i work as a emergency physician at tertiary hospital in nepal. i need a protocol of anticholinergic toxidromes. make me a ready to use evidence based protocol. keep the international guideline references and used protocol internationally

Reading File

Now let me search the medical library and PubMed simultaneously for comprehensive information on anticholinergic toxidrome management.

Finding Sources

Searching PubMed

anticholinergic toxidrome management physostigmine

Searching the Web

anticholinergic toxidrome emergency protocol guidelines 2023 2024 physostigmine benzodiazepine

Now let me read the key textbook sections in parallel:

Reading File

Finding Sources

Searching PubMed

anticholinergic poisoning treatment emergency

Excellent - I have the RCT (PMID 33295809) comparing physostigmine vs lorazepam. Let me get its abstract and the Tintinalli's treatment table:

Reading Article

PMID: 33295809

Reading File

Reading Article

PMID: 39978865

Reading Article

PMID: 40791148

I now have sufficient comprehensive data. Let me compile the full evidence-based protocol.Here is your ready-to-use, evidence-based emergency protocol:

ANTICHOLINERGIC TOXIDROME - EMERGENCY MANAGEMENT PROTOCOL

Tertiary Emergency Department - Nepal

Version 1.0 | June 2026 | Review Date: June 2028

SECTION 1: QUICK REFERENCE CARD

Feature	Anticholinergic	Sympathomimetic	Cholinergic
Heart rate	Tachycardia	Tachycardia	Bradycardia
Pupils	Mydriasis	Mydriasis	Miosis
Skin	Dry, flushed	Diaphoretic	Diaphoretic
Bowel sounds	Absent/decreased	Normal/increased	Hyperactive
Bladder	Urinary retention	Normal	Incontinence
Mental status	Agitated delirium	Agitated, alert	SLUDGE/DUMBELS
Temperature	Hyperthermia	Hyperthermia	Normal/low
Mucous membranes	Dry	Wet	Wet

Memory Aid - "Mad as a Hatter, Blind as a Bat, Dry as a Bone, Red as a Beet, Hot as a Hare"

SECTION 2: BACKGROUND & EPIDEMIOLOGY

Definition: Anticholinergic toxidrome (antimuscarinic syndrome) results from blockade of muscarinic acetylcholine receptors, producing characteristic central and peripheral signs.

Common causative agents in Nepal context:

Category	Common Agents
Antihistamines (most common OD)	Diphenhydramine, chlorpheniramine, promethazine, hydroxyzine
Plants (relevant in Nepal)	Datura stramonium (Dhatura), Atropa belladonna, Brugmansia spp.
Antipsychotics	Haloperidol, olanzapine, quetiapine, chlorpromazine
Tricyclic antidepressants	Amitriptyline, imipramine, nortriptyline
Antispasmodics	Hyoscine butylbromide (Buscopan), dicyclomine
Antiparkinson drugs	Trihexyphenidyl (Pacitane - widely available in Nepal)
Mydriatics (ocular)	Atropine, cyclopentolate, tropicamide
Urological	Oxybutynin, tolterodine
GI	Atropine, loperamide
Cardiac	Disopyramide

Nepal-specific note: Datura poisoning and trihexyphenidyl (Pacitane) abuse are well-documented in South Asia. Promethazine is widely available OTC.

SECTION 3: CLINICAL RECOGNITION

3A. Peripheral Signs (due to muscarinic blockade in peripheral organs)

System	Signs/Symptoms
Cardiovascular	Sinus tachycardia (most consistent sign), palpitations
Ophthalmic	Mydriasis (bilateral, nonreactive), blurred vision, cycloplegia
Skin	Dry, flushed, warm skin; absence of sweating
GI	Decreased/absent bowel sounds, constipation, dry mouth, dysphagia
GU	Urinary retention, decreased bladder tone
Exocrine	Decreased salivation, decreased lacrimation

3B. Central Signs (due to CNS muscarinic blockade)

Agitation, restlessness, irritability (early)
Confusion, disorientation, delirium
Auditory and visual hallucinations (often Lilliputian - "little people"; picking at imaginary objects)
Dysarthria, staccato/incoherent speech
Anxiety, psychosis
Seizures (severe toxicity)
Stupor, coma (high-dose; especially TCAs)

3C. Severity Classification

Severity	Features
Mild	Tachycardia, mild mydriasis, dry mouth, mild agitation; alert and oriented
Moderate	Above + delirium, significant agitation, urinary retention, decreased BS, temp 37.5-38.5°C
Severe	Above + hyperthermia >38.5°C, seizures, wide-complex dysrhythmia (QRS >100ms), coma, cardiovascular instability

SECTION 4: IMMEDIATE ACTIONS (First 10 minutes)

All patients - simultaneous:

Airway: Assess - protect if GCS ≤8 or uncontrolled seizures
Breathing: O2 supplementation; SpO2 monitoring
Circulation: IV access x2 large bore; cardiac monitor; 12-lead ECG
Disability: GCS, pupil exam, blood glucose (ALWAYS - rule out hypoglycemia)
Exposure: Core temperature, skin exam, look for trauma

Immediate ECG interpretation:

Sinus tachycardia - expected, does NOT require treatment
QRS >100 ms - sodium channel blockade (TCA pattern) - CRITICAL, act immediately
QTc >500 ms - risk of torsades - correct electrolytes
PR prolongation, heart block - physostigmine CONTRAINDICATED

SECTION 5: INVESTIGATIONS

Investigation	Rationale
Blood glucose (stat bedside)	Rule out hypoglycemia as AMS cause
12-lead ECG (stat)	QRS width, QTc, conduction defects - guide physostigmine safety
Serum electrolytes (Na, K, Cl, HCO3)	Hyponatremia (seizure cause), electrolyte disturbance
Renal function (creatinine, urea)	Rhabdomyolysis-related AKI
Creatine kinase (CK)	Rhabdomyolysis (agitation + hyperthermia)
Urine dipstick + myoglobin	If CK elevated; rhabdomyolysis protocol
ABG	If respiratory compromise, severe acidosis suspected
Paracetamol level	Co-ingestion (very common in OD)
Paracetamol and salicylate	Unsupervised polypharmacy; co-ingestion OD
CBC	Infection to rule out in delirium DDx
Urine drug screen	If available; confirms exposure but rarely changes management
CT head	If head trauma, focal neuro deficits, or no improvement with treatment

SECTION 6: DIFFERENTIAL DIAGNOSIS

Must exclude before diagnosing anticholinergic toxidrome:

Condition	Differentiating Feature
Sympathomimetic toxidrome	Diaphoretic skin (wet), present bowel sounds
Serotonin syndrome	Clonus, hyperreflexia, myoclonus, diaphoresis
NMS	Rigidity, hyperthermia post-antipsychotic; develops over hours-days
Alcohol/sedative withdrawal	Diaphoresis, tremor, hyper-reflexia, history
Viral/bacterial encephalitis	Fever, meningismus, CSF findings
Acute psychosis	No true delirium; oriented; no autonomic signs
Postictal state	History of seizure, self-limited
Head trauma/intracranial bleed	CT head; focal signs
Hypoglycemia	BG <3.5 mmol/L; responds to dextrose

Key distinguishing feature: Dry skin + absent bowel sounds + urinary retention = anticholinergic (NOT sympathomimetic)

SECTION 7: MANAGEMENT ALGORITHM

ANTICHOLINERGIC TOXIDROME CONFIRMED
              |
     ┌────────┴────────┐
   MILD             MODERATE / SEVERE
     |                    |
Activated charcoal   ABCs + monitoring
(if <1-2h, no CI)   Activated charcoal (if <1-2h, no CI, protecting airway)
Reassurance         Cooling measures if temp >38.5°C
Monitor 6h          IV fluids
Consider discharge         |
if improving         ┌─────┴──────┐
                  AGITATION/    ECG SHOWS
                  DELIRIUM      QRS >100ms
                     |               |
             Benzodiazepines    Sodium Bicarb 1-2mEq/kg IVP
             (FIRST LINE)       (see Section 9)
                     |
         ┌───────────┴───────────┐
    RESPONDS              REFRACTORY AGITATION
    Continue BZD           or CENTRAL DELIRIUM predominant
    Supportive care        Check ECG - no contraindications?
                                    |
                             YES → PHYSOSTIGMINE
                             NO → Continue BZD + supportive

SECTION 8: GASTROINTESTINAL DECONTAMINATION

Activated Charcoal (AC)

Dose: 1 g/kg PO/NG (adult: 50g; child: 25g or 1g/kg)
When to give: Within 1-2 hours of ingestion (may extend to 2+ hours for anticholinergic overdose because GI motility is reduced - this is a clinically important point)
Contraindications: Unprotected airway (GCS ≤8, no intubation), intestinal obstruction, bowel perforation, caustic ingestion
Do NOT give if patient cannot protect airway

Gastric lavage: Not routinely recommended. Consider only if massive potentially lethal ingestion within 60 minutes with protected airway.

Whole bowel irrigation: Not indicated for anticholinergic overdose.

Tintinalli's Emergency Medicine, 9th Ed: "May be more effective [for anticholinergic agents] due to the decreased GI motility" - supports a broader window for charcoal administration.

SECTION 9: PHARMACOLOGICAL MANAGEMENT

9A. Benzodiazepines (First-line for agitation/seizures)

Indications: Agitation, delirium, seizures, hyperthermia reduction (via reduced muscle activity)

Drug	Dose - Adult	Dose - Pediatric	Route	Repeat
Diazepam	5-10 mg IV	0.1-0.3 mg/kg IV	IV slow push	Q10-15 min PRN
Lorazepam	1-2 mg IV	0.05-0.1 mg/kg IV	IV	Q10-15 min PRN
Midazolam	2-5 mg IV/IM	0.1-0.2 mg/kg IV/IM	IV or IM	Q5-10 min PRN

Titrate to mild sedation, NOT deep sedation
Use large doses if needed - do NOT under-dose
First-line for seizures - repeat q5 min x2, then consider phenobarbital
Available in most Nepal hospitals - preferred first-line

9B. Physostigmine (Specific antidote - use with caution)

Mechanism: Reversible acetylcholinesterase inhibitor; crosses BBB; reverses both central and peripheral effects.

Indications (ALL must be met):

Confirmed or highly suspected anticholinergic toxidrome
Moderate-severe central delirium (not just agitation)
Agitation refractory to adequate benzodiazepines, OR central delirium is predominant
ECG reviewed - NO contraindications

Absolute Contraindications:

QRS prolongation >100 ms (risk of asystole - especially TCA overdose)
PR prolongation, any heart block, bradycardia
Reactive airway disease (bronchospasm risk)
Known or suspected TCA overdose (DO NOT give - risk of seizures and asystole)
Peripheral vascular disease, intestinal/urinary obstruction
Known hypersensitivity

Relative Contraindications:

Asthma, COPD
Diabetes mellitus (increased cholinergic sensitivity)
Active seizures

Dosing:

Patient	Dose	Route	Rate
Adult	1-2 mg IV	IV	Infuse over 5 minutes (slow!)
Pediatric	0.02 mg/kg IV	IV	Max 0.5 mg; infuse over 5 min
Repeat dose	Same dose if symptoms recur	IV	After 30-60 min (effect lasts 45-60 min)

Infusion (if available): 0.02 mg/kg/h continuous in adolescents (per Wang et al. 2021 RCT)

Pre-requisites before administering physostigmine:

12-lead ECG reviewed - QRS <100ms, no heart block, no TCA pattern
Atropine at bedside (0.5 mg IV adult; 0.01 mg/kg pediatric) - antidote for cholinergic crisis
Resuscitation equipment ready
Continuous cardiac monitoring

Adverse effects to monitor: Bradycardia, bronchospasm, increased secretions, seizures, asystole (with TCA co-ingestion)

Physostigmine vs Lorazepam Evidence:

Wang et al. (2021) RCT (Clin Toxicol) - PMID 33295809: Physostigmine was superior to lorazepam in controlling antimuscarinic delirium after bolus (44% vs 100% still delirious, p=0.01) and at 4h (22% vs 100%, p<0.001). No serious adverse events in either arm.

Burns et al. (2000) Ann Emerg Med: Physostigmine significantly more effective than benzodiazepines for anticholinergic poisoning with no increase in adverse events.

Nepal context: Physostigmine may not be consistently available at all centers. If unavailable, benzodiazepines remain effective.

9C. Alternative Antidote: Rivastigmine (if Physostigmine unavailable)

New evidence (2024): Chiew et al. (Clin Toxicol 2024): Oral/transdermal rivastigmine used successfully for anticholinergic delirium in 50 patients when physostigmine was unavailable.

Dose: Rivastigmine 3 mg oral (patch 4.6 mg/24h transdermal)
Onset slower than IV physostigmine
May be more accessible in resource-limited settings
Not yet a standard recommendation but emerging evidence

9D. Sodium Bicarbonate (for TCA-pattern / QRS prolongation)

Indication: QRS >100-120 ms (sodium channel blockade) - wide-complex dysrhythmia


Dose	1-2 mEq/kg IV bolus
Route	IV push
Repeat	Every 3-5 min until QRS narrows
Infusion	150 mEq/L NaHCO3 in 5% dextrose at 1.5x maintenance if boluses required repeatedly
Target	Blood pH 7.50-7.55
Monitor	ABG, serum K+ (bicarb drives K+ intracellularly - watch for hypokalemia)

Rosen's Emergency Medicine: "Widening of the QRS due to sodium channel blockade is managed similarly to cyclic antidepressant toxicity. Sodium bicarbonate 1-2 mEq/kg IVP, repeated every 3-5 minutes until QRS narrowing."

9E. Management of Hyperthermia

Temperature	Action
37.5-38.5°C	Benzodiazepines for agitation (reduce heat production); monitor
>38.5°C	Active external cooling: undress, mist + fan, ice packs to axilla/groin/neck
>40°C (critical)	Aggressive cooling; consider ICU; check CK, creatinine, coagulation

Do NOT use antipyretics (paracetamol/aspirin) - hyperthermia is from agitation/decreased heat dissipation, NOT from prostaglandins
Do NOT use diphenhydramine for agitation (itself anticholinergic!)
Benzodiazepines reduce muscular hyperactivity and are the most effective treatment for anticholinergic hyperthermia

9F. Seizure Management

Step	Drug	Dose
First line	Lorazepam OR diazepam IV	Lorazepam 0.1 mg/kg IV (max 4 mg); repeat x1 at 5 min
Second line	Phenobarbital	10-20 mg/kg IV (slow infusion over 30-60 min)
Refractory	Propofol infusion	80-200 mcg/kg/min (requires intubation)
AVOID	Phenytoin	Ineffective for toxin-induced seizures; worsens cardiac conduction

9G. Urinary Retention

Bladder scan or palpation to assess
Insert urinary catheter if retention confirmed or suspected
Bethanechol NOT indicated in acute setting

9H. Fluid Management

IV fluids (Normal Saline or Ringer's Lactate): 10-20 mL/kg if hypotension, signs of dehydration, or CK elevation
If CK >1000 U/L (rhabdomyolysis protocol): target urine output 1-3 mL/kg/h; avoid mannitol unless renal failure developing

SECTION 10: SPECIAL SITUATIONS

10A. Datura Stramonium Poisoning (Nepal-specific)

All parts toxic (seeds most concentrated); scopolamine + hyoscyamine + atropine content
Intentional misuse for intoxication; accidental ingestion in children
Physostigmine often highly effective; titrate carefully
Duration of toxicity may be prolonged (12-48h) due to alkaloid kinetics

10B. Trihexyphenidyl (Pacitane) Abuse

Common in South Asia; sold OTC in Nepal
Used recreationally for euphoric/hallucinogenic effects
Usually oral; moderate-severe central delirium
Benzodiazepines first line; physostigmine if available

10C. TCA Overdose with Anticholinergic Features

DO NOT give physostigmine - risk of asystole and seizures
Prioritize ECG; sodium bicarbonate for QRS >100ms
Benzodiazepines for agitation and seizures
ICU admission mandatory

10D. Pediatric Patients

More sensitive to anticholinergic agents; toxicity at lower doses
Diphenhydramine: toxicity at 7.5 mg/kg; severe at 15 mg/kg
Physostigmine dose: 0.02 mg/kg IV (max 0.5 mg)
Higher risk of seizures
Body surface area proportionally larger - evaporative cooling MORE effective

10E. Pregnancy

Benzodiazepines (caution in 1st trimester, but use in life-threatening situations)
Physostigmine - limited data; use if clearly indicated and benefits outweigh risks
Obstetric consultation early
Fetal monitoring if >24 weeks

SECTION 11: DISPOSITION

Clinical Status	Disposition
Asymptomatic (accidental ingestion, low dose)	Activated charcoal, observe 6h in ED. Discharge if remains asymptomatic.
Mild toxicity (resolving within 6h)	AC if applicable, benzodiazepines if needed, observe 6h. Discharge if symptoms fully resolve.
Moderate toxicity (persisting symptoms at 6h)	Admit to general ward/monitored bed. Continue observation.
Severe toxicity (hyperthermia, seizures, coma, dysrhythmia)	ICU admission
Physostigmine administered	ICU admission (minimum)
TCA overdose with cardiac manifestations	ICU/HDU mandatory

Psychiatric consultation: All intentional overdoses require formal psychiatric evaluation before discharge.

SECTION 12: MONITORING PARAMETERS

Parameter	Frequency	Alert Threshold
Vital signs (BP, HR, Temp, RR, SpO2)	Every 15-30 min (acute phase)	HR >150, Temp >38.5°C, SpO2 <94%
Cardiac monitor	Continuous	QRS >100ms, VT, bradycardia
GCS/agitation score	Every 30 min	GCS drop, worsening agitation
Urine output	Hourly if catheterized	<0.5 mL/kg/h
ECG	On arrival, 2h, 4h and PRN	QRS >100ms, new dysrhythmia
Temperature (rectal/axillary)	Every 30 min if hyperthermia	>40°C = critical

SECTION 13: WHAT NOT TO DO

Intervention	Why Avoid
Physostigmine in TCA overdose	Risk of asystole and seizures
Physostigmine when QRS >100ms	Life-threatening cardiac complication
Phenytoin for seizures	Ineffective for toxin-induced seizures
Antipyretics for hyperthermia	Ineffective (not prostaglandin-mediated)
Physical restraints alone	Worsens agitation and hyperthermia; rhabdomyolysis risk
Flumazenil if BZD given for seizures	May re-precipitate seizures
Haloperidol for agitation	Lowers seizure threshold; worsens QTc; avoid until TCA excluded

SECTION 14: POISON CONTROL & CONSULTATION

Nepal: No national 24h poison control center currently exists. Use these international resources:

South Asia Poison Control Resources: WHO/SEARO guidance
UK TOXBASE / NPIS: www.toxbase.org (registration required)
US Poison Control: 1-800-222-1222 (for reference)
Clinical Toxicology (journal): Major reference
Local toxicology consultation: B.P. Koirala Institute of Health Sciences (BPKIHS), Tribhuvan University Teaching Hospital toxicology department

SECTION 15: EVIDENCE BASE & REFERENCES

Reference	Level of Evidence	Key Recommendation
Wang GS et al. (2021). Clin Toxicol. PMID 33295809	RCT	Physostigmine superior to lorazepam for antimuscarinic delirium; safe in adolescents
Burns MJ et al. (2000). Ann Emerg Med 35(4):374-381	RCT	Physostigmine more effective and no less safe than benzodiazepines
Dawson AH, Buckley NA. (2016). Br J Clin Pharmacol 81(3):516-524	Review	Pharmacological management of anticholinergic delirium - theory and evidence
Chiew AL et al. (2024). Clin Toxicol 62(2):82-87	Case series	Rivastigmine as alternative when physostigmine unavailable
Pentel P, Peterson CD. (1980). Ann Emerg Med 9(11):588-590	Case series	Asystole with physostigmine in TCA OD - basis for contraindication
Hoffman RJ, Nillas A. (2025). Arch Dis Child. PMID 39978865	Review	Toxidromes approach, antidote role
Pannu AK. (2025). Trop Doct. PMID 40791148	Review	Managing agitated toxidromes in resource-limited settings
Rosen's Emergency Medicine, 9th Ed (2023)	Textbook	Physostigmine dosing; sodium bicarb for QRS; BZD for agitation
Tintinalli's Emergency Medicine, 9th Ed (2020)	Textbook	GI decontamination; severity classification; treatment algorithm
Goldman-Cecil Medicine, 26th Ed	Textbook	Toxidrome classification, clinical features
Harrison's Principles of Internal Medicine, 22nd Ed (2025)	Textbook	Differential diagnosis, systemic management
StatPearls - Broderick ED et al. (2023)	Review	Physostigmine dosing; BZD first-line; AC timing
Goldfrank's Toxicologic Emergencies, 11th Ed	Reference textbook	Antihistamines, anticholinergic mechanisms
CHEMM (HHS/ASPR) Anticholinergic Protocol	Government protocol	Treatment protocols used internationally

APPENDIX A: PHYSOSTIGMINE ADMINISTRATION CHECKLIST

Before giving:

Clinical diagnosis confirmed - peripheral AND central signs present
ECG reviewed: QRS <100ms confirmed
No bradycardia, no heart block, no PR prolongation
TCA overdose excluded
No bronchospasm/asthma history
Atropine 0.5mg drawn up and at bedside
Resuscitation cart confirmed available
Continuous cardiac monitoring active
IV access confirmed patent

Administration:

Dose calculated (adult: 1-2mg; pediatric: 0.02mg/kg, max 0.5mg)
Diluted in 10mL NS
Administered IV over 5 minutes (slow!)
Monitor HR, BP, SpO2 continuously during infusion

After:

Response assessed at 15-20 minutes
If recurrence at 30-60 min, repeat dose is acceptable
ICU/HDU admission arranged

APPENDIX B: QUICK DRUG DOSING SUMMARY

Drug	Adult Dose	Pediatric Dose	Route	Notes
Diazepam	5-10 mg q10-15 min	0.1-0.3 mg/kg q10-15 min	IV slow	1st-line agitation/seizure
Lorazepam	1-2 mg q10-15 min	0.05-0.1 mg/kg	IV	1st-line agitation/seizure
Midazolam	2-5 mg q5-10 min	0.1-0.2 mg/kg	IV/IM	Useful when no IV access
Physostigmine	1-2 mg over 5 min	0.02 mg/kg (max 0.5mg)	IV slow	Antidote; see checklist
Sodium bicarbonate	1-2 mEq/kg bolus	1-2 mEq/kg bolus	IV push	QRS >100ms only
Activated charcoal	50g (1g/kg)	25g or 1g/kg	PO/NG	Within 1-2h, protected airway
Atropine (rescue)	0.5-1 mg IV	0.01-0.02 mg/kg IV	IV	If physostigmine causes bradycardia
Phenobarbital	10-20 mg/kg	10-20 mg/kg	IV slow (30-60 min)	Refractory seizures

Protocol developed for tertiary emergency practice in Nepal. All doses represent standard international guidelines adapted for local drug availability. Always verify drug availability locally. This protocol should be reviewed every 2 years or when new evidence emerges.

Approved by: _________________ Date: _________________

---This protocol is built from the following sources synthesized together:

Textbooks consulted:

Rosen's Emergency Medicine (9th Ed) - physostigmine dosing, sodium bicarb, BZD titration
Tintinalli's Emergency Medicine (9th Ed) - treatment algorithm, decontamination
Goldman-Cecil Medicine (26th Ed) - toxidrome classification
Harrison's Principles (22nd Ed, 2025) - differential diagnosis
Tietz Laboratory Medicine - TCA and anticholinergic overlap

Key literature:

Wang et al. 2021 RCT (PMID 33295809) - the only RCT comparing physostigmine vs lorazepam; physostigmine was significantly superior for delirium control with no serious adverse events
Burns et al. 2000 Ann Emerg Med - foundational RCT on physostigmine safety
Chiew et al. 2024 Clin Toxicol - rivastigmine as physostigmine alternative
CHEMM (HHS) international treatment protocols

Nepal-specific additions:

Datura poisoning section (common in South Asia)
Trihexyphenidyl (Pacitane) abuse - documented problem across Nepal/India
Drug availability considerations (diazepam/lorazepam/midazolam over physostigmine as first-line given supply constraints)

If you need this as a downloadable Word or PDF file, or as a laminated quick-reference card format, let me know and I can generate that for you.

I already built this full protocol for you in our previous session. Let me generate it as a downloadable Word document (.docx) so you have a ready-to-use, printable file.

Reading File

Running Command

ls /home/daytona/workspace/ 2>/dev/null && ls /home/daytona/skills/docx/scripts/office/ 2>/dev/null

Running Command

mkdir -p /home/daytona/workspace/anticholinergic-protocol && node --version && npm list -g docx 2>/dev/null | head -5

Writing File

~/anticholinergic-protocol/generate.js

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// ─────────────────────────────────────────────────────────────────────────────
//  DOCUMENT CONTENT
// ─────────────────────────────────────────────────────────────────────────────

const doc = new Document({
  creator: "Emergency Department Protocol System",
  title: "Anticholinergic Toxidrome Emergency Protocol",
  description: "Evidence-based emergency management protocol for anticholinergic toxidrome",
  styles: {
    default: {
      document: {
        run: { font: "Calibri", size: 20 }
      }
    }
  },
  sections: [{
    properties: {
      page: {
        margin: { top: 720, bottom: 720, left: 900, right: 900 }
      }
    },
    headers: {
      default: new Header({
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            rows: [new TableRow({ children: [
              new TableCell({ width: { size: 70, type: WidthType.PERCENTAGE }, children: [new Paragraph({ children: [new TextRun({ text: "ANTICHOLINERGIC TOXIDROME PROTOCOL", bold: true, color: DKBLUE, size: 18, font: "Calibri" })] })], borders: { top: { style: BorderStyle.NONE }, bottom: { style: BorderStyle.NONE }, left: { style: BorderStyle.NONE }, right: { style: BorderStyle.NONE } } }),
              new TableCell({ width: { size: 30, type: WidthType.PERCENTAGE }, children: [new Paragraph({ alignment: AlignmentType.RIGHT, children: [new TextRun({ text: "Tertiary ED | Nepal | v1.0 | June 2026", size: 16, color: "666666", font: "Calibri" })] })], borders: { top: { style: BorderStyle.NONE }, bottom: { style: BorderStyle.NONE }, left: { style: BorderStyle.NONE }, right: { style: BorderStyle.NONE } } })
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        ]
      })
    },
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            rows: [new TableRow({ children: [
              new TableCell({ width: { size: 70, type: WidthType.PERCENTAGE }, children: [new Paragraph({ children: [new TextRun({ text: "For clinical use only. Verify drug availability locally. Review annually.", size: 16, color: "666666", font: "Calibri", italics: true })] })], borders: { top: { style: BorderStyle.NONE }, bottom: { style: BorderStyle.NONE }, left: { style: BorderStyle.NONE }, right: { style: BorderStyle.NONE } } }),
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            ]})]
          })
        ]
      })
    },
    children: [

      // ═══════════════════════════════════════════════════════════════════════
      // TITLE PAGE
      // ═══════════════════════════════════════════════════════════════════════
      new Paragraph({
        children: [new TextRun({ text: "ANTICHOLINERGIC TOXIDROME", bold: true, color: WHITE, size: 52, font: "Calibri" })],
        alignment: AlignmentType.CENTER,
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        spacing: { before: 400, after: 0 },
        border: { top: { color: RED, size: 24, style: BorderStyle.SINGLE } }
      }),
      new Paragraph({
        children: [new TextRun({ text: "EMERGENCY MANAGEMENT PROTOCOL", bold: true, color: WHITE, size: 36, font: "Calibri" })],
        alignment: AlignmentType.CENTER,
        shading: { type: ShadingType.SOLID, fill: RED },
        spacing: { before: 0, after: 0 },
      }),
      new Paragraph({
        children: [new TextRun({ text: "Tertiary Emergency Department | Nepal", color: WHITE, size: 24, font: "Calibri" })],
        alignment: AlignmentType.CENTER,
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        spacing: { before: 0, after: 400 },
        border: { bottom: { color: RED, size: 24, style: BorderStyle.SINGLE } }
      }),

      new Paragraph({ spacing: { before: 200, after: 120 }, children: [] }),

      makeTable(
        ["Document Reference", "Value"],
        [
          ["Version", "1.0"],
          ["Effective Date", "June 2026"],
          ["Review Date", "June 2028"],
          ["Prepared for", "Tertiary Emergency Department, Nepal"],
          ["Evidence Base", "Rosen's EM, Tintinalli's EM, Harrison's, Goldman-Cecil, PubMed RCTs"],
          ["Approved by", "_________________________________"],
        ],
        [40, 60]
      ),

      noteBox(
        "⚠  CLINICAL REMINDER: This protocol is a clinical aid. Individual patient management must be based on clinical assessment, local drug availability, and experienced clinical judgment. All dosages should be verified before administration.",
        AMBERT, AMBER
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 1 — QUICK REFERENCE
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 1: TOXIDROME QUICK REFERENCE"),

      para('Memory Aid: "Mad as a Hatter | Blind as a Bat | Dry as a Bone | Red as a Beet | Hot as a Hare"', { bold: true, color: RED }),
      new Paragraph({ spacing: { before: 80, after: 80 }, children: [] }),

      makeTable(
        ["Feature", "Anticholinergic", "Sympathomimetic", "Cholinergic", "Serotonin Syndrome"],
        [
          ["Heart rate", "Tachycardia", "Tachycardia", "Bradycardia", "Tachycardia"],
          ["Pupils", "Mydriasis (fixed)", "Mydriasis", "Miosis", "Mydriasis"],
          ["Skin", "DRY, flushed, warm", "Diaphoretic (WET)", "Diaphoretic (WET)", "Diaphoretic"],
          ["Bowel sounds", "Absent / decreased", "Normal / increased", "Hyperactive", "Hyperactive"],
          ["Bladder", "Urinary retention", "Normal", "Incontinence", "Normal"],
          ["Temp", "Hyperthermia", "Hyperthermia", "Normal / low", "Hyperthermia"],
          ["Mental status", "Agitated DELIRIUM", "Agitated, alert", "SLUDGE symptoms", "Agitation + clonus"],
          ["Mucous membranes", "DRY", "Wet", "Wet / hypersecretion", "Normal"],
          ["Key differentiator", "Dry skin + absent BS", "Wet + BS present", "SLUDGE/DUMBELS", "Clonus + myoclonus"],
        ],
        [22, 20, 20, 19, 19]
      ),

      heading2("Classic Peripheral Signs of Anticholinergic Toxidrome"),
      makeTable(
        ["System", "Signs / Symptoms"],
        [
          ["Cardiovascular", "Sinus tachycardia (most consistent sign), palpitations"],
          ["Ophthalmic", "Bilateral mydriasis (fixed, non-reactive), blurred vision, cycloplegia"],
          ["Skin", "Dry, flushed, warm, erythematous skin; absence of sweating"],
          ["GI tract", "Absent / decreased bowel sounds, dry mouth, dysphagia, constipation"],
          ["Genitourinary", "Urinary retention, inability to void"],
          ["Exocrine glands", "Decreased salivation, decreased lacrimation"],
        ],
        [35, 65]
      ),

      heading2("Classic Central Signs"),
      makeTable(
        ["Severity", "CNS Manifestations"],
        [
          ["Early / mild", "Restlessness, anxiety, irritability, mild confusion"],
          ["Moderate", "Disorientation, agitated delirium, visual/auditory hallucinations (Lilliputian - 'little people'), picking at imaginary objects, staccato dysarthric speech"],
          ["Severe", "Seizures, coma, cardiovascular collapse, hyperthermia > 40°C, rhabdomyolysis"],
        ],
        [25, 75]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 2 — CAUSATIVE AGENTS
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 2: COMMON CAUSATIVE AGENTS (Nepal Context)"),

      makeTable(
        ["Category", "Agents", "Nepal Relevance"],
        [
          ["Antihistamines (most common OD)", "Diphenhydramine, chlorpheniramine, promethazine, hydroxyzine", "OTC access; promethazine widely sold"],
          ["Plants (South Asia specific)", "Datura stramonium (Dhatura), Atropa belladonna, Brugmansia spp.", "HIGH — intentional misuse & accidental ingestion"],
          ["Antipsychotics", "Haloperidol, olanzapine, quetiapine, chlorpromazine", "Psychiatric polypharmacy; olanzapine variable"],
          ["Tricyclic antidepressants (TCAs)", "Amitriptyline, imipramine, nortriptyline", "Chronic pain / depression Rx; narrow TI"],
          ["Antispasmodics", "Hyoscine butylbromide (Buscopan), dicyclomine", "Widely used GI antispasmodic; OTC"],
          ["Antiparkinson drugs", "Trihexyphenidyl (Pacitane)", "HIGH — recreational misuse documented in Nepal/India"],
          ["Mydriatics (ophthalmic)", "Atropine eye drops, cyclopentolate, tropicamide", "Inadvertent systemic in children"],
          ["Urological agents", "Oxybutynin, tolterodine", "Overactive bladder Rx"],
          ["Cardiac drugs", "Disopyramide, digoxin toxicity (indirect)", "Less common; co-ingestion risk"],
          ["Muscle relaxants", "Cyclobenzaprine", "Moderate anticholinergic effect"],
        ],
        [28, 42, 30]
      ),

      noteBox(
        "NEPAL ALERT: Datura (Dhatura) poisoning and Trihexyphenidyl (Pacitane) abuse are the two most clinically significant locally prevalent causes. Both may produce severe prolonged central anticholinergic toxicity lasting 12–48 hours. Physostigmine is often highly effective for these agents.",
        "FFF3E0", "E65100"
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 3 — SEVERITY
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 3: SEVERITY CLASSIFICATION"),

      makeTable(
        ["Severity", "Clinical Features", "Action"],
        [
          ["MILD", "Tachycardia, mild mydriasis, dry mouth, mild anxiety/agitation; alert and oriented; afebrile", "ED observation 6h; AC if <2h; discharge if resolving"],
          ["MODERATE", "Above PLUS delirium, significant agitation, urinary retention, absent BS, temp 37.5–38.5°C", "Admit monitored bed; BZD; 6h minimum observation"],
          ["SEVERE", "Hyperthermia >38.5°C, seizures, QRS >100ms, coma, cardiovascular instability, rhabdomyolysis", "IMMEDIATE ICU admission; aggressive management"],
        ],
        [20, 55, 25]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 4 — IMMEDIATE ACTIONS
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 4: IMMEDIATE ACTIONS — First 10 Minutes"),

      heading2("A — ABCDE Simultaneous Assessment"),
      makeTable(
        ["Step", "Action", "Alert Threshold"],
        [
          ["Airway", "Assess patency; intubate if GCS ≤8, uncontrolled vomiting, or refractory seizures", "GCS ≤8 or unable to protect airway → RSI"],
          ["Breathing", "O2 supplementation; SpO2 and RR monitoring", "SpO2 <94% → escalate O2; consider ABG"],
          ["Circulation", "IV access x2 large bore; continuous cardiac monitor; 12-lead ECG", "QRS >100ms → CRITICAL (Section 9D)"],
          ["Disability", "GCS, pupil exam, STAT bedside blood glucose", "BG <3.5 mmol/L → 50mL 50% dextrose IV"],
          ["Exposure", "Core temperature, full skin exam, trauma assessment", "Temp >38.5°C → cooling protocol (Section 9E)"],
        ],
        [18, 55, 27]
      ),

      heading2("B — Immediate ECG Interpretation"),
      makeTable(
        ["ECG Finding", "Interpretation", "Action Required"],
        [
          ["Sinus tachycardia, narrow QRS", "Expected in anticholinergic toxidrome", "No treatment needed; monitor"],
          ["QRS > 100 ms", "Sodium channel blockade (TCA pattern)", "SODIUM BICARBONATE immediately (Section 9D)"],
          ["QTc > 500 ms", "Risk of torsades de pointes", "Correct electrolytes (K+, Mg2+); avoid QT-prolonging drugs"],
          ["Bradycardia / Heart block", "Contraindication to physostigmine", "DO NOT give physostigmine; supportive care"],
          ["Wide-complex tachycardia / VT", "Life-threatening dysrhythmia", "NaHCO3 + resuscitation; likely TCA — no physostigmine"],
        ],
        [28, 35, 37]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 5 — INVESTIGATIONS
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 5: INVESTIGATIONS"),

      makeTable(
        ["Investigation", "Rationale", "Priority"],
        [
          ["Bedside blood glucose (STAT)", "Rule out hypoglycemia as cause of AMS", "IMMEDIATE"],
          ["12-lead ECG (STAT)", "QRS width, QTc, conduction defects — determine physostigmine safety", "IMMEDIATE"],
          ["Serum electrolytes (Na, K, Cl, HCO3)", "Hyponatremia (seizure), K+ for torsades risk", "Urgent"],
          ["Renal function (creatinine, urea)", "Rhabdomyolysis-related AKI, dehydration", "Urgent"],
          ["Creatine kinase (CK)", "Rhabdomyolysis — hyperthermia + agitation risk", "Urgent (moderate/severe)"],
          ["Urine dipstick / myoglobin", "Confirm rhabdomyolysis if CK elevated", "If CK abnormal"],
          ["Arterial blood gas (ABG)", "Respiratory compromise, acidosis assessment", "Severe / intubated"],
          ["Paracetamol level", "Co-ingestion (extremely common in OD)", "All intentional OD"],
          ["Salicylate level", "Co-ingestion with common OTC drugs", "All intentional OD"],
          ["Full blood count", "Infection as differential for delirium", "Moderate/severe"],
          ["Urine drug screen", "Confirms exposure; rarely changes acute management", "If available"],
          ["CT head (non-contrast)", "Focal neuro signs, trauma, no improvement with treatment", "Selective"],
        ],
        [38, 46, 16]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 6 — DIFFERENTIAL DIAGNOSIS
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 6: DIFFERENTIAL DIAGNOSIS"),

      makeTable(
        ["Condition", "Key Differentiating Feature", "Test"],
        [
          ["Sympathomimetic toxidrome", "WET skin (diaphoretic); bowel sounds PRESENT", "Clinical"],
          ["Serotonin syndrome", "Clonus, hyperreflexia, myoclonus, diaphoresis; rapid onset", "Clinical (Hunter Criteria)"],
          ["Neuroleptic Malignant Syndrome (NMS)", "Lead-pipe rigidity; antipsychotic history; develops over hours–days", "Clinical + CK, CXR"],
          ["Alcohol / sedative-hypnotic withdrawal", "Diaphoresis, tremor, hyperreflexia, seizures; history of use", "History + clinical"],
          ["Viral encephalitis / meningitis", "Fever, meningismus, progressive; no autonomic signs", "LP, CT head, CSF"],
          ["Acute psychosis", "No true delirium; patient oriented; no autonomic signs", "Clinical + history"],
          ["Postictal state", "Self-limited; history of seizure; gradual clearing", "Clinical + glucose"],
          ["Head trauma / intracranial bleed", "Focal neurological signs; mechanism of injury", "CT head"],
          ["Hypoglycemia", "Rapidly reversible; BG <3.5 mmol/L", "Bedside BG → dextrose"],
        ],
        [28, 45, 27]
      ),

      noteBox(
        "KEY DIFFERENTIATOR: Dry skin + absent bowel sounds + urinary retention = ANTICHOLINERGIC (not sympathomimetic).\nIf skin is wet and sweaty, reconsider the diagnosis.",
        GREENT, GREEN
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 7 — MANAGEMENT ALGORITHM
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 7: MANAGEMENT ALGORITHM"),

      makeTable(
        ["Step", "Action"],
        [
          ["1. CONFIRM DIAGNOSIS", "Peripheral signs (dry skin, tachycardia, mydriasis, absent BS) + Central signs (delirium, agitation) + exposure history"],
          ["2. AIRWAY / BREATHING", "Protect airway if GCS ≤8. Supplemental O2. Pulse oximetry."],
          ["3. IV ACCESS + MONITORING", "Two large-bore IVs, cardiac monitor, 12-lead ECG, bedside glucose"],
          ["4. GI DECONTAMINATION", "Activated charcoal 1 g/kg PO/NG if within 1–2 h and airway protected (see Section 8)"],
          ["5. TREAT AGITATION", "Benzodiazepines IV — FIRST LINE (see Section 9A). Do NOT restrain without sedation."],
          ["6. CONSIDER PHYSOSTIGMINE", "If central delirium + ECG safe (QRS <100ms, no heart block, no TCA) — see checklist Section 9B"],
          ["7. QRS > 100 ms?", "Sodium bicarbonate 1–2 mEq/kg IV bolus; do NOT give physostigmine"],
          ["8. SEIZURES", "Benzodiazepines first. Phenobarbital if refractory. Avoid phenytoin."],
          ["9. HYPERTHERMIA >38.5°C", "External cooling + BZD for agitation. Do NOT use antipyretics."],
          ["10. RHABDOMYOLYSIS?", "Aggressive IV fluids; target UO 1–3 mL/kg/h; CK trending"],
          ["11. DISPOSITION", "See Section 11 — Mild = 6h obs; Moderate = admit; Severe / physostigmine given = ICU"],
          ["12. PSYCHIATRIC REVIEW", "All intentional overdoses require formal psychiatric evaluation before discharge"],
        ],
        [22, 78]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 8 — GI DECONTAMINATION
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 8: GASTROINTESTINAL DECONTAMINATION"),

      heading2("Activated Charcoal (AC)"),
      makeTable(
        ["Parameter", "Details"],
        [
          ["Adult dose", "50 g (1 g/kg) PO or via NG tube"],
          ["Pediatric dose", "1 g/kg PO/NG (max 50 g)"],
          ["Window", "Within 1–2 hours of ingestion. May extend to 2+ hours for anticholinergics due to decreased GI motility (Tintinalli's)."],
          ["Contraindications", "Unprotected airway (GCS ≤8 without intubation), intestinal obstruction, bowel perforation, caustic ingestion"],
          ["Administration", "Mix in water or juice. Position upright. Have suction ready."],
        ],
        [30, 70]
      ),

      noteBox(
        "Anticholinergics reduce GI motility, meaning activated charcoal may remain effective beyond the usual 1-hour window. Consider even if ingestion was 1–2 hours prior, provided the airway is protected.",
        LTBLUE, DKBLUE
      ),

      heading2("Other Decontamination Methods"),
      makeTable(
        ["Method", "Recommendation"],
        [
          ["Gastric lavage", "NOT routinely recommended. Consider ONLY for massive potentially lethal ingestion within 60 min with protected airway."],
          ["Whole bowel irrigation", "NOT indicated for anticholinergic overdose."],
          ["Induced emesis (ipecac)", "CONTRAINDICATED — aspiration risk; not recommended."],
        ],
        [30, 70]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 9 — PHARMACOLOGICAL MANAGEMENT
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 9: PHARMACOLOGICAL MANAGEMENT"),

      heading2("9A. Benzodiazepines — FIRST-LINE for Agitation and Seizures"),

      noteBox(
        "Benzodiazepines are the cornerstone of anticholinergic toxidrome management. They reduce agitation, decrease muscular hyperactivity that drives hyperthermia, and are effective for seizures. Use IV route. Do NOT under-dose.",
        GREENT, GREEN
      ),

      makeTable(
        ["Drug", "Adult Dose", "Pediatric Dose", "Route", "Repeat Interval"],
        [
          ["Diazepam (preferred in Nepal — widely available)", "5–10 mg", "0.1–0.3 mg/kg", "IV slow push", "Every 10–15 min PRN"],
          ["Lorazepam", "1–2 mg", "0.05–0.1 mg/kg", "IV", "Every 10–15 min PRN"],
          ["Midazolam (when no IV access)", "5 mg", "0.1–0.2 mg/kg", "IM or IV", "Every 5–10 min PRN"],
        ],
        [30, 17, 17, 13, 23]
      ),

      para("Titrate to mild sedation. Large doses may be required — do NOT under-sedation. Continue as long as agitation/hyperthermia persists.", { italic: true }),

      heading2("9B. Physostigmine — Specific Antidote"),

      para("Mechanism: Reversible acetylcholinesterase inhibitor. Crosses blood–brain barrier. Reverses BOTH central and peripheral anticholinergic effects.", { bold: false }),
      new Paragraph({ spacing: { before: 60, after: 60 }, children: [] }),

      heading3("Indications (ALL criteria must be met):"),
      makeTable(
        ["Criterion", "Requirement"],
        [
          ["Toxidrome", "Confirmed or strongly suspected anticholinergic toxidrome"],
          ["Symptom severity", "Moderate–severe central delirium, OR agitation refractory to adequate benzodiazepines"],
          ["ECG", "QRS < 100 ms; no bradycardia; no heart block; no PR prolongation"],
          ["Agent", "NOT a TCA overdose (absolute contraindication)"],
          ["Resources", "Atropine at bedside; resuscitation equipment immediately available"],
        ],
        [35, 65]
      ),

      heading3("Contraindications:"),
      makeTable(
        ["Type", "Contraindication"],
        [
          ["ABSOLUTE", "QRS > 100 ms — risk of fatal asystole"],
          ["ABSOLUTE", "Known or suspected TCA overdose — asystole and seizure risk"],
          ["ABSOLUTE", "Bradycardia or any degree of heart block"],
          ["ABSOLUTE", "Reactive airway disease (asthma, COPD with bronchospasm)"],
          ["ABSOLUTE", "Intestinal or urinary tract obstruction"],
          ["RELATIVE", "Asthma / COPD (stable, no active bronchospasm)"],
          ["RELATIVE", "Diabetes mellitus"],
          ["RELATIVE", "Active seizures (treat seizures first with BZD)"],
        ],
        [20, 80]
      ),

      heading3("Dosing:"),
      makeTable(
        ["Patient", "Dose", "Route", "Rate", "Repeat"],
        [
          ["Adult", "1–2 mg IV", "IV", "Infuse SLOWLY over 5 minutes", "Repeat after 30–60 min if symptoms recur"],
          ["Pediatric", "0.02 mg/kg IV (max 0.5 mg)", "IV", "Infuse SLOWLY over 5 minutes", "Repeat after 30–60 min if symptoms recur"],
          ["Infusion (if needed)", "0.02 mg/kg/h", "IV infusion", "Continuous 4-hour infusion", "Per Wang et al. 2021 RCT"],
        ],
        [17, 20, 10, 33, 20]
      ),

      noteBox(
        "EVIDENCE: Wang et al. (2021) RCT — Physostigmine superior to lorazepam for antimuscarinic delirium: 44% vs 100% still delirious after bolus (p=0.01); 22% vs 100% at 4h (p<0.001). No serious adverse events in either arm. [PMID 33295809, Clin Toxicol]\n\nBurns et al. (2000) Ann Emerg Med — Physostigmine significantly more effective than benzodiazepines with no increase in adverse events.",
        LTBLUE, DKBLUE
      ),

      heading3("Pre-Administration Checklist (MUST complete before giving physostigmine):"),
      makeTable(
        ["#", "Checklist Item"],
        [
          ["1", "ECG reviewed: QRS < 100 ms confirmed"],
          ["2", "No bradycardia, no heart block, no PR prolongation"],
          ["3", "TCA overdose excluded (history, ECG pattern)"],
          ["4", "No history of bronchospasm / reactive airway disease"],
          ["5", "Atropine 0.5 mg (adult) / 0.01–0.02 mg/kg (pediatric) drawn up and at bedside"],
          ["6", "Resuscitation cart confirmed at bedside"],
          ["7", "Continuous cardiac monitoring and SpO2 active"],
          ["8", "IV access patent and confirmed"],
          ["9", "Dose calculated and drawn up in 10 mL NS syringe"],
          ["10", "Prepared to infuse over MINIMUM 5 minutes"],
        ],
        [10, 90]
      ),

      heading2("9C. Rivastigmine — Alternative when Physostigmine Unavailable"),
      makeTable(
        ["Parameter", "Details"],
        [
          ["Indication", "Anticholinergic delirium when IV physostigmine unavailable or in shortage"],
          ["Adult dose", "3 mg oral tablet OR 4.6 mg/24h transdermal patch"],
          ["Evidence", "Chiew et al. (2024) Clin Toxicol — 50-patient case series; effective for anticholinergic delirium"],
          ["Onset", "Slower than IV physostigmine; useful for subacute/persistent delirium"],
          ["Status", "Emerging evidence; not standard first-line; use when physostigmine not available"],
        ],
        [30, 70]
      ),

      heading2("9D. Sodium Bicarbonate — for QRS > 100 ms (TCA-pattern / Sodium Channel Blockade)"),

      noteBox(
        "CRITICAL: If QRS > 100 ms is present, this indicates sodium channel blockade (typically TCA). DO NOT give physostigmine. Give sodium bicarbonate immediately.",
        AMBERT, AMBER
      ),

      makeTable(
        ["Parameter", "Details"],
        [
          ["Indication", "QRS > 100–120 ms (sodium channel blockade); wide-complex dysrhythmia"],
          ["Bolus dose", "1–2 mEq/kg IV push — may repeat every 3–5 min until QRS narrows"],
          ["Infusion (if boluses needed repeatedly)", "150 mEq/L NaHCO3 in 5% dextrose at 1.5x calculated maintenance rate"],
          ["Target pH", "7.50–7.55 (do not exceed 7.60)"],
          ["Monitor", "ABG every 30–60 min; serum K+ (bicarb drives K+ intracellularly — replace K+)"],
          ["Stop when", "QRS narrows to < 100 ms, pH > 7.55, or clinical improvement"],
        ],
        [32, 68]
      ),

      heading2("9E. Hyperthermia Management"),
      makeTable(
        ["Temperature", "Action"],
        [
          ["37.5–38.5°C", "Benzodiazepines for agitation (primary intervention); ensure adequate sedation; remove excess clothing"],
          ["> 38.5°C", "Active external cooling: undress fully, mist + fan, ice packs to axilla / groin / neck / forehead; IV fluids"],
          ["> 40°C (critical)", "Aggressive cooling; ICU; check CK q2–4h, creatinine, coagulation; consider intubation"],
        ],
        [22, 78]
      ),

      noteBox(
        "DO NOT use paracetamol or NSAIDs — hyperthermia is caused by agitation and inability to sweat, NOT by prostaglandins. Antipyretics are ineffective.\nDO NOT use diphenhydramine for agitation — it is itself an anticholinergic agent.",
        AMBERT, AMBER
      ),

      heading2("9F. Seizure Management"),
      makeTable(
        ["Step", "Drug", "Adult Dose", "Pediatric Dose", "Notes"],
        [
          ["1st line", "Lorazepam or Diazepam IV", "Lorz: 0.1mg/kg (max 4mg); Diaz: 0.1–0.3mg/kg", "0.05–0.1 mg/kg lorazepam", "Repeat x1 at 5 min if no response"],
          ["2nd line", "Phenobarbital", "10–20 mg/kg IV", "10–20 mg/kg IV", "Slow infusion over 30–60 min; may cause hypotension"],
          ["3rd line / Refractory", "Propofol infusion", "80–200 mcg/kg/min", "Titrate carefully", "Requires intubation and mechanical ventilation"],
          ["AVOID", "Phenytoin / Fosphenytoin", "—", "—", "Ineffective for toxin-induced seizures; worsens cardiac conduction"],
        ],
        [14, 20, 22, 20, 24]
      ),

      heading2("9G. Other Supportive Measures"),
      makeTable(
        ["Intervention", "Indication", "Details"],
        [
          ["IV fluids (NS or RL)", "Dehydration, hypotension, CK elevation", "10–20 mL/kg bolus; titrate to effect"],
          ["Urinary catheter", "Urinary retention (confirmed by palpation or bladder scan)", "Insert Foley catheter; monitor UO hourly"],
          ["Rhabdomyolysis protocol", "CK > 1000 U/L", "Target urine output 1–3 mL/kg/h; IV fluid titration; urine alkalinization if pH < 6.5"],
          ["Vasopressors", "Refractory hypotension unresponsive to fluids", "Noradrenaline 0.05–0.5 mcg/kg/min IV infusion; ICU"],
          ["Intubation / RSI", "GCS ≤8, refractory seizures, respiratory failure", "Use ketamine or propofol for induction; avoid succinylcholine if rhabdo suspected"],
        ],
        [25, 30, 45]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 10 — SPECIAL SITUATIONS
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 10: SPECIAL SITUATIONS"),

      heading2("10A. Datura stramonium (Dhatura) Poisoning — Nepal High Priority"),
      makeTable(
        ["Aspect", "Details"],
        [
          ["Toxins", "Scopolamine, hyoscyamine, atropine alkaloids (all parts toxic; seeds most concentrated)"],
          ["Setting", "Intentional misuse for intoxication; accidental ingestion in children; rare homicidal/criminal use"],
          ["Clinical course", "Prolonged toxicity — 12–48 hours due to alkaloid kinetics; may wax and wane"],
          ["Management", "Physostigmine often highly effective; titrate carefully; repeat dosing likely needed; ICU admission for severe cases"],
          ["Pitfall", "Do NOT discharge early — toxicity can recrudesce"],
        ],
        [25, 75]
      ),

      heading2("10B. Trihexyphenidyl (Pacitane) Abuse"),
      makeTable(
        ["Aspect", "Details"],
        [
          ["Pattern", "Recreational misuse for euphoria / hallucinations; documented across Nepal, India, Bangladesh"],
          ["Availability", "Sold OTC in many Nepali pharmacies; inexpensive"],
          ["Clinical features", "Moderate–severe central delirium dominant; peripheral signs usually present; dose-dependent"],
          ["Management", "Benzodiazepines first line; physostigmine if available and ECG safe; counseling on abuse potential"],
        ],
        [25, 75]
      ),

      heading2("10C. TCA Overdose with Anticholinergic Features — Critical Alert"),
      noteBox(
        "DO NOT GIVE PHYSOSTIGMINE in TCA overdose. Risk of asystole and status epilepticus is well-documented (Pentel & Peterson, 1980).\nPrioritize: 12-lead ECG → sodium bicarbonate for QRS > 100 ms → benzodiazepines for agitation/seizures → ICU.",
        AMBERT, RED
      ),
      makeTable(
        ["Priority", "Action"],
        [
          ["1", "12-lead ECG — measure QRS width IMMEDIATELY"],
          ["2", "QRS > 100 ms → Sodium bicarbonate 1–2 mEq/kg IVP; repeat PRN"],
          ["3", "Benzodiazepines for agitation AND seizures"],
          ["4", "Mandatory ICU admission"],
          ["5", "Physostigmine is ABSOLUTELY CONTRAINDICATED"],
        ],
        [10, 90]
      ),

      heading2("10D. Pediatric Patients"),
      makeTable(
        ["Aspect", "Details"],
        [
          ["Sensitivity", "Children more sensitive; toxicity at lower doses (diphenhydramine: 7.5 mg/kg; severe: 15 mg/kg)"],
          ["Common causes", "Eye drops (atropine/cyclopentolate), antihistamine syrups, plant ingestions"],
          ["Physostigmine dose", "0.02 mg/kg IV slow (max 0.5 mg); repeat after 30–60 min PRN"],
          ["Seizure risk", "Higher than adults; aggressively treat with BZD"],
          ["Cooling", "Body surface area proportionally larger — evaporative cooling more effective"],
        ],
        [28, 72]
      ),

      heading2("10E. Pregnancy"),
      makeTable(
        ["Aspect", "Details"],
        [
          ["Benzodiazepines", "Use in life-threatening situations despite risks (fetal sedation); risk of harm to mother outweighs fetal risk"],
          ["Physostigmine", "Limited data; use if clearly indicated and benefits outweigh risks; obstetric consultation required"],
          ["Fetal monitoring", "Continuous CTG if > 24 weeks gestation"],
          ["Obstetric consult", "Early, concurrent with resuscitation"],
        ],
        [28, 72]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 11 — DISPOSITION
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 11: DISPOSITION"),

      makeTable(
        ["Clinical Status", "Disposition", "Minimum Observation"],
        [
          ["Asymptomatic (accidental, low dose)", "Activated charcoal; observe in ED; discharge if remains asymptomatic", "6 hours"],
          ["Mild (symptoms resolving within 6h)", "AC if applicable; BZD if needed; observe; discharge if fully resolved", "6 hours"],
          ["Moderate (symptoms persisting at 6h)", "Admit to monitored general ward or HDU", "Admit — until symptoms resolve"],
          ["Severe (hyperthermia, seizures, coma, dysrhythmia)", "ICU admission — urgent", "ICU until clinically stable"],
          ["Any patient who received physostigmine", "ICU or monitored HDU admission", "Minimum 12–24 hours ICU"],
          ["TCA overdose with cardiac manifestations", "ICU/HDU mandatory", "Until ECG and vitals stable"],
        ],
        [33, 42, 25]
      ),

      noteBox(
        "ALL intentional overdoses require formal psychiatric evaluation before discharge, regardless of clinical severity. This is a mandatory step — do not discharge without psychiatric clearance.",
        AMBERT, AMBER
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 12 — MONITORING
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 12: MONITORING PARAMETERS"),

      makeTable(
        ["Parameter", "Frequency (Acute Phase)", "Alert Threshold / Action"],
        [
          ["Vital signs (BP, HR, Temp, RR, SpO2)", "Every 15–30 minutes", "HR > 150; Temp > 38.5°C; SpO2 < 94%"],
          ["Cardiac monitor (continuous)", "Continuous", "QRS > 100 ms; VT; bradycardia → act immediately"],
          ["GCS / Agitation scale", "Every 30 minutes", "Deteriorating GCS or worsening agitation"],
          ["Urine output (if catheterized)", "Hourly", "< 0.5 mL/kg/h → IV fluids; rhabdomyolysis protocol"],
          ["12-lead ECG", "On arrival; 2h; 4h; and PRN", "QRS > 100 ms; new dysrhythmia"],
          ["Core temperature", "Every 30 min if hyperthermic", "> 40°C = critical — escalate cooling"],
          ["CK (if agitated / hyperthermic)", "On admission; repeat at 4–6h", "Rising CK > 1000 → rhabdomyolysis protocol"],
          ["Serum K+", "On admission; repeat 4h if NaHCO3 given", "K+ < 3.0 → replace before NaHCO3 infusion"],
        ],
        [33, 28, 39]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 13 — WHAT NOT TO DO
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 13: WHAT NOT TO DO — Common Pitfalls"),

      makeTable(
        ["Intervention", "Why Avoid"],
        [
          ["Physostigmine in TCA overdose", "Risk of asystole and status epilepticus — potentially fatal (Pentel & Peterson, 1980)"],
          ["Physostigmine when QRS > 100 ms", "Sodium channel blockade present — life-threatening cardiac complication"],
          ["Phenytoin for toxin-induced seizures", "Ineffective mechanism; worsens cardiac conduction; avoid"],
          ["Antipyretics (paracetamol/aspirin) for hyperthermia", "Ineffective — hyperthermia is not prostaglandin-mediated; wasted time"],
          ["Diphenhydramine for agitation", "It IS an anticholinergic agent — will worsen toxidrome"],
          ["Physical restraints without sedation", "Worsens agitation and hyperthermia; causes rhabdomyolysis; dangerous"],
          ["Haloperidol / droperidol for agitation", "Lowers seizure threshold; prolongs QTc; avoid until TCA excluded"],
          ["Flumazenil if benzodiazepines given for seizures", "Reverses anticonvulsant cover — may precipitate seizures"],
          ["Early discharge after Datura poisoning", "Toxicity may recrudesce — minimum 12–24h observation for severe plant alkaloid exposures"],
          ["Discharging without psychiatric review (intentional OD)", "Missed suicide risk assessment — mandatory before discharge"],
        ],
        [38, 62]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 14 — QUICK DRUG SUMMARY
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 14: QUICK DRUG DOSING REFERENCE"),

      makeTable(
        ["Drug", "Adult Dose", "Pediatric Dose", "Route", "Indication / Notes"],
        [
          ["Diazepam", "5–10 mg q10–15 min", "0.1–0.3 mg/kg q10–15 min", "IV slow", "1st-line agitation / seizure"],
          ["Lorazepam", "1–2 mg q10–15 min", "0.05–0.1 mg/kg", "IV", "1st-line agitation / seizure"],
          ["Midazolam", "2–5 mg q5–10 min", "0.1–0.2 mg/kg", "IV / IM", "When no IV access; IM option"],
          ["Physostigmine", "1–2 mg over 5 min", "0.02 mg/kg (max 0.5 mg)", "IV slow", "Antidote — see full checklist Sec 9B"],
          ["Atropine (rescue)", "0.5–1 mg IV", "0.01–0.02 mg/kg IV", "IV", "For physostigmine-induced bradycardia"],
          ["Sodium bicarbonate", "1–2 mEq/kg bolus", "1–2 mEq/kg bolus", "IV push", "QRS > 100 ms ONLY"],
          ["Activated charcoal", "50 g (1 g/kg)", "1 g/kg (max 50 g)", "PO / NG", "Within 1–2 h; protected airway"],
          ["Phenobarbital", "10–20 mg/kg IV", "10–20 mg/kg IV", "IV slow (30–60 min)", "Refractory seizures"],
          ["Noradrenaline", "0.05–0.5 mcg/kg/min", "0.05–0.3 mcg/kg/min", "IV infusion", "Refractory hypotension; ICU"],
          ["Rivastigmine", "3 mg oral / 4.6 mg patch", "Avoid if < 18 (limited data)", "PO / transdermal", "If physostigmine unavailable"],
        ],
        [18, 20, 18, 12, 32]
      ),

      noteBox(
        "ALWAYS verify drug doses before administration. Have resuscitation equipment immediately available when administering physostigmine.",
        AMBERT, AMBER
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // SECTION 15 — EVIDENCE BASE
      // ═══════════════════════════════════════════════════════════════════════
      heading1("SECTION 15: EVIDENCE BASE & REFERENCES"),

      heading2("Landmark Clinical Studies"),
      makeTable(
        ["Reference", "Evidence Level", "Key Finding / Recommendation"],
        [
          ["Wang GS et al. (2021). Clin Toxicol. PMID 33295809", "RCT (Level II)", "Physostigmine superior to lorazepam for antimuscarinic delirium; safe in adolescents; no serious adverse events"],
          ["Burns MJ et al. (2000). Ann Emerg Med 35(4):374–381", "RCT (Level II)", "Physostigmine significantly more effective than benzodiazepines; no increase in adverse events"],
          ["Chiew AL et al. (2024). Clin Toxicol 62(2):82–87", "Case series (Level IV)", "Rivastigmine effective alternative for anticholinergic delirium when physostigmine unavailable"],
          ["Pentel P, Peterson CD. (1980). Ann Emerg Med 9(11):588–590", "Case series (Level IV)", "Asystole complicating physostigmine in TCA OD — basis for absolute contraindication"],
          ["Dawson AH, Buckley NA. (2016). Br J Clin Pharmacol 81(3):516–524", "Review (Level V)", "Comprehensive pharmacological management framework for anticholinergic delirium"],
          ["Hoffman RJ, Nillas A. (2025). Arch Dis Child. PMID 39978865", "Review (Level V)", "Toxidromes approach; antidote role; 2025 updated guidance"],
          ["Pannu AK. (2025). Trop Doct. PMID 40791148", "Review (Level V)", "Practical approach to agitated toxidromes in resource-limited/tropical settings"],
          ["Serrano WC, Maldonado J. (2021). PMID 34102130", "Review (Level V)", "Physostigmine in antipsychotic (olanzapine) overdose — diagnosis and treatment framework"],
        ],
        [36, 15, 49]
      ),

      heading2("Authoritative Textbooks"),
      makeTable(
        ["Textbook", "Edition", "Key Sections Used"],
        [
          ["Rosen's Emergency Medicine: Concepts and Clinical Practice", "9th Ed (2023)", "Anticholinergic Toxidrome; Physostigmine dosing; Sodium bicarbonate protocol; BZD titration"],
          ["Tintinalli's Emergency Medicine: A Comprehensive Study Guide", "9th Ed (2020)", "GI decontamination; Treatment algorithm; Severity classification; Drug dosing tables"],
          ["Goldman-Cecil Medicine", "26th Ed (International)", "Toxidrome classification table; Clinical features; Representative drugs"],
          ["Harrison's Principles of Internal Medicine", "22nd Ed (2025)", "Differential diagnosis; Systemic management approach; Updated clinical guidelines"],
          ["Goldfrank's Toxicologic Emergencies", "11th Ed", "Mechanism of toxicity; Antihistamines; Anticholinergic pharmacology"],
          ["Tietz Textbook of Laboratory Medicine", "7th Ed", "Agents related to anticholinergic toxidrome; TCA overlap; Laboratory evaluation"],
        ],
        [40, 18, 42]
      ),

      heading2("International Protocols and Guidelines"),
      makeTable(
        ["Source", "Relevance"],
        [
          ["CHEMM (HHS/ASPR) — Anticholinergic Toxidrome Protocol", "US government emergency chemical hazard protocol; used by first responders and ED physicians internationally"],
          ["US Poison Control Centers — AAPCC", "Management guidelines for anticholinergic exposures; 1-800-222-1222"],
          ["UK TOXBASE / NPIS (National Poisons Information Service)", "UK national clinical guidelines; available at www.toxbase.org (registration required)"],
          ["StatPearls — Broderick ED et al. (2023)", "Current evidence-based summary; physostigmine dosing; BZD first-line; AC timing"],
          ["WHO SEARO", "Regional guidance for South-East Asia including Nepal"],
          ["Medscape Emergency Medicine Protocols", "Anticholinergic toxicity treatment and management; regularly updated"],
        ],
        [40, 60]
      ),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // APPENDIX A — PHYSOSTIGMINE ADMINISTRATION CHECKLIST
      // ═══════════════════════════════════════════════════════════════════════
      heading1("APPENDIX A: PHYSOSTIGMINE ADMINISTRATION SAFETY CHECKLIST"),
      para("Complete ALL items before administering physostigmine. Sign and date for medico-legal record.", { bold: true, color: RED }),
      new Paragraph({ spacing: { before: 80, after: 80 }, children: [] }),

      makeTable(
        ["#", "Checklist Item", "Confirmed (initial)"],
        [
          ["PRE-1", "Clinical diagnosis confirmed: peripheral AND central anticholinergic signs present", "___"],
          ["PRE-2", "ECG reviewed: QRS < 100 ms confirmed", "___"],
          ["PRE-3", "No bradycardia; no heart block; no PR prolongation on ECG", "___"],
          ["PRE-4", "TCA overdose excluded (history, ECG — no rightward axis, no Brugada-like pattern)", "___"],
          ["PRE-5", "No bronchospasm; no reactive airway disease history", "___"],
          ["PRE-6", "Atropine 0.5 mg (adult) drawn up; at bedside", "___"],
          ["PRE-7", "Resuscitation cart at bedside; defibrillator ready", "___"],
          ["PRE-8", "Continuous cardiac monitor active; SpO2 probe applied", "___"],
          ["PRE-9", "IV access patent and confirmed", "___"],
          ["PRE-10", "Dose calculated and drawn up in 10 mL NS syringe", "___"],
          ["ADMIN-1", "Administer SLOWLY over minimum 5 minutes", "___"],
          ["ADMIN-2", "Monitoring HR, BP, SpO2 continuously during infusion", "___"],
          ["POST-1", "Response assessed at 15–20 minutes post-dose", "___"],
          ["POST-2", "If recurrence at 30–60 min, repeat dose acceptable", "___"],
          ["POST-3", "ICU / monitored HDU admission arranged", "___"],
        ],
        [12, 72, 16]
      ),
      new Paragraph({ spacing: { before: 120, after: 60 }, children: [new TextRun({ text: "Physician Name: _______________________________    Signature: ___________________    Date/Time: ______________", size: 18, font: "Calibri" })] }),

      pageBreak(),

      // ═══════════════════════════════════════════════════════════════════════
      // APPENDIX B — APPROVAL
      // ═══════════════════════════════════════════════════════════════════════
      heading1("APPENDIX B: PROTOCOL APPROVAL AND REVIEW"),

      makeTable(
        ["Field", "Details"],
        [
          ["Protocol Title", "Anticholinergic Toxidrome Emergency Management Protocol"],
          ["Version", "1.0"],
          ["Date of Issue", "June 2026"],
          ["Next Review Date", "June 2028 (or earlier if new major evidence published)"],
          ["Prepared by", "_________________________________"],
          ["Reviewed by (Senior Physician)", "_________________________________"],
          ["Approved by (HOD / Medical Director)", "_________________________________"],
          ["Department", "Emergency Medicine"],
          ["Hospital", "_________________ Hospital, Nepal"],
        ],
        [35, 65]
      ),

      noteBox(
        "This protocol is intended for use by qualified emergency physicians. All drug doses must be verified before administration. Drug availability varies by institution — verify locally. Protocol should be reviewed every 2 years or when significant new evidence is published.",
        LTBLUE, DKBLUE
      ),

    ]
  }]
});

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Anticholinergic Toxidrome Protocol Nepal ED
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What's inside the document

The protocol is formatted as a professional Word document (34 KB, fully editable) with:

Header/footer on every page with hospital/version info and page numbers
Color-coded tables throughout (dark blue headers, amber warnings, green safety notes)
Alert boxes (e.g., "DO NOT give physostigmine in TCA overdose" in red border)

15 sections included:

Section	Content
1	Toxidrome quick reference — 5-toxidrome comparison table + memory aid
2	Causative agents with Nepal-specific relevance ratings
3	Severity classification (Mild / Moderate / Severe)
4	Immediate actions — ABCDE + ECG interpretation table
5	Investigations with priority tiers
6	Differential diagnosis with differentiating features
7	Step-by-step management algorithm
8	GI decontamination (activated charcoal dosing + window)
9	Full pharmacological management — BZD, physostigmine, rivastigmine, NaHCO3, hyperthermia, seizures
10	Special situations — Datura, Pacitane, TCA, pediatric, pregnancy
11	Disposition criteria
12	Monitoring parameters table
13	What NOT to do (10 common pitfalls)
14	Quick drug dosing reference table
15	Full evidence base + references
Appendix A	Physostigmine administration safety checklist (signable)
Appendix B	Protocol approval/review page

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