Study guide
28.3 Specific Poisonings: Sodium-Channel Blockers, Lithium, Valproate, Theophylline, Iron, Sulfonylureas & Methemoglobinemia
ABIM Critical Care Medicine Study Guide Exam
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1 Chapter 1: Exam Orientation: Format, Blueprint & Study Strategy
1.1 ABIM Critical Care Medicine Exam: Format, Blueprint & Study Strategy
2 Chapter 2: Acute Respiratory Failure & ARDS
2.1 ARDS Definition, Pathophysiology & Phenotypes 2.2 Lung-Protective Mechanical Ventilation 2.3 Refractory ARDS: Prone Positioning, Neuromuscular Blockade & VV-ECMO
3 Chapter 3: Obstructive Airways, Pulmonary Vascular & Pleural Emergencies
3.1 Severe Asthma & COPD Exacerbations in the ICU 3.2 Massive & Submassive Pulmonary Embolism 3.3 Pulmonary Hypertension & Right Ventricular Failure in the ICU 3.4 Massive Hemoptysis, Complex Pleural Effusions & Thoracic Drainage
4 Chapter 4: Airway, Parenchymal & Nonthrombotic Pulmonary Emergencies
4.1 Airway Management, Upper-Airway Obstruction & Artificial-Airway Complications 4.2 Diffuse Alveolar Hemorrhage, Interstitial Lung Disease, Pulmonary Vasculitis & Noncardiogenic Edema 4.3 Severe Community-Acquired & Viral Pneumonia 4.4 Nonthrombotic Embolism (Air, Fat, Amniotic Fluid, Tumor, Septic) & Acute Chest Syndrome
5 Chapter 5: Mechanical Ventilation Modes, Dyssynchrony & Liberation
5.1 Mechanical Ventilator Modes & Advanced Breath Delivery 5.2 Patient-Ventilator Dyssynchrony & Waveform Analysis 5.3 Ventilator Liberation, Spontaneous Breathing Trials & Post-Extubation Support
6 Chapter 6: Shock Syndromes & Hemodynamic Principles
6.1 Shock Classification, Cellular Pathophysiology & Biomarkers 6.2 Hemodynamic Monitoring: Arterial Lines, CVP & Pulmonary Artery Catheter 6.3 Dynamic Assessment of Fluid Responsiveness & Resuscitation Targets
7 Chapter 7: Vasoactive Therapies & Mechanical Circulatory Support
7.1 Vasopressors & Inotropes: Pharmacology & Clinical Titration 7.2 Temporary Mechanical Circulatory Support: IABP, Impella & TandemHeart 7.3 Venoarterial ECMO (VA-ECMO) & Differential Hypoxemia 7.4 Post-Cardiac Arrest Care, Targeted Temperature Management & Neuroprognostication
8 Chapter 8: Acute Kidney Injury & Renal Replacement Therapy
8.1 KDIGO AKI Classification, Etiologies & Diagnostic Evaluation 8.2 Continuous Renal Replacement Therapy (CRRT) vs Intermittent Hemodialysis 8.3 Indications & Timing for RRT in Critical Illness: AKIKI & STARRT-AKI
9 Chapter 9: Electrolyte, Acid-Base & Endocrine Emergencies
9.1 Severe Dysnatremias: Hyponatremia, Hypernatremia & Osmotic Demyelination 9.2 Potassium, Calcium, Magnesium & Phosphate Disorders 9.3 Complex & Mixed Acid-Base Disorders: Boston vs Copenhagen vs Stewart 9.4 Endocrine Crises: DKA, HHS, Thyroid Storm, Myxedema Coma & Adrenal Crisis
10 Chapter 10: Glycemic Control, Hyperammonemia, Pituitary & Adrenal Disorders
10.1 ICU Glycemic Control & Severe Hypoglycemia 10.2 Non-Hepatic Hyperammonemia & Metabolic Encephalopathy 10.3 Pituitary Emergencies, Adrenal Excess & Critical Illness-Related Corticosteroid Insufficiency
11 Chapter 11: Acute Coronary Syndromes & Cardiac Arrhythmias
11.1 Acute Coronary Syndromes & Mechanical Complications of Myocardial Infarction 11.2 Critical Tachyarrhythmias: Atrial Fibrillation with RVR, VT & VF 11.3 Critical Bradyarrhythmias, Conduction Blocks & Temporary Cardiac Pacing
12 Chapter 12: Acute Heart Failure, Valvular & Pericardial Emergencies
12.1 Acute Decompensated Heart Failure & Cardiogenic Pulmonary Edema 12.2 Acute Valvular Regurgitation & Prosthetic Valve Emergencies 12.3 Pericardial Tamponade & Acute Aortic Syndromes
13 Chapter 13: Myocardial Disease, Hypertensive & Cardiac Device Emergencies
13.1 Fulminant Myocarditis, Stress & Peripartum Cardiomyopathy, and Hypertrophic Cardiomyopathy 13.2 Hypertensive Emergencies & Ruptured Abdominal Aortic Aneurysm 13.3 Implanted Cardiac Devices, LVAD Emergencies & Electrical Storm
14 Chapter 14: Sepsis & Systemic Infectious Diseases
14.1 Sepsis-3 Definitions & Surviving Sepsis Campaign 2026 Guidelines 14.2 Refractory Septic Shock & Adjunctive Therapies 14.3 Multidrug-Resistant Pathogens & Antimicrobial Stewardship in the ICU
15 Chapter 15: ICU-Acquired & Severe Focal Infections
15.1 Hospital-Acquired & Ventilator-Associated Pneumonia 15.2 Central Line-Associated Bloodstream Infections & Catheter-Associated UTIs 15.3 Intra-Abdominal Sepsis, Necrotizing Soft Tissue Infections & CNS Infections
16 Chapter 16: Focal, Special-Host & Systemic Infections
16.1 CNS Infections Beyond Bacterial Meningitis: Encephalitis, Brain Abscess & Epidural Abscess 16.2 Infections in the Immunocompromised Host, Tropical & Bioterror Infections 16.3 Infective Endocarditis, Device Infections & Other Focal Cardiovascular Infections 16.4 Antimicrobial Pharmacokinetics, Allergy, Toxicity & Infection Prevention 16.5 Gastrointestinal & Hepatobiliary Infections: Fulminant C. difficile, Typhlitis, CMV Colitis & Abscesses
17 Chapter 17: Neurocritical Care & Coma
17.1 Coma, Altered Mental Status & Acute Delirium in the ICU 17.2 Status Epilepticus & Non-Convulsive Status Epilepticus 17.3 Acute Ischemic Stroke & Intracranial Hemorrhage
18 Chapter 18: Cerebrovascular Syndromes, Encephalopathy & Withdrawal States
18.1 Cerebral Venous Sinus Thrombosis, PRES & Reversible Cerebral Vasoconstriction Syndrome 18.2 Alcohol & Sedative Withdrawal, Wernicke Encephalopathy & Drug-Induced Encephalopathy
19 Chapter 19: Intracranial Hypertension & Neuromuscular Weakness
19.1 Intracranial Pressure Monitoring, Cerebral Perfusion & Tiered ICP Management 19.2 Acute Neuromuscular Respiratory Failure, ICU-Acquired Weakness & Brain Death Determination
20 Chapter 20: Traumatic Brain Injury, Spinal Cord Injury & Toxin-Mediated Paralysis
20.1 Traumatic Brain Injury Management & Paroxysmal Sympathetic Hyperactivity 20.2 Acute Spinal Cord Injury, Neurogenic Shock & Autonomic Dysreflexia 20.3 Toxin-Mediated Paralysis & Neuromuscular Crises: Botulism, Tetanus, Tick Paralysis & Myasthenic Crisis
21 Chapter 21: Gastrointestinal, Hepatic & Abdominal Emergencies
21.1 Acute Upper & Lower Gastrointestinal Bleeding in the ICU 21.2 Acute Liver Failure & Severe Acute Pancreatitis 21.3 Abdominal Compartment Syndrome & Acute Mesenteric Ischemia
22 Chapter 22: Luminal GI Emergencies & Complications of Cirrhosis
22.1 Esophageal, Gastric & Bowel Emergencies: Perforation, Obstruction, Ogilvie Syndrome & Colonic Ischemia 22.2 Complications of Cirrhosis: Alcohol-Associated Hepatitis, Hepatorenal Syndrome & Pulmonary Vascular Syndromes
23 Chapter 23: Trauma, Burns & Perioperative Critical Care
23.1 Polytrauma Resuscitation, Damage Control & Massive Transfusion 23.2 Severe Burn Injury, Inhalation Injury & Environmental Emergencies 23.3 Perioperative Critical Care for High-Risk Surgical Patients
24 Chapter 24: Thoracic Trauma, Environmental Injury & Obstetric Critical Care
24.1 Thoracic Trauma: Flail Chest, Pulmonary Contusion, Great Vessel & Tracheobronchial Injury 24.2 Environmental Injury: Drowning, Diving, Altitude, Heat, Cold, Electrical & Radiation 24.3 Obstetric & Genitourinary Emergencies and the Physiology of Pregnancy
25 Chapter 25: Transplantation, Donor Management & Post-Cardiac Surgery Care
25.1 Solid Organ Transplant Recipients & Deceased Donor Management 25.2 Post-Cardiac Surgery Critical Care: Bleeding, Tamponade, Low Output & Vasoplegia
26 Chapter 26: Hematologic Emergencies, Toxicology, Critical Ultrasound & ICU Liberation
26.1 Hematologic Emergencies in the ICU: HIT, DIC, TMA & Anticoagulant Reversal 26.2 Critical Care Toxicology, Toxidromes & Specific Antidotes 26.3 Critical Care Point-of-Care Ultrasound (POCUS) 26.4 ICU Liberation, Analgosedation, Goals of Care & Critical Care Ethics
27 Chapter 27: Transfusion Medicine, Hematologic & Oncologic Disorders
27.1 Transfusion Medicine: Products, Thresholds, Reactions & Apheresis 27.2 Red and White Cell Disorders, Hemoglobinopathies, Factor Deficiencies & Hypercoagulable States 27.3 Oncologic Emergencies, Hematopoietic Cell Transplant Complications & Cellular Therapy Toxicity
28 Chapter 28: Clinical Pharmacology, Adverse Drug Reactions & Specific Poisonings
28.1 Pharmacokinetic Principles, Dose Adjustment & Drug Interactions in Critical Illness 28.2 Adverse Drug Reactions: Anaphylaxis, Severe Cutaneous Reactions & Hyperthermic Syndromes 28.3 Specific Poisonings: Sodium-Channel Blockers, Lithium, Valproate, Theophylline, Iron, Sulfonylureas & Methemoglobinemia
29 Chapter 29: Ethics, Research Methods, Administration & Abdominal Ultrasound
29.1 Advance Care Planning, Nonbeneficial Treatment, Informed Consent & Confidentiality 29.2 Critical Care Research Methods, Statistics, IRB Oversight & Quality Improvement 29.3 Abdominal, Vascular & Procedural Point-of-Care Ultrasound
28.3 Specific Poisonings: Sodium-Channel Blockers, Lithium, Valproate, Theophylline, Iron, Sulfonylureas & Methemoglobinemia
Key Takeaways Explain This Topic AI
A QRS duration above 100 ms after tricyclic overdose predicts seizures and above 160 ms predicts ventricular arrhythmia; treatment is sodium bicarbonate boluses targeting QRS narrowing and a pH of 7.45 to 7.55.
EXTRIP recommends hemodialysis for lithium when the level exceeds 4 mEq/L with impaired kidney function, or above 5 mEq/L, or with severe neurologic features.
Theophylline toxicity causes vomiting, tachyarrhythmia, seizures, hypokalemia, and hyperglycemia, and is an indication for dialysis at lower levels in chronic than in acute poisoning.
Deferoxamine is indicated for iron poisoning with shock, acidosis, persistent vomiting, or a serum iron above about 500 micrograms/dL.
Methylene blue is contraindicated in G6PD deficiency, where exchange transfusion or hyperbaric oxygen is used for severe methemoglobinemia.
Last updated: October 2026
- Sodium-Channel Blocking Agents
- Tricyclic Antidepressants
Tricyclics combine sodium-channel blockade (wide QRS, negative inotropy), anticholinergic effects, alpha-1 blockade (hypotension), potassium-channel blockade (QT prolongation), and amine reuptake inhibition.
ECG predictors : a QRS above 100 ms predicts seizures, a QRS above 160 ms predicts ventricular arrhythmia, and a terminal rightward 40 ms axis deviation (a prominent R in aVR, S in I and aVL) is characteristic.
Management :
Sodium bicarbonate : 1 to 2 mEq/kg boluses repeated for QRS narrowing and hypotension, then an infusion; target a serum pH of about 7.45 to 7.55 . Both the sodium load and alkalinization reduce channel binding. Hypertonic saline is an alternative when alkalemia limits bicarbonate.
Seizures : benzodiazepines. Avoid phenytoin , which is itself a sodium-channel blocker.
Hypotension : fluids, then norepinephrine (direct-acting) rather than dopamine.
Arrhythmias : bicarbonate and magnesium; lidocaine is the antiarrhythmic of choice if needed. Avoid class IA and IC agents, and avoid amiodarone (which prolongs QT and causes hypotension).
Avoid physostigmine in tricyclic overdose: it has precipitated bradyasystolic arrest.
Lipid emulsion and VA-ECMO for refractory cardiovascular collapse.
Other sodium-channel blockers follow the same logic: diphenhydramine in massive overdose, carbamazepine, cocaine, propranolol (membrane-stabilizing), flecainide and other class I agents, hydroxychloroquine (also causing hypokalemia, treated with bicarbonate, potassium, and high-dose diazepam), and bupropion (seizures and wide complex).
Local anesthetic systemic toxicity : neurologic excitation then cardiovascular collapse after regional anesthesia; treat with 20% lipid emulsion (1.5 mL/kg bolus then infusion), reduced-dose epinephrine, benzodiazepines, and prolonged resuscitation with ECMO standby. Avoid vasopressin, calcium-channel blockers, beta-blockers, and local anesthetic antiarrhythmics.
Lithium
Acute toxicity : gastrointestinal symptoms predominate early, with neurologic features developing as lithium distributes into cells.
Chronic toxicity : neurologic findings dominate at lower levels (tremor, ataxia, confusion, myoclonus, seizures), often precipitated by volume depletion, thiazides, NSAIDs, ACE inhibitors or ARBs , or kidney injury.
Other effects : nephrogenic diabetes insipidus, hypothyroidism, hypercalcemia, and a low or negative anion gap from the unmeasured cation. Leukocytosis and ECG changes occur.
Management :
Volume resuscitation with isotonic saline to restore kidney clearance; stop lithium and interacting drugs.
Whole-bowel irrigation with polyethylene glycol for sustained-release preparations; activated charcoal does not bind lithium.
Hemodialysis (EXTRIP 2015) : recommended when the level is above 4 mEq/L with impaired kidney function , or above 5 mEq/L , or with severe neurologic features such as seizures or decreased consciousness; also suggested when the expected time to reach a level below 1 mEq/L exceeds 36 hours. Levels rebound after dialysis as lithium leaves cells, so recheck and repeat as needed.
SILENT syndrome (syndrome of irreversible lithium-effectuated neurotoxicity) can leave permanent cerebellar deficits.
Valproate
Features of severe overdose : central nervous system depression and coma, hyperammonemia (with or without hepatic injury), metabolic acidosis, hypernatremia from sodium valproate load, hypocalcemia, cerebral edema, and pancreatitis or marrow suppression.
Management :
Supportive care and airway protection; activated charcoal early.
L-carnitine 100 mg/kg IV (then 15 mg/kg every 4 to 6 hours) for hyperammonemia and hepatotoxicity.
Hemodialysis (EXTRIP 2015): recommended for a valproate concentration above about 1,300 micrograms/mL, or for coma, respiratory depression requiring mechanical ventilation, acute hyperammonemia, or a pH of 7.10 or less; suggested above about 900 micrograms/mL. Protein binding saturates at high concentrations, which makes the drug dialyzable.
Monitor ammonia and liver function; see also the hyperammonemia section.
Theophylline and Other Xanthines
Toxicity : adenosine antagonism and catecholamine release produce vomiting, tachycardia, tachyarrhythmias, agitation, tremor, and seizures that are often refractory.
Metabolic signature : hypokalemia, hypophosphatemia, hypomagnesemia, hyperglycemia, and a lactic and metabolic acidosis .
Acute versus chronic : acute overdose causes toxicity at higher levels (above about 90 to 100 micrograms/mL), while chronic accumulation causes seizures at much lower levels (as low as 40 to 60 micrograms/mL) in older patients.
Management :
Multiple-dose activated charcoal (theophylline has enterohepatic and enteroenteric recirculation).
Benzodiazepines, then barbiturates , for seizures; avoid phenytoin , which is ineffective.
Beta-blockade (esmolol, with caution in asthma) for tachyarrhythmia with hypotension.
Potassium replacement , recognizing that hypokalemia is a shift and will rebound.
Hemodialysis for seizures, life-threatening arrhythmia, shock, or a very high level (EXTRIP recommends it above 100 micrograms/mL in acute poisoning and above 60 micrograms/mL in chronic toxicity, or at lower levels with severe features). Caffeine overdose follows the same approach.
Iron
Five phases : gastrointestinal (0 to 6 hours, with vomiting and hematemesis), apparent improvement (6 to 24 hours), shock with metabolic acidosis and hepatotoxicity (12 to 48 hours), hepatic failure (2 to 3 days), and late gastric outlet obstruction from scarring (weeks).
Diagnosis : a serum iron level 4 to 6 hours after ingestion (toxic above about 350 micrograms/dL, severe above 500), an anion gap acidosis, radiopaque tablets on abdominal radiograph, and leukocytosis with hyperglycemia.
Management :
Whole-bowel irrigation for large ingestions; charcoal does not bind iron.
Aggressive fluid resuscitation.
Deferoxamine 15 mg/kg/h IV for shock, acidosis, persistent vomiting, lethargy, or a serum iron above about 500 micrograms/dL. It turns urine "vin rose." Watch for hypotension (infusion rate-related), ARDS with prolonged infusion beyond 24 hours, and Yersinia infection risk.
Endoscopy or surgery for gastric bezoars.
Sulfonylureas and Other Antihyperglycemics
Sulfonylureas and meglitinides : prolonged hypoglycemia; treat with dextrose plus octreotide 50 to 100 micrograms subcutaneously every 6 to 12 hours to suppress insulin secretion, and observe for at least 24 hours after the last octreotide dose (see the hypoglycemia section).
Metformin : overdose or accumulation in kidney failure causes metformin-associated lactic acidosis with a very high lactate and severe acidemia. Treat with supportive care, bicarbonate for severe acidemia, and hemodialysis (EXTRIP recommends it for a lactate above 20 mmol/L, pH of 7.0 or less, or failure of standard measures), which corrects acidosis and removes the drug.
Insulin overdose : dextrose infusion with potassium replacement and prolonged observation.
GLP-1 receptor agonists and DPP-4 inhibitors : rarely cause hypoglycemia alone, but cause vomiting, pancreatitis, and delayed gastric emptying that matters for aspiration risk.
SGLT2 inhibitors : euglycemic ketoacidosis (see the endocrine section).
Methemoglobinemia
Mechanism : oxidation of heme iron to the ferric state, which cannot bind oxygen and shifts the remaining hemoglobin's dissociation curve leftward.
Causes : dapsone , local anesthetics ( benzocaine , prilocaine), nitrates and nitrites (including "poppers"), phenazopyridine, sulfonamides, rasburicase, nitric oxide, aniline dyes, and well water nitrates.
Clues :
Cyanosis that does not improve with oxygen .
A saturation gap : pulse oximetry reads around 85% (often fixed) while the arterial PaO2 and calculated saturation are normal or high.
Chocolate-brown blood that does not turn red on exposure to air.
Co-oximetry confirms the methemoglobin fraction.
Severity : symptoms begin around 15% to 20% (headache, fatigue), with dyspnea and confusion by 30% to 50%, and seizures, acidosis, arrhythmia, and death above about 50% to 70%. Anemia makes any fraction more dangerous, since the absolute functional hemoglobin is lower.
Treatment :
Remove the agent; give oxygen.
Methylene blue 1 to 2 mg/kg IV over 5 minutes for symptomatic patients or a level above about 20% to 30%, repeated once if needed. It acts through NADPH methemoglobin reductase.
Contraindicated or ineffective in G6PD deficiency (it causes hemolysis and depends on NADPH); use exchange transfusion or hyperbaric oxygen instead.
Avoid methylene blue with serotonergic drugs when possible (serotonin syndrome risk), and note that it transiently makes pulse oximetry read falsely low.
Dapsone-induced methemoglobinemia recurs because of the long half-life and active metabolites: use cimetidine and repeat methylene blue dosing, with activated charcoal for recirculation.
Sulfhemoglobinemia looks similar but does not respond to methylene blue.