2/16/2014 The unstable overdose patient The unstable overdose - - PDF document

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2/16/2014 The unstable overdose patient The unstable overdose - - PDF document

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2/16/2014 The unstable overdose patient The unstable overdose patient Craig Smollin MD Associate Medical Director California Poison Control Center, SF Division Rob Ford - Mayor of Toronto Objective Discuss clinical scenarios unique to

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The unstable overdose patient

Craig Smollin MD Associate Medical Director California Poison Control Center, SF Division

The unstable overdose patient

Rob Ford - Mayor of Toronto

Objective

  • Discuss clinical scenarios unique to

the acutely poisoned unstable patients and representing high risk situations.

QuickTime™ and a decompressor are needed to see this picture.
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Remember

What are the most common interventions performed in acute poisoning?

Poison control center data 2011 Reminder

  • Poisoned patient need really good supportive care !

Clinical Scenarios

  • Aspirin overdose - Issues concerning airway
  • A case of severe acidosis
  • Cardiotoxicity - How is this shock different?
  • Drug induced seizures
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Unstable overdose case #1

  • A 58 year-old male presents after

ingesting an unknown quantity of aspirin in a suicide attempt. The patient appears diaphoretic and tachypneic, with a respiratory rate of 32. Lungs are clear to auscultation bilateral.

  • Initial aspirin level = 110 mg/dL
  • pH = 7.5, pCO2 = 17 mmHg, HCO3 = 13

mmol/L

Unstable overdose case #1

  • Initial treatment should include which of the

following?

  • a. Intravenous fluids
  • b. Bicarbonate drip
  • c. Potassium supplementation
  • d. Nephrology consultation
  • e. All of the above

Unstable overdose case #1

  • Initial treatment should include which of the

following?

  • a. Intravenous fluids
  • b. Bicarbonate drip
  • c. Potassium supplementation
  • d. Nephrology consultation
  • e. All of the above

http://www.acmt.net/

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Unstable overdose case #1

  • Intravenous fluids - hypovolemia often not addressed
  • Bicarbonate drip - enhanced elimination

Unstable overdose case #1

  • Intravenous fluids - hypovolemia often not addressed
  • Bicarbonate drip - enhanced elimination
  • K+ supplementation - hypokalemia works against you
  • Nephrology consultation - aspirin can be dialyzed

Unstable overdose case #1

  • Indications for dialysis:
  • Rising levels
  • AMS, cerebral edema, seizures
  • Pulmonary edema
  • Renal insufficiency
  • Deteriorating clinical condition
  • Profound acidemia
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What about intubation?

  • A 58 year-old male presents after

ingesting an unknown quantity of aspirin in a suicide attempt. The patient appears diaphoretic and tachypneic, with a respiratory rate of 32. Lungs are clear to auscultation bilateral.

  • Initial aspirin level = 110 mg/dL
  • pH = 7.5, pCO2 = 17 mmHg, HCO3 = 13

mmol/L

What about intubation?

  • A 58 year-old male presents after

ingesting an unknown quantity of aspirin in a suicide attempt. The patient appears diaphoretic and tachypneic, with a respiratory rate of 32. Lungs are clear to auscultation bilateral.

  • Initial aspirin level = 110 mg/dL
  • pH = 7.5, pCO2 = 17 mmHg, HCO3 = 13

mmol/L

Unstable overdose case #1

  • The treating physician is concerned that the patient

is tiring and elects for rapid sequence intubation with etomidate and succinylcholine.

  • Post intubation ABG
  • pH = 7.04, pCO2 55 mmHg, HCO3 = 9 mmol/L.

(pH = 7.5, pCO2 = 17 mmHg, HCO3 = 13 mmol/L)

Unstable overdose case #1

  • The patient died 40 minutes post

intubation.

Think twice about intubating the aspirin poisoned patient !

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Mechanical ventilation in aspirin poisoning

  • Case series of 7 patients with salicylate poisoning

(asa level > 50mg/dL) who underwent mechanical ventilation

  • post-MV pH in all patients was <7.4
  • In 5 patients post-MV pCO2 was > 50 mmHg
  • 2/7 died post intubation (within hours)
  • One patient with severe neurologic injury

Stolbach et. al. Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients. Acad Emer Med 2008 Sep;15(9): 866-9

Mechanical ventilation in aspirin poisoning

  • Individual case reports of hypoventilation in

salicylate poisoned patient resulting in death:

  • Salicylate-Associated Asystole: Report of Two Cases Am

J Med 1989;86: 505-6

  • Deleterious effects of endotracheal intubation in

salicylate poisoning Ann Emerg Med 2003; 41:583-4

Expert Opinion

  • Hyperventilation is not itself an indication for

intubation

  • Intubation and mechanical ventilation can be

associated with rapid worsening of toxicity and increased mortality.

  • Maintain alkalosis through hyperventilation and

intravenous sodium bicarbonate.

  • Once intubated, maintain minute ventilation and low

pCO2.

American College of Medical Toxicology (ACMT) Guidance Document: Management Priorities in Salicylate Toxicity http://www.acmt.net accessed 1/2014

  • Coingestion or therapeutic administration of

CNS/respiratory depressant drugs may also precipitate clinical deterioration

  • Alcohol
  • Opiates
  • Benzodiazepines
  • Antihistamines

American College of Medical Toxicology (ACMT) Guidance Document: Management Priorities in Salicylate Toxicity http://www.acmt.net accessed 1/2014

Expert Opinion

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When is intubation indicated?

  • Altered mental status
  • Pulmonary edema
  • Hypoventilation
  • Aspiration risk

Unstable overdose case #2

  • A 25 year-old female with no sig

PMH suddenly collapsed while at

  • work. Upon arrival to the

emergency department she was unresponsive with a GCS of 5.

  • BP is 90/p, HR 110 bpm, O2 Sat

100%, T afebrile.

  • Pupils 4 mm, sluggishly reactive,

lungs sounds clear, neuro exam restless, nonpurposful movements.

Unstable overdose case #2

  • A 25 year-old female with no sig

PMH suddenly collapsed while at

  • work. Upon arrival to the

emergency department she was unresponsive with a GCS of 5.

  • BP is 90/p, HR 110 bpm, O2 Sat

100%, T afebrile.

  • Pupils 4 mm, sluggishly reactive,

lungs sounds clear, neuro exam restless, nonpurposful movements.

Unstable overdose case #2

  • Blood glucose = 158 mg/dL
  • ABG: pH 7.01, pCO2 = 21 mmHg HCO3 = 8 mmol/L
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Unstable overdose case #2

  • Blood glucose = 158 mg/dL
  • ABG: pH 7.01, pCO2 = 21 mmHg HCO3 = 8 mmol/L

Unstable overdose case #2

25 year old female with sudden collapse? Call poison control ! Did you call poison control ! Call poison control 1-800-222-1222 ! Call them already !

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Unstable overdose case #2

  • Initial treatment includes the following:
  • Intubation
  • IV fluids
  • Additional laboratory studies
  • STAT head CT negative

Unstable overdose case #2

  • Additional laboratory studies:
  • Tylenol, aspirin, ethanol levels negative
  • WBC 19K
  • Na 142, K 4.3, Cl 101, HCO3 9, BUN 8, Cr 1.5, Glucose

155

  • Anion gap 22
  • Serum ketones negative
  • Lactate 10 mmol/L

Unstable overdose case #2

  • Additional laboratory studies:
  • Tylenol, aspirin, ethanol levels negative
  • WBC 19K
  • Na 142, K 4.3, Cl 101, HCO3 9, BUN 8, Cr 1.5, Glucose

155

  • Anion gap 22
  • Serum ketones negative
  • Lactate 10 mmol/L

Clinical clues to the diagnosis

Sudden collapse Severe acidosis Elevated anion gap No ketones Elevated lactate

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Selected drugs and toxins causing lactic acidosis

Acetaminophen Antiretroviral drugs Beta agonists Caffeine Carbon Monoxide Cyanide Hydrogen sulfide Iron Isoniazid

Metformin Propofol Salicylates Seizures, shock, hypoxia Sodium azide Theophyilline

Unstable overdose case #2

  • Additional history
  • Works in a laboratory with access to chemicals
  • Has access to potassium cyanide
  • Co-oximetry reveals no evidence of CO

Cyanide: Pathophysiology

Electron Transport Chain

Mitochondrial Matrix

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Electron Transport Chain

NADH

e-

Electron Transport Chain

NADH

e-

H+ H+ H+

Electron Transport Chain

NADH

H+ H+ H+

e-

Electron Transport Chain

NADH

H+ H+ H+

ADP ATP

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Electron Transport Chain

NADH ADP ATP cytochrome aa3

CN

Electron Transport Chain

NADH ADP ATP cytochrome aa3

CN

Treatment of CN Poisoning

  • Removal from source
  • 100% oxygen by tight-fitting mask/ET tube
  • Cyanide antidote kit?
  • Hydroxocobalamin?

Vit B12

hydroxoCob

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Vit B12

hydroxoCob

Shuttle Dumps Chelates

Cyanide Antidote Kit Nitrites Nitrites

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Nitrites Sodium thiosulfate Sodium thiosulfate Hydroxocobolamin

  • Combines with CN to form

Vitamin B12.

  • Appears to be effective and safe
  • Preferred drug for CN due to

smoke inhalation (safer than nitrites)

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57

Hydroxocobolamin

  • Side effects:

– Red Skin, secretions 2-7 days – Nausea, vomiting – Occasional HTN and muscle twitching

from Clin Toxicol 2006; 14.17

Unstable overdose case #3

  • A 45 year-old female with a history of

depression presents 1 hour after a large ingestion of her antihypertensive

  • medications. On arrival she is

somnolent but arousable and has a GCS of 14.

  • Vital signs: BP 83/50, HR 65, RR 18,

O2 sat 98% RA

  • Finger stick glucose = 235
  • Venous lactate = 5 mmol/L

Unstable overdose case #3

  • A 45 year-old female with a history of

depression presents 1 hour after a large ingestion of her antihypertensive

  • medications. On arrival she is

somnolent but arousable and has a GCS of 14.

  • Vital signs: BP 83/50, HR 65, RR 18,

O2 sat 98% RA

  • Finger stick glucose = 235
  • Venous lactate = 5 mmol/L
  • rr

Calcium Channel Blockers Beta Blocker Digoxin Clonidine Hyperkalemia

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Unstable overdose case #3

  • Further history reveals that the patient

took verapamil

Therapeutic approaches to shock

General CCB Poisoning IV fluids Atropine Vasopressors Cardiac Pacing High dose insulin Calcium Novel antidotes?

Therapeutic approaches to shock

General CCB Poisoning IV fluids Atropine Vasopressors Cardiac Pacing High dose insulin Calcium Novel antidotes?

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Vasopressors Vasopressors

  • 48 patients with verapamil or diltiazem overdose:
  • IV fluids and vasopressors used almost exclusively
  • Only 1 death
  • Doses of vasopressors higher than usual (NE 100

ug/min, DA 100 ug/kg/min)

  • Many patients required more than one pressor and

some up to 5

  • Conclusion: fluids and aggressive use of vasopressors is

treatment of choice

Unstable overdose case #3

  • How does shock in the context of poisoning differ

than shock from other causes?

  • May need higher doses of vasopressors
  • May need multiple different vasopressors

High dose insulin therapy

  • Proposed mechanisms:
  • Increased ionotropy
  • Improved uptake of carbohydrates in myocytes
  • Vasodilation of peripheral vascular beds
  • Strong animal evidence of efficacy
  • Human evidence primarily case reports and case

series

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Evidence - animal

  • Experimental studies:
  • Kline et al. Verapamil dog model
  • Kline JA, Raymond RM, Schroeder JD, Watts JA. The diabetogenic effects
  • f acute verapamil poisoning. Toxicol Appl Pharmacol 1997;145:357–362.
  • 26. Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM. Insulinis a

superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther1993; 267:744–750.

  • Kline JA, Lenova E, Raymond RM. Beneficial myocardial metabolic effects
  • f insulin during verapamil toxicity in the anesthetized canine.Crit Care Med

1995; 23:1251–1263.

  • Kline JA, Lenova E, Williams TC, Schroeder JD, Watts JA.Myocardial

metabolism during graded intraportal verapamil infusionin awake dogs. J Cardiovasc Pharmacol 1996; 27:719–726.

  • Kline JA, Raymond RM, Leonova ED, Williams TC, Watts JA.Insulin

improves heart function and metabolism during non-ischemiccardiogenic shock in awake canines. Cardiovasc Res 1997; 34:289–298.

Kline et al, Insulin a superior antidote for cardiovascular toxicity induced by verapamil in the canine.

Evidence - animal Evidence Clinical

  • 12 patients treated with a standardized protocol
  • Primary toxin was: BB (5 patients), CCB (2 patients),

Combined BB and CCB (2 patients), Polydrug (3 patients)

  • 7 pts on pre-existing vasopressors, all tapered off
  • 2 pts PEA arrest subsequently improved and

survived after HIET

Evidence Clinical

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High dose insulin euglycemia therapy (HIET)

  • Bolus = 1 unit / kg
  • Drip = 1-10 unit / kg / hour
  • Start dextrose infusion (D10)
  • Measure glucose q 10 min

Unstable overdose case #3

  • How does shock in the context of poisoning differ

than shock from other causes?

  • May need higher doses of vasopressors
  • May need multiple different vasopressors
  • May consider unusual antidotes
  • High dose insulin

Other Antidotes?

  • What is the mechanism?
  • Animal evidence in verapamil models
  • No good human data

lipidrescue.org

Other Antidotes?

Methylene blue administered at 2 mg/kg followed by infusion

  • f 1 mg/kg/hr rapidly improved blood pressure and allowed for

weaning of all pressors in a patient with severe amlodipine

  • verdose.
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Other Antidotes?

Mechanism is through decreased nitric oxide release.

Unstable overdose case #3

  • How does shock in the context of poisoning differ than

shock from other causes?

  • May need higher doses of vasopressors
  • May need multiple different vasopressors
  • May consider unusual antidotes
  • High dose insulin
  • Intravenous lipid emulsion
  • Methylene blue

Atropine Vasopressors Cardiac Pacing High dose insulin Intralipid Vasopressors Methylene blue

Unstable overdose case #4

  • A 26 year-old female presents to the emergency

department brought in by medics after a witnessed generalized tonic clonic seizure. She was given 2 mg of Ativan in the field which initially stopped the seizure, however upon arrival in the emergency department she begins seizing again. Additional doses of ativan result in transient cessation of seizure activity followed by recurrent seizures activity.

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Unstable overdose case #4

  • Most acute idiopathic seizures are treated with:
  • Benzodiazepines
  • Phenytoin
  • Barbiturates
  • Propofol

Should drug induced seizures be treated the same way?

What causes drug induced seizures?

Idiopathic Drug induced

  • Impaired inhibition
  • Enhanced excitation
  • Disorders of conduction
  • Metabolic failure

What causes drug induced seizures? What causes drug induced seizures?

Impaired inhibition Enhanced excitation Conduction abnormalities Metabolic failure Withdrawal Isoniazid Theophylline Withdrawal Cocaine TCA’s Glyburide CO CN

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Why not phenytoin for drug induced seizures? Because it doesn’t work! Why not phenytoin for drug induced seizures?

Theophylline and mice

Why not phenytoin for drug induced seizures?

Theophylline and mice

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Why not phenytoin for drug induced seizures?

TCA’s and mice

Why not phenytoin for drug induced seizures?

  • 90 patients with alcohol related seizures
  • Random assignment to phenytoin (1gm) or placebo
  • End points
  • Seizure recurrence
  • 12 hour seizure free period
  • Phenytoin group had no benefit

Unstable overdose case #4

  • A 26 year-old female presents to the emergency

department brought in by medics after a witnessed generalized tonic clonic seizure. She was given 2 mg of Ativan in the field which initially stopped the seizure, however upon arrival in the emergency department she begins seizing again. Additional doses of ativan result in transient cessation of seizure activity followed by recurrent seizures activity.

  • Further history reveals that the patient overdosed on

isoniazid

Pyridoxine (B6) and GABA

Glutamine Glutamic Acid (brain) GABA

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Treatment of INH seizures

  • Benzos, Benzos, Benzos
  • No role for phenytoin
  • Give pyridoxine (5 grams empiric dose)
  • Intubation and paralysis may be necessary

General approach to drug induced seizures

  • Try to define the etiology
  • Always start with a benzodiazepine
  • Avoid phenytoin
  • Think about antidotes
  • Add barbiturates for synergy

In summary

  • Case #1 - Aspirin
  • Intubation can be tricky and can lead to rapid

deterioration

  • Do not intubate simply for tachypnea
  • Case #2 - Cyanide
  • Think of CN in patients with severe lactic acidosis
  • Use hydroxycobalamin or cyanide antidote kit

In summary

  • Case # 3 - Verapamil overdose
  • High dose vasopressors
  • High dose insulin
  • Think about intralipid and methylene blue
  • Case # 4 - Isoniazid
  • Benzo first line in drug induced sz
  • Think about antidotes (pyridoxine)