9.4 Endocrine Crises: DKA, HHS, Thyroid Storm, Myxedema Coma & Adrenal Crisis

ABIM Critical Care Medicine Study Guide Exam

Track your progress as you read

Finished sections get a check mark.

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

9.4 Endocrine Crises: DKA, HHS, Thyroid Storm, Myxedema Coma & Adrenal Crisis

Key Takeaways Explain This Topic AI

The 2024 ADA/EASD/JBDS/AACE/DTS consensus defines DKA as glucose >= 200 mg/dL (or known diabetes), beta-hydroxybutyrate >= 3.0 mmol/L, and pH < 7.3 or bicarbonate < 18; HHS as glucose >= 600 mg/dL with effective osmolality > 300 mOsm/kg, pH >= 7.3, and bicarbonate >= 15.

Delay insulin if serum potassium is < 3.5 mmol/L and replace potassium (about 10 mmol/h) first; add dextrose when glucose falls below 250 mg/dL; DKA resolves when beta-hydroxybutyrate < 0.6 mmol/L with venous pH >= 7.3 or bicarbonate >= 18; overlap basal insulin 2-4 hours before stopping the infusion.

Euglycemic DKA presents with normal or minimally elevated blood glucose ( < 250 mg/dL < 250\text{ mg/dL} < 250 mg/dL ) in patients receiving SGLT2 inhibitors or experiencing profound fasting, demanding ketoacidosis-focused diagnostic workup and dextrose-supplemented insulin infusion.

Thyroid storm management mandates a strict chronological sequence: beta-blockers, thionamides (PTU preferred over methimazole), inorganic iodine administered at least 1 hour AFTER thionamides to prevent the Jod-Basedow phenomenon, and stress-dose corticosteroids.

Myxedema coma requires immediate empiric stress-dose hydrocortisone administered BEFORE thyroid hormone replacement to avoid precipitating fatal adrenal crisis, alongside cautious levothyroxine/liothyronine repletion and passive rewarming.

Last updated: October 2026

Diabetic Ketoacidosis (DKA) vs. Hyperosmolar Hyperglycemic State (HHS)

Diabetic emergencies represent a spectrum of insulin deficiency and counter-regulatory hormone excess (glucagon, catecholamines, cortisol, growth hormone). DKA is driven by absolute or near-absolute insulin deficiency , releasing the brake on lipolysis and hepatic ketogenesis. HHS is characterized by relative insulin deficiency sufficient to suppress hormone-sensitive lipase and prevent massive ketogenesis, but insufficient to stimulate peripheral glucose utilization, resulting in profound hyperglycemia, severe osmotic diuresis, and dehydration.

Diagnostic Comparison: DKA vs. HHS

Diagnostic Parameter Mild DKA Moderate DKA Severe DKA Hyperosmolar Hyperglycemic State (HHS)

Plasma Glucose (mg/dL) ≥ 200 \ge 200 ≥ 200 or known diabetes (any value in euDKA) ≥ 200 \ge 200 ≥ 200 or known diabetes ≥ 200 \ge 200 ≥ 200 or known diabetes ≥ 600 \ge 600 ≥ 600 (frequently 800 − 1200 800-1200 800 − 1200 )

Venous or Arterial pH 7.25 to < 7.30 7.25\text{ to }< 7.30 7.25 to < 7.30 7.00 to < 7.25 7.00\text{ to }< 7.25 7.00 to < 7.25 < 7.00 < 7.00 < 7.00 ≥ 7.30 \ge 7.30 ≥ 7.30

Serum Bicarbonate (mmol/L) 15 to < 18 15\text{ to }< 18 15 to < 18 10 to < 15 10\text{ to }< 15 10 to < 15 < 10 < 10 < 10 ≥ 15 \ge 15 ≥ 15

Urine Ketones ≥ 2 + \ge 2+ ≥ 2 + if BOHB unavailable ≥ 2 + \ge 2+ ≥ 2 + ≥ 2 + \ge 2+ ≥ 2 + None or small

Serum Beta-Hydroxybutyrate ≥ 3.0 mmol/L \ge 3.0\text{ mmol/L} ≥ 3.0 mmol/L ≥ 3.0 mmol/L \ge 3.0\text{ mmol/L} ≥ 3.0 mmol/L > 3.0 − 5.0 mmol/L > 3.0-5.0\text{ mmol/L} > 3.0 − 5.0 mmol/L < 3.0 mmol/L < 3.0\text{ mmol/L} < 3.0 mmol/L (normal or mildly elevated)

Effective Serum Osmolality Variable Variable Variable > 300 mOsm/kg > 300\text{ mOsm/kg} > 300 mOsm/kg (or total osmolality > 320 > 320 > 320 )

Serum Anion Gap Elevated, but no longer a diagnostic or resolution criterion in the 2024 consensus Elevated Elevated (often > 20 > 20 > 20 ) Variable

Mental Sensorium Alert Alert / drowsy Stupor / coma Profound lethargy, stupor, or coma

Average Fluid Deficit ≈ 100 mL/kg \approx 100\text{ mL/kg} ≈ 100 mL/kg ( 5 − 6 L 5-6\text{ L} 5 − 6 L ) ≈ 100 mL/kg \approx 100\text{ mL/kg} ≈ 100 mL/kg ( 6 − 7 L 6-7\text{ L} 6 − 7 L ) ≈ 100 mL/kg \approx 100\text{ mL/kg} ≈ 100 mL/kg ( 7 − 8 L 7-8\text{ L} 7 − 8 L ) ≈ 100 − 200 mL/kg \approx 100-200\text{ mL/kg} ≈ 100 − 200 mL/kg ( 8 − 12 L 8-12\text{ L} 8 − 12 L )

Calculation of Effective Serum Osmolality

Urea diffuses freely across cell membranes and does not generate an osmotic driving force for intracellular water translocation. Therefore, effective osmolality (tonicity) omits BUN:

Effective S Osm = 2 × [ Na + ] + Glucose (mg/dL) 18 \text{Effective } S_{\text{Osm}} = 2 \times [\text{Na}^+] + \frac{\text{Glucose (mg/dL)}}{18} Effective S Osm ​ = 2 × [ Na + ] + 18 Glucose (mg/dL) ​

In HHS, the 2024 consensus threshold is effective osmolality > 300 mOsm/kg > 300\text{ mOsm/kg} > 300 mOsm/kg (or total measured osmolality > 320 > 320 > 320 ); the degree of hyperosmolality, especially above about 320 mOsm/kg 320\text{ mOsm/kg} 320 mOsm/kg , correlates with depressed consciousness. About one-third of patients have mixed DKA-HHS features and are treated as DKA.

Fluid, Insulin, and Electrolyte Resuscitation Protocols

Loading diagram...

Phase 1: Intravascular Volume Resuscitation

Hour 1 : Infuse 1000 to 1500 mL 1000\text{ to }1500\text{ mL} 1000 to 1500 mL (or 15 − 20 mL/kg 15-20\text{ mL/kg} 15 − 20 mL/kg ) of balanced crystalloid (Plasma-Lyte or Lactated Ringer's) or 0.9 % 0.9\% 0.9% normal saline over the first hour to restore effective circulating arterial volume and renal perfusion. Balanced crystalloids reduce the incidence of hyperchloremic metabolic acidosis and accelerate time to DKA resolution compared to normal saline.

Hours 2-24 : Assess corrected sodium ( [ Na + ] + 0.016 × [ Glucose − 100 ] [\text{Na}^+] + 0.016 \times [\text{Glucose} - 100] [ Na + ] + 0.016 × [ Glucose − 100 ] ):

If corrected sodium is normal or elevated: switch to 0.45 % 0.45\% 0.45% saline at 250 to 500 mL/h 250\text{ to }500\text{ mL/h} 250 to 500 mL/h ;

If corrected sodium is low: continue isotonic crystalloid at 250 to 500 mL/h 250\text{ to }500\text{ mL/h} 250 to 500 mL/h .

Phase 2: Potassium Management Rules

Insulin drives potassium into skeletal muscle and hepatic cells. Initiating insulin before correcting hypokalemia causes precipitous cardiac arrest.

Warning

The Potassium Safety Rule :

If Serum K < 3.5 mmol/L K < 3.5\text{ mmol/L} K < 3.5 mmol/L (2024 consensus) : Delay insulin. Start intravenous potassium replacement at about 10 mmol/h 10\text{ mmol/h} 10 mmol/h and continue until serum potassium is above 3.5 mmol/L 3.5\text{ mmol/L} 3.5 mmol/L ; only then start insulin. (The 2009 ADA statement used 3.3 mEq/L 3.3\text{ mEq/L} 3.3 mEq/L , a threshold still seen in older questions.)

If Serum K = 3.5 to 5.0 mmol/L K = 3.5\text{ to }5.0\text{ mmol/L} K = 3.5 to 5.0 mmol/L : Start insulin and add potassium to the IV fluids (commonly 20 to 30 mmol 20\text{ to }30\text{ mmol} 20 to 30 mmol per liter) to keep serum potassium between 4.0 and 5.0 mmol/L 4.0\text{ and }5.0\text{ mmol/L} 4.0 and 5.0 mmol/L .

If Serum K > 5.0 mmol/L K > 5.0\text{ mmol/L} K > 5.0 mmol/L : Do not add potassium yet; recheck at 2 hours after starting insulin and then every 4 hours, because potassium falls rapidly as insulin takes effect.

Phase 3: Continuous Insulin Infusion Kinetics

Dosing : Continuous IV infusion of Regular Insulin at 0.1 units/kg/h 0.1\text{ units/kg/h} 0.1 units/kg/h (or a fixed rate of 0.14 units/kg/h 0.14\text{ units/kg/h} 0.14 units/kg/h without an initial bolus). An initial IV bolus ( 0.1 units/kg 0.1\text{ units/kg} 0.1 units/kg ) is optional but not required.

Target Glycemic Fall : Blood glucose should fall by 50 to 75 mg/dL/h 50\text{ to }75\text{ mg/dL/h} 50 to 75 mg/dL/h . If glucose falls slower than 50 mg/dL/h 50\text{ mg/dL/h} 50 mg/dL/h , verify intravenous line patency; if patent, double the insulin infusion rate hourly until the target fall rate is achieved.

The Dextrose Transition Threshold :

When plasma glucose falls below 250 mg/dL 250\text{ mg/dL} 250 mg/dL in DKA or HHS (2024 consensus; older protocols used 200 mg/dL for DKA and 300 mg/dL for HHS), add 5 % 5\% 5% to 10 % 10\% 10% dextrose to the IV fluids while continuing insulin (usually reduced to about 0.05 units/kg/h 0.05\text{ units/kg/h} 0.05 units/kg/h ), keeping glucose about 150 to 200 mg/dL 150\text{ to }200\text{ mg/dL} 150 to 200 mg/dL in DKA and 200 to 250 mg/dL 200\text{ to }250\text{ mg/dL} 200 to 250 mg/dL in HHS until resolution. In HHS, fluids alone lower glucose substantially, so insulin is started at a lower rate (about 0.05 units/kg/h 0.05\text{ units/kg/h} 0.05 units/kg/h ) unless significant ketonemia is present.

Rationale : In DKA, insulin is required to turn off lipolysis and clear ketoacidemia, which takes significantly longer than normalizing blood glucose. Halting insulin when glucose drops to 200 mg/dL 200\text{ mg/dL} 200 mg/dL allows unabated ketoacid production to resume. Dextrose co-infusion prevents hypoglycemia while allowing insulin-mediated ketoacidosis clearance and preventing rapid osmotic shifts that provoke cerebral edema .

DKA Resolution and Subcutaneous Transition

Under the 2024 consensus, DKA is resolved when serum beta-hydroxybutyrate is < 0.6 mmol/L < 0.6\text{ mmol/L} < 0.6 mmol/L together with venous pH ≥ 7.3 \text{pH} \ge 7.3 pH ≥ 7.3 or bicarbonate ≥ 18 mmol/L \ge 18\text{ mmol/L} ≥ 18 mmol/L (glucose and anion gap are no longer resolution criteria). HHS is resolved when effective osmolality is < 300 mOsm/kg < 300\text{ mOsm/kg} < 300 mOsm/kg , glucose is < 250 mg/dL < 250\text{ mg/dL} < 250 mg/dL , urine output exceeds 0.5 mL/kg/h 0.5\text{ mL/kg/h} 0.5 mL/kg/h , and cognition has returned to baseline.

Important

The Subcutaneous Overlap Rule : Administer basal subcutaneous insulin (glargine, detemir, or degludec) 2 to 4 hours 2\text{ to }4\text{ hours} 2 to 4 hours BEFORE discontinuing the intravenous insulin infusion . The plasma half-life of intravenous regular insulin is only 4 to 5 minutes; abrupt cessation without active circulating subcutaneous basal insulin leads to rapid rebound ketoacidosis within hours.

Euglycemic DKA (euDKA) and SGLT2 Inhibitors

Euglycemic DKA is defined as severe ketoacidosis (anion gap metabolic acidosis with elevated serum beta-hydroxybutyrate ≥ 3.0 mmol/L \ge 3.0\text{ mmol/L} ≥ 3.0 mmol/L and venous pH ≤ 7.30 \text{pH} \le 7.30 pH ≤ 7.30 ) presenting with normal or near-normal blood glucose ( < 250 mg/dL < 250\text{ mg/dL} < 250 mg/dL , frequently 150 − 200 mg/dL 150-200\text{ mg/dL} 150 − 200 mg/dL ) .

Pathophysiological Mechanism

SGLT2 Inhibitors (Empagliflozin, Dapagliflozin, Canagliflozin) : Block the sodium-glucose cotransporter-2 in the early proximal renal tubule, inducing constant, high-volume glucosuria ( 50 − 100 g/day 50-100\text{ g/day} 50 − 100 g/day ). Glucosuria lowers circulating blood glucose without requiring insulin.

The Ketogenic Shift : Depressed blood glucose decreases pancreatic beta-cell insulin secretion and stimulates alpha-cell glucagon release . The resulting low insulin-to-glucagon ratio activates adipose tissue hormone-sensitive lipase, unleashing a flood of free fatty acids into hepatic mitochondria. There, carnitine palmitoyltransferase-1 (CPT-1) channels fatty acids into beta-oxidation and massive synthesis of beta-hydroxybutyrate and acetoacetate .

Clinical Pitfall : Clinicians fail to order ketones or blood gases because "the glucose is not high." euDKA is triggered by physiologic stressors (surgery, sepsis, trauma, acute MI, prolonged fasting) in patients taking SGLT2 inhibitors.

Management : Immediately discontinue the SGLT2 inhibitor. euDKA requires the same insulin infusion protocol as hyperglycemic DKA , but dextrose (D5W or D10W) must be initiated concurrently from the very beginning of insulin therapy to support carbohydrate oxidation while insulin halts ketoacidosis.

Thyroid Storm: Burch-Wartofsky Criteria and Sequential Pharmacotherapy

Thyroid storm is a hypermetabolic, decompensated medical crisis triggered by excessive circulating thyroid hormone ( T 3 / T 4 T_3/T_4 T 3 ​ / T 4 ​ ) combined with massive adrenergic hypersensitivity, often precipitated by systemic infection, surgery, non-compliance, trauma, or iodinated radiocontrast in patients with pre-existing thyrotoxicosis.

Diagnostic Stratification: Burch-Wartofsky Point Scale (BWPS)

The BWPS assigns points across six clinical domains: thermoregulatory dysfunction (temperature up to 30 pts), central nervous system agitation/delirium/coma (up to 30 pts), gastrointestinal-hepatic dysfunction (diarrhea/jaundice up to 20 pts), cardiovascular tachycardia (up to 25 pts), congestive heart failure (up to 15 pts), atrial fibrillation (10 pts), and precipitating event history (10 pts):

• BWPS ≥ 45 \ge 45 ≥ 45 : Highly suggestive of Thyroid Storm (mandates immediate ICU protocol therapy);
• BWPS 25 − 44 25-44 25 − 44 : Impending thyroid storm;

BWPS < 25 < 25 < 25 : Thyroid storm unlikely.

Strict Pharmacologic Sequencing Protocol

Therapy must follow an unvarying, rigid sequence. Violating the timing sequence can precipitate fatal worsening of thyrotoxicosis:

Loading diagram...

Order Drug Class Agent & ICU Dosing Pharmacologic Mechanism Critical Clinical Pitfalls & Timing

1st Beta-Adrenergic Blockade Propranolol 60 − 80 mg 60-80\text{ mg} 60 − 80 mg PO/NG q4h (or 1 − 2 mg 1-2\text{ mg} 1 − 2 mg IV q15m); Esmolol IV infusion ( 50 − 300 μ g/kg/min 50-300\ \mu\text{g/kg/min} 50 − 300 μ g/kg/min ) Controls hyperadrenergic cardiovascular collapse, controls ventricular response in AF; high-dose propranolol inhibits peripheral T 4 T_4 T 4 ​ -to- T 3 T_3 T 3 ​ conversion Esmolol preferred in hemodynamically unstable ICU patients due to ultra-short half-life (9 min), allowing rapid titration if heart failure worsens.

2nd Thionamides Propylthiouracil (PTU) 500 to 1000 mg 500\text{ to }1000\text{ mg} 500 to 1000 mg PO/NG load, then 200 − 250 mg 200-250\text{ mg} 200 − 250 mg q4h. (Alternative: Methimazole 20 − 25 mg 20-25\text{ mg} 20 − 25 mg PO q4-6h) Inhibits thyroid peroxidase (TPO), blocking organification of iodide and coupling of iodotyrosines PTU is preferred over methimazole in thyroid storm because PTU uniquely blocks peripheral 5'-monodeiodinase, immediately halting conversion of T 4 T_4 T 4 ​ to biologically active T 3 T_3 T 3 ​ . (Methimazole lacks this peripheral effect).

3rd Inorganic Iodine SSKI (Saturated Solution of Potassium Iodide) 5 drops PO/NG q6h; Lugol's Solution 8-10 drops PO/NG q8h; or IV Sodium Iodide 500 mg 500\text{ mg} 500 mg q12h High-dose iodide acutely blocks the release of preformed T 4 T_4 T 4 ​ and T 3 T_3 T 3 ​ from thyroid colloid via the Wolff-Chaikoff effect MANDATORY TIMING : Iodine MUST be administered at least 1 hour (ideally 1 to 2 hours) AFTER the thionamide dose . If iodine is given before or concurrently with thionamide, the thyroid gland utilizes the exogenous iodine as substrate to synthesize massive new waves of thyroid hormone, triggering catastrophic worsening of storm ( Jod-Basedow phenomenon ).

4th Corticosteroids Hydrocortisone 100 mg 100\text{ mg} 100 mg IV q8h (or Dexamethasone 2 mg 2\text{ mg} 2 mg IV q6h) Inhibits peripheral T 4 T_4 T 4 ​ -to- T 3 T_3 T 3 ​ conversion; stabilizes vasomotor tone; treats relative adrenal exhaustion Mandatory in all ICU patients with storm. Rapidly reduces circulating T 3 T_3 T 3 ​ levels within hours.

5th Bile Acid Sequestrant Cholestyramine 4 g 4\text{ g} 4 g PO/NG q6h Binds thyroid hormones in the gastrointestinal lumen Interrupts the enterohepatic recirculation of thyroid hormone, accelerating clearance.

Myxedema Coma: Pathophysiology and Emergency Resuscitation

Myxedema coma is life-threatening, end-stage hypothyroidism characterized by multi-system organ slowdown, severe hypothermia, and neuropsychiatric depression. Despite its name, patients need not be in an absolute vegetative coma; profound lethargy, stupor, or delirium in an elderly patient during winter months is diagnostic.

Clinical Tetrad of Myxedema Coma

Severe Hypothermia : Core body temperature frequently < 35.5 ∘ C < 35.5^\circ\text{C} < 35. 5 ∘ C ( < 95 ∘ F < 95^\circ\text{F} < 9 5 ∘ F ), often as low as 28 − 32 ∘ C 28-32^\circ\text{C} 28 − 3 2 ∘ C . Shivering is absent due to profound metabolic depression.

Altered Mental Status : Stupor, apathy, hallucinations ("myxedema madness"), coma.

Hypoventilation and Hypercapnic Respiratory Failure : Depressed hypoxic and hypercapnic central ventilatory drive, combined with diaphragmatic weakness and upper airway obstruction from macroglossia and myxedematous vocal cord edema. Frequently requires early endotracheal intubation.

Cardiovascular Collapse & Severe Bradycardia : Decreased cardiac output, marked sinus bradycardia, low-voltage QRS, flattened/inverted T waves, pericardial effusion, and refractory hypotension.

Classic Laboratory Hallmarks : Profound hypotonic hyponatremia (impaired free water clearance via non-osmotic ADH release), hypoglycemia , elevated creatine kinase (CK), and elevated TSH with low or undetectable free T 4 T_4 T 4 ​ .

Emergency Management Protocol

Caution

The Corticosteroid Priority Rule : In suspected myxedema coma, stress-dose glucocorticoids MUST be administered BEFORE or CONCURRENTLY WITH thyroid hormone replacement! Hypothyroidism markedly downregulates hepatic clearance of endogenous cortisol. Administering thyroid hormone abruptly revs up cellular metabolism and increases hepatic cortisol clearance. If concurrent primary or secondary adrenal insufficiency is present, giving thyroid hormone without steroids will precipitate fatal acute adrenal collapse .

Step 1: Immediate Glucocorticoid Administration :

Draw baseline random cortisol and ACTH;

Administer Hydrocortisone 100 mg 100\text{ mg} 100 mg IV bolus , followed by 100 mg 100\text{ mg} 100 mg IV every 8 hours (or continuous infusion of 200 mg/24h 200\text{ mg/24h} 200 mg/24h ).

Step 2: Thyroid Hormone Replacement :

Intravenous Levothyroxine ( T 4 T_4 T 4 ​ ) : Loading dose of 200 to 400 μ g 200\text{ to }400\ \mu\text{g} 200 to 400 μ g IV slow bolus , followed by a daily maintenance dose of 1.2 μ g/kg/day 1.2\ \mu\text{g/kg/day} 1.2 μ g/kg/day IV (use lower end of dosing in elderly patients or those with known coronary artery disease to avoid precipitating myocardial infarction or fatal ventricular arrhythmias).

Intravenous Liothyronine ( T 3 T_3 T 3 ​ ) : Co-administration of IV T 3 T_3 T 3 ​ is recommended because 5'-monodeiodinase activity (converting T 4 T_4 T 4 ​ to active T 3 T_3 T 3 ​ ) is severely impaired in critical illness. Administer 5 to 20 μ g 5\text{ to }20\ \mu\text{g} 5 to 20 μ g IV loading dose , followed by 2.5 to 10 μ g 2.5\text{ to }10\ \mu\text{g} 2.5 to 10 μ g IV every 8 hours until clinical improvement occurs and oral intake is restored.

Step 3: Passive External Rewarming :

Use warm blankets and heated ambient air. Avoid active aggressive external rewarming (such as heating pads or forced-air warmers set to high), as sudden peripheral cutaneous vasodilation shifts blood away from the core, precipitating fatal refractory distributive shock.

Step 4: Fluid Management :

Avoid hypotonic maintenance fluids; manage severe hyponatremia with water restriction and cautious 3 % 3\% 3% hypertonic saline if seizures or brainstem displacement occur.

Acute Adrenal Crisis in the ICU

Acute adrenal crisis represents a critical lack of circulating glucocorticoids and mineralocorticoids relative to cellular demand during acute physiological stress.

Etiologic Categories

Primary Adrenal Insufficiency (Addisonian Crisis) : Destruction of the adrenal cortex. Causes include autoimmune adrenalitis, bilateral adrenal hemorrhage in severe sepsis ( Waterhouse-Friderichsen syndrome classically secondary to Neisseria meningitidis or Streptococcus pneumoniae ), bilateral adrenal vein thrombosis in antiphospholipid syndrome (APS), or systemic fungal/mycobacterial infections. Involves both glucocorticoid and mineralocorticoid deficiency .

Secondary / Tertiary Adrenal Insufficiency : Pituitary or hypothalamic failure, or abrupt cessation of chronic exogenous corticosteroid therapy (suppressed hypothalamic-pituitary-adrenal [HPA] axis). Mineralocorticoid synthesis (governed by the renin-angiotensin-aldosterone system) remains largely intact; only glucocorticoids are deficient.

Diagnostic Presentation in the ICU

Refractory Vasodilatory Shock : Hypotension unresponsive to aggressive fluid resuscitation and high-dose vasopressor infusions (norepinephrine, vasopressin). Cortisol is required for adrenergic receptor expression and vascular smooth muscle sensitivity to catecholamines; in its absence, systemic vascular resistance (SVR) remains profoundly depressed.

Associated Manifestations : Severe abdominal pain, nausea, vomiting (frequently misdiagnosed as acute surgical abdomen), fever, hypoglycemia , and in primary disease, hyperkalemia, hyponatremia, and hyperpigmentation .

Diagnostic Evaluation and Resuscitation Protocol

Cosyntropin Stimulation Test : Administer synthetic ACTH ( 250 μ g 250\ \mu\text{g} 250 μ g IV). Measure serum cortisol at baseline, 30 minutes, and 60 minutes post-dose. A normal, intact adrenal response produces a peak cortisol ≥ 18 μ g/dL \ge 18\ \mu\text{g/dL} ≥ 18 μ g/dL with older polyclonal immunoassays; with newer monoclonal immunoassays and LC-MS/MS the cutoff is lower (about 14 to 15 μ g/dL 14\text{ to }15\ \mu\text{g/dL} 14 to 15 μ g/dL ), so interpret against the laboratory's assay. However, diagnostic testing must NEVER delay life-saving steroid administration in suspected crisis!

Emergency Treatment Protocol :

Immediate Hydrocortisone : Administer Hydrocortisone 100 mg 100\text{ mg} 100 mg IV bolus , followed by 200 mg 200\text{ mg} 200 mg per 24 hours (administered as 50 mg 50\text{ mg} 50 mg IV every 6 hours or a continuous infusion of 8.3 mg/h 8.3\text{ mg/h} 8.3 mg/h ).

Steroid Selection if Testing Pending : If the clinical team insists on performing an immediate Cosyntropin stimulation test before steroid administration, Dexamethasone 4 mg 4\text{ mg} 4 mg IV may be substituted. Dexamethasone is a potent glucocorticoid that does not cross-react with the serum cortisol radioimmunoassay , allowing uninhibited testing. (Hydrocortisone cross-reacts directly and invalidates subsequent cortisol assays).

Fluid and Glucose Resuscitation : Infuse 5 % 5\% 5% Dextrose in 0.9 % 0.9\% 0.9% Normal Saline (D5NS) to aggressively reverse hypovolemia, correct hyponatremia, and treat life-threatening hypoglycemia.

Role of Mineralocorticoids : Fludrocortisone is NOT needed in acute adrenal crisis. At hydrocortisone doses ≥ 100 mg/day \ge 100\text{ mg/day} ≥ 100 mg/day , hydrocortisone exhibits massive cross-activation of mineralocorticoid receptors that saturates renal tubular transport. Fludrocortisone ( 0.05 − 0.1 mg/day 0.05-0.1\text{ mg/day} 0.05 − 0.1 mg/day PO) is initiated only later, when the hydrocortisone dose is tapered below 50 mg/day 50\text{ mg/day} 50 mg/day .