Cookbook 370: Offline Clinical Medical Toxicology & Critical Care CCB and Beta-Blocker Overdose, HIET & Lipid Emulsion Titrator Engine

"""
Offline Clinical Medical Toxicology & Critical Care CCB and Beta-Blocker Overdose,
HIET & Lipid Emulsion Titrator Engine.
Zero external cloud API reliance. Pure offline Python.
"""

import sys
from dataclasses import dataclass, field
from enum import Enum
from typing import List, Optional

# Enforce UTF-8 standard output for Windows CLI environments
if hasattr(sys.stdout, "reconfigure"):
    sys.stdout.reconfigure(encoding="utf-8")


class ToxicAgentClass(str, Enum):
    CCB_NON_DIHYDROPYRIDINE = "CCB: Non-Dihydropyridine (Verapamil / Diltiazem - Severe Myocardial & Nodal Depression)"
    CCB_DIHYDROPYRIDINE = "CCB: Dihydropyridine (Amlodipine / Nifedipine - Profound Refractory Vasoplegia)"
    BB_LIPOPHILIC_MSA = "Beta-Blocker: Lipophilic with Membrane Stabilizing Activity (Propranolol - Sodium Channel Blockade & CNS Toxicity)"
    BB_POTASSIUM_BLOCK = "Beta-Blocker: Potassium Channel Blocker (Sotalol - Marked QTc Prolongation & TdP Risk)"
    BB_STANDARD = "Beta-Blocker: Standard (Metoprolol / Atenolol / Carvedilol / Bisoprolol)"
    MIXED_OR_UNKNOWN = "Mixed / Unidentified Cardiotoxic Overdose"


class ShockSeverityTier(str, Enum):
    MILD_MODERATE = "Tier 1: Compensated / Mild Toxicity (Bradycardia, Borderline Normotension)"
    SEVERE_SHOCK = "Tier 2: Severe Decompensated Cardiotoxic Shock (Profound Hypotension SBP < 80, Refractory Bradycardia)"
    EXTREMIS_CARDIAC_ARREST = "Tier 3: Peri-Arrest / Severe Cardiogenic Shock in Extremis (PEA, Asystole, Severe Acidemia)"


@dataclass
class ToxPatientProfile:
    patient_id: str
    weight_kg: float
    agent_class: ToxicAgentClass
    ingested_agent_name: str
    time_since_ingestion_hours: float
    # Hemodynamics
    heart_rate_bpm: float = 42.0
    systolic_bp_mmhg: float = 74.0
    diastolic_bp_mmhg: float = 40.0
    mean_arterial_pressure_mmhg: float = 51.3
    # ECG Findings
    qrs_duration_ms: float = 88.0
    qtc_interval_ms: float = 430.0
    has_high_grade_av_block: bool = False
    has_seizures: bool = False
    # Metabolic & Lab Values
    blood_glucose_mg_dl: float = 290.0
    serum_potassium_meq_l: float = 4.2
    arterial_ph: float = 7.18
    serum_lactate_mmol_l: float = 5.6
    # Response to initial fluid & vasopressors
    is_refractory_to_standard_vasopressors: bool = True
    central_line_in_place: bool = True


@dataclass
class ToxResuscitationAssessment:
    patient_id: str
    shock_tier: ShockSeverityTier
    phenotype_differentiation: str
    first_line_antidotes: List[str]
    hiet_insulin_bolus_units: float
    hiet_insulin_initial_rate_units_h: float
    hiet_insulin_max_titration_rate_units_h: float
    dextrose_infusion_prescription: str
    potassium_stewardship_directive: str
    ile_lipid_bolus_ml: float
    ile_lipid_infusion_rate_ml_min: float
    conduction_and_ecg_directives: List[str]
    va_ecmo_triage_recommendation: str
    safety_sentinels: List[str]
    clinical_executive_directive: str


class CardiotoxicOverdoseEngine:
    """
    Precision Medical Toxicology & Critical Care Decision Engine for CCB & Beta-Blocker Overdoses.
    Conforms to ACMT, AACT, and EXTRIP Consensus Guidelines.
    """

    def evaluate_case(self, p: ToxPatientProfile) -> ToxResuscitationAssessment:
        sentinels: List[str] = []
        first_line_antidotes: List[str] = []
        ecg_directives: List[str] = []

        # 1. Stratify Shock Severity Tier
        if p.heart_rate_bpm < 35.0 or p.systolic_bp_mmhg < 60.0 or p.serum_lactate_mmol_l >= 8.0:
            shock_tier = ShockSeverityTier.EXTREMIS_CARDIAC_ARREST
        elif p.systolic_bp_mmhg < 85.0 or p.mean_arterial_pressure_mmhg < 60.0 or p.heart_rate_bpm < 50.0:
            shock_tier = ShockSeverityTier.SEVERE_SHOCK
        else:
            shock_tier = ShockSeverityTier.MILD_MODERATE

        # 2. Phenotypic Differentiation & Diagnostic Insights
        if p.agent_class in [ToxicAgentClass.CCB_NON_DIHYDROPYRIDINE, ToxicAgentClass.CCB_DIHYDROPYRIDINE]:
            phenotype = (
                f"Calcium Channel Blocker Overdose ({p.ingested_agent_name}): "
                f"Hyperglycemia ({p.blood_glucose_mg_dl:.0f} mg/dL) reflects L-type calcium channel inhibition in pancreatic islet beta-cells, "
                f"causing impaired insulin secretion. Severity of hyperglycemia correlates directly with shock severity."
            )
            # First line CCB antidote: IV Calcium
            first_line_antidotes.append(
                "IV CALCIUM CHLORIDE 10%: Administer 10-20 mL (1-2 grams) IV over 5-10 minutes via central line (or Calcium Gluconate 30-60 mL via peripheral line). "
                "Repeat q10-15m for up to 3 doses or start continuous infusion (0.2-0.4 mL/kg/h of 10% Calcium Chloride). Target ionized Calcium 1.5 - 2.0 mmol/L."
            )
        else:
            phenotype = (
                f"Beta-Blocker Overdose ({p.ingested_agent_name}): "
                f"Inhibition of beta-2 mediated gluconeogenesis/glycogenolysis typically produces euglycemia or hypoglycemia ({p.blood_glucose_mg_dl:.0f} mg/dL)."
            )
            # First line BB antidote: IV Glucagon
            first_line_antidotes.append(
                "IV GLUCAGON: Administer 5-10 mg IV bolus over 1-2 minutes. If positive chronotropic/inotropic response occurs within 10 minutes, "
                "initiate continuous maintenance infusion at the successful bolus dose per hour (2-5 mg/h). Co-prescribe IV Ondansetron for severe emesis."
            )

        # Vasopressor support
        first_line_antidotes.append(
            "VASOPRESSOR SUPPORT: Initiate Norepinephrine (0.1 - 1.0 mcg/kg/min) for systemic vasoplegia plus Epinephrine (0.05 - 0.5 mcg/kg/min) for cardiogenic inotropy."
        )

        # 3. High-Dose Insulin Euglycemia Therapy (HIET) Calculations
        # Regular insulin bolus: 1 unit/kg
        insulin_bolus = round(1.0 * p.weight_kg, 1)
        # Regular insulin starting rate: 1 unit/kg/h
        insulin_start_rate = round(1.0 * p.weight_kg, 1)
        # Max titration rate: up to 10 units/kg/h for severe refractory shock
        insulin_max_rate = round(10.0 * p.weight_kg, 1)

        # Dextrose co-administration rules
        if p.blood_glucose_mg_dl < 250.0:
            dextrose_bolus_str = f"Co-administer Dextrose 0.5-1.0 g/kg (D50W: {round(p.weight_kg * 1.5, 0):.0f} mL IV bolus) with the insulin bolus."
        else:
            dextrose_bolus_str = f"Initial blood glucose is elevated ({p.blood_glucose_mg_dl:.0f} mg/dL); hold initial D50W bolus but prepare concentrated dextrose infusion."

        dextrose_rx = (
            f"{dextrose_bolus_str} Initiate continuous concentrated Dextrose (D10W or D20W via central line) at 0.5-1.5 g/kg/h "
            f"({round(p.weight_kg * 5.0, 0):.0f} - {round(p.weight_kg * 10.0, 0):.0f} mL/h of D10W). "
            f"Target blood glucose: 150 - 250 mg/dL. Monitor point-of-care glucose q15-30m during titration, then q1h."
        )

        # Potassium stewardship directive
        potassium_directive = (
            f"POTASSIUM STEWARDSHIP PROTOCOL: Baseline K+ is {p.serum_potassium_meq_l:.1f} mEq/L. "
            f"Insulin drives extracellular potassium intracellularly. Do NOT aggressively treat hypokalemia unless serum K+ < 2.8 - 3.0 mEq/L, "
            f"as intracellular redistribution does not indicate total body depletion. Maintain serum K+ strictly between 3.0 - 3.5 mEq/L "
            f"to prevent fatal rebound hyperkalemia upon insulin weaning."
        )

        # 4. Intravenous Lipid Emulsion (20% ILE) Calculations
        # Bolus: 1.5 mL/kg over 2-3 minutes
        ile_bolus_ml = round(1.5 * p.weight_kg, 1)
        # Infusion: 0.25 mL/kg/min
        ile_infusion_rate = round(0.25 * p.weight_kg, 1)

        # 5. Conduction & ECG Directives (Sodium & Potassium Channel Blockade)
        if p.qrs_duration_ms > 100.0 or p.agent_class == ToxicAgentClass.BB_LIPOPHILIC_MSA:
            if p.qrs_duration_ms > 100.0:
                ecg_directives.append(
                    f"🚨 MEMBRANE-STABILIZING ACTIVITY / SODIUM CHANNEL BLOCKADE (QRS {p.qrs_duration_ms:.0f} ms > 100 ms): "
                    f"Immediate IV Sodium Bicarbonate: 1-2 mEq/kg (1-2 ampules of 8.4% NaHCO3) IV push q3-5m until QRS narrows, "
                    f"followed by continuous NaHCO3 infusion (150 mEq in 1L D5W at 150-250 mL/h) targeting arterial pH 7.50 - 7.55."
                )
            else:
                ecg_directives.append(
                    "PROPRANOLOL MEMBRANE STABILIZATION WATCH: Monitor 12-lead ECG continuously for QRS widening (> 100 ms) and administer IV NaHCO3 immediately upon widening."
                )

        if p.qtc_interval_ms > 500.0 or p.agent_class == ToxicAgentClass.BB_POTASSIUM_BLOCK:
            ecg_directives.append(
                f"🚨 SOTALOL / POTASSIUM CHANNEL BLOCKADE (QTc {p.qtc_interval_ms:.0f} ms > 500 ms): "
                f"High risk of Torsades de Pointes. Administer IV Magnesium Sulfate 2.0 grams IV over 10-15 minutes; maintain serum Mg > 2.5 mg/dL and K+ > 4.0 mEq/L."
            )

        if p.has_high_grade_av_block:
            ecg_directives.append(
                "HIGH-GRADE AV BLOCK: Transcutaneous or temporary transvenous pacing setup indicated. "
                "Note that electrical capture without mechanical pulsatile output (electromechanical dissociation) frequently occurs in CCB overdose until HIET reverses cellular uncoupling."
            )

        # 6. Safety Sentinels & Prohibitions
        sentinels.append(
            "VASODILATOR & PURE INOTROPE CONTRAINDICATION: Prohibit pure direct vasodilators, phosphodiesterase inhibitors (Milrinone), or high-dose Isoproterenol as monotherapy due to exacerbation of profound peripheral vasoplegia and cardiovascular collapse."
        )
        sentinels.append(
            "HYPOGLYCEMIA MONITORING GUARDRAIL: HIET-induced hypoglycemia may be delayed for 1-4 hours post-initiation. Never discontinue dextrose infusion prematurely."
        )
        if not p.central_line_in_place:
            sentinels.append(
                "CENTRAL LINE PLACEMENT WARNING: Concentrated dextrose (D20W) and Calcium Chloride require central venous access to prevent severe peripheral extravasation tissue necrosis."
            )

        # 7. Extracorporeal Life Support (VA-ECMO) Triage
        if shock_tier in [ShockSeverityTier.SEVERE_SHOCK, ShockSeverityTier.EXTREMIS_CARDIAC_ARREST] and p.is_refractory_to_standard_vasopressors:
            ecmo_triage = (
                "🚨 LEVEL 1 EXTRACORPOREAL LIFE SUPPORT (VA-ECMO / ECPR) MOBILIZATION: "
                "Patient demonstrates cardiotoxic shock refractory to first-line antidotes and dual vasopressors. "
                "Alert ECMO cannulation team immediately. VA-ECMO provides temporary mechanical cardiopulmonary bypass "
                "until toxic xenobiotic clearance and hepatic/renal metabolic degradation occur (typically 24-72 hours)."
            )
        else:
            ecmo_triage = "Continue advanced pharmacological resuscitation (HIET + ILE + Vasopressors); keep ECMO team on standby if MAP < 60 mmHg persists."

        directive = (
            f"EXECUTIVE TOXICOLOGY DIRECTIVE: {shock_tier.value}. {phenotype} "
            f"Initiate HIET immediately: Regular Insulin {insulin_bolus} units IV bolus + {insulin_start_rate} units/h infusion, "
            f"titrating up to {insulin_max_rate} units/h. Co-infuse concentrated dextrose targeting 150-250 mg/dL. "
            f"If refractory shock or cardiac arrest occurs, administer 20% Lipid Emulsion {ile_bolus_ml} mL IV bolus."
        )

        return ToxResuscitationAssessment(
            patient_id=p.patient_id,
            shock_tier=shock_tier,
            phenotype_differentiation=phenotype,
            first_line_antidotes=first_line_antidotes,
            hiet_insulin_bolus_units=insulin_bolus,
            hiet_insulin_initial_rate_units_h=insulin_start_rate,
            hiet_insulin_max_titration_rate_units_h=insulin_max_rate,
            dextrose_infusion_prescription=dextrose_rx,
            potassium_stewardship_directive=potassium_directive,
            ile_lipid_bolus_ml=ile_bolus_ml,
            ile_lipid_infusion_rate_ml_min=ile_infusion_rate,
            conduction_and_ecg_directives=ecg_directives,
            va_ecmo_triage_recommendation=ecmo_triage,
            safety_sentinels=sentinels,
            clinical_executive_directive=directive
        )


# =====================================================================
# Verification & Self-Testing Suite
# =====================================================================
if __name__ == "__main__":
    engine = CardiotoxicOverdoseEngine()

    print("================================================================================")
    print("DEMO 1: Severe Verapamil Overdose with Refractory Shock & Hyperglycemia")
    print("================================================================================")
    case_ccb = ToxPatientProfile(
        patient_id="TOX-CCB-VERAP-701",
        weight_kg=70.0,
        agent_class=ToxicAgentClass.CCB_NON_DIHYDROPYRIDINE,
        ingested_agent_name="Verapamil Sustained-Release (4.8 grams)",
        time_since_ingestion_hours=3.5,
        heart_rate_bpm=38.0,
        systolic_bp_mmhg=68.0,
        diastolic_bp_mmhg=36.0,
        mean_arterial_pressure_mmhg=46.7,
        qrs_duration_ms=92.0,
        qtc_interval_ms=445.0,
        has_high_grade_av_block=True,
        blood_glucose_mg_dl=340.0,
        serum_potassium_meq_l=4.4,
        arterial_ph=7.14,
        serum_lactate_mmol_l=6.8,
        is_refractory_to_standard_vasopressors=True,
        central_line_in_place=True
    )

    eval1 = engine.evaluate_case(case_ccb)
    print(f"Patient ID: {eval1.patient_id} ({case_ccb.weight_kg} kg)")
    print(f"Shock Tier: {eval1.shock_tier.value}")
    print(f"Phenotype: {eval1.phenotype_differentiation}")
    print(f"HIET Insulin Bolus: {eval1.hiet_insulin_bolus_units} units IV")
    print(f"HIET Insulin Infusion: {eval1.hiet_insulin_initial_rate_units_h} units/h (Max titration: {eval1.hiet_insulin_max_titration_rate_units_h} units/h)")
    print(f"Dextrose Protocol: {eval1.dextrose_infusion_prescription}")
    print(f"Potassium Protocol: {eval1.potassium_stewardship_directive}")
    print(f"ILE 20% Rescue Bolus: {eval1.ile_lipid_bolus_ml} mL IV over 2-3 min (Infusion: {eval1.ile_lipid_infusion_rate_ml_min} mL/min)")
    print(f"ECMO Triage: {eval1.va_ecmo_triage_recommendation}")
    print("\nFirst-Line Antidotes:")
    for a in eval1.first_line_antidotes:
        print(f"  {a}")
    print("\nSafety Sentinels:")
    for s in eval1.safety_sentinels:
        print(f"  🚨 {s}")

    print("\n================================================================================")
    print("DEMO 2: Massive Propranolol Overdose with QRS Widening & Seizures")
    print("================================================================================")
    case_bb = ToxPatientProfile(
        patient_id="TOX-BB-PROP-702",
        weight_kg=80.0,
        agent_class=ToxicAgentClass.BB_LIPOPHILIC_MSA,
        ingested_agent_name="Propranolol (2.0 grams)",
        time_since_ingestion_hours=2.0,
        heart_rate_bpm=34.0,
        systolic_bp_mmhg=58.0,
        diastolic_bp_mmhg=30.0,
        mean_arterial_pressure_mmhg=39.3,
        qrs_duration_ms=138.0,
        qtc_interval_ms=490.0,
        has_seizures=True,
        blood_glucose_mg_dl=62.0,
        serum_potassium_meq_l=3.9,
        arterial_ph=7.08,
        serum_lactate_mmol_l=8.4,
        is_refractory_to_standard_vasopressors=True,
        central_line_in_place=True
    )

    eval2 = engine.evaluate_case(case_bb)
    print(f"Patient ID: {eval2.patient_id} ({case_bb.weight_kg} kg)")
    print(f"Shock Tier: {eval2.shock_tier.value}")
    print(f"Phenotype: {eval2.phenotype_differentiation}")
    print(f"HIET Insulin Bolus: {eval2.hiet_insulin_bolus_units} units IV")
    print(f"HIET Insulin Infusion: {eval2.hiet_insulin_initial_rate_units_h} units/h")
    print(f"ILE 20% Rescue Bolus: {eval2.ile_lipid_bolus_ml} mL IV")
    print("\nECG / Conduction Directives:")
    for d in eval2.conduction_and_ecg_directives:
        print(f"  {d}")