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Controversies in the management of TCA toxicity: bicarb and then what??. Rob Hall MD Case of the week November 28, 2003. Case of the week. TCA case from this week. ECG. Treatment. Intubation, Gastric Lavage NS 2 L bolus

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controversies in the management of tca toxicity bicarb and then what

Controversies in the management of TCA toxicity: bicarb and then what??

Rob Hall MD

Case of the week

November 28, 2003

case of the week
Case of the week
  • TCA case from this week
treatment
Treatment
  • Intubation, Gastric Lavage
  • NS 2 L bolus
  • Sodium Bicarbonate 2 amps iv bolus followed by bicarb drip: repeat boluses bicarb (total 6 amps)
  • What if there is no response to the above treatment despite pH being in target 7.50 – 7.55?
objectives
Objectives
  • Is there any role for Hypertonic Saline or Phenytoin in the management of TCA overdoses?
hypertonic saline
Hypertonic Saline
  • Theory
    • Na+ load to overcome Na+ channel blockade by the TCA
    • Na+ load without the adverse effects of alkalosis as seen with sodium bicarbonate
    • Able to give a lot more Na+ than with normal saline
      • Normal Saline: 0.9% NaCl
      • Hypertonic Saline: 7.5% NaCl
hypertonic saline7
Hypertonic Saline
  • Goldfrank 2003
    • Theoretical benefit but not adequately studied
  • Ford 2001
    • Not mentioned
hypertonic saline8
Hypertonic Saline
  • Hoegholm. Clinical Toxicology. 1991
    • Case Report of TCA overdose
    • Hypotensive, wide QRS, recurrent VT and VF
    • Intubated, lavaged
    • Sodium bicarb, lidocaine, dopamine, and hyperventilation (how much of each???)
    • Sodium chloride 170 mEq given over 5 min
      • Immediate narrowing of the QRS, increased BP, no further VT or VF
  • One case report, not much for details, amount of bicarb could have been more important
hypertonic saline9
Hypertonic Saline
  • McCabe. Acad Emerg Med. 1994
    • Swine model of TCA toxicity
    • Nortiptyline until SBP 50% of baseline and QRS > 120 msec
    • Randomized groups
      • 10 ml/kg of 7.5% hypertonic saline + 6% dextran
      • 10 ml/kg of 0.9% normal saline
    • NO bicarbonate treatment arm
hypertonic saline11
Hypertonic Saline
  • McKinney. Ann Emerg Med. 2003
    • Case Report
    • 29 yo female ingested 8 gm of nortryptylline
    • Coma, BP 80/40, QRS 124 msec
    • Intubated, lavaged, hyperventilation, 3L normal saline, dopamine 20 ug/kg/min, norepinephrine 22 ug/min, 4 amps bolus sodium bicarb, pH 7.54
    • QRS 135 msec
    • Given 200 ml of hypertonic saline (7.5%)
hypertonic saline12
Hypertonic Saline
  • McKinney. Ann Emerg Med. 2003
    • BP 0 3 5 10 30 min
        • 78/42 85/50 104/60 112/68 115/68
    • QRS
        • 136 msec 120msec
hypertonic saline other case reports
Hypertonic Saline:other case reports
  • Dolara. J Clin Tox
    • No bicarb given before H.S., physostigmine used
  • Seitz. Dtsch Med Wochesnschr
    • ?german
hypertonic saline14
Hypertonic Saline
  • McCabe. Ann Emerg Med 1998
    • Swine model (N=24)
    • Nortyptyline until SBP < 50 and QRS > 120 msec
    • Group 1 = D5W 10 ml/kg
    • Group 2 = Hypertonic Saline 7.5% 10 ml/kg
    • Group 3 = Sodium Bicarb 8.4% 3mEq/kg
    • Group 4 = Hyperventilation to target pH 7.5-7.6 and D5W 10 ml/kg
  • Hypertonic saline looked pretty good!!
hypertonic saline conclusions
Hypertonic Saline: Conclusions
  • There is animal evidence to support the use of hypertonic saline after other therapies have been maximized
  • Human evidence is limited to case reports
  • Consider Hypertonic Saline for TCA toxicity if sodium bicarbonate ineffective and pH of 7.50-7.55 has been reached
hypertonic saline conclusions17
Hypertonic Saline: Conclusions
  • Should Hypertonic Saline be used instead of sodium bicarbonate?
  • NO
    • Lots of evidence for sodium bicarb and not much for hypertonic saline
    • Needs more study
phenytoin
Phenytoin
  • Theory: increases AV conduction thus enhances delivery of supraventricular impulses and suppresses ventricular rhythms; also decreases re-entry
  • BUT isn’t phenytoin a Na+ channel blocker ---------------- could make things worse!
phenytoin20
Phenytoin
  • Goldfranks 2003
    • Not recommended
  • Ford 2001
    • Not even discussed
  • So what evidence is there?
phenytoin21
Phenytoin
  • Callaham. J Pharmacol Exp Ther. 1988
    • Dog model
    • Control group: amitriptyline infusion
    • Experimental group: phenytoin loading before amitriptyline infusion
    • Results
      • No differences in physiologic parameters
      • Ventricular tachycardia dramatically increased in phenytoin group
phenytoin22
Phenytoin
  • Kulig. Vet Hum Toxicol 1984 (abstract)
    • Canine model
    • Amitiptyline until QRS 160 msec
    • Phenytoin pretreatment and rescue
    • No bicarb, no pressors
    • Phenytoin prevented ventricular arrythmias only when given as pretreatment
    • Details not provided
phenytoin23
Phenytoin
  • Mayron. Ann Emerg Med 1986.
    • Rabbit model
    • Amitripyline
    • Looked at “prophylaxis” and “rescue” treatment with phenytoin
    • Outcome measure was dose of amitriptyline necessary to cause wide QRS/arrythmia or death
    • NO BP data
    • Specifics of QRS width not presented
phenytoin24
Phenytoin
  • Mayron. Ann Emerg Med 1986.
    • Phenytoin had NO effect on the amitriptyline dose required to cause “toxicity”
      • No pretreatment: mean 11.4 mg/kg (2 – 39range)
      • Phenytoin pretx: mean 10.0 mg/kg (2.8-23.3 range)
    • Phenytoin had NO effect on the amitriptyline dose required for lethality
    • Phenytoin rescue dose after toxicity had an effect in 2/12 (narrowed the QRS) and no effect in 10/12
  • Concluded: no effect with pretreatment or rescue
phenytoin25
Phenytoin
  • Cantrill. J Emerg Med. 1983
    • Case Report
    • 33yo female with amitripyline overdose
    • BP 70, QRS 170 msec, comatose
    • Intubated, lavaged, charcoal, bicarb drip
    • Phenytoin given
    • QRS narrowed to 90 msec on an ECG 30 minutes later
  • Concluded: Phenytoin is the drug of choice for TCA toxicity
phenytoin26
Phenytoin
  • Several other case reports exist in the literature
phenytoin27
Phenytoin
  • Hagerman. Ann Emerg Med. 1981
    • 10 patients with TCA poisoning
    • 9/10 had wide QRS, 1/10 had normal QRS but wide PR interval
    • Phenytoin dose was 5 – 7 mg/kg
    • Don’t mention the use of bicarb, hyperventilation, normal or hypertonic saline
    • Note: there is NO control group
phenytoin28
Phenytoin
  • Hagerman. Ann Emerg Med. 1981
    • Pre Treatment Post Treatment
    • Mean QRS 130 +/-7 106 +/-6
    • Range QRS 100 – 160 80 – 140
    • Mean PR 204 +/- 12 175 +/- 5
  • Concluded that phenytoin was useful
phenytoin conclusions
Phenytoin:Conclusions
  • Animal Data is conflicting
  • Human data limited to case reports and case series
  • No controlled human data exists
  • Bicarbonate is the treatment of choice for QRS conduction abnormalities
  • Effect of phenytoin in cases refractory to bicarb essentially unknown
    • Hypertonic saline seems like a better choice
what other options are there

What other options are there?

Lidocaine

Magnesium

Propranolol

Topics for another day ………

questions comments
Questions?

Comments?