Urine Alkalinizatin Passawat Na Nakrn, MD. R 3 Emergency Medicine
H + secretin
HCO 3 - reabsrptin
Mechanism Alkalinizatin f the urine increases urinary excretin f weak acids different frms f the acid have different lipid slubility Alkalinisatin - reducing the cncentratin f free H +, mre the inised frm t maintain an equilibrium less lipid sluble Inised frm has lw lipid and high water slubility 'trapped' in the renal tubules and is excreted in the urine
In Trapping
Applicable drugs Drugs must have the fllwing characteristics fr this prcess t effectively increase ttal clearance 1. Weak acid (pka 3.0 7.5) 2. Lw prtein binding & primarily extracellular fluid 3. Renal excretin is a substantial part f ttal excretin 4. Clinically significant txicity salicylate, chlrprpamide, phenbarbital, fluride chlrphenxy herbicides, diflunisal, methtrexate
Applicable drugs Dimercaprl therapy Dimercaprl-metal cmplex dissciates faster in acidic urine The released metal can damage the kidney Rhabdmylysis Alkalinizatin f the urine has been pstulated t minimize the breakdwn f myglbin int its nephrtxic metablites & t reduce crystallizatin f uric acid Sme authrities believe that aggressive hydratin sufficiently causes a slute diuresis that alkalizes the urine Evidence fr urine alkalinizatin mstly frm animal studies and retrspective adult studies
Frced Diuresis Urine vlumes f 200 300 ml/hur inhibited slute tubular reabsrptin dilute urine prevented a favrable cncentratin gradient fr passive reabsrptin in the distal tubule Increased urine vlume thrugh frced diuresis did nt significantly enhance drug eliminatin when cmbined with urinary alkalinizatin Cmplicatin f frce diuresis: vlume verlad, pulmnary edema, cerebral edema, electrlyte disrders
Methd (Olsn) 50 100 meq in 1 L f 5% dextrse in 0.25% NSS r 100 150 meq in 1 L f 5% dextrse at 2 3 ml/kg/h (adults: 150 200 ml/h) Check urine ph and adjust flw rate hurly t maintain urine ph level at 7 8.5 Keep bld ph < 7.55 and prevent hypernatremia Add 20 40 meq f K t each 1 L unless renal failure
Methd (Brenner & Rectrs) 50 meq IV blus f sdium bicarbnate fllw by 100 150 meq in 1 L f 5% dextrse at 250 ml/h Rate f infusin based n vlume status Gal f urine utput: 2 3 ml/kg/h Mnitred electrlyte and urine ph q2-3h Target urine ph: 7.5 8.5 Carbnic anhydrase inhibitrs nt recmmended Systemic metablic acidsis, hypkalemia
Cntraindicatins Significant metablic r respiratry alkalemia r hypernatremia Severe pulmnary edema assciated with vlume verlad Intlerance t sdium lad (renal failure, CHF)
Adverese effects Excessive alkalemia Impaired O 2 release frm Hb Paradxical intracellular acidsis Hypcalcemic tetany Hypkalemia Hypernatremia and hypersmlality Aggravatin f CHF and pulmnary edema Extravasatin -> tissue inflammatin & necrsis
Salicylates keeps salicylates away frm brain tissue and in the bld with enhancing urinary excretin Raising the urinary ph level frm 6.1 t 8.1 results in a mre than 18-fld increase in renal clearance by preventing nn-inic tubular back-diffusin decreases the half-life f salicylates frm 20-24 hurs t less than 8 hurs Severe cases nt meeting criteria fr hemdialysis
Phenbarbital supprtive Rx nly is preferred fr phenbarbital shrter half life achieved with alkalinizatin increases the risk f withdrawal symptms Multiple dse activated charcal may be mre effective
Others Methtrexate Cnsider hemperfusin instead Chlrprpamide Dextrse infusin alne usually adequate 2,4-Dichlrphenxyacetic Gal urine ph > 8 Urine utput > 600 ml/h