Cases from Downunder

Sophie Gosselin.MD,CSPQ,FRCPCNewcastle Mater Misericordiae

NSW, Australia

Case one – Miss R.Call at 01h3013 yrs old female brought by police and EMS after suspected DSH by ingestion of medicationBest friend called at 23h and told « good bye forever ».Friend called mother, 000 called and patient ran out back doorFound at 00h30 by EMS and brought to JHH

Case one – Miss R.On arrivalAlert, oriented 67 kgHR 120 NSRRR 16BP 110/70sat 100%Glucose 5.1T 37.8

Case one – Miss R.Took around 22h30

Prednisone 50mg x 20 1000 mgParacetamol 500 mg x 64 32 gr Codeine 30 mg x 24 720 mgPseudoephedrine 60 mg x 24 1440 mgIbuprofen 200 mg x 24 4800 mgMedication X 0.5mg x 50-64 25-32 mgDimenhydrate 50 mg x 12 600 mg

Case one – Miss R.What would you do next?What would you expect to find on physical exam to confirm if she did take all these?

Case one – Miss R.Level of counsciousness - belligerant Airways - not a problemBreathing - not a problemCirculation – not a problemDecontamination

Gastric lavage?Charcoal?WBI?

Case one – Miss R.We are 2 hours post ingestion.Do we have indications to consider decontamination?

Case one – Miss R.Police went home and did medication search.We knew then what Medication X was.

Here is what we did and what happened.Can you identify the toxin?Note your answers as we go alongAsk all questions you wantDo not yell out your answersWe will poll the assistance at the end and

get a top 5 lists of toxin

Case one – Miss R. 01h15

Intubated in ED for decontaminationCharcoal one dose 50 grWBI startedN-acetylcysteine started empirically pending levelAdmitted to ICUHR 160 BP 100/60ECG sinus tachycardia

Case one – Miss R. 04h00

Hbg 137WBC 4.3Platelets 278Na 133K 3.0Creatinine 57BUN 3.5INR 1.1Paracetamol 950 at 3h30CK 146Troponin negative

Day one – Miss R. 04h00

SedatedVomiting +++Unable to continue charcoal HR 160 sinusBP 95/60

14h00No change in statusGiven Neostigmine 2.5 mg IV Decontamination continued with charcoal alone until black stools

Day two – Miss R.HR 160 sinusBP 75/55 started on norepinephrineSwan Ganz

Output slightly decreasedSystemic vascular resistance decreased

LabsUnchanged except CK 1307

Which investigation would you want?

Day two – Miss R.Cardiac echo

Normal valvesImpaired LV contractionEF 35%No pericardial effusion.

Day three – Miss R.Still requiring inotropesStools black after MDACHR 140 BP with support 105/60Hgb 133WBC 4.9Plat 99LFTs and INR unchanged NAC stopped.

Day four to six – Miss R.Still requiring inotropes (dobutamine)Still intubatedFever 39Abdominal distensionHGB 105WBC 2.2Platelets 31CK 4142Troponins 1.87

Given GCSF for 24h

Day six to eight – Miss R.

Weaned off inotropesExtubatedTreated for Aspiration Given neostigmine againHGB 116WBC 9.0Platelets 111CK 541Troponins going downCardiac echo normal EF

Data on toxin-Miss R.Significant toxicityBound by charcoalInitial symptoms?Pancytopenia in 48hCardiac depressionResolution within one week.

????

Colchicine intoxicationPatient has gout.Took 0.5 mg x 64 = 32 mgPer kg = 0.48Phase 1

0-24h GI, leukocytosis, hypovolemia, DIC

Phase 22-7 days bone marrow suppression, cardiac depression, hepatic failure, MOF, ARDS

Phase 3 Resolution DeathAlopecia

Colchicine intoxicationAlkaloid from Colchicum autumnaleNarrow therapeutic-toxix index

GI side effects

High rates of morbidityAbsorbed 2 h after ingestionNot delayed in overdose unless by coingestantsFirst pass hepatic metabolismDistribution t1/2 45-90 minutesExcreted in the bile with enterohepatic circulation

Colchicine intoxicationBinds to tubulin Impairs microtubules formationNeutrophils, gastrointestinal musco, hematopoeitic cells, hair follicles.Toxicity is dose related

0.5 mg/kg or less usual recover0.8 mg/kg or more usual die

3 stagesGI 0-24hMOF 24-72hRecovery 6-8 days p.i.

Colchicine intoxicationAsymptomatic initiallyN/V/D

GI mucosal damage

Hypovolemic shockSepsis

impaired macrophage function

Cardiogenic shockRhabdomyolysisRenal failureSeizures, ascending paralysis, transverse myelitis

Colchicine intoxicationIngestion known

Asymptomatic drug ODToxic causes of gastroenteritis• Iron• Salicylates• Fluoride• Caustics• Cardiac glycosides• Nicotine• OPP/carbamates• Paraquat• Mushrooms

Ingestion unknownAcute abdomenCardiogenic shockGastroenteritisHypovolemic shockSeptic shock

Colchicine intoxicationExtensive baseline lab studiesLevels can be done

Takes a few daysRetrospective, post mortem

No increase in AG, osmolar gapAcid base abnormality are not specificEarly, aggressive GI decontaminationEnhanced elimination not indicated

Large Vd 21L/kgIntracellular binding sites

GSCF true response versus natural course?Death are rarely from marrow aplasia

No antidotes commercially available

Colchicine intoxicationFab antibodiesSimilar to digitalis Fab fragmentProduced in goat immunized with conjugate of colchicine and albuminEffectively reverse toxicity in miceNEJM Mar 15 1995. Baud and al.

One human case report 27 hrs p.i of 60 mg of colchicine 0.98 mg/kgImprovement within 30 minutes after FabSevere cardiogenic shockIncreased the urinary excretion of Fab-colchicine compound by 6 fold

Colchicine intoxicationPatient has gout.Took 0.5 mg x 64 = 32 mgPer kg = 0.48Phase 1

0-24h GI, leukocytosis, hypovolemia,

Phase 22-7 days bone marrow suppression, cardiac depression, rhabdomyolysis

Phase 3 Resolution

Case 2- Mrs. B45 years old patient found on highwayAfter serious MVATransported to Trauma Center

Case 2- Mrs. BA patentB GAEBC BP 50/ … HR 40No external woundsNo other signs of injuryNormal temperatureNormal glucose

Case 2- Mrs. BProlonged QTWide QRS

Differential diagnosisTraumatic injury after OD?No traumatic injury but signs are the OD?

Traumatic vs toxicologic?

TraumaticSingle vehicule MVASeatbeltNo airbagUnknown speedDamages important

ToxicologicNo associated signs of injury

Case 2- Mrs. BHow would you manage this patient?

Case 2- Mrs. BNaHCO3 infusion?

External pacerExtracorporeal supportEmergency bypass?Thoracotomy?Transthoracic ultrasound?Gastrointestinal decontamination?

Differential diagnosis?Traumatic

TamponnadeHypovolemic shock?Pneumothorax?CNS bleed?

ToxicologicAntidysrhythmic TCAPhenothiazinesCocaineAmantadinePropoxypheneChloral hydrateOPPTerfenadineBB; CCB;HypokalemiaHypocalcemia

Case 2- Mrs. BNo significant response to many boluses of NaHCO3

Normal CXR, Normal FASTNormal HgbAcidosisHigh lactateStarted seizing…Would you give her amiodarone?Would you start pressors and if so which one?

Class

Effect Clinical Drugs

IA Decreases upstrokeDecreased conductionNa and K blockade

QT prolongationQRS wideningHypotensionLethargy, coma

QuinidineProcainamide

IB Depresses rapid action potential

Confusion,SeizuresAsystoly, Ventricular Wide QRS

Lidocaine

IC Marked depression rapid action potentialNo K blockade

QT prolongationHypotension,BradycardiaComa, seizures

PropafenoneFlecainide

II B receptors blockade Beta-blockers

III K channel blockadeLittle or no Na blockade

Rapid hypotension, QTIncreased PR, bradycardiaProfound coma, hypotension

SotalolAmiodaroneBretylium

IV L type Ca channel BradycardiaPeripheral D

CCB

Vaughan-Williams Classification

Case 2- Mrs. BAre you able to tell which one is which?

Degree of hypotension?Degree of bradycardia?Anticholinergic features?Presence of seizures?

IA or ICCardiac conduction delayNaHCO3 ph 7.5

Fluid for hypotensionNorepinephrineMagnesium if TDPOverdrive pacingIsoproterenol

IBLorazepam for szPhenobarbitalFluid for hypotensionnorepinephrine

Treatment

Case 2- Mrs. BNaHCO3 infusion increasing

Overdrive pacingNorepinephrine increasing dosesShe went in PEAArrestedUnable to ressuscitate

Case 2- Mrs. BPolice found suicide noteEmpty bottle of flecainide

Could we have done anything to save her?

Flecainide overdoseIC antidysrhythmicNa channel blockadeAll condution pathways depressedHigh mortality rate 23% compared with other classesQuick absorption within 30 minutes95% bioavailabilitySerious cardiac effect 30-120 minutesWeak acid ; AlkalinizationVd 9 L/kg ; dialysis ineffectiveLong half life

Flecainide overdoseHemoperfusion

A blood pressure is needed

ECMOCritical Care Medicine April 2001Case report • After 8 mg epi, 1.2 mg atropine, 125 mmol NaHCO3

• Epi drip 100 mg/min• TC pacer to 100 mA• T pacer to 20 mA asynchronous mode• Fixed dilated pupils, no palpable pulse, pH 7.26

Successful recovery after 26 hours

Australian experienceA paramedical case report

John Hunter HospitalLevel 6 trauma centerBuilt 1991Ressuscitation Room

Combined pediatric Adult emergency department One ressuscitation area

8 monitored bed18 acute care beds

Doctors desks

Isolated Monitored beds

Longitudinal hallDepartments on either sides

Special 4 isolation ICU type beds« for SARS or the like »

Stand-by isolation ward