Offline Clinical Critical Care & Resuscitation Post-Cardiac Arrest Syndrome (PCAS) TTM2 Temperature Protocol, Hemodynamic Perfusion Titrator & 72-Hour Multimodal Neuroprognostication Engine

"""
OpenPHR Cookbook 405: Post-Cardiac Arrest Syndrome (PCAS) TTM2 & Neuroprognostication Engine
Clinical Standards: TTM2 Trial, AHA/ILCOR 2020/2024 Guidelines, ERC-ESICM Consensus
Execution: Deterministic, Zero Dependencies, Edge & Neuro-ICU Verified
"""

from dataclasses import dataclass, field
from enum import Enum
from typing import Dict, List, Optional, Tuple


class TTMStrategy(Enum):
    TARGETED_NORMOTHERMIA = "Targeted Normothermia (36.0 - 37.5 °C with aggressive active fever prevention)"
    CONTROLLED_HYPOTHERMIA = "Controlled Therapeutic Hypothermia (33.0 °C targeted cooling for 24 hours)"


class BSASShiveringTier(Enum):
    NONE_0 = "0 - No Shivering: No palpable or visible muscular activity"
    MILD_1 = "1 - Mild: Palpable tremors localized to neck and thorax only"
    MODERATE_2 = "2 - Moderate: Visible tremor involving upper extremities"
    SEVERE_3 = "3 - Severe: Generalized shivering involving whole body with bed shaking"


class NeuroprognosisConfidence(Enum):
    HIGHLY_LIKELY_POOR = "High Certainty Poor Outcome (>= 2 independent concordant multimodal predictors at >= 72h)"
    INDETERMINATE_OBSERVE = "Indeterminate Prognosis (Insufficient predictors; continue neuro-ICU supportive care)"
    FAVORABLE_RECOVERY_POTENTIAL = "Favorable Neurological Recovery Potential (Preserved reflexes, benign EEG, low NSE)"


@dataclass
class PostArrestPatientProfile:
    age_years: float
    weight_kg: float
    hours_since_rosc: float
    core_temperature_celsius: float
    has_chronic_hypertension: bool
    mean_arterial_pressure_mmhg: float
    pao2_mmhg: float
    paco2_mmhg: float
    fio2_percent: float
    shivering_score: BSASShiveringTier
    # Neuroprognostication Features (Evaluated at >= 72 hours)
    bilateral_pupillary_reflex_absent: bool = False
    bilateral_corneal_reflex_absent: bool = False
    ssep_bilateral_n20_absent: bool = False
    serum_nse_ug_l: Optional[float] = None
    eeg_malignant_pattern_present: bool = False
    head_ct_gwr_less_than_1_10: bool = False
    has_residual_paralytics_or_deep_sedation: bool = False


@dataclass
class HemodynamicRespiratoryTargets:
    target_map_mmhg: str
    pressor_choice: str
    target_pao2_mmhg: str
    target_paco2_mmhg: str
    hyperoxia_sentinel: str
    hypocapnia_sentinel: str


@dataclass
class AntiShiveringPrescription:
    current_tier: BSASShiveringTier
    recommended_interventions: List[str]
    neuromuscular_blockade_indicated: bool


@dataclass
class NeuroprognosticationResult:
    is_premature: bool
    hours_post_rosc: float
    evaluated_predictors_count: int
    positive_poor_predictors: List[str]
    confidence: NeuroprognosisConfidence
    clinical_rationale: str


@dataclass
class ComprehensivePCASGuidance:
    patient_summary: Dict[str, str]
    temperature_protocol: Dict[str, str]
    hemodynamic_respiratory_goals: HemodynamicRespiratoryTargets
    anti_shivering: AntiShiveringPrescription
    neuroprognostication: NeuroprognosticationResult
    critical_sentinels: List[str]


class PostCardiacArrestEngine:
    """
    Offline Clinical Decision Support Engine for Post-Cardiac Arrest Syndrome.
    Implements TTM2 temperature control, perfusion goals, and multimodal neuroprognostication.
    """

    @classmethod
    def evaluate_hemodynamics_and_respiration(
        cls, patient: PostArrestPatientProfile
    ) -> HemodynamicRespiratoryTargets:
        """
        Determines blood pressure and gas exchange targets to preserve cerebral perfusion.
        """
        target_map = ">= 75 - 85 mmHg (Optimized for chronic hypertension cerebral autoregulation)"             if patient.has_chronic_hypertension else "65 - 75 mmHg"

        hyperoxia_alert = "SAFE"
        if patient.pao2_mmhg > 150.0 or (patient.fio2_percent > 50.0 and patient.pao2_mmhg > 100.0):
            hyperoxia_alert = (
                f"DANGEROUS HYPEROXIA DETECTED (PaO2 {patient.pao2_mmhg} mmHg). "
                "Excess reactive oxygen species (ROS) accelerate secondary neuronal apoptosis during reperfusion. "
                "Wean FiO2 immediately to target PaO2 75 - 100 mmHg (SpO2 92 - 98%)."
            )

        hypocapnia_alert = "SAFE"
        if patient.paco2_mmhg < 35.0:
            hypocapnia_alert = (
                f"CRITICAL HYPOCAPNIA DETECTED (PaCO2 {patient.paco2_mmhg} mmHg). "
                "Alkalosis produces profound cerebral arteriolar vasoconstriction, critically decreasing cerebral blood flow (CBF). "
                "Adjust minute ventilation immediately to target strict normocapnia: PaCO2 35 - 45 mmHg."
            )

        return HemodynamicRespiratoryTargets(
            target_map_mmhg=target_map,
            pressor_choice="Norepinephrine (First-line). Add Dobutamine if cardiac index < 2.2 L/min/m2 with myocardial stunning.",
            target_pao2_mmhg="75 - 100 mmHg (SpO2 92 - 98%)",
            target_paco2_mmhg="35 - 45 mmHg (Strict Normocapnia)",
            hyperoxia_sentinel=hyperoxia_alert,
            hypocapnia_sentinel=hypocapnia_alert,
        )

    @classmethod
    def evaluate_temperature_management(
        cls, patient: PostArrestPatientProfile
    ) -> Dict[str, str]:
        """
        Implements TTM2 guidelines for targeted temperature management.
        """
        temp = patient.core_temperature_celsius
        is_febrile = temp >= 37.8

        if is_febrile:
            status = "FEVER DETECTED - ACTIVE COOLING MANDATED"
            action = (
                f"Core temperature is {temp:.1f} °C. Initiate immediate active surface or endovascular cooling. "
                "Target strict normothermia 36.0 - 37.5 °C. Hyperthermia significantly worsens anoxic brain injury."
            )
        else:
            status = "TARGET NORMOTHERMIA MAINTAINED"
            action = (
                f"Core temperature is {temp:.1f} °C (within safe target 36.0 - 37.5 °C). "
                "Maintain continuous core temperature monitoring (esophageal or bladder probe). "
                "Prevent any rise above 37.7 °C for a minimum of 72 hours post-ROSC."
            )

        return {
            "protocol_name": "TTM2 Targeted Temperature & Fever Prevention Protocol",
            "temperature_status": status,
            "clinical_action": action,
            "target_range": "36.0 - 37.5 °C (Active cooling triggered at >= 37.8 °C)",
            "duration": "Minimum 72 hours continuous fever prevention post-ROSC",
        }

    @classmethod
    def evaluate_anti_shivering(
        cls, patient: PostArrestPatientProfile
    ) -> AntiShiveringPrescription:
        """
        Step-wise anti-shivering pharmacotherapy based on BSAS scoring.
        """
        tier = patient.shivering_score
        interventions: List[str] = []
        nmb = False

        if tier == BSASShiveringTier.NONE_0:
            interventions.append("Step 0: Maintain baseline skin counter-warming of distal extremities.")
            interventions.append("Scheduled Acetaminophen 1000 mg IV q6h as primary anti-pyretic/anti-shivering baseline.")
        elif tier == BSASShiveringTier.MILD_1:
            interventions.append("Step 1: Apply warm blankets or air-warming blankets to hands and feet (counter-warming).")
            interventions.append("Administer IV Magnesium Sulfate 2 - 4 g bolus, targeting serum Mg >= 2.5 - 3.0 mg/dL.")
            interventions.append("Administer Buspirone 30 mg via enteral tube q8h (lowers shivering threshold).")
        elif tier == BSASShiveringTier.MODERATE_2:
            interventions.append("Step 2: Escalate sedation. Initiate or titrate Dexmedetomidine infusion (0.2 - 1.4 mcg/kg/hr).")
            interventions.append("Alternative/Adjunct: Low-dose IV Fentanyl bolus (25 - 50 mcg) or continuous infusion.")
        elif tier == BSASShiveringTier.SEVERE_3:
            interventions.append("Step 3: High-intensity shivering causing massive oxygen consumption and metabolic acidosis.")
            interventions.append("Ensure deep sedation (Propofol / Fentanyl with continuous EEG monitoring).")
            interventions.append("Administer Neuromuscular Blockade: Cisatracurium 0.15 mg/kg IV bolus or Rocuronium 0.6 mg/kg.")
            nmb = True

        return AntiShiveringPrescription(
            current_tier=tier,
            recommended_interventions=interventions,
            neuromuscular_blockade_indicated=nmb,
        )

    @classmethod
    def evaluate_neuroprognostication(
        cls, patient: PostArrestPatientProfile
    ) -> NeuroprognosticationResult:
        """
        Multimodal 72-hour neuroprognostication strictly prohibiting premature prognostication.
        """
        if patient.hours_since_rosc < 72.0:
            return NeuroprognosticationResult(
                is_premature=True,
                hours_post_rosc=patient.hours_since_rosc,
                evaluated_predictors_count=0,
                positive_poor_predictors=[],
                confidence=NeuroprognosisConfidence.INDETERMINATE_OBSERVE,
                clinical_rationale=(
                    f"PREMATURE PROGNOSTICATION STRICTLY PROSCRIBED (Current: {patient.hours_since_rosc:.1f}h post-ROSC). "
                    "AHA/ILCOR guidelines mandate that formal neuroprognostication CANNOT occur before 72 hours post-ROSC. "
                    "Brain edema, therapeutic hypothermia, and delayed drug clearance confound early assessments. "
                    "Continue active neuro-critical care supportive therapy."
                ),
            )

        if patient.has_residual_paralytics_or_deep_sedation:
            return NeuroprognosticationResult(
                is_premature=True,
                hours_post_rosc=patient.hours_since_rosc,
                evaluated_predictors_count=0,
                positive_poor_predictors=[],
                confidence=NeuroprognosisConfidence.INDETERMINATE_OBSERVE,
                clinical_rationale=(
                    "CONFOUNDING SEDATION / RESIDUAL BLOCK DETECTED. Brainstem reflexes and clinical examination "
                    "cannot be reliably evaluated while under paralytic block or deep sedation. "
                    "Perform Train-of-Four (TOF) testing and allow complete drug clearance before testing."
                ),
            )

        predictors: List[str] = []
        if patient.bilateral_pupillary_reflex_absent and patient.bilateral_corneal_reflex_absent:
            predictors.append("Bilateral absence of pupillary light and corneal reflexes at >= 72h (FPR < 2%)")
        if patient.ssep_bilateral_n20_absent:
            predictors.append("Bilateral absence of Somatosensory Evoked Potential SSEP N20 cortical response (FPR < 1%)")
        if patient.serum_nse_ug_l is not None and patient.serum_nse_ug_l > 60.0:
            predictors.append(f"Neuron-Specific Enolase markedly elevated ({patient.serum_nse_ug_l:.1f} ug/L > 60 ug/L threshold)")
        if patient.eeg_malignant_pattern_present:
            predictors.append("Highly malignant EEG pattern (Suppression-burst, generalized periodic discharges, or status epilepticus)")
        if patient.head_ct_gwr_less_than_1_10:
            predictors.append("Severe diffuse cerebral edema with marked Gray-White Ratio loss (GWR < 1.10) on Head CT")

        count = len(predictors)
        if count >= 2:
            confidence = NeuroprognosisConfidence.HIGHLY_LIKELY_POOR
            rationale = (
                f"High certainty of poor neurological recovery. Met {count} independent concordant predictors "
                "evaluated at >= 72h post-ROSC in the absence of confounding factors."
            )
        elif count == 1:
            confidence = NeuroprognosisConfidence.INDETERMINATE_OBSERVE
            rationale = (
                "Only 1 poor predictor identified. Guidelines mandate at least 2 independent concordant multimodal "
                "findings to support a high-confidence poor prognosis. Continue observation."
            )
        else:
            confidence = NeuroprognosisConfidence.FAVORABLE_RECOVERY_POTENTIAL
            rationale = (
                "No malignant multimodal predictors identified at >= 72h. Preserved brainstem reflexes and "
                "absence of severe electrophysiological failure suggest potential for favorable neurological recovery."
            )

        return NeuroprognosticationResult(
            is_premature=False,
            hours_post_rosc=patient.hours_since_rosc,
            evaluated_predictors_count=count,
            positive_poor_predictors=predictors,
            confidence=confidence,
            clinical_rationale=rationale,
        )

    @classmethod
    def run_assessment(cls, patient: PostArrestPatientProfile) -> ComprehensivePCASGuidance:
        """
        Executes comprehensive post-cardiac arrest multimodal evaluation.
        """
        hemo_resp = cls.evaluate_hemodynamics_and_respiration(patient)
        temp_proto = cls.evaluate_temperature_management(patient)
        anti_shivering = cls.evaluate_anti_shivering(patient)
        neuro = cls.evaluate_neuroprognostication(patient)

        sentinels: List[str] = []
        if hemo_resp.hyperoxia_sentinel != "SAFE":
            sentinels.append(hemo_resp.hyperoxia_sentinel)
        if hemo_resp.hypocapnia_sentinel != "SAFE":
            sentinels.append(hemo_resp.hypocapnia_sentinel)
        if anti_shivering.neuromuscular_blockade_indicated:
            sentinels.append(
                "NMB SAFETY SENTINEL: Continuous Neuromuscular Blockade administered. "
                "Ensure continuous depth of sedation monitoring (Processed EEG / BIS) to prevent accidental awareness under paralysis."
            )
        if neuro.is_premature:
            sentinels.append(f"MANDATORY DELAY: {neuro.clinical_rationale}")

        summary = {
            "Time Since ROSC": f"{patient.hours_since_rosc:.1f} hours",
            "Core Temperature": f"{patient.core_temperature_celsius:.1f} °C",
            "Hemodynamics": f"MAP {patient.mean_arterial_pressure_mmhg:.1f} mmHg (Chronic HTN: {patient.has_chronic_hypertension})",
            "Arterial Blood Gas": f"PaO2 {patient.pao2_mmhg:.1f} mmHg (FiO2 {patient.fio2_percent:.0f}%), PaCO2 {patient.paco2_mmhg:.1f} mmHg",
            "Shivering Score": patient.shivering_score.value,
            "Neuroprognostication Status": neuro.confidence.value,
        }

        return ComprehensivePCASGuidance(
            patient_summary=summary,
            temperature_protocol=temp_proto,
            hemodynamic_respiratory_goals=hemo_resp,
            anti_shivering=anti_shivering,
            neuroprognostication=neuro,
            critical_sentinels=sentinels,
        )


# ==============================================================================
# Clinical Verification & Validation Suite
# ==============================================================================

def verify_clinical_scenarios():
    print("=" * 80)
    print("OpenPHR Cookbook 405: Post-Cardiac Arrest Syndrome TTM2 & Neuroprognosticator")
    print("=" * 80)

    # Scenario 1: Early Post-ROSC (14h) - Severe Fever, Shivering & Hyperoxia Sentinel
    p1 = PostArrestPatientProfile(
        age_years=62.0,
        weight_kg=78.0,
        hours_since_rosc=14.0,
        core_temperature_celsius=38.4,  # Active fever
        has_chronic_hypertension=True,
        mean_arterial_pressure_mmhg=68.0,  # Below chronic HTN target
        pao2_mmhg=185.0,  # Dangerous hyperoxia
        paco2_mmhg=32.0,  # Hypocapnic vasoconstriction
        fio2_percent=70.0,
        shivering_score=BSASShiveringTier.SEVERE_3,
    )
    res1 = PostCardiacArrestEngine.run_assessment(p1)

    assert res1.neuroprognostication.is_premature is True
    assert "PREMATURE PROGNOSTICATION STRICTLY PROSCRIBED" in res1.neuroprognostication.clinical_rationale
    assert "FEVER DETECTED" in res1.temperature_protocol["temperature_status"]
    assert res1.anti_shivering.neuromuscular_blockade_indicated is True
    assert "DANGEROUS HYPEROXIA" in res1.hemodynamic_respiratory_goals.hyperoxia_sentinel
    assert "CRITICAL HYPOCAPNIA" in res1.hemodynamic_respiratory_goals.hypocapnia_sentinel

    print("[*] Test Case 1 (Acute Phase 14h Post-ROSC with Hyperthermia & Severe Shivering) PASSED")
    print(f"    - Temperature Action: {res1.temperature_protocol['temperature_status']}")
    print(f"    - Anti-Shivering: Tier {res1.anti_shivering.current_tier.name} -> NMB Indicated: {res1.anti_shivering.neuromuscular_blockade_indicated}")
    print(f"    - Neuroprognostication: Premature Gate Active ({res1.neuroprognostication.hours_post_rosc}h < 72h)")

    # Scenario 2: Late Post-ROSC (76h) - Multimodal Concordance for Poor Neurological Outcome
    p2 = PostArrestPatientProfile(
        age_years=68.0,
        weight_kg=72.0,
        hours_since_rosc=76.0,  # Past 72h threshold
        core_temperature_celsius=36.8,
        has_chronic_hypertension=False,
        mean_arterial_pressure_mmhg=74.0,
        pao2_mmhg=88.0,
        paco2_mmhg=38.0,
        fio2_percent=35.0,
        shivering_score=BSASShiveringTier.NONE_0,
        bilateral_pupillary_reflex_absent=True,
        bilateral_corneal_reflex_absent=True,
        ssep_bilateral_n20_absent=True,
        serum_nse_ug_l=84.0,  # > 60 ug/L
        eeg_malignant_pattern_present=True,
        has_residual_paralytics_or_deep_sedation=False,
    )
    res2 = PostCardiacArrestEngine.run_assessment(p2)

    assert res2.neuroprognostication.is_premature is False
    assert res2.neuroprognostication.evaluated_predictors_count >= 3
    assert res2.neuroprognostication.confidence == NeuroprognosisConfidence.HIGHLY_LIKELY_POOR

    print("\n[*] Test Case 2 (Late Phase 76h Multimodal Poor Outcome Determination) PASSED")
    print(f"    - Evaluated Predictors: {res2.neuroprognostication.evaluated_predictors_count} concordant findings")
    print(f"    - Confidence Tier: {res2.neuroprognostication.confidence.value}")

    print("\n>>> ALL CLINICAL VERIFICATION TESTS PASSED (100% CONCORDANCE) <<<")


if __name__ == "__main__":
    verify_clinical_scenarios()