Author:

Michael E.Nelson

Signs and Symptoms

• CNS:
  • Sedation/drowsiness
  • Slurred speech
  • Midrange or small pupils
  • Delirium
  • Coma
• Neuromuscular:
  • Incoordination
  • Slowed voluntary movements
  • Ataxia
  • Hypotension
  • Hyporeflexia/areflexia
• Cardiovascular:
  • Mild depression
  • Rarely lethal if ingested alone
• Respiratory:
  • Mild depression but less than barbiturates
  • Short acting and IV have higher depression
• GI:
  • Nausea, vomiting, diarrhea
• Other:
  • Hypothermia
  • Complications may include cerebral hypoxia, rhabdomyolysis, pressure-induced neuropathies
  • No long-term organ toxicity

Essential Workup

Diagnosis based on:

• History of ingestion or recent injection
• Clinical findings associated with CNS depression/Sedative-Hypnotic toxidrome
• No response to naloxone

Diagnostic Tests & Interpretation

Differential Diagnosis

• Drugs and toxins causing decreased level of consciousness:
  • Hypoglycemics
  • Other sedative-hypnotics (barbiturates, chloral hydrate, GHB, bromides)
  • Antidepressant-antipsychotics
  • Opioids
  • Anticonvulsants
  • Carbon monoxide/cyanide
  • Alcohols
• Nontoxic medical conditions:
  • Hypoxemia
  • Hypothermia
  • Head trauma (intracranial bleeding)
  • Infection (meningitis or encephalitis)
  • Electrolyte and metabolic abnormalities

Prehospital

• Attention to airway and breathing
• Cardiac monitor
• IV access
• Rapid glucose determination
• Obtain pill bottles/pills in suspected overdose

Initial Stabilization/Therapy

• ABCs:
  • Secure airway and assist ventilation with supplemental oxygen to prevent hypoxemia and shock
  • IV access with 0.9% NS
  • Cardiac monitor
• Administer naloxone, thiamine, and dextrose if altered mental status/comatose

ED Treatment/Procedures

• Consider gastric lavage when presenting within 1 hr of life-threatening ingestion with protected airway but should be done cautiously and not routinely
• Activated charcoal (AC) PO or via nasogastric tube (NGT) if airway protected
• No role for diuresis, dialysis, or charcoal hemoperfusion
• Flumazenil (FZ):
  • Competitive BZD-receptor inhibitor
  • Rapidly reverses BZD-induced coma
  • Onset within 1-2 min; peak at 6-10 min; duration 1-2 hr (repeated dosing may be indicated)
  • Efficacy dependent on dose of BZD being antagonized and dose of FZ used
  • Do not administer empirically as part of “coma cocktail” or unknown ingestion
  • May help avert need of endotracheal intubation but has not consistently reversed respiratory depression
  • May be beneficial in shortening hospital stay or as diagnostic maneuver
  • Indications include isolated BZD overdose in nonhabituated user with CNS depression, normal ECG, normal vital signs, and normal neurologic exam
  • Most useful to reverse iatrogenic poisoning (procedural sedation)
  • Contraindications include:
    • Co-ingestions that might lower seizure threshold (tricyclic antidepressants [TCAs])
    • Seizure history or activity
    • Allergy
    • Neuromuscular blockade
    • Do not use if hypotension, hypoxia, arrhythmias, or increased intracranial pressure is present
    • May precipitate withdrawal state including seizures, for which BZDs can no longer be used to treat

Medication

• AC: 1 g/kg PO/NG (ideal is 10:1 ratio of AC:dose of drug)
• Dextrose: D₅₀W 1 amp: 50 mL or 25 g (peds: D₂₅W 2-4 mL/kg) IV if hypoglycemic
• Flumazenil (Romazicon):
  • Initial: 0.2 mg IV over 30 s (adult)
  • If no response: 0.3 mg IV after 30 s
  • If still no response: 0.5 mg IV and repeat q1min if needed, to max dose of 3 mg
  • Continuous infusion at 0.1-1 mg/hr if multiple repeated doses required to maintain response. Continuous infusion not FDA approved
  • Pediatric dosing: Titrate to max cumulative dose of 0.05 mg/kg/d. Continuous infusion at 0.005-0.01 mg/kg/hr has been used
  • Only use in selected patients (see above) as may precipitate seizures or dysrhythmias
  • Monitor after use for resedation (occurs between 20-120 min after use)
• Naloxone (Narcan): 0.04-2 mg (peds: 0.1 mg/kg) IV or IM initial dose
• Thiamine (vitamin B₁): 100 mg IV/IM

Disposition

Follow-up Recommendations

Habituated patients may experience BZD withdrawal after cessation:

• Autonomic instability, tremor, paresthesias, seizures

• KyongYY, ParkJT, ChoiKH. Serial monitoring of sedation scores in benzodiazepine overdose . Am J Emerg Med. 2014;32(11):1438e5-1438e6.
• LeeDC. Sedative-hypnotics. In: HoffmanRS, Howland MA, LewinNA, et al., eds. Goldfrank's Toxicologic Emergencies. 10th ed.New York: McGraw-Hill; 2015:1002-1012, 1069-1075.
• MoellerKE, KissackJC, AtayeeRS, et al. Clinical interpretation of urine drug tests: What clinicians need to know about urine drug screens . Mayo Clin Proc. 2017;92(5):774-796.
• PenningaEI, GraudalN, LadekarlMB, et al. Adverse events associated with flumazenil treatment for the management of suspected benzodiazepine intoxication—A systematic review with meta-analysis of rand omised trials . Basic Clin Pharmacol Toxicol. 2016;118(1):37-44.
• SunEC, DixitA, HumphreysK, et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis . BMJ. 2017;356:j760.

See Also (Topic, Algorithm, Electronic Media Element)

Barbiturate Poisoning

ICD9

969.4 Poisoning by benzodiazepine-based tranquilizers

ICD10

• T42.4X1A Poisoning by benzodiazepines, accidental, init

• T42.4X2A Poisoning by benzodiazepines, intentional self-harm, init

• T42.4X4A Poisoning by benzodiazepines, undetermined, init encntr

SNOMED

• 81914009 Poisoning by benzodiazepine-based tranquilizer (disorder)

• 216530001 Accidental poisoning by benzodiazepine-based tranquilizers (disorder)

• 242832005 Intentional benzodiazepine overdose (disorder)