Urine Alkalinization. Passawat Na Nakorn, MD. R 3 Emergency Medicine
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1 Urine Alkalinizatin Passawat Na Nakrn, MD. R 3 Emergency Medicine
2 H + secretin
3 HCO 3 - reabsrptin
4 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
5
6 In Trapping
7 Applicable drugs Drugs must have the fllwing characteristics fr this prcess t effectively increase ttal clearance 1. Weak acid (pka ) 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
8 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
9 Frced Diuresis Urine vlumes f 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
10 Methd (Olsn) meq in 1 L f 5% dextrse in 0.25% NSS r meq in 1 L f 5% dextrse at 2 3 ml/kg/h (adults: ml/h) Check urine ph and adjust flw rate hurly t maintain urine ph level at Keep bld ph < 7.55 and prevent hypernatremia Add meq f K t each 1 L unless renal failure
11 Methd (Brenner & Rectrs) 50 meq IV blus f sdium bicarbnate fllw by 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: Carbnic anhydrase inhibitrs nt recmmended Systemic metablic acidsis, hypkalemia
12 Cntraindicatins Significant metablic r respiratry alkalemia r hypernatremia Severe pulmnary edema assciated with vlume verlad Intlerance t sdium lad (renal failure, CHF)
13 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
14 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 hurs t less than 8 hurs Severe cases nt meeting criteria fr hemdialysis
15 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
16 Others Methtrexate Cnsider hemperfusin instead Chlrprpamide Dextrse infusin alne usually adequate 2,4-Dichlrphenxyacetic Gal urine ph > 8 Urine utput > 600 ml/h
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