Poisonings and Toxicities

Poisonings/Toxicities Part I

Objectives

• Describe common drug toxicities.

• Recognize the signs and symptoms associated with drug toxicities.

• Discuss appropriate management plans for drug toxicities.

• Understand how drug toxicities can impact the geriatric patient.

Drug Overdose Deaths

• United States: The slideshow includes a graph (Figure 1a) illustrating 12-month ending provisional counts of drug overdose deaths in the United States. The graph spans from January 2015 to January 2023, showing both predicted and reported values.

• Alabama: A similar graph (Figure 1a) shows drug overdose deaths in Alabama, with data from January 2015 to January 2023, displaying predicted and reported values.

• United States by Drug Class: Figure 2 presents a breakdown of drug overdose deaths in the United States by specific drugs or drug classes, including:

  • Cocaine (T40.5)

  • Heroin (T40.1)

  • Methadone (T40.3)

  • Natural & semi-synthetic opioids (T40.2)

  • Opioids (T40.0-T40.4, T40.6)

  • Psychostimulants with abuse potential (T43.6)

  • Synthetic opioids, excl. methadone (T40.4)

Initial Evaluation

• Asymptomatic Patient:

  • Assess for potential danger.

  • Consider gut and skin decontamination to prevent absorption.

  • Treat complications as they occur.

  • Observe the asymptomatic patient for the appropriate time interval.

• Symptomatic Patient:

  • Treat life-threatening complications first, before in-depth diagnostic evaluation.

  • Admit these patients to the hospital with close surveillance (ICU).

Complications

• Coma

• Hypothermia

• Hypotension

• Hypertension

• Arrhythmias

• Seizures

• Hyperthermia

Other Treatments

• Antidotes

• Decontamination of the skin

• Decontamination of the eyes

• Gastrointestinal decontamination

• Activated charcoal

• Whole bowel irrigation

• Urinary Manipulation

• Hemodialysis

Acetaminophen & Salicylate Toxicity

• Medications:

  • Acetaminophen: Tylenol, Anacin-3, Combo drugs (Rx: Norco, Tylenol w/Codeine, Vicodin, Percocet; OTC: NyQuil, Unison, Tylenol PM)

  • Salicylate

• Subjective Findings:

  • Asymptomatic early

  • Nausea/Vomiting within 24hrs

  • RUQ pain

  • Hypotension/hypothermia

  • Nausea/Vomiting (acute ingestion) (Both Acet and Salicylate)

  • Fever (Salicylate)

  • Tinnitus (Salicylate)

  • Headache/Dizziness (Salicylate)

• Physical Exam Findings:

  • Hepatotoxicity: jaundice, ⬆INR

  • AMS, stupor, delirium, coma, asterixis, flapping tremor

  • Salicylate:

  • Tachypnea, Cyanosis (Mod. intoxication)

  • Agitation, Confusion, Coma, Seizures, Hyperthermia, CV/pulm collapse/death (Serious intoxication)

• Diagnostics:

• Acetaminophen

  • Acetaminophen level time of arrival

  • Four hours after ingestion

  • ⬆AST (most sensitive)

  • ⬆ ALT, BUN, Cr. T-Bili

  • Prolong PT, Metabolic Acidosis

  • Monitor LA, ALK Phos, PO4

  • Salicylate

  • ABG c/w Respiratory alkalosis with underlying metabolic acidosis.

  • Serum salicylate concentration w/elytes

• Management:

  • Acetaminophen

    • Activated Charcoal (4hrs of ingestion)

    • N-acetylcysteine (Mucomyst)

    • Acetylcysteine IV as Acetadote, diluted in 5% dextrose and given in (3) doses

    • Salicylate:

    • Activated charcoal orally and gastric lavage followed by extra activated charcoal if >10grams ingested.

    • Volume replacement with NS or dextrose with NS to prevent cerebral hypoglycemia

    • Sodium bicarbonate to increase urinary excretion of acids (treat metabolic acidosis)

    • Hemodialysis in patient with e-lyte or acid-base abnormalities

• Additional Info:

• Acetaminophen

  • Toxicity/liver injury seen with doses > 7.5grams (adult).

  • ⬆ risk of hepatic injury w/ETOH, liver disease or taking hepatoxic meds

  • Hemodialysis for massive OD may be needed

  • Salicylate:

  • Diagnosis of salicylate poisoning should be suspected in any patient with metabolic acidosis and confirmed by measuring salicylate levels.

Antidysrhythmic and Digoxin Toxicity

• Medications:

  • Class I antiarrhythmics: Flecainide, Lidocaine, Procainamide, Quinidine

  • Digoxin

• Subjective Findings:

• Class I:

  • Nausea/Vomiting/Diarrhea

  • Dizziness/Blurred Vision

  • Tinnitus/Hearing loss

  • Confusion

  • Digoxin

  • Nausea/Vomiting/Diarrhea

  • Blurred vision/Yellow-Green Halos

  • Anorexia

  • Abdominal pain

  • Fatigue/Dizziness/Confusion/Headache

  • Hallucinations

• Physical Exam Findings:

  • Class I

  • Bradycardia, Hypotension, CV collapse

  • Seizures/Coma/Delirium

  • Respiratory depression

  • Acute lung injury

  • Digoxin:

  • Bradycardia

  • AV block

  • Supraventricular tachydysrhythmias supraventricular bradydysrhythmias. Atrial tachydysrhythmias

  • Ventricular tachycardia/Ventricular dysrhythmias

  • Hypotension

• Diagnostics:

  • Class I

  • Serum levels can confirm OD

  • ECG: Bradycardia wAV block, prolong QRS, PR interval, QTC interval, or Ventricular arrhythmias (Torsade de pointes)

  • Leukopenia

  • Hemolytic anemia

  • Thrombocytopenia

  • Hepatotoxicity

  • Drug-induced lupus w/procainamide OD

  • Digoxin

  • Hyperkalemia in acute OD

  • Digoxin levels > 2.4ng/ml

• Management:

  • Class I

  • Continuous ECG monitoring and e-lyte monitoring

  • Sodium bicarbonate

  • Bradycardia-adm atropine, isoproterenol or transcutaneous or intravenous OD pacing

  • IV lipid emulsion can be used if refractory to other treatments

  • Digoxin

  • Continuous ECG monitoring

  • Monitor K+ levels and maintain high normal range.

  • Dysrhythmias can be managed with lidocaine

  • Bradycardia can be managed with Atropine or transcutaneous external pacing/

  • Activated charcoal can be given if OD detected early

  • Digoxin immune Fab (DigiFab)

Calcium Channel Blockers and Beta Blocker Toxicity

• Medications:

  • CCB: Amlodipine, Bepridil, Diltiazem, Felodipine, Nicardipine, Nifedipine, Nisoldipine, Verapamil

  • Beta Blockers: Propranolol, Timolol, Atenolol, Labetalol, Metoprolol, Nadolol, Sotalol, and Pindolol

• Subjective Findings:

  • Mental status changes (confusion)

  • Light headiness, headache

  • Nausea/Vomiting/Diarrhea

• Physical Exam Findings:

  • Bradycardia

  • Conduction disturbance

  • Hypotension

  • Cyanosis

  • Seizures/Coma/Death

  • Bradycardia/Hypotension

  • CNS depression

  • Delirium/Coma/Seizures

  • Bronchospasms/Respiratory Depression

  • Myocardial depression/Cardiogenic shock

  • Heart failure

  • Pindolol: tachycardia and HTN

  • Labetalol and carvedilol: hypotension

  • Sotalol: prolong TC interval, can lead to torsade de pointes and ventricular fibrillation.

  • Propranolol: seizures and coma

• Diagnostics:

  • AV block

  • Prolong QRS complex

  • Asystole

  • Metabolic Acidosis

  • Hyperglycemia

  • Blood levels not helpful

  • Hyperkalemia

  • Hypoglycemia

  • AV block, prolong QRS, QT prolongation, or asystole on ECG

• Management:

  • Hypotension: calcium chloride via CVL or calcium gluconate via peripheral line

  • Glucagon bolus

  • Atropine, isoproterenol, or transcutaneous cardiac pacing for bradycardia

  • Aggressive GI decontamination when sustained release meds are suspected.

  • Activated charcoal if given early

  • High dose insulin with D50 followed by D10 to maintain euglycemia.

  • IV lipid emulsion for patients who are refractory

  • Continuous cardiac monitoring, 12-lead ECG 1-2 hrs then 6 hrs, monitor glucose and potassium

  • Assess ABCs

  • Glucagon bolus followed by continuous infusion

  • Activated charcoal (ingested within one hour of presentation)

  • Consider whole bowel irrigation if sustained-release preparation

  • Calcium chloride reverse inotropic effect

  • Treat hypotension w/B-adrenergic agonists (titrate vasopressors)

  • IV lipid emulsion has been successful in propranolol overdose

  • Temporary transvenous pacing, IABP and ECMO for refractory shock.

Barbiturate and Anticonvulsants Toxicity

• Medications:

  • Barbiturates: Amobarbital, Meprobamate, Pentobarbital, Phenobarbital, & Secobarbital

  • Anticonvulsants: Carbamazepine, Phenytoin, Valproic Acid (newer agents: Gabapentin, Levetiracetam, Lacosamide, Vigabatrin, & Zonisamide)

• Subjective Findings:

  • Confusion

  • Slurred speech

  • Impaired coordination

  • Drowsiness

  • Stupor (carbamazepine intoxication)

  • Dizziness (newer agents)

• Physical Exam Findings:

  • CNS depression, drowsiness

  • Ataxia

  • Stupor

  • Coma

  • Hypothermia

  • Respiratory depression/Respiratory Acidosis

  • ⬇ or absent DTR, gag, or corneal reflexes

  • Miosis

  • Nystagmus

  • Ataxia

  • AV blocks (carbamazepine)

  • Coma (carbamazepine)

  • Seizures (carbamazepine)

  • Somnolence/Confusion (new agents)

• Diagnostics:

  • Valproic acid can lead to: Hypernatremia, Metabolic Acidosis, Hypocalcemia, Elevated Serum Ammonia, and mild liver ALT. Hypoglycemia may occur as a result of hepatic metabolic dysfunction. In severe cases: Encephalopathy and cerebral edema.

• Management:

  • ABCs, may require intubation/vent support for respiratory acidosis.

  • Single dose of activated charcoal if clinically stable and within one hour of ingestion of medication.

  • Repeat dose of charcoal can enhance elimination of phenobarbital. HD may be needed for patients with severe phenobarbital intoxication

  • Hemodynamic support, includes dopamine or norepinephrine to correct hypotension.

  • Hemodialysis or hemoperfusion for severely intoxicated patients.

  • Venovenous hemodiafiltration can accelerate elimination

  • Recent ingestions: activated charcoal

  • Large ingestions of carbamazepine or valproic acid, especially in sustained-release formulations, can consider whole bowel irrigation.

  • No antidotes. Carnitine can be useful in valproic acid-induced hyperammonemia.

  • Carbapenem antibiotics can reduce serum VPA concentrations.

  • Hemodialysis for massive intoxication with Valproic Acid (levels > 800mg/L) or Carbamazepine levels > 60mg/L

• Additional Info:

  • Valproic acid can mimic Opioid poisoning with coma and small pupils on PE.

Antidepressants & Antipsychotic Toxicity

• Medications:

  • Antidepressants: Amitriptyline, Bupropion, Citalopram, Fluoxetine, Imipramine, Nortriptyline, Protriptyline, Sertraline, Venlafaxine, Trazadone, Paroxetine

  • Antipsychotics: Clozapine, Haloperidol, Loxapine, Olanzapine, Quetiapine, Risperidone, Sertindole, Thioridazine, Ziprasidone

• Subjective Findings:

  • Confusion/AMS

  • Blurred vision

  • Urinary retention

  • Hallucinations

  • Lethargy

  • Deep sleep

  • Dystonia and extrapyramidal symptoms (Rigidity, Stiff Neck and Hyperreflexia)

  • Urinary retention

• Physical Exam Findings:

  • Tachycardia/Arrhythmias

  • Hypotension

  • Seizures

  • Hypothermia or Hyperthermia

  • Anticholinergic effect

  • Tricyclic antidepressants: have anticholinergic effects/cardiotoxic effects (arrhythmias, QRS widening), not seen with SSRIs, or SNRIs.

  • Decreased bowel sounds

  • Cardiovascular alterations

  • Neuroleptic malignant syndrome (increased temperature, rigidity)

  • Hypotension

  • AV block/tachycardia

  • Atrial and ventricular arrhythmias

  • Widened QRS complex, prolong QT interval

• Management:

  • Evidence of CNS or cardiac toxicity within 6 hours of antidepressant ingestion warrants admission to ICU.

  • Drug identification is key since certain antidepressants (tricyclic antidepressants) can have cardiotoxic effects.

  • Activated charcoal: avoid emesis if risk for seizures

  • TCA OD: sodium bicarbonate IV

  • Benzodiazepine to control seizures

  • Supportive measures such as colling blanket to control temperature

  • SSRI and SNRI OD if has evidence of delirium, agitation or enhanced skeletal muscle tone can use cyproheptadine. (Serotonin Syndrome)

  • Monitor for hypotension and treat w/vasopressors

  • Alert then activated charcoal

  • Benztropine mesylate (Cogentin) or diphenhydramine if evidence of extrapyramidal signs

  • NMS symptoms: dantrolene sodium (Dantrium)

  • Seizures, IV benzodiazepines

  • Supportive care, including cooling blankets

  • Monitor for hypotension and treat with vasopressors and IVF.

  • IV sodium bicarbonate for arrhythmias

  • Severe hyperthermia provide rapid neuromuscular paralysis.

• Additional Info:

  • Tricyclic and related cyclic antidepressants are among the most dangerous drugs involved in suicidal OD. They have anticholinergic effects and cardiac depressant properties. Signs of severe intoxication can occur abruptly (within 30-60 min) after acute tricyclic OD.

  • Tricyclic OD should be suspected in any OD patient who presents with anticholinergic side effects and widened QRS intervals or seizures.

Alcohol (Ethanol) and Opioids Toxicity

• Medications:

  • ETOH

  • Opioid: Codeine, Heroin, Hydrocodone, Meperidine, Methadone, Morphine, Opium, Oxycodone, Oxymorphone & Fentanyl

• Subjective Findings:

  • Emotional liability

  • Impaired coordination

  • Nausea/Vomiting

  • Facial Flushing/Diaphoresis

  • Drowsiness/Euphoria (mild intoxication)

  • Mental status change

• Physical Exam Findings:

  • Respiratory Depression

  • Stupor

  • Mydriasis

  • Nystagmus

  • Diplopia

  • Seizures

  • Coma

  • Tachycardia

  • Hypotension

  • Hypoglycemia

  • Pinpoint pupils (miosis) (mild intoxication)

  • Hypotension/Bradycardia/Hypothermia/Coma/Respiratory Arrest (severe intoxication)

  • Pulmonary edema can occur

  • QT interval prolongation and torsades de pointes (Methadone)

  • Seizures (seen with Meperidine, and Tramadol)

• Diagnostics:

  • Blood levels ranging from 50-100mg/dl (mild toxicity)

  • Blood levels ranging from 100-300mg/dl (moderate toxicity)

  • Blood levels 250-400mg/dl (severe toxicity)

  • Electrolyte abnormalities

  • Evaluate toxicology screen (blood) or urine

  • Monitor glucose and serum creatine phosphokinase

• Management:

  • ABC

  • Hemodialysis may be used to reduce ethanol levels in severe toxicity.

  • IV glucose 200-500mg/kg in D50%W or 50% dextrose in patients who have hypoglycemia

  • Pretreatment with thiamine 100mg IV/IM/PO for three days, MVI and folic acid 1mg daily

  • Fluid/e-lytes prn

  • ABCs

  • Continuous ECG monitoring

  • Naloxone (Narcan) 0.4-2mg every 2-3 min prn IV/IM or intranasally.

  • Continuous infusions (0.4-0/8mg/hr) should be considered only if the patient responded to naloxone bolus and required repeat administration.

  • Decontamination with 1gram/kg PO single dose activated charcoal. Protection of airway to prevent aspiration. Large bore OG or NG tube can be used.

  • Consider initiation of medications for opioid use disorder (Buprenorphine)

• Additional Info:

  • Illicit fentanyl derivatives are up to 2000 times more potent than morphine.

  • The opioid epidemic in the US has become increasingly dangerous due to the presence of fentanyl replacement for drugs sold illegally.

  • Death is usually 2/2 apnea or pulmonary aspiration of gastric contents

  • Continuous observation for at least 3 hours after the last naloxone dose is mandatory.

  • Opioid deaths in 2023 were 81, 083, down from 84, 181 in 2022.

Stimulants & Benzodiazepine Toxicity

• Medications:

  • Stimulants: Amphetamine, Cocaine, Dextroamphetamine, Methylphenidate, MDMA (Ecstasy or Molly), Spice & K2

  • Benzodiazepines: Clonazepam, Clorazepate, Diazepam, Flurazepam, Prazepam, & Alprazolam

• Subjective Findings:

  • 3 I’s (Irritability, Increased talkativeness, Insomnia)

  • Dry mouth

  • Anorexia

  • Euphoria/Paranoia

  • Drowsiness/Confusion

  • Slurred speech

  • Unsteady gait

• Physical Exam Findings:

  • Arrhythmias/Heart blocks

  • Anginal chest pain

  • HTN (can lead to ICH, aortic dissection or MI or cause chronic cardiomyopathy)

  • Tachycardia

  • Dilated pupils (mydriasis)

  • Excited Delirium/Seizures

  • Hyperthermia

  • Metabolic Acidosis/Rhabdomyolysis

  • Ataxia

  • Respiratory depression

  • Hypoactive reflexes

• Diagnostics:

  • Presence of amphetamines in the urine

  • Note that many drugs give false-positive results on the immunoassay for amphetamines. Most synthetic stimulants do not react with immunoassay giving false-negative results.

  • Toxicological confirmation and analysis

• Management:

  • Activated charcoal 1gram/kg PO

  • Reduce external stimuli

  • Midazolam (2mg) Diazepam, (5mg IV), Lorazepam (2mg IV) and repeat every 15min until calm, monitor ABC.

  • HTN: Vasodilator such as phentolamine 1-5mg IV), nitroprusside 0.2-8mcg/kg/min and titrate by 0.1mcg/kg/min to titrate SBP < 140mmHG. Nicardipine can also be used or labetalol 10-20mg IV.

  • Treat seizures with Lorazepam 4mg IV or Diazepam 5-10mg IV. Can add phenobarbital 15mg/kg IV for persistent seizure activity

  • Cooling blanket for hyperthermia (if temperature higher than 39-40C)

  • IV fluids to prevent myoglobinuric kidney injury from rhabdomyolysis

  • Monitor for wide complex tachydysrhythmias and QRS complex prolongation. Treat tachyarrhythmias with short acting with esmolol (25-100mcg/kg/min)

  • Monitor BP and support respiratory status. May require intubation.

  • Flumazenil (Romazicon) not recommended for patients who have been provided a benzo for control of ICP or status epilepticus or patients who are showing signs of serious cyclic antidepressant OD or have a history of benzodiazepine tolerance.

  • Gastric lavage or activated charcoal.

• Additional Info:

  • Do not administer pure beta blocker such as propranolol alone as it can result in paradoxical worsening of HTN as a result of unopposed alpha-adrenergic effect.

  • Death or serious morbidity in these cases are usually a result of pulmonary aspiration from gastric contents

Anticoagulants Toxicity

• Medications:

  • Heparin

  • Warfarin, LMWH: Enoxaprin (Lovenox), Dalteparin (Fragmin), Tinzaprin (Innohep)

  • Factor Xa Inhibitors: Fondaparinux (Arixtra), Rivaroxaban (Xarelto), Apixiban (Eliquis), Edoxaban (Savaysa)

  • Direct thrombin inhibitors: Lepirudin (Refludan), Argatroban (Acova), Bivalirudin (Angiomax), Dabigatran (Pradaxa), Desirudin (Iprivask)

• Subjective Findings:

  • Bleeding

• Physical Exam Findings:

  • Severe hemorrhage

• Diagnostics:

  • Heparin: ⬆PTT to 1.5-2.5 times control

  • Warfarin: ⬆ PT to 1.3-2 times control; INR ratio higher than 3 (increased within 12-24 hours and peaks 36-48 hours after OD)

  • SDOACs: specialized coag studies include hemaclot and ecarin clotting assay and anti-factor Xa

• Management:

  • Discontinue drug at the first sign of gross bleeding and determine the INR.

  • Heparin Overdose: Protamine sulfate IVPB over 15-30min 1mg/100u (Max 50mg IVPB over 15-30min

  • LMWH: Protamine Sulfate 1mg/100 units dalteparin or 1mg for enoxaparin if LMWH was given in last 8hrs. Reduce dose by ½ for 8-12hrs. Protamine is not useful >12 hrs.

  • Warfarin: Vitamin K (phytonadione) IM, PO, SC, or IVPB 2.5-10mg (wait for evidence of INR level), use smaller doses if the patient has a medical indication for anticoagulation (i.e., heart valve/LVAD), can also use FFP or both and titrate to desired PT/INR.

  • Vitamin K does not work to review anticoagulant effect of DOACS

  • Apixaban and rivaroxaban bolus of Coag. factor Xa.

  • Dabigatran reversal, idarucizumab (Praxbind) Ingested within 2hrs, consider activated charcoal.

  • Other anticoagulants: use procoagulant reversal agents: PCC, activated PCC.

• Additional Info:

  • If reversal agents are not readily available, then prothrombin complex concentrate (PCC) or activated prothrombin complex concentrate can be used.

Lithium Toxicity

• Medications:

  • Eskalith & Lithobid

• Subjective Findings/Physical Exam Findings:

  • Nausea/Vomiting/Diarrhea

  • Muscles weakness/Tremors/Rigidity/Ataxia

  • Dementia/Delirium/Stupor

  • Seizures/Coma

  • 10% risk of permanent neurological sequelae

• Diagnostics:

  • Lithium levels > 1.5meq/L

  • Elevated BUN/Cr.

  • Hyperglycemia

  • AV block

  • Sinus node arrest

  • Bradycardia

  • Prolong QT interval

  • Leukocytosis

  • Nephrogenic diabetes insipidus can occur with OD and with therapeutic doses

  • Dysfunction of the thyroid and parathyroid glands has been reported with prolonged lithium exposure

• Management:

  • IV NS bolus 1L followed by 100-200ml/hr

  • Activated charcoal is ineffective (not absorbed)

  • Gastric lavage or whole bowel irrigation can be used for acute ingestion (occurred w/in 1 hr) or large quantities of sustained release products ingested. This helps prevent systemic absorption.

  • Supportive care

  • Diuretics for lithium serum levels >2-3 meq/L

  • Hemodialysis in acute intoxication (levels >4meq/L) and symptomatic

  • Benzodiazepines IV for seizure management

Theophylline Toxicity

• Medications:

  • Theophylline

• Subjective Findings/Physical Exam Findings:

  • Vomiting/Hematemesis

  • Restlessness/Agitation/Irritability

  • Tachycardia/PVCs/Atrial Arrhythmias

  • Hypotension

  • Seizures in severe OD

• Diagnostics:

  • Theophylline levels 20-60mg/L in chronic OD

  • Levels of 60-100mg/L in acute OD are associated with seizures and hypotension

  • Hypokalemia

  • Hyperglycemia

  • Metabolic Acidosis

• Management:

  • ABCs

  • Treat arrhythmias

  • Multiple doses of activated charcoal 1gram/kg, followed by 20grams Q2-6 hours until theophylline levels are <20mg/L (”gut dialysis”)

  • Consider whole bowel irrigation.

  • Charcoal hemoperfusion in acute ingestion w/levels >100mg/L, patients with seizures or serious dysrhythmias.

  • Monitor patient for seizures and can treat with midazolam (2mg), lorazepam 2-4mg IV or diazepam 5-10mg IV

  • Use phenobarbital only when escalating doses of benzos are ineffective.

  • Phenytoin is not effective

  • Hypotension and tachycardia respond to beta-blockers therapy even at low doses (esmolol 25-50mcg/kg/min by IV infusion or propranolol 0.5-1mg IV)

  • Hemodialysis is effective in removing theophylline and indicated for patients with status epilepticus or markedly elevated serum levels >100mg/L with acute ingestion or >60mg/L with chronic intoxication.

Hypoglycemic Toxicity

• Medications:

  • Insulin

  • Sulfonylureas, Insulin secretagogues, alpha-glucosidase inhibitor, biguanides, thiazolidinediones, sodium glucose transporter (SGLT2) inhibitors, and peptide analogs or enhancers.

• Subjective Findings/Physical Exam Findings:

  • Hypoglycemia (more likely with insulin and insulin secretagogues)

  • Lactic Acidosis (Metformin with impaired kidney dysfunction)

  • Evidence of Euglycemic diabetic ketoacidosis reported with SGLT2 use

• Management:

  • Provide sugar and carbohydrate-containing food or liquid by mouth

  • IV dextrose if the patient is unable to swallow safely

  • Severe hypoglycemia: start D50W 50mL IV; repeat if needed. Follow up with dextrose-containing IV fluids (D5W or D10W) to maintain glucose >70-80mg/dL

  • Hypoglycemia caused by sulfonylureas and related insulin secretagogues: use Octreotide (blocks pancreatic insulin release). Dose 50-100mcg SQ Q6-12 hours.

  • Admit all patients with symptomatic hypoglycemia or after sulfonylurea OD

  • Observe asymptomatic OD patients for at least 12 hours.

  • Hemodialysis for patients with metformin OD and severe lactic acidosis (lactate >20mmol/L or pH <7.0).

Isoniazid Toxicity

• Medications:

  • INH

• Subjective Findings/Physical Exam Findings:

  • Confusion, slurred speech, and seizures can occur abruptly after acute OD

• Diagnostics:

  • Lactic acidosis out of proportion to the severity of seizures 2/2 to inhibited metabolism lactate.

  • INH is not included in routine toxicology levels, which means serum drug levels are not readily available.

• Management:

  • Seizures may require higher than normal doses of benzodiazepines (lorazepam 3-5mg IV).

  • Administration of pyridoxine (Vitamin B6) as an antidote, 5grams IV over 1-2 minutes, or if the amount ingested is unknown, then gram for gram equivalent.

  • Activated charcoal after large recent ingestions but with caution because of risk of abrupt onset of seizures.

  • Patients taking INH are usually given 25-50 mg of pyridoxine orally daily to help prevent neuropathy associated with the drug.

Gerontological Considerations

• Subjective Findings: Mental status changes in OD and toxicity can be more pronounced.

  • Drowsiness/Decreased alertness

  • Ataxia/Weakness

  • Confusion

  • Agitation/Irritability

  • It’s important to differentiate delirium, drug OD, and dementia

• PE Findings:

  • Altered liver function

  • Altered renal function, monitor creatine clearance

  • Presence of multiple comorbidities

• Management:

  • Treatment as discussed but assess compliance with drug regimens

  • Monitor for polypharmacy

  • Medication reconciliation is important for this patient population

Antidotes