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} = require('docx');
const fs = require('fs');

// ── Colour palette ──────────────────────────────────────────────────────────
const RED    = "C0392B";   // headings / alert
const DKBLUE = "1A3A5C";   // section headers
const LTBLUE = "D6E4F0";   // table header fill
const AMBER  = "F39C12";   // warning rows
const AMBERT = "FEF9E7";   // warning row light fill
const GREEN  = "1E8449";   // positive/safe
const GREENT = "EAFAF1";   // green row fill
const GREY   = "F2F3F4";   // alternating table rows
const WHITE  = "FFFFFF";

// ── Helpers ──────────────────────────────────────────────────────────────────
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// ── Generic table builder ─────────────────────────────────────────────────────
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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({
        children: [
          new Table({
            width: { size: 100, type: WidthType.PERCENTAGE },
            borders: { bottom: { style: BorderStyle.SINGLE, size: 4, color: RED }, top: { style: BorderStyle.NONE, size: 0, color: WHITE }, left: { style: BorderStyle.NONE, size: 0, color: WHITE }, right: { style: BorderStyle.NONE, size: 0, color: WHITE }, insideH: { style: BorderStyle.NONE }, insideV: { style: BorderStyle.NONE } },
            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 } } })
            ]})]
          })
        ]
      })
    },
    footers: {
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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 },
      }),
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        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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