Drug induced Drug induced Metabolic & Electrolytes Metabolic & Electrolytes

ProblemProblem

YC ChanYC Chan

Why is it important?Why is it important?

Common problems in AED practiceCommon problems in AED practice Within our ability to manageWithin our ability to manage Pitfalls in “drug induced”Pitfalls in “drug induced”

RecognitionRecognition ManagementManagement

Simple Stuffs - You all know Simple Stuffs - You all know this ! this !

Metabolic Metabolic Respiratory acidosisRespiratory acidosis Respiratory Respiratory

alkalosisalkalosis Metabolic acidosisMetabolic acidosis Metabolic alkalosisMetabolic alkalosis

ElectrolytesElectrolytes SodiumSodium PotassiumPotassium CalciumCalcium MagnesiumMagnesium

ElectrolytesElectrolytes

Too much or too littleToo much or too little Absolute changes Vs Shift between Absolute changes Vs Shift between

compartmentscompartments SymptomsSymptoms

Absolute valueAbsolute value Rapidity of the changeRapidity of the change

Electrolytes Problem in Electrolytes Problem in Poisoning Poisoning

ExpectedExpected Therapeutic effectTherapeutic effect Common side effectCommon side effect Uncommon but well recognized side effectUncommon but well recognized side effect

UnexpectedUnexpected Case reportsCase reports ? Association ? Causation? Association ? Causation

Electrolytes Problem in Electrolytes Problem in poisoning poisoning

Na, K, Ca, MgNa, K, Ca, Mg CommonCommon

↓ ↓ Na, ↓ K, ↑ KNa, ↓ K, ↑ K Less commonLess common

↓ ↓ Ca, ↓ MgCa, ↓ Mg RareRare

↑ ↑ Na, ↑ Ca, ↑ MgNa, ↑ Ca, ↑ Mg

HyponatremiaHyponatremia

PitfallsPitfalls Known psychiatric history on treatment, change of Known psychiatric history on treatment, change of

medications recently, worsening of psychiatric medications recently, worsening of psychiatric symptoms, admitting to PYNEHsymptoms, admitting to PYNEH

After party, confused, triage +ve MDMA, After party, confused, triage +ve MDMA, admitting to observation wardadmitting to observation ward

Known epilepsy, breakthrough seizure, Known epilepsy, breakthrough seizure, admitting to observation wardadmitting to observation ward

Known DM on OHA, hypoglycemic attack presented Known DM on OHA, hypoglycemic attack presented with convulsion, given valium and D50, waiting with convulsion, given valium and D50, waiting medical bedmedical bed

Madhusoodanan. Hyponatremia associated with psychotropic Madhusoodanan. Hyponatremia associated with psychotropic medicationsmedicationsAdv Drug React Toxicol Rev 2002: 21 (1-2): 17-29Adv Drug React Toxicol Rev 2002: 21 (1-2): 17-29

Psychiatric drugs - Psychiatric drugs - hyponatremiahyponatremia

SSRISSRI IncidenceIncidence

<1% - 39%<1% - 39% Wilkinson TJ. Br J Clin Pharmacol. 1999;47:211-217Wilkinson TJ. Br J Clin Pharmacol. 1999;47:211-217 Strachan J. Strachan J. Aust N Z J Psychiatry. Aust N Z J Psychiatry. 1998;32:295-2981998;32:295-298 Fabian TJ. Arch Intern Med. 2004;164:327-332Fabian TJ. Arch Intern Med. 2004;164:327-332 Kirby D. Int J Geriatr Psychiatry 2002;17:231-7Kirby D. Int J Geriatr Psychiatry 2002;17:231-7

Likely in the first Likely in the first 2-3 weeks2-3 weeks Mean/Median 9 days (range 1-14 days)Mean/Median 9 days (range 1-14 days)

Fabian TJ. Arch Intern Med. 2004;164:327-33Fabian TJ. Arch Intern Med. 2004;164:327-33

Mean 18 days, Median 13 days (range 4-64 days)Mean 18 days, Median 13 days (range 4-64 days) Kirby D. Int J Geriatr Psychiatry 2002;17:231-7Kirby D. Int J Geriatr Psychiatry 2002;17:231-7

SeveritySeverity 4-14 mmol/l drops from baseline4-14 mmol/l drops from baseline

Fabian TJ. Arch Intern Med. 2004;164:327-33Fabian TJ. Arch Intern Med. 2004;164:327-33

Psychiatric drugs - Psychiatric drugs - hyponatremiahyponatremia

TCA TCA

Psychiatric drugs - Psychiatric drugs - hyponatremiahyponatremia

AntipsychoticAntipsychotic Typical and AtypicalTypical and Atypical

SummarySummary Psychiatric drugs is associated with SIADH & Psychiatric drugs is associated with SIADH &

hyponatremiahyponatremia Causal for SSRI, ? TCA and antipsychoticCausal for SSRI, ? TCA and antipsychotic Risks include:Risks include:

Age (>65)Age (>65) Female genderFemale gender Use of other medicationsUse of other medications Prior historyPrior history Early phase on medicationEarly phase on medication

< 3/52< 3/52

MDMA induced MDMA induced hyponatremiahyponatremia

4 fatalities in literatures4 fatalities in literatures All women and all died from cerebellar tonsillar All women and all died from cerebellar tonsillar

herniationherniation Budisavljevic MN. Am J Med Sci. 2003 Aug;326(2):89-93Budisavljevic MN. Am J Med Sci. 2003 Aug;326(2):89-93

As low as 101mmol/l reportedAs low as 101mmol/l reported Holmes SB. Postgrad Med J. 1999 Jan;75(879):32-3Holmes SB. Postgrad Med J. 1999 Jan;75(879):32-3

Commonly in next morningCommonly in next morning

Anticonvulsants - Anticonvulsants - hyponatremiahyponatremia

Problem SeizureProblem Seizure CarbamazepineCarbamazepine Oxcarbazepine Oxcarbazepine VPAVPA Miyaoka T. Int Clin Psychopharmacol. 2001 Jan;16(1):59-61Miyaoka T. Int Clin Psychopharmacol. 2001 Jan;16(1):59-61

OHA - hyponatremiaOHA - hyponatremia

ChlorpropamideChlorpropamide Well recognizedWell recognized 2.1% to 15.3%2.1% to 15.3%

Hirokawa CA Ann Pharmacotherapy. Hirokawa CA Ann Pharmacotherapy. 1992 Oct;26(10):1243-41992 Oct;26(10):1243-4

Sloan RW. J Farm Pract. 1983; 16: 937-42Sloan RW. J Farm Pract. 1983; 16: 937-42

TolbutamideTolbutamide Glipizide Glipizide

Only few case reportsOnly few case reports

Bottom-lineBottom-line

Any altered mental status/convulsionAny altered mental status/convulsion Always Always

GlucoseGlucose ElectrolytesElectrolytes CT if focal neurologyCT if focal neurology

Before diagnosisBefore diagnosis

Management of SIADHManagement of SIADH Fluid restrictionFluid restriction

NOT Normal SalineNOT Normal Saline Hypertonic SodiumHypertonic Sodium

Convulsion (hard)Convulsion (hard) Mental status (soft)Mental status (soft)

DoseDose Aim at 1-2mmol/l per hour in first few Aim at 1-2mmol/l per hour in first few

hours hours Not more than 8-10mmol/l in 1Not more than 8-10mmol/l in 1stst 24 hours 24 hours Generally, 1ml/kg of hypertonic saline over Generally, 1ml/kg of hypertonic saline over

11stst hour in ED hour in ED

PotassiumPotassium RenalRenal GIGI ShiftShift

Bradberry. Clinical Toxicology 1995:33(4); Bradberry. Clinical Toxicology 1995:33(4); 295-310295-310

HyperkalemiaHyperkalemia

PrimaryPrimary Absolute increaseAbsolute increase

K, K-sparing diuretic, ACE IK, K-sparing diuretic, ACE I ShiftShift

Cardiac glycosides, Beta blocker, HFCardiac glycosides, Beta blocker, HF

SecondarySecondary Cellular damageCellular damage Rhabdomyolysis Rhabdomyolysis ARFARF AcidemiaAcidemia

HyperkalemiaHyperkalemia

Remove the offending agentRemove the offending agent Treatment options for hyperkalemiaTreatment options for hyperkalemia

ResoniumResonium Dextrose/InsulinDextrose/Insulin ββ agonist (puff) agonist (puff) CalciumCalcium NaHCONaHCO33

Cardiac GlycosidesCardiac Glycosides

Hyperkalemia Hyperkalemia Reflects the toxicityReflects the toxicity Prognostic indicatorPrognostic indicator K > 5 mmol/l – DigiFabK > 5 mmol/l – DigiFab

No other explainable cause for No other explainable cause for hyperkalemiahyperkalemia

Calcium in treating hyperkalemiaCalcium in treating hyperkalemia ControversialControversial

Bismuth C. Clin Toxicol 1973;6:153-162Bismuth C. Clin Toxicol 1973;6:153-162

Calcium + Digoxin Calcium + Digoxin ? synergism? synergism

My bottom lineMy bottom line

Avoid Ca in digitalis poisoning Avoid Ca in digitalis poisoning Clinical + ECGClinical + ECG

ACE I induced hyperkalemiaACE I induced hyperkalemia

10% of patient in 110% of patient in 1stst year of ACE I year of ACE I treatmenttreatment K > 6mmol/lK > 6mmol/l Risk – age >70, Renal impaired, CCFRisk – age >70, Renal impaired, CCF

Reardon LC Arch Intern Med 1998;158:26-32

10-38% of hyperkalemic patients in 10-38% of hyperkalemic patients in hospital is secondary to ACE Ihospital is secondary to ACE I

Palmer BF N Engl J Med 2004;351:585-92

HypokalemiaHypokalemia PrimaryPrimary

Absolute lossAbsolute loss Diuretic, RTA – TolueneDiuretic, RTA – Toluene CatharticsCathartics

ShiftShift Beta agonist, MethylxanthinesBeta agonist, Methylxanthines OHA/insulin/glucoseOHA/insulin/glucose Chloroquine, HCQ, BariumChloroquine, HCQ, Barium

SecondarySecondary AlkalemiaAlkalemia

ChannelsChannels DrugDrug K level mean(SD) in K level mean(SD) in mmol/lmmol/l

NaK ATPaseNaK ATPase Beta-Beta-agonistagonist

2.9 (0.6)2.9 (0.6)

TheophyllinTheophyllinee

Acute 2.8 (0.2)Acute 2.8 (0.2)

Chronic 4.1 (0.7)Chronic 4.1 (0.7)

InsulinInsulin 23% < 3.023% < 3.0

58% 3.0-3.558% 3.0-3.5K channelK channel CQ/HCQCQ/HCQ 2.4 ((0.4)2.4 ((0.4)

BariumBarium 1.9 (0.7)1.9 (0.7)

Bradberry SM. Disturbances of Potassium Homestasis in Poisoning.Bradberry SM. Disturbances of Potassium Homestasis in Poisoning.Clinical Toxicology 1995; 33(4): 295-310Clinical Toxicology 1995; 33(4): 295-310

Replacement of PotassiumReplacement of Potassium

Yes or NoYes or No Weakness, ECG abnormalitiesWeakness, ECG abnormalities Beware in the “shift” groupBeware in the “shift” group

Risk of hyperkalemiaRisk of hyperkalemia IV or OralIV or Oral

IV preferredIV preferred

Sigue G. Arch Intern Med. 2000 Feb 28;160(4):548-Sigue G. Arch Intern Med. 2000 Feb 28;160(4):548-5151

HypocalcemiaHypocalcemia Acute poisoningAcute poisoning

HFHF Ethylene glycolEthylene glycol

Therapeutic DrugsTherapeutic Drugs Anticonvulsants (VPA, Phenytoin, Anticonvulsants (VPA, Phenytoin,

Phenobarbital)Phenobarbital) AminoglycosidesAminoglycosides BisphosphonatesBisphosphonates Fleet enema (Na phosphate, esp in kid and Fleet enema (Na phosphate, esp in kid and

infant)infant)

HypomagnesiumHypomagnesium

Rarely life threateningRarely life threatening Hand in hand with hypokalemiaHand in hand with hypokalemia

EthanolEthanol DiureticDiuretic

Long QTcLong QTc Long list of drugsLong list of drugs

www.qtdrugs.orgwww.qtdrugs.org Correct hypo K, Ca and MgCorrect hypo K, Ca and Mg

HypernatremiaHypernatremia

Simply “salts”Simply “salts” Tablet salt Tablet salt

Na 234 mmol/lNa 234 mmol/l SurvivedSurvived Kupiec TC. J Anal Toxicol. 2004 Kupiec TC. J Anal Toxicol. 2004 Sep;28(6):526-8Sep;28(6):526-8

Na 255 mmol/lNa 255 mmol/l DiedDied Ofran Y.J Intern Med. 2004 Dec;256(6):525-8 Ofran Y.J Intern Med. 2004 Dec;256(6):525-8

Soy sauce Soy sauce Na 176 mmo/lNa 176 mmo/l Survived Survived Sakai Y. Chudoku Kenkyu. 2004 Sakai Y. Chudoku Kenkyu. 2004

Jan;17(1):61-3 Jan;17(1):61-3

DIDI LithiumLithium Others rareOthers rare

A few moreA few more

HypercalcaemiaHypercalcaemia Cholecalciferol, Vitamin A, Milk alkali syndromeCholecalciferol, Vitamin A, Milk alkali syndrome

HypermagnesemiaHypermagnesemia Mg containing antacids or catharticsMg containing antacids or cathartics

Med J Aust 2005; 182 (7): 350-351

Simple Stuffs - You all know Simple Stuffs - You all know this ! this !

Metabolic Metabolic Respiratory acidosisRespiratory acidosis Respiratory Respiratory

alkalosisalkalosis Metabolic acidosisMetabolic acidosis Metabolic alkalosisMetabolic alkalosis

ElectrolytesElectrolytes SodiumSodium PotassiumPotassium CalciumCalcium MagnesiumMagnesium

Principle Principle Toxin induced respiratory Toxin induced respiratory

problemproblem

Directly stimulate or depress respiratory Directly stimulate or depress respiratory centrecentre

Alter chemoreceptor response to PaCO2 or Alter chemoreceptor response to PaCO2 or pHpH

Affect respiratory musclesAffect respiratory muscles Secondary to metabolic changesSecondary to metabolic changes

Respiratory AcidosisRespiratory Acidosis HypoventilationHypoventilation

Rate Vs Tidal volumeRate Vs Tidal volume Oxygenation = VentilationOxygenation = Ventilation

Two mechanismsTwo mechanisms CNS e.g. opioidsCNS e.g. opioids Non-CNS e.g. NMBNon-CNS e.g. NMB

ManagementManagement Supportive (BVM)Supportive (BVM) Antidotes Antidotes

Respiratory AlkalosisRespiratory Alkalosis

DirectDirect Aspirin (Protective)Aspirin (Protective) MethylxanthinesMethylxanthines SympathemimeticsSympathemimetics

Secondary Secondary Metabolic acidosisMetabolic acidosis

ManagementManagement Usually not necessary but may be harmfulUsually not necessary but may be harmful

Metabolic acidosisMetabolic acidosis

Challenging problemChallenging problem MUDPILESMUDPILES KULTKULT

KetonesKetones UremiaUremia LactateLactate Toxic alcoholToxic alcohol

LactateLactate

Source of lactateSource of lactate EndogenousEndogenous

Impaired aerobic respirationImpaired aerobic respiration Primary (Cyanide) or Primary (Cyanide) or Secondary (Hypoxia, Hypotension)Secondary (Hypoxia, Hypotension)

ExogenousExogenous Propylene glycolPropylene glycol Intestine BacteriaIntestine Bacteria

Unit to unit for anion gapUnit to unit for anion gap

C C C

OH OH

C C C

OH O

OH

Ketones (Ketoacids)Ketones (Ketoacids)

AspirinAspirin DKA/AKA/SKADKA/AKA/SKA Ketosis without acidosisKetosis without acidosis

Isopropyl alcohol - AcetoneIsopropyl alcohol - Acetone KetoacidsKetoacids

ββ-Hydroxybutyrate-Hydroxybutyrate AcetoacetateAcetoacetate

UremiaUremia

Need Cr ~ 400 Need Cr ~ 400 Urea NOT related to the anion gap Urea NOT related to the anion gap

metabolic acidosismetabolic acidosis Failure to deal with “acid” renallyFailure to deal with “acid” renally Unmeasured anionUnmeasured anion

PhosphatePhosphate SulphateSulphate

Toxic AlcoholToxic Alcohol

MethanolMethanol Formic acidFormic acid

Ethylene GlycolEthylene Glycol Glycolic acidGlycolic acid

Toxic alcohol “Hint” Toxic alcohol “Hint” Symptoms and SignsSymptoms and Signs High Osmol GapHigh Osmol Gap Urine FluorescenceUrine Fluorescence CrystaluriaCrystaluria

An approachAn approach

Any obvious “lactate” production causesAny obvious “lactate” production causes Urine ketones/Bedside glucose/Alcohol hxUrine ketones/Bedside glucose/Alcohol hx RFTRFT LactateLactate Toxic alcohol “hints” + send level (TRL)Toxic alcohol “hints” + send level (TRL)

Metabolic alkalosisMetabolic alkalosis

Least likely metabolic problemLeast likely metabolic problem Base administrationBase administration

BicarbonateBicarbonate

Management of Management of Metabolic problems in Metabolic problems in

poisoningpoisoning Pyramid againPyramid again TreatmentTreatment

Assisted ventilationAssisted ventilation SedativeSedative Sodium bicarbonateSodium bicarbonate

Specific Treatment

Antidote

Decontamination

Supportive Management

Exposure Prevention

Thank YouThank You