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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Landiolol- Game Changer in Management Atrial Fibrillation ICU Patients ( Sepsis)

Landiolol is an ultra-short-acting, highly cardioselective β1-blocker developed primarily in Japan and increasingly studied worldwide for rapid rate control in atrial fibrillation (AF), especially in acute care settings.

Key Pharmacologic Properties:

• Half-life: ~4 minutes, enabling rapid titration and withdrawal.

• β1/β2 selectivity: ~255:1 (far higher than esmolol), minimizing bronchospasm and vasodilation.

• Onset: Within minutes.

• Clearance: Independent of hepatic or renal function.

Clinical Benefits:

• Effective rate control in AF (especially postoperative, ICU, or hemodynamically unstable patients).

• Minimal negative inotropic effect, making it safer in patients with impaired LV function compared to other beta-blockers.

• Less hypotension than esmolol or diltiazem due to high β1 selectivity and absence of β2-mediated vasodilation.

• Rapid titration allows tight control of HR without prolonged hemodynamic compromise.

Dosing:

• Initiate without a bolus: e.g., 1–10 mcg/kg/min, titrate every 10–15 minutes.

• Max doses vary by indication but typically up to 40 mcg/kg/min.

• No loading dose is necessary, unlike esmolol.

Use in Sepsis and Critical Illness:

• In septic patients with persistent tachycardia after adequate fluid resuscitation, landiolol has been studied for:

  • Reducing heart rate

  • Preserving or improving cardiac output

  • Avoiding hypotension seen with other beta-blockers

• J-Land Study (2013) and subsequent European studies have shown:

  • Safe HR control in septic shock with no increased risk of hypotension or organ dysfunction

  • Improved diastolic filling, reduced myocardial oxygen demand, and possible anti-inflammatory effects

  • No benefit on controlling persistent sinus tachycardia in sepsis- more recent studies

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Clinical Considerations:

• Ideal for ICU patients with AF, particularly in postoperative cardiac surgery, sepsis, or HF with reduced ejection fraction.

• Caution in patients with severe bradycardia, AV block, or profound shock.

• Offers advantages over amiodarone (slower onset, QT prolongation, poor rate control) and diltiazem (vasodilation, hypotension).

• When transitioning to oral beta-blockers:

  1. Administer the oral beta-blocker

  2. Ten minutes later, reduce the landiolol infusion rate by 50%

  3. If satisfactory control is maintained for at least one hour, discontinue landiolol

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Summary Statement:

Landiolol is an ultra-short-acting, β1-selective IV beta-blocker that provides rapid, titratable rate control in atrial fibrillation with minimal risk of hypotension or negative inotropy. Its excellent hemodynamic profile makes it suitable for use in critically ill patients, including those with sepsis and persistent tachycardia, where conventional beta-blockers may be poorly tolerated.

Shock Index

Explaining shock index (SI)

Shock index (SI) is the ratio of heart rate (HR) to systolic blood pressure (SBP), expressed in beats per minute over mmHg. A normal resting SI is about 0.5 to 0.7 in healthy adults. When there's hypovolemia or shock, SI increases, providing an earlier warning than HR or SBP alone. It helps in risk stratification for conditions like trauma, sepsis, or MI. Thresholds above 0.7 signal abnormality, and values over 1.3 suggest high risk or need for interventions. However, it's limited in certain conditions like beta-blockade or hypertension.

Shock Index (SI) = heart rate ÷ systolic blood pressure
 e.g. 110 beats min⁻¹ ÷ 100 mm Hg = 1.10 (unit‑less)

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Why it matters physiologically

When circulating volume falls or systemic vascular tone drops, the body tries to maintain cardiac output by raising heart rate while SBP drifts downward. The ratio changes earlier than either vital sign alone, so SI flags occult shock before frank hypotension appears. 

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What the number tells you

Range (adult)	Typical interpretation	Clinical evidence/examples
0.5 – 0.7	Normal resting SI in healthy adults	—
> 0.7	Early hemodynamic stress; prompts closer monitoring	Predicts need for intervention in ED sepsis cohort.
≥ 0.9	Abnormal—high likelihood of compensated shock	Used as escalation trigger in obstetric hemorrhage guidelines.
≥ 1.0	Decompensation imminent; higher ICU admission & mortality	Linked to massive‑transfusion requirement after trauma.
≥ 1.4–1.7	Severe shock; urgent resuscitation needed	Strong predictor of adverse outcome in postpartum hemorrhage and septic shock meta‑analyses.

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Key clinical uses

• Trauma & hemorrhage – SI > 0.9 at arrival identifies patients who will need massive transfusion or operative control even when vital signs look “normal.” 

• Sepsis – Persistently elevated SI after fluids correlates with progression to septic shock, vasopressor requirement, and increased 28‑day mortality. 

• Post‑partum hemorrhage – Obstetric protocols use SI ≥ 0.9 for transfer/activation and ≥ 1.3–1.7 for calling massive‑bleed teams. 

• Myocardial infarction, pulmonary embolism, stroke – SI adds prognostic discrimination over SBP or HR alone. 

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Practical points & limitations

• Trend it. A rising SI is often more informative than any single value.

• Age or pediatric adjustment. In children SI normally runs higher; the SIPA score uses age‑specific cut‑offs. 

• Confounders. β‑blockers, pacemakers, atrial fibrillation, high spinal cord injury, or severe pain/anxiety can mask or exaggerate SI.

• Derived variants. Modified SI (HR ÷ MAP), Delta‑SI (arrival vs. prehospital), and Age‑SI (SI × age) may improve accuracy in specific settings but are not yet widely adopted.

Take‑home: Shock index is a quick bedside metric that integrates heart rate and systolic blood pressure into a single early‑warning number—values ≥ 0.9 signal compensated or overt shock and should trigger an immediate search for bleeding, sepsis, cardiogenic failure, or other causes, plus aggressive resuscitation and monitoring.

Explaining Sepsis Reassessment

What the chart auditors are looking for

Under the CMS SEP‑1 six‑hour bundle, any patient who is still hypotensive after the 30 mL kg‑¹ bolus or whose initial lactate is ≥ 4 mmol L‑¹ must have a “repeat volume‑status and tissue‑perfusion assessment” completed and documented by an LIP before the 6‑hour clock runs out. If that note is missing or incomplete, the entire case fails the measure. 

Auditors often key on boiler‑plate phrases such as “Sepsis reassessment completed”—but the note must also satisfy one of the three documentation pathways below.

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1. Focused exam (the classic five‑bullet exam)

A single attestation that the LIP performed a repeat focused exam after the fluid bolus and documented all five of these items:

1. Vital signs

2. Cardiopulmonary exam

3. Capillary‑refill time

4. Peripheral‑pulses assessment

5. Skin findings

If any of the five bullets is missing, the element fails.

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2. Review of ≥ 5 of the 8 CMS‑listed parameters

Instead of a physical exam, the LIP may state that they reviewed at least five of the following eight data points:

• Vital signs

• Cardiopulmonary assessment

• Capillary‑refill

• Peripheral pulses

• Skin colour/condition

• Arterial O₂ saturation

• Urine output

• Shock index (HR/SBP)

Example text that passes:

“Sepsis reassessment completed 14:12. Reviewed VS, cardiopulmonary exam, cap‑refill < 2 s, peripheral pulses 2+, skin warm, UO 45 mL h‑¹.” 

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3. Any 2 of 4 hemodynamic tests

The LIP may instead document that they obtained or interpreted two of these:

• Central‑venous pressure (CVP)

• Central‑venous oxygen saturation (ScvO₂)

• Bedside cardiovascular ultrasound (IVC or LV filling)

• Dynamic fluid‑responsiveness test (passive‑leg‑raise or 250‑mL fluid challenge)

Example:

“Reassessment 15:05 – CVP 10 mm Hg; PLR ↑ stroke volume 16 %. No further fluid indicated.” 

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Practical documentation tips

Tip	Why it helps
Use an EHR smart phrase such as “.sepsisreassessment” that auto-populates all five bullets or prompts you to pick the 8‑parameter route.	Prevents missing elements.
Time‑stamp the note after the bolus but before 6 h.	Auditors match it to the bundle clock.
If nurses collect pulses or urine output, the LIP must explicitly state they reviewed those RN findings.	RN data alone doesn’t count.

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Bottom line:
“Sepsis reassessment completed” only meets SEP‑1 when the note shows either the five‑bullet focused exam, or review of ≥ 5 of CMS’s eight surrogate parameters, or two hemodynamic tests—documented by an LIP and time‑stamped within the 6‑hour window. Anything less will be marked non‑compliant.

Thoracentesis in Acute Decompensated Heart Failure

 Clinical Perspective

What Is New?

•

TAP-IT (Thoracentesis to Alleviate Cardiac Pleural Effusion–Interventional Trial) is the first randomized controlled trial to investigate the effectiveness of upfront therapeutic thoracentesis in addition to standard medical therapy compared with medical therapy alone in patients admitted to the hospital with acute heart failure and pleural effusion.

•

A strategy of referring to upfront therapeutic thoracentesis did not increase the number of days alive out of the hospital over the following 90 days, survival probability, or patient-reported quality of life, and did not reduce the duration of the index admission.

What Are the Clinical Implications?

•

In patients with acute heart failure, left ventricular ejection fraction ≤45%, and sizable pleural effusion (amenable for thoracentesis but less than two-thirds of the hemithorax), reducing filling pressures with diuretics and guideline-directed medical therapy should be the primary treatment target, because the addition of therapeutic thoracentesis does not contribute to a shorter duration of admission or a more favorable prognosis in the following 90 days.

•

Routine referral to upfront therapeutic thoracentesis is not recommended, but can be considered on an individual basis after carefully considering potential complications.

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.073521

direct link to PDF in Paperpile