Toxicology ProgramCase presentation

Dr. KK LamTMH

23rd March 2005

F / 53

• Hypertension• DO 4 hrs ago• Drowsy

GCS 356

P 40

BP 54/36

RR 18

34.80C

H’stix 14

DDx?

Exact amount of drugs uncertain

• Adalat retard • Metoprolol (Betaloc)• Natrilix

0845 40 56/43 NS 300 ml

0850 40 65/42 Atropine 1.8 mg

0854 44 72/45 CaCl2 2 g

0905 40 86/43 Glucagon 6 mg

0918 61 92/55 Dopamine 500 mcg/min

0924 73 103/71 AC 50 g

0949 63 91/48 Dopamine 630 mcg/min

Prog

ress

& T

reat

men

t

AED I-stat results

• Na 142 mmol/L• K 3.3 mmol/L• I-Ca 1.91 mmol/L• Hb 12.9 g/dL

• pH 7.141• pCO2 5.54 kPa

• pO2 20.4 kPa

• HCO3 14 mmol/L• BE –15 mmol/L• SO2 99%

ICU D1

• GCS 356• P 59 83• BP 67/40 109/67• CVP 23 15• 34.80C 38.20C

• CaCl2 160 mg/h• Glucagon 1 mg• Isoprenaline 40 mcg/h• Transvenous pacing• AC 2 doses

ICU D2

• GCS 356• P 80• BP 145/70• CVP 6

• Stop CaCl2, Isoprenaline, pacing

• Phenylephrine 2 ml/h– Alpha agonist

• AC 3 doses• To Medical

Toxicology result

• Metoprolol

Myocardial cell contraction• Ca++ flow through voltage

sensitive channel• Trigger opening of Ca++

releasing channel at sacroplasmic reticulum

• Ca++ induce Ca++ release phenomenon

• Ca++ bind to troponin, actin-myosin sliding

Myocardial cell relaxation• Ca++ actively pump into

sacroplasmic reticulum • Ca-Na antiporter: passive

transport– 3Na in, 1Ca out• Ca++ATPase • Fall intracellular Ca++

conc• Ca++ release from troponin

Beta adrenergic agonist• Activation of beta adrenergic

receptor• Activate G-protein• Increase cAMP• Activate protein kinase• Phosphorylation of

phospholamban increase Ca++ store in SR

• Increase Ca++ influx from voltage sensitive Ca++ channel

• Phosphorylation of troponin facilitating unbinding of Ca++

Characteristic of beta blocker

• Membrane stabilizing – Inhibit fast Na channel– Propanolol, acebutolol

• Lipid solubility – Cross BBB– Propanolol, metoprolol, labetalol

• Instrinic sympathomimetic activity– acebutolol

Characteristic of beta blocker

• Beta1 selectivity– Acebutolol, metoprolol– Loss cardioselectivity in overdose

• K+ channel blockage– Sotalol (anti-arrhythmic property)

• Vasodilation (alpha antagonist activity)– labetalol

Clinical features• Cardiogenic shock

– hypotension, bradyarthymia, heart block• Hypoglycemia

– common in child, uncommon in adult• Depressed mental state• Respiratory depression• Prolong QRS, QTc• Coma, confusion, convulsion• Slightly hyperkalemia• Bronchospasm (uncommon)

Clinical features

• All major symptoms develop within 6 hours• Except controlled release preparation• Except sotalol

DDX of Bradyarrthymia• Overdose of:

– Beta-adrenergic antagonist– Calcium channel blocker– Digoxin– Na channel blocker– Anticholinerstase– Alpha 1 agonist

– Alpha 2 agonist (e.g. clonidine)

– Opioids– Sedative hypnotics– GHB (gamma

hydroxybutyrate)– Coingestion

• P   Propranolol and other Beta-blockers, Poppies

• A  Anitcholinesterase• C  Calcium channel

blockers , clonidine• E   Ethanol and other

sedatives.• D Digoxin

Treatments

• General– ABC– Decontamination– IVF – Atropine

Specific treatments

• Glucagon• Calcium• Insulin• Inotropes• Phosphodiesterase inhibitor• Pacing• Extracorporeal removal• Mechanical pump

• Glucagon– glucagon receptor increase cAMP

• Calcium – increase Ca++ influx during depolarization

• Phosphodiesterase inhibitor increase cAMP

• Inotropes – beta adrenergic agnoist increase cAMP

Glucagon• First line after IVF and atropine• Adult:Initial 3-5mg IVI, up to 10mg• Child:50-150ug/kg• Followed by infusion

– “response dose” per hour or– 2-5mg/hr– Up to 10mg/hr even glucagon is not responsive– Pedi: 50ug/kg/hr on to max adult dose

• HA preparation NS as diluent (does not contain phenol

Calcium

• Adult– CaCl3 1-3g IVI, up to 5gm in adult

• Children– Ca gluconate 10-20mg/kg IVI

Insulin• Combined with glucose, maintain euglycemia

(monitor glucose during and several hr after discontinuing insulin)

• Effective in beta adrenergic antagonist and CCB overdose

• May increase glucose utilization or Ca++ handling in myocardial cell

• Delayed onset of response (15-30 minutes)• 0.5-1unit/kg/hr with glucose 1g/kg/hr• Frequent glucose monitoring

Catecholamines (inotropes)

• Isoproterenol• Epineprine• Unopposed alpha effect• Invasive monitor

Phosphodiesterase inhibitor

• Amrinone• Long half life • Vasodilatation• Invasive monitor

Other treatments

• Ventricular pacing• Extracorporeal removal

– Water soluble drugs only e.g. atenolol– Difficult in bradycardia and hypotension

• Intra-aortic balloon pump/ extracorporeal circulation

Special conditions

• Membrane stabilizing effect– NaHCO3

• Peripheral vasodilation effect – alpha adrenergic agonist

• Sotalol– Correct electrolyte disturbance– Mg/ overdrive pacing for ventricular

dysrrthymia

Observation

• ICU for all symptomatic• For regular-release preparation

– Medically fit for discharge if adequate GI decontamination, asymptomatic, normal vital sign and ECG for 6-8 hours,

• Sotalol overdose or extended release preparation -- 24 hours observation

Summary

• Beta adrenergic antagonist is one of commonest drugs cause hypotension and bradyarrthymia

• Aggressive treatment should be initiated at AED• Glucogan is an antidote• All symptomatic cases should be managed amd

monitored in ICU• Prolong observation for extended release

preparation and sotalol

•Thank you