King: Poisonings treated (and caused) by the ICU!

Clinical Pearls (Assisted by Dr. Shane Kappler)

• Agitated Delirium: Sympathomimetic, Anticholinergic, and Serotonin syndrome 
  • General symptoms of tox induced agitated delirium
    • Hypertension
    • Tachycardia
    • Mydriasis
    • Hallucinations
    • Paranoia
    • Agitation
    • Confusion
    • Diaphoresis (less AC)
    • Clonus/hyperreflexia (Serotonin)
  • Which can all eventually lead down the common pathway of:
    • Seizures
    • Tachyarrhythmias
    • Hyperthermia
    • Rhabdomyolysis 
• Novel drugs of abuse: “Novel psychoactive agents” aka NPAs
  • Ex: Synthetic cannabinoids
  • Primarily affects the CB1 receptor which induce serotonin, dopamine, NE release
  • Symptoms:
    • Largely sympathomimetic and serotonergic in nature (see above)
    • Tremor, diaphoresis, HTN, tachcardia, mydriasis
    • Hallucinations, agitation, delirim, paranoia
    • Choreoform movements
  • SEVERE effects:
    • Uncoupling of oxidative phosphorylation → rhabdomyolysis, Sz, AKI, tachyarrhythmias, hyperthermia
    • Vascular events: CVA, STEMI
    • Non-resolving psychosis
  • Testing for NPAs difficult secondary to unusual chemical structures and frequent changes by labs to stay ahead of regulations; will not show up on UDS
  • Goals of patient management 
    • Control agitation
    • Decrease sympathomimetic output
    • Reduce serotonergic tone
    • Address end organ toxicity
  • Treatment
    • GABA-A agonists, principally benzodiazepines
    • IV fluids
    • Antipsychotics for behavioral control
    • Refractory seizures: benzos→ propofol→ barbiturates
      • Avoid phenytoin, simply not effective
    • Hyperthermia/uncoupling syndrome: GABA agonists, Dexmedetomidine as adjunct (not good for seizures)
    • Hypertensive crisis: Vasodilators (nitro, nicardipine) and GABA agonists
      • Avoid beta-blockers (uninterrupted alpha effect)
• Newer antidotes
  • “Lipid sink” 
    • Isolates drugs outside of tissue
      • Typically used for cardiogenic shock or arrest
    • Usually intralipid; 1.5 ml/kg initially and 0.25 ml/kg/min x 15 minutes
      • Used for lipophilic drugs
    • Reasonable evidence for bupivacaine and has also been used for other local anesthetics
      • “Scattered evidence” for cardiac sodium channel blockers (flecainide, TCAs, cocaine, diphenhydramine), CCBs, beta-blockers, antipsychotics
    • Adverse effects:
      • Pancreatitis, ARDS, AKI, and worsening shock
      • Can interfere with CRRT and ECMO
  • Methylene blue
    • Established role in methemoglobinemia
    • Used in vasoplegia post cardiac surgery
      • Potential use in refractory shock– makes less responsive to NO vasodilation through blocking guanidine cyclase activity (less cGMP)
    • Scattered case reports and animal studies for CCBs, B-blocker, Amlodipine, septic shock, anaphylactic shock; unclear benefit although could be considered for salvage therapy
  • Hydroxocobalamin
    • Combines with CN to make vitamin B12
      • Most frequently used for smoke inhalation/cyanide
      • Evidence that it scavenges nitric oxide
    • Case for cardiac surgery vasoplegia
    • Animal models for Shock: septic, hemorrhagic, and cardiogenic
      • Probably “not ready for prime time”
    • Classified as salvage as last resort after lipids, methylene blue
    • Can cause blood leak alarm on HD

Selected cases and key points

• Serotonin Syndrome
  • Excessive stimulation of 5HT1a + 5HT2a receptors
    • Hyperreflexia and clonus are pathognomonic (if not present consider other diagnosis)
  • Serotonergic drugs:
    • SSRIs, SNRIs, TCAs, other antidepressants (bupropion)
    • Dextromethorphan, tramadol, meperidine, fentanyl, triptans
    • MAOIs including linezolid and methylene blue, lithium
  • Treatment
    • Benzos, benzos, benzos (or propofol)
    • Dexmedetomidine (as adjunct only)
    • Cyproheptadine for mild cases (oral, can cloud picture)

NEJM

Nature

• Cefepime toxicity
  • Cefepime crosses blood brain barrier, acts as GABA antagonist
    • High levels→ renal failure
  • Adverse effects:
    • Myoclonus, encephalopathy, agitation, seizures, death
  • Treatment
    • Discontinuation, GABA agonists, hemodialysis
• Excipient toxicity
  • Lorazepam and phenytoin dissolved in propylene glycol which is metabolized to lactic acid
  • Bumetanide infusions can cause myalgias due to excipient
  • Propofol-Related Infusion Syndromet
    • Believed to be related to lipids in propofol compounded over prolonged, high-dose use.
    • Can see refractory bradycardia/asystole, rhabdo, lactic acidosis, shock
  • Extra fact: Ethylene glycol?
    • Calculate “lactate gap”
      • Some blood gas analyzers use lactate oxidase, which misreads glycolic acid (ethylene glycol metabolite) as lactic acid

10 poisonings that scare me! 

1. Salicylates
   • Danger of not recognizing patient acuity
2. Buproprion XL formulations
   • Risk fo late-onset szs
3. Long-acting opioids
   • Risk of resedation, must be watched carefully
4. TCAs
   • Danger of abrupt decompensation
5. Baclofen
   • Unrecognized withdrawal syndrome after overdose resolved
6. CCBs
   • Refractory hypotension
7. INH
   • Risk of refractory seizures
8. CO
   • Misdiagnosis
9. HF acid (wheel cleansers)
   • Acute torsades and/or V fib (QTc: 700-800)
10. Any sedative-hypnotic (Baclofen, TCA, barbs)
    • Misdiagnosis of brain death by clinical and EEG findings