylates

• keeps salicylates away from brain tissue and in the

blood with enhancing urinary excretion

• Raising the urinary pH level from 6.1 to 8.1 results in a

more than 18-fold increase in renal clearance by

preventing non-ionic tubular back-diffusion o decreases the half-life of salicylates from 20-24 hours to less than 8 hours

• Severe cases not meeting criteria for hemodialysis

Phenobarbital

• supportive Rx only is preferred for phenobarbital o shorter half life achieved with alkalinization increases the risk of withdrawal

symptoms

• Multiple dose activated charcoal may be more

effective

Others

• Methotrexate o Consider hemoperfusion instead

• Chlorpropamide o Dextrose infusion alone usually adequate

• 2,4-Dichlorophenoxyacetic o Goal urine pH > 8

o Urine output > 600 mL/h