The key to increasing or decreasing urine clearance of drugs is to alter the pH of the urine. Attempts to increase urine volume beyond 100-150 mL per hour, increase the risk of complications from fluid overload but increase clearance only minimally.
Alkalinisation of the urine increases urinary excretion of weak acids (e.g. salicylates, phenobarbitone). This occurs because the two different forms of the acid have different lipid solubility and therefore are reabsorbed by the renal tubules to a greater or lesser extent. As an acid loses a hydrogen ion it becomes ionised and less lipid soluble (HA equilibrates with H+ and A -). Alkalinisation of the urine, by reducing the concentration of free hydrogen ions, causes more of the acid to dissociate to the ionised form to maintain an equilibrium. As the ionised form has low lipid and high water solubility it remains 'trapped' in the renal tubules and is excreted in the urine.
For mild toxicity add 1-2 mEq of sodium bicarbonate per kg body weight to the first litre of dextrose/saline. If alkalinisation is not achieved within several hours the dose may be repeated.
Moderate to severe intoxications may require additional boluses of 50-100 mEq of sodium bicarbonate over 1-2 hours with close monitoring of blood pH. If the urine pH does not rise to above 7.5 (paradoxical aciduria) in spite of correction of systemic acidosis and the production of a systemic alkalosis this usually indicates the patient is potassium depleted.
Alkaline diuresis should not be attempted in patients who have evidence of pulmonary oedema or those with renal failure.
Hypokalaemic patients are unable to produce an alkaline urine and potassium must be corrected concurrently.
Drugs must have the following characteristics for this process to effectively increase total clearance and be worthwhile:
In practice this means only salicylates, chlorpropamide, phenobarbitone and possibly the chlorphenoxy herbicides. However, supportive treatment only is generally preferred for phenobarbitone as the shorter half life achieved with alkalinisation increases the risk of withdrawal symptoms.
Barbiturate withdrawal is treated with loading with phenobarbitone and acidification of the urine (with oral vitamin C) to decrease clearance and prolong the half life. This uses the same principle but acidification decreases ion trapping.