Advanced Anti- Hypertensive Therapy in the ICU

Intravenous Antihypertensive Options for Refractory Acute Hypertension

When an IV nicardipine infusion (titrated up to its usual ceiling of ≈ 15 mg/h) plus intermittent IV hydralazine fails to achieve the desired blood-pressure target, the next steps are to add—or switch to—agents from different pharmacologic classes. Continuous arterial-line monitoring is essential to avoid precipitous drops in MAP.

Class / Agent	Typical ICU Dosing & Key Pearls	Cautions in This Patient (CKD stage 3, diabetes)
β-Blocker (α1-blocking) Labetalol	• 20 mg IV bolus → repeat 20–80 mg q10 min (max 300 mg) • Continuous 0.5–2 mg / min	Avoid if acute HF, bronchospasm, brady-arrhythmia; synergistic with nicardipine for “balanced” control
Ultra–short-acting β-Blocker Esmolol	500 µg/kg IV load over 1 min → 50–300 µg/kg/min	Ideal for tachy-adrenergic surges; titrate if HR < 60 bpm
Alternative dihydropyridine CCB Clevidipine	1–2 mg/h → double q5–10 min (max 32 mg/h)	Rapid offset (~5 min); lipid emulsion—avoid if TG > 400 mg/dL or egg/soy allergy
Direct arterial/venous vasodilator Sodium Nitroprusside	0.3 µg/kg/min → titrate (max 10 µg/kg/min)	Cyanide/thiocyanate accumulation with > 48 h use or renal failure—limit duration, monitor levels
Venodilator (coronary-friendly) Nitroglycerin	5 µg/min → ↑ by 5–10 µg/min q5–10 min (typ max 200 µg/min)	Best when myocardial ischemia or pulmonary edema present; tachyphylaxis after 24–48 h
Dopamine-1 agonist Fenoldopam	0.1 µg/kg/min → titrate q15 min (max 1.6 µg/kg/min)	Improves renal perfusion & diuresis; watch reflex tachycardia, glaucoma
IV ACE-I Enalaprilat	0.625–1.25 mg IV q6 h (max 5 mg)	Slower onset (15–30 min); monitor K+ & creatinine
α-Blocker Phentolamine	5 mg IV → repeat to total 15 mg	Reserve for catecholamine excess (pheochromocytoma, cocaine)
Adjuncts	• Loop diuretic (furosemide 20–40 mg IV) for volume overload • Sedation/analgesia (dexmedetomidine, fentanyl) to blunt sympathetic drive	Account for volume status, renal function, neurologic monitoring needs

Practical Escalation Strategy

1. Optimize nicardipine first (up-titrate to 15 mg/h).
2. Add a β-blocker—labetalol bolus or esmolol infusion—if tachycardia or high cardiac output contributes.
3. Switch to—or layer—clevidipine if BP remains labile despite maximal nicardipine.
4. Introduce nitroprusside or nitroglycerin for rapid afterload reduction (nitroprusside) or when myocardial ischemia/pulmonary edema coexist (nitroglycerin).
5. Consider fenoldopam instead of nitroprusside in CKD to avoid cyanide toxicity and preserve renal blood flow.
6. Use enalaprilat as an adjunct when renin–angiotensin activation is suspected and BP control remains unsatisfactory.
7. Search for reversible drivers (pain, agitation, fluid overload, drug interactions, missed home meds).

Monitoring & Safety

• Continuous arterial BP and cardiac telemetry.
• Serum creatinine & electrolytes q6–12 h (especially K⁺ with ACE-I / ARB, Na⁺/Cr with nitroprusside).
• Avoid overshoot hypotension—target a 10–20 % MAP reduction in the first hour, then gradual normalization over 24 h unless aortic dissection, eclampsia, or intracranial pathology mandates faster control.

Management of Atrial Fibrillation in the ICU

Overview : Atrial fibrillation (AF) in critically ill patients—whether pre-existing or new-onset (NOAF)—often resolves after the precipitating illness is treated and reversible factors (electrolyte imbalance, volume status, acidosis, adrenergic surge) are corrected.

Hemodynamically unstable patients : Although guidelines recommend immediate electrical cardioversion, success rates in the ICU are <30 % and recurrences are common. Intravenous amiodarone remains the most frequently used drug; landiolol, esmolol, digoxin, and propafenone each have specific advantages depending on ventricular function and blood-pressure profile.

Hemodynamically stable patients : For acute rate control when left-ventricular ejection fraction is >40 %, beta-blockers, diltiazem or verapamil, and digoxin are recommended. Observational data link beta-blockade to lower 90-day mortality, whereas amiodarone is associated with higher mortality; small trials suggest diltiazem achieves faster rate control than amiodarone but at the cost of more hypotension.

Knowledge gaps : Optimal timing of intervention, the best heart-rate target, and whether rhythm or rate control improves outcomes remain uncertain. Most survivors ultimately convert to sinus rhythm by discharge, supporting an individualized rather than one-size-fits-all strategy.

• Key management points for hemodynamic instability
  • Electrical cardioversion: low success & high recurrence in ICU.
  • First-line IV agents: amiodarone, digoxin, esmolol, landiolol.
  • Landiolol: rapid heart-rate control with minimal hypotension.
  • Esmolol: superior early rate control vs amiodarone.
  • Digoxin: useful when LV systolic dysfunction is present.
  • Propafenone: faster conversion and fewer recurrences vs amiodarone in septic shock with preserved LV function.
• Key management points for hemodynamic stability
  • Preferred drugs: beta-blockers, diltiazem/verapamil, or digoxin (LVEF > 40 %).
  • Beta-blockers linked to improved 90-day mortality.
  • Amiodarone widely used but associated with higher mortality in observational data.
  • Diltiazem bolus + infusion outperforms amiodarone for short-term rate control, though hypotension limits use.
• Unresolved questions
  • Wait-and-see vs immediate intervention: no ICU-specific evidence.
  • Ideal heart-rate target in critical illness remains undefined.
  • Long-term impact of rate vs rhythm control strategies needs study.

Risk of Thrombo-Embolic Events & Anticoagulation in Critical-Illness Atrial Fibrillation

New-onset atrial fibrillation (NOAF) during critical illness markedly raises the short-term risk of thrombo-embolic events—most notably in-hospital stroke, limb and visceral ischaemia—because turbulent atrial flow, blood stasis and a pro-coagulant inflammatory milieu compound the baseline comorbidity and immobility of ICU patients. Reported stroke rates reach 2.4 – 7.3 % during admission and up to 9 % for any thrombo-embolic event by 90 days.

Traditional scores created for ambulatory atrial fibrillation (e.g., CHA₂DS₂-VASc) perform poorly in this context: a large cohort showed a C-statistic of only 0.526 for predicting ischaemic stroke during septic episodes, and several studies demonstrate over-estimation of one-year stroke risk in sepsis survivors. Consequently, clinicians lack a validated tool to discriminate which critically ill patients truly need anticoagulation.

Even when a high-risk patient can be identified, optimal timing and agent remain uncertain. Early anticoagulation (< 48 h from AF onset) did not improve a composite of mortality and stroke compared with later initiation, and warfarin or unfractionated heparin frequently fails to maintain therapeutic range in ICU settings. Paradoxically, one large sepsis discharge study linked oral anticoagulant prescriptions—predominantly warfarin—to higher one-year stroke/TIA without extra bleeding, underscoring the need to evaluate direct oral anticoagulants (DOACs) in this population.

Echocardiography provides practical bedside insight: reduced LVEF, left-atrial (LA) dilation and diastolic dysfunction predict NOAF occurrence and burden; large LA area independently correlates with higher AF burden. TOE can visualise left-atrial appendage thrombi, while transthoracic imaging guides rhythm versus rate-control decisions and refines bleeding/thrombotic risk estimates.

Key Take-Home Points

• Incidence & Impact
  • Stroke during ICU stay occurs in 2.4 – 7.3 % of NOAF patients; overall thrombo-embolism up to 9 % by 90 days.
  • Mechanisms: atrial stasis, systemic inflammation, immobility and pro-coagulant drugs/procedures.
• Risk Stratification Gaps
  • CHA₂DS₂-VASc and related scores show poor discrimination (C-statistic ≈ 0.5) in critical-illness AF.
  • No validated dynamic score incorporates ICU-specific factors (vasoactives, acute cardiac function).
• Anticoagulation Uncertainties
  • Ideal timing: early (< 48 h) versus delayed anticoagulation shows no clear benefit.
  • Warfarin achieves therapeutic INR < 50 % of ICU time; associated with paradoxically higher long-term stroke risk post-sepsis.
  • DOACs offer improved safety in ambulatory AF, but robust ICU evidence is lacking—urgent research priority.
• Role of Echocardiography
  • Predictors of NOAF/burden: LVEF < 35 %, LA dilation, diastolic dysfunction, large LA area (> ≈ 24 cm²).
  • Guides therapy choices—rhythm control favoured when atrial kick is critical (e.g., LV relaxation disorder).
  • TOE assessment of LAA velocities/clots refines anticoagulation decisions.
  • A patient in AF with normal echocardiography findings has a 1.5%  risk of intracardiac thrombus formation; this rises to 20%  in a patient with dilated LA, reduced LV systolic function  and an absence of mitral regurgitation 
• Research Priorities
  • Develop ICU-specific thrombo-embolic risk models incorporating dynamic variables.
  • Randomised trials of DOACs versus heparin/warfarin focusing on timing, dosing and monitoring strategies.

Hyponatremia - Differential Diagnosis

Algorithm for Evaluation of Hyponatremia (Na < 135 mmol/L)

1. Confirm true hyponatremia
   • Repeat serum sodium to exclude lab error.
   • Measure Serum Osmolality (S Osm):
     • S Osm > 295 mOsm/kg → Hypertonic hyponatremia (hyperglycemia, mannitol, etc.).
     • S Osm 280–295 mOsm/kg → Isotonic (pseudo-) hyponatremia (severe hyperlipidemia/proteinemia).
     • S Osm < 280 mOsm/kg → Hypotonic (true) hyponatremia — continue below.
2. Assess acuity & symptoms (seizure, coma, severe confusion). If present, begin hypertonic saline while continuing evaluation (see treatment table).
3. Estimate volume status by history & exam:
   • Hypovolemic — orthostasis, tachycardia, dry mucous membranes.
   • Euvolemic — no edema, normal skin turgor.
   • Hypervolemic — edema, ascites, pulmonary rales.
4. Check Urine Osmolality (U Osm)
   • U Osm < 100 mOsm/kg → Primary polydipsia, “beer potomania,” low-solute diet.
   • U Osm ≥ 100 mOsm/kg → proceed to urine sodium.
5. Check Spot Urine Sodium (U Na)
   • Hypovolemic
     • U Na < 20 mmol/L → Extrarenal Na⁺ loss (GI, skin, third spacing).
     • U Na > 40 mmol/L → Renal Na⁺ loss (diuretics, mineralocorticoid deficiency, salt-wasting nephropathy).
   • Euvolemic (U Na > 40 mmol/L, U Osm > 100)
     • SIADH (CNS, pulmonary, malignancy, drugs)
     • Glucocorticoid deficiency (Addison’s)
     • Hypothyroidism
     • Reset osmostat, post-surgery, endurance exercise
   • Hypervolemic
     • U Na < 20 mmol/L → CHF, cirrhosis, nephrotic syndrome.
     • U Na > 40 mmol/L → Advanced renal failure (GFR < 15 mL/min).

Key Lab Patterns & Differential Diagnosis

Volume Status	Urine Osm (mOsm/kg)	Urine Na (mmol/L)	Likely Etiologies
Hypovolemic	> 100	< 20	Extrarenal loss: vomiting, diarrhea, burns, pancreatitis / third-spacing
	> 100	> 40	Renal loss: diuretics, adrenal insufficiency, salt-wasting nephropathy
Euvolemic	> 100	> 40	SIADH, hypothyroidism, glucocorticoid deficiency, SSRIs, carbamazepine
Hypervolemic	> 100	< 20	CHF, cirrhosis, nephrotic syndrome
	> 100	> 40	Renal failure (late CKD/ESRD)
Any	< 100	Variable	Primary polydipsia, beer potomania, low-solute diet

Treatment of Hyponatremia

General rule: Correct Na⁺ no faster than 8–10 mmol/L in 24 h (≤ 18 mmol/L in 48 h) to prevent osmotic demyelination. Monitor serum Na every 2–4 h during active therapy.

Etiology / Category	First-Line Therapy	Adjuncts & Pearls
Severe symptomatic (seizure, coma)	100 mL 3% NaCl IV over 10 min; repeat ×2 if needed (goal +4–6 mmol/L Na)	Continuous neuro monitoring; then infusion 0.5–1 mL/kg/h
Hypertonic (hyperglycemia)	Insulin + IV fluids	Na rises ~1.6–2.4 mmol/L per 100 mg/dL glucose corrected
Isotonic (pseudo-)	Treat hyperlipidemia / paraproteinemia	No Na therapy; use direct ISE for accurate sodium
Hypovolemic — extrarenal	0.9% NaCl IV (1–2 L then maintenance)	Replace K+; stop GI losses
Hypovolemic — renal (diuretics, adrenal)	0.9% NaCl IV; stop diuretic	If adrenal insufficiency: hydrocortisone 100 mg IV q8 h
Euvolemic — SIADH	Fluid restriction ≤ 800–1000 mL/day	+ Salt tabs & loop diuretic; consider urea, demeclocycline, or tolvaptan
Euvolemic — endocrine (hypothyroid / adrenal)	Hormone replacement	Re-check Na after correction
Hypervolemic — CHF, cirrhosis, nephrotic	Fluid & Na restriction + loop diuretic	± Tolvaptan; optimize heart / liver / renal therapy
Hypervolemic — renal failure	Dialysis (IHD or CRRT)	Customize dialysate Na to avoid rapid shifts
Primary polydipsia / beer potomania	Fluid restriction; ↑ dietary solute (protein, salt)	Monitor for rapid Na rise once restriction begins

Disclaimer: For educational use by healthcare professionals. Management should be individualized; seek specialist input for complex cases.

Hyperthermia - alternate approach

🔥 Hyperthermia Syndromes in the ICU – Comparison of Symptoms and Treatment

Comparative Table

Syndrome	Key Triggers	Core Features	Muscle Involvement	Labs	Main Treatments
Neuroleptic Malignant Syndrome (NMS)	Dopamine antagonists (e.g., haloperidol); abrupt withdrawal of dopaminergic drugs	Gradual onset (1–3 days), fever, rigidity, mental status changes, autonomic instability	Lead-pipe rigidity	↑ CK, ↑ WBC, ↑ LFTs, metabolic acidosis	Stop offending agent, dantrolene, bromocriptine, supportive care
Serotonin Syndrome	SSRIs, MAOIs, TCAs, linezolid, fentanyl, tramadol	Rapid onset (<24h), fever, agitation, tremor, hyperreflexia, clonus	Hyperreflexia, clonus	Mild ↑ CK, ↑ WBC	Stop agent, benzodiazepines, cyproheptadine, cooling
Malignant Hyperthermia (MH)	Inhaled anesthetics (e.g., halothane), succinylcholine	Acute onset during/after anesthesia, fever, rigidity, tachycardia, hypercarbia	Generalized rigidity, masseter spasm	↑↑ CK, ↑ K+, metabolic/resp acidosis	Stop agent, dantrolene, cooling, manage acidosis
Heat Stroke	Environmental heat + exertion or impaired thermoregulation	Sudden collapse, AMS, anhidrosis or sweating, core temp >40°C	Possible rigidity or flaccidity	↑ LFTs, ↑ CK, coagulopathy, DIC	Rapid cooling, IV fluids, ICU support
Thyroid Storm	Untreated or undertreated hyperthyroidism, stress, infection	Fever, agitation, tremor, tachycardia, diarrhea, AMS	No rigidity	↑ T3/T4, ↓ TSH	Beta-blockers, PTU, iodine, steroids, cooling
Sepsis/Septic Shock	Infection (bacterial, fungal, etc.)	Fever (or hypothermia), hypotension, AMS, multi-organ dysfunction	No rigidity	↑ lactate, ↑ WBC, positive cultures	Broad-spectrum antibiotics, fluids, vasopressors

🔬 Key Diagnostic Clues & Distinctions

• NMS: Dopamine blockade, rigidity without clonus, onset over days, bromocriptine responsive.
• Serotonin Syndrome: Serotonergic drugs, clonus/hyperreflexia, rapid onset, responds to cyproheptadine.
• MH: Genetic predisposition, intraoperative onset, masseter rigidity, requires dantrolene emergently.
• Heat Stroke: History of heat exposure, absence of drug triggers, rapid cooling is essential.
• Thyroid Storm: History of hyperthyroidism, systemic symptoms, thyroid panel essential.
• Sepsis: Infection signs, positive cultures, lactic acidosis, systemic organ dysfunction.

💊 Medications Summary

Medication	Used In	Mechanism
Dantrolene	NMS, MH	Inhibits Ca²⁺ release from sarcoplasmic reticulum
Bromocriptine	NMS	Dopamine agonist
Cyproheptadine	Serotonin Syndrome	5-HT₂A antagonist
Propranolol / Esmolol	Thyroid Storm	Controls tachycardia, blocks T4 → T3 conversion
PTU / Methimazole	Thyroid Storm	Inhibit thyroid hormone synthesis
Antibiotics	Sepsis	Treat underlying infection

Effect of Xenobiotics on the EKG

ECG Manifestations & Treatment of Major Xenobiotic Overdoses

Quick-reference for critical-care & toxicology settings.
Always consult a poison center / medical toxicologist; consider ECMO for refractory shock.

Xenobiotic Class (common agents)	Key ECG Findings	Electrophysiologic Mechanism	First-Line Treatment	Escalation / Adjuncts
Sodium channel blockers TCAs, quinidine, flecainide, cocaine, diphenhydramine	QRS > 100 ms (often > 160 ms) Dominant R or R′ in aVR > 3 mm / R : S > 0.7 Right-axis deviation, QT prolongation, VT/VF	Fast Na+ channel blockade → slowed phase 0 depolarization & conduction	IV sodium bicarbonate 1–2 mEq/kg bolus → infusion (target pH 7.45-7.55)	Hypertonic saline if acidemic Lidocaine, lipid emulsion Vasopressors, Mg, mechanical pacing / ECMO
Potassium channel blockers Sotalol, amiodarone, dofetilide, some antihistamines/macrolides	Marked QTc prolongation Polymorphic VT / torsades de pointes Bradyarrhythmias	Delayed repolarization via K+ channel inhibition	IV magnesium sulfate 2 g (repeat PRN) Replete K+ (>4.5 mmol/L)	Overdrive pacing 90-110 bpm / isoproterenol Lipid emulsion (lipophilic agents) Hemodialysis for sotalol, defibrillation if unstable
Digoxin (cardiac glycosides)	Bradycardia, high-grade AV block Atrial tachycardia + 2:1 block Bidirectional VT, PVCs “Reverse-tick” ST sagging	Na⁺/K⁺-ATPase inhibition → ↑vagal tone & intracellular Ca²⁺; hyper-K	Digoxin-immune Fab (4–6 vials empiric, titrate)	Atropine, pacing Mg for ventricular arrhythmias Avoid Ca²⁺ in hyper-K unless life-threatening
Beta blockers Propranolol, atenolol, metoprolol, labetalol, sotalol*	Sinus bradycardia, AV block Propranolol: QRS widening (Na+ block) Hypotension, possible VT/VF	β-adrenergic blockade ± membrane-stabilizing Na⁺ block	IV glucagon 5-10 mg bolus → 1-10 mg/h High-dose insulin euglycemic therapy (1 U/kg bolus → 0.5-1 U/kg/h + dextrose)	Calcium salts, vasopressors Lipid emulsion, pacing, ECMO
Calcium channel blockers Verapamil, diltiazem, amlodipine, nifedipine	Bradycardia, AV block (non-DHP) Sinus tachy / minimal ECG change (DHP with vasoplegia) Hypotension, hyperglycemia	L-type Ca²⁺ channel inhibition → ↓nodal conduction & contractility	IV calcium chloride 10–20 mL 10% (or gluconate 30–60 mL) High-dose insulin euglycemic therapy (as above)	Vasopressors (epi/norepi), glucagon Lipid emulsion, methylene blue (refractory vasoplegia) ECMO for profound shock

*Sotalol exhibits both β-blockade & potassium-channel blockade.

High-Dose Insulin Euglycemic Therapy Protocol

For severe β-blocker or calcium-channel-blocker toxicity (and select refractory cardiogenic shock) in an ICU/ED with toxicology support.
Always consult a regional poison center and be prepared for rapid escalation (vasopressors, VA-ECMO).

1 · Indications

• Persistent hypotension, bradycardia, or cardiogenic shock from β-blocker or Ca-channel-blocker overdose despite initial resuscitation.
• Refractory hypoperfusion in mixed or unknown xenobiotic toxicity when NaHCO₃, calcium, vasopressors, and lipid emulsion have failed.

2 · Contra-Indications & Cautions

• Relative: profound hyperglycemia (> 400 mg/dL), severe hypokalemia (< 3.0 mmol/L), DKA.
• Absolute: true insulin allergy (extremely rare) or inability to monitor glucose/potassium frequently.

3 · Drug Preparation

Solution	Concentration	Comment
Regular insulin (Humulin® R / Novolin® R)	1 unit / mL (e.g. 100 U in 100 mL 0.9 % NaCl via syringe pump)	Prime tubing with 20 mL to saturate binding sites.
Dextrose 10 % (D10W)	Standard premix	Titrate to keep BG 100–150 mg/dL.
KCl replacement	10–20 mmol in 100 mL	Maintain K+ 4.0–4.5 mmol/L.

4 · Dosing Algorithm

1. IV Insulin Bolus： 1 unit / kg actual body weight (ABW).
   — If BG < 200 mg/dL, give Dextrose 25 g (50 mL D50W) simultaneously.
2. Continuous Insulin Infusion： Start at 0.5–1 unit / kg / hr.
   — Titrate q15–30 min by 0.5–1 unit / kg / hr to achieve:
   • MAP > 65 mmHg or > baseline, AND/OR
   • Cardiac index > 2.5 L ∙ min⁻¹ ∙ m⁻², AND/OR
   • Lactate trending down > 10 % per hr.
   Maximum commonly reported: 10 unit / kg / hr (rare case reports up to 16).
3. Dextrose Infusion： Start D10W at 0.5 g / kg / hr (≈ 5 mL / kg / hr).
   — Adjust rate or supplement with D50W boluses to keep BG 100–150 mg/dL.
4. Potassium： Check q30 min for first 2 hr, then hourly.
   — If < 3.5 mmol/L, give 20–40 mmol KCl IV over 1 hr.

5 · Monitoring Checklist

• Blood glucose q15 min × 4, then q30 min × 2, then hourly when stable.
• K⁺, Mg²⁺, Phos, iCa²⁺ q1 h for 4 h, then q2 h.
• Arterial blood gas & lactate q1–2 h to track perfusion.
• Continuous ECG & invasive BP (arterial line recommended).
• Urine output q1 h; consider indwelling catheter.

6 · Troubleshooting

Problem	Action
Hypoglycemia (BG < 90 mg/dL)	50 mL D50W IV push; ↑ D10W rate; re-check BG in 5 min.
Hypo-K (< 3.0 mmol/L)	Hold insulin escalation; give 40 mmol KCl IV over 1 hr; resume when K > 3.0.
Volume overload	Switch to D20–30W via central line; judicious diuretics.
No hemodynamic response after 30 min at 2 U / kg / hr	Double rate every 15–30 min up to 10 U / kg / hr; add vasopressors, consider VA-ECMO.

7 · Weaning & Disposition

• Begin taper when vasopressors off & stable for ≥ 2 hr.
• ↓ insulin rate by 50 % every 30 min while maintaining dextrose; stop when at 0.5 U / kg / hr and hemodynamics remain stable.
• Continue dextrose for 1–2 hr after insulin discontinuation; monitor BG q15 min for rebound hypoglycemia.

8 · Sample Adult Order Set (70 kg)

• Regular insulin 70 U IV bolus now
• Start insulin infusion 70 U/hr (1 U/mL) via syringe pump
• Start D10W at 350 mL/hr (0.5 g/kg/hr) via peripheral line
• Titrate insulin by 35 U/hr q15 min to MAP ≥ 65 mmHg
• Check BG q15 min × 4, then q30 min × 2, then q1 hr
• Replace potassium to maintain 4–4.5 mmol/L

Remember： Insulin is an inotrope.
Its positive effects may take 20-30 minutes; be patient and avoid prematurely abandoning therapy.

Last updated May 2025 — Compiled by critical-care.tox

Toxidromes in the ICU

ICU Toxidromes — Quick-Reference Comparison

This table summarizes the hallmark clinical patterns (“toxidromes”) you’ll encounter in critical-care toxicology, with key physiologic clues and first-line treatments.

Toxidrome	Common Agents	Classic Signs & Symptoms	Pupils / Skin	Key Labs / ECG	First-Line Treatment(s)
Anticholinergic	Diphenhydramine, TCA, atropine, jimson weed	“Dry as a bone, hot as a hare, red as a beet, blind as a bat, mad as a hatter”: dry mucosa, urinary retention, tachycardia, hyperthermia, delirium	Mydriasis; dry, flushed skin	± QRS > 100 ms (TCA), metabolic acidosis	IV fluids, active cooling, benzodiazepines for agitation; physostigmine 0.5–2 mg IV only if severe & no conduction delay; NaHCO3 for TCA QRS > 120 ms
Sympathomimetic	Cocaine, amphetamines, MDMA, synthetic cathinones	Severe agitation, tachycardia, hypertension, diaphoresis, hyperthermia, seizures	Mydriasis; moist skin, profuse sweat	Troponin, CK↑, lactate↑; ECG: ischemia, wide QRS if Na+ channel block (cocaine)	Large-dose benzodiazepines, fluids, active cooling; avoid β-blockers alone (unopposed α); vasodilators or phentolamine for refractory HTN
Opioid	Heroin, fentanyl, oxycodone, methadone, loperamide (abuse)	CNS depression, bradypnea/apnea, hypotension, hypothermia	Pinpoint (miosis); skin usually normal	Respiratory acidosis, hypercapnia; QT prolongation (methadone)	Naloxone 0.04–2 mg IV/IN titrated; airway & ventilation support; consider infusion for long-acting opioids
Sedative-Hypnotic	Benzodiazepines, barbiturates, zolpidem, ethanol	CNS depression, ataxia, slurred speech, hypoventilation, hypotension (barbs), hypothermia	Normal – slightly miotic pupils; cool/clammy skin	↓ RR/PaO2; barbs → hypo-Na/HCO3	Airway/ventilation, fluids/pressors; flumazenil only if isolated benzo OD and no seizure risk; consider HD for phenobarb
Cholinergic (Muscarinic & Nicotinic)	Organophosphates, carbamates, nerve agents, physostigmine overdose	Muscarinic: SLUDGE – salivation, lacrimation, urination, diarrhea, GI cramps, emesis; bronchorrhea/bronchospasm. Nicotinic: fasciculations, muscle weakness, paralysis	Miosis; diaphoresis	↓ Cholinesterase activity; hypoxia, mixed acidosis	Atropine 1–3 mg IV q5 min until secretions dry; pralidoxime 2 g IV over 30 min (repeat q1 h then infusion); airway + high-dose benzos for seizures
Serotonin Syndrome	SSRI/SNRI, MAOI, linezolid, tramadol, MDMA; combos	Agitation, hyperreflexia, inducible/sustained clonus, tremor, hyperthermia	Mydriasis; diaphoretic skin	Mild CK↑, metabolic acidosis; ECG usually normal	Stop serotonergic drugs; large-dose benzodiazepines, active cooling; cyproheptadine 12 mg load then 2 mg q2 h (max 32 mg/24 h)

Clinical Pearls

• Mydriasis + dry skin → think anticholinergic; if sweaty, consider sympathomimetic.
• Pinpoint pupils + bradypnea strongly favors opioid toxidrome—even if patient is restless (fentanyl chest-wall rigidity).
• Cholinergic crises kill by airway flooding & paralysis—titrate atropine until secretions dry, not until HR normalizes.
• Wide QRS (>100 ms) after TCA or cocaine = give sodium bicarbonate 1–2 mEq/kg.

Selected References

1. Goldfrank’s Toxicologic Emergencies, 12th ed. 2024.
2. Tintinalli, Emergency Medicine, Ch. Toxicology, 2023.
3. UpToDate. Approach to the poisoned patient. 2025.
4. American Heart Association. 2020 ACLS Toxicology Algorithms.

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Hyperthermia Syndromes

Hyperthermia Syndromes in the ICU — Comparative Guide

This quick-reference table compares the major non-infectious hyperthermia syndromes encountered in critical care, highlighting typical triggers, timing, clinical features, laboratory clues, and first-line treatments.

Syndrome	Typical Trigger(s)	Onset Tempo	Key Neuromuscular Findings	Autonomic / Systemic Features	Lab Clues	First-Line Treatment(s)
Malignant Hyperthermia (MH)	Volatile anesthetics, succinylcholine (RYR1 / CACNA1S variants)	Minutes during anesthesia; may recur post-op	Generalized or masseter rigidity	Rapid ETCO2 rise, tachycardia, late hyperthermia	CK > 10 000, hyper-K+, acidosis, ↑ lactate	IV dantrolene 2.5 mg/kg bolus (repeat to 10 mg/kg), aggressive cooling, treat K+/acidosis
Neuroleptic Malignant Syndrome (NMS)	D2 antagonists (e.g., haloperidol) or dopamine-agonist withdrawal	Days (gradual)	“Lead-pipe” rigidity, bradyreflexia, mutism	Fever, autonomic storms, altered mental status	CK > 1 000, leukocytosis, acidosis	Stop culprit; dantrolene 1–2 mg/kg q6 h or bromocriptine 2.5–10 mg q6-8 h + support
Serotonin Syndrome (SS)	Serotonergic agent(s) / interaction (e.g., SSRI + MAOI)	Hours (< 24 h)	Hyperreflexia, inducible/sustained clonus, myoclonus, tremor	Fever, diaphoresis, mydriasis, hypertension, agitation	Mild CK rise, ± acidosis	Stop serotonergic drugs; cyproheptadine 12 mg load then 2 mg q2 h (max 32 mg/24 h), benzodiazepines, cooling
Thyroid Storm	Stress in hyperthyroid pt (surgery, sepsis, trauma)	Hours – days	Tremor, agitation ± weakness	High fever, tachyarrhythmias, heart failure, GI symptoms	↓ TSH, ↑ free T4/T3	PTU or methimazole, β-blocker, iodide (≥ 1 h post-thionamide), hydrocortisone, cooling
Heat Stroke (Exertional / Classic)	Environmental heat ± exertion, impaired heat dissipation	Acute collapse (mins–hrs)	Ataxia, seizures, possible rhabdo	Core T ≥ 40 °C, CNS dysfunction, DIC	CK↑, ↑ AST/ALT, coagulopathy, ↑ creatinine	Rapid whole-body cooling (ice bath preferred); airway/BP support; dantrolene if shivering refractory

Clonus — Clinical Significance

Clonus is a rhythmic, involuntary, self-sustaining muscle contraction triggered by sudden passive stretch (classically at the ankle). In serotonin syndrome, inducible or sustained (≥ 5-beat) clonus is a key diagnostic clue and correlates with severity. Clonus is typically absent in MH and NMS, where rigidity is “lead-pipe” or generalized.

Selected References

1. Chiew AL et al. Management of serotonin syndrome. Br J Clin Pharmacol. 2025.
2. StatPearls. Neuroleptic Malignant Syndrome. 2024.
3. UpToDate. Serotonin syndrome (serotonin toxicity). 2024.
4. Critical Care Medicine. Malignant Hyperthermia Review. 2024.
5. NCBI Bookshelf. Malignant Hyperthermia. 2024.

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