01Approach to the Critical Patient/attcp73

Immediate priorities

›Airway and breathing threats

›Respiratory failure — primary cause of death

›Bronchorrhea with copious secretions

›Bronchospasm and wheezing

›Central apnea from CNS cholinergic excess

›Respiratory muscle paralysis from nicotinic receptor activation

›Criteria for immediate intubation

›GCS < 9 or inability to protect airway

›SpO2 < 90% refractory to supplemental oxygen

›Rising PaCO2 with fatigue

›If intubating, avoid succinylcholine — pseudocholinesterase inhibited

›Use rocuronium or vecuronium instead

›Prolonged paralysis risk with succinylcholine (hours)

›Decontamination — must precede or occur simultaneously with resuscitation

›Provider PPE donned before patient contact

›Nitrile gloves, gown, eye protection

›Secondary contamination risk to healthcare workers documented

›Clothing and jewelry removed

›Place in sealed bags

›Irrigate skin with copious water and soap

›Eye irrigation if ocular exposure

›Minimum 15 minutes irrigation with NS

›Morgan lens if available

›Antidote initiation — do not delay for labs

›Atropine IV without delay

›Adults: 1–2 mg IV bolus, double every 5 minutes until atropinized

›Severe presentation: 3–5 mg IV initially

02History/hx76

Exposure details

›Route and timing of exposure

›Ingestion

›Onset 30–90 minutes from exposure

›Amount and concentration if known

›Inhalation

›Onset seconds to minutes

›Nerve agent vs pesticide spray context

›Dermal

›Onset up to 48 hours delayed

›Site of skin contact

›Agent identification

›Pesticide product name and concentration

›Chlorpyrifos, methamidophos, mevinphos, parathion

›Container brought to ED when possible

›Nerve agent exposure context

›Sarin, VX, Novichok — mass casualty or chemical warfare setting

›CBRN notification if suspected

›Medication source

›Neostigmine, pyridostigmine — reversible inhibitors

›Distinct from irreversible OP compounds

Symptom history

›Cholinergic toxidrome symptoms

›Muscarinic (SLUDGE) symptoms

›Salivation

›Lacrimation

›Urination

›Defecation

03Physical Exam/exam61

Vital signs

›Vital sign pattern

›Heart rate

›Bradycardia from muscarinic excess (most common)

›Tachycardia from nicotinic stimulation also possible

›Blood pressure

›Hypotension from bradycardia and vasodilation

›Hypertension early from nicotinic stimulation

›Respiratory rate

›Tachypnea from secretions and bronchospasm

›Central apnea in severe cases

›Temperature

›Diaphoresis with normal or elevated temperature

Secretion and airway exam

›Airway secretion assessment

›Bronchorrhea

›Copious frothy secretions from mouth and airways

›Audible gurgling with breathing

›Salivation

›Drooling and excessive oral secretions

›Primary endpoint for atropine adequacy

›Lacrimation

›Excessive tearing

›Combined with rhinorrhea

›Lung auscultation

›Wheezing

›Bronchospasm pattern

›Clearing of wheeze is secondary atropine endpoint

04Differential Diagnosis/ddx45

Cholinergic toxidrome spectrum

›Organophosphate pesticide poisoning

›ICD-10 T60.0 toxic effects of organophosphate and carbamate insecticides

›Irreversible AChE inhibition without treatment

›Carbamate poisoning

›Clinically indistinguishable acutely

›Spontaneous hydrolysis of AChE within hours

›Generally shorter and self-limiting course

›Pralidoxime role debated for carbamates

›Nerve agent exposure

›Sarin (GB), VX, Novichok

›Rapid onset — seconds to minutes via inhalation

›Mass casualty context

›Irreversible aging faster than most pesticide OPs

Pharmacological mimics

›Cholinergic medication overdose

›Neostigmine, physostigmine, pyridostigmine

›Reversible inhibitors with shorter duration

›Medication history key differentiator

›Pilocarpine eye drops — systemic absorption if high concentration

›Muscarinic mushroom poisoning

›Amanita muscaria and Clitocybe species

›SLUDGE symptoms without nicotinic features

›No fasciculations typically

›ICD-10 T62.0 toxic effects of mushrooms

Conditions mimicking selected features

›Myasthenia gravis crisis

›Weakness and respiratory failure

05Laboratory Tests/lt53

Cholinesterase levels

›Serum butyrylcholinesterase (pseudocholinesterase)

›Readily available emergently in most centers

›Depressed by > 50% from baseline suggests significant exposure

›Serial values more useful than single measurement

›Limitations

›Baseline varies widely between individuals

›Reduced by liver disease, malnutrition, pregnancy

›RBC acetylcholinesterase

›More specific marker of true synaptic AChE inhibition

›Correlates better with clinical severity

›Not widely available in emergency setting

›Do not delay treatment awaiting results

›Diagnosis is clinical — labs are confirmatory

Critical chemistry and perfusion markers

›Arterial or venous blood gas

›Acidosis (pH < 7.35) present in 73% of non-survivors

›Mixed respiratory and metabolic

›Guides ventilation strategy if intubated

›PaCO2 retention as ventilatory failure marker

›Serum lactate

›> 2 mmol/L in 90% of non-survivors

›End-organ hypoperfusion marker

›Repeat every 2 hours if elevated

›Basic metabolic panel

›Hypokalemia

›Present in 73% of non-survivors

›Contributes to QTc prolongation

06Diagnostic Tests/dt79

Scoring Systems

›Peradeniya Organophosphorus Poisoning (POP) scale

›Miosis (0–2 points)

›0 = absent, 1 = partial, 2 = complete

›Bradycardia (0–2 points)

›HR > 80 = 0, 60–80 = 1, < 60 = 2

›Fasciculations (0–2 points)

›0 = absent, 1 = facial only, 2 = generalized

›Consciousness level (0–2 points)

›0 = normal, 1 = drowsy, 2 = coma

›Score >= 7 predicts severe toxicity requiring ICU

›Atropine response as diagnostic test

›Failure to develop tachycardia or mydriasis after standard doses

›Strongly supports cholinesterase inhibitor poisoning

›Documented in real-time to guide further dosing

›Not a standalone scoring tool but a dynamic clinical assessment

›qSOFA for sepsis overlay

›RR >= 22 per minute

›SBP <= 100 mmHg

›Altered mental status

›Applicable if aspiration pneumonia complicates course

MRI

›MRI brain role in OP poisoning

›Not an acute priority

›Hypoxic-ischemic injury assessment post-resuscitation

›Delayed toxic leukoencephalopathy evaluation

›Indications after stabilization

›Persistent neurological deficits unexplained by systemic toxidrome

›Delayed neuropsychiatric syndrome assessment

›Contraindications and limitations

›Unstable patient — CT preferred acutely

›Non-compatible implants

CT

›CT head indications

›Altered mental status with unclear etiology

›Exclude structural cause (hemorrhage, edema)

›Post-seizure evaluation when localization suspected

›Hypoxic-ischemic injury evaluation

›After prolonged respiratory arrest or cardiac arrest

›Prognosis assessment

›CT chest indications

›Pulmonary edema assessment

›Non-cardiogenic pulmonary edema seen in approximately 43% of cases

›Distinguish from aspiration pneumonia

›Aspiration pneumonia

›Present in approximately 51% of elderly severe OP cases

›Bilateral infiltrates distribution pattern

›CT head and chest generally deferred until hemodynamic stability achieved

›Do not delay antidote for imaging

›ACEP Level C recommendation for imaging as adjunct

Ultrasound

›Cardiac POCUS

›Left ventricular function assessment

›Reversible LV dysfunction reported — EF may fall to approximately 42% acutely

›Recovery to approximately 59% EF with treatment

›Pericardial effusion screen

›Rare but excludes tamponade as shock contributor

›Lung ultrasound

›B-lines bilaterally

›Pulmonary edema pattern

›Consolidation from aspiration

›Pleural effusion

›Identifies parapneumonic effusion

›Guides drainage decisions

›IVC assessment

›Fluid responsiveness guide

›Collapsibility with respiration in spontaneously breathing patient

›Integrate with clinical exam and lactate

›ECG — essential diagnostic tool

›QTc prolongation

›Most common abnormality in 56–67% of patients

›Torsades de pointes risk if QTc > 500 ms

›Sinus tachycardia (32–90%)

›Or sinus bradycardia (28%)

›ST-T changes

›ST elevation or depression in 18–41% of patients

›Demand ischemia vs OP-induced myocarditis

›AV conduction disturbances

›Heart block risk

›Transcutaneous pacing readiness if complete block

›Repetitive nerve stimulation (specialized)

›Decremental response at 30 Hz may predict intermediate syndrome

›Performed after acute stabilization

07Disposition/dispo44

ICU admission

›ICU indications

›Respiratory failure or intubation

›Mechanical ventilation management

›Prolonged atropine infusion monitoring

›Hemodynamic instability

›Vasopressor requirement

›Cardiac arrhythmia management

›Seizures

›Continuous EEG monitoring in refractory cases

›Antiepileptic titration

›Moderate to severe poisoning (POP scale >= 7)

›ICU-level monitoring for intermediate syndrome

›Pralidoxime infusion continuation

›Intermediate syndrome anticipation

›Onset 24–96 hours after acute cholinergic crisis resolution

›Proximal limb and respiratory muscle weakness

›Cranial nerve palsies

›ICU stay extended if respiratory weakness develops

›Weaning trials may be prolonged days to weeks

Step-down and floor admission

›Floor admission criteria

›Mild to moderate poisoning responding to atropine

›Secretions controlled

›No respiratory failure

›Hemodynamic stability achieved

›No vasopressor requirement

›Oral fluids tolerated

08Treatment/t95

Decontamination

›Skin and eye decontamination

›Remove all clothing and jewelry

›Double-bag contaminated materials

›Perform before or concurrently with resuscitation

›Skin irrigation

›Water and soap scrubbing minimum 10–15 minutes

›Ensure water runoff does not contaminate staff

›Eye irrigation

›NS irrigation minimum 15 minutes

›Morgan lens preferred for sustained delivery

›GI decontamination

›Activated charcoal 50 g PO or via NG tube

›Only after airway is protected

›Within 1–2 hours of ingestion for maximum benefit

›Contraindicated if unable to protect airway

›Gastric lavage not routinely recommended

›Consider within 1 hour for massive ingestion with protected airway

›Risk of aspiration must be weighed

Atropine

›Atropine dosing protocol

›Initial dose

›Mild to moderate: 1–2 mg IV bolus

›Severe or hemodynamically compromised: 3–5 mg IV bolus

›Titration

›Double dose every 5 minutes until atropinization achieved

›Total dose may reach hundreds of milligrams in severe cases

›Atropinization endpoints

›Lungs clear of secretions (primary endpoint)

›HR > 80 beats/min

›SBP > 80 mmHg

›Dry secretions

›Maintenance infusion

›10–20% of total loading dose per hour IV infusion

›Wean as clinical status permits

›Caution

›Correct hypoxia before atropine — ventricular fibrillation risk if hypoxic

›Mydriasis and tachycardia are NOT reliable atropinization endpoints

›Avoid morphine, theophylline, phenothiazines concurrently

Pralidoxime (oxime therapy)

›Pralidoxime 2-PAM dosing

›Loading dose

›2 g IV over 15–30 minutes

›Reduce rate to minimize tachycardia and hypertension side effects

›Maintenance infusion

›1 g/hr continuous IV infusion

›High-dose regimens associated with faster AChE reactivation

›Timing — critical for efficacy

›Must initiate before aging (irreversible AChE-OP binding)

›Aging time varies by agent: hours (parathion) to days (chlorpyrifos)

›After aging, pralidoxime is ineffective

›Duration

›Continue until atropine no longer required

›Typical 24–72 hours for most OP pesticides

›Controversy

›Large WHO IPPF trial showed no mortality benefit for standard doses

›High-dose pralidoxime regimens remain favored by toxicology experts

›Discuss with toxicology consultant

Benzodiazepines for seizures and agitation

›Seizure management

›Diazepam first-line

›5–10 mg IV, repeat every 5–10 minutes as needed

›Maximum 30 mg initial series

›Midazolam alternative

›0.1–0.2 mg/kg IV or IM

›Faster onset via IM route when IV access delayed

›Refractory status epilepticus

›Phenobarbital 20 mg/kg IV at 50–100 mg/min

›Propofol infusion 1–4 mg/kg/hr with ICU monitoring

›Phenytoin is NOT effective for OP-induced seizures

›Seizures are cholinergic in origin, not sodium channel based

Airway management

›Intubation and ventilation

›Rapid sequence intubation

›Rocuronium 1.2 mg/kg IV preferred

›Vecuronium 0.1 mg/kg IV as alternative

›Succinylcholine absolutely contraindicated

›Ventilation targets

›PaO2 > 60 mmHg or SpO2 >= 94%

›PaCO2 35–45 mmHg unless acidosis strategy

›Secretion management

›Inline suction catheter

›Frequent suctioning of ETT

›Atropine to reduce secretion burden ongoing

Supportive care

›Fluids

›IV NS boluses for hypotension

›500 mL NS bolus, repeat to SBP > 80 mmHg

›Urine output target > 0.5 mL/kg/hr

›Electrolyte replacement

›Potassium replacement for hypokalemia

›QTc monitoring during replacement

›QTc management

›Avoid QT-prolonging drugs

›Fluoroquinolones, antipsychotics, azithromycin — avoid if QTc > 450 ms

›Magnesium sulfate for torsades

›2 g IV over 5–15 minutes

›Repeat as needed

›NPO during acute phase

›Resume oral intake only after full toxidrome resolution

›Swallow assessment before oral feeding

09Special Populations/sp63

Pregnancy

›Pregnancy-specific considerations

›Fetal risk from maternal hypoxia

›Maintain maternal SpO2 >= 95% to optimize fetal oxygenation

›Fetal monitoring in viable gestation (>= 24 weeks)

›Decontamination unchanged from standard protocol

›Benefit outweighs risk of skin irrigation

›Lead apron if radiation studies required

›Atropine safety

›Category C — risk-benefit strongly favors use in life-threatening poisoning

›Fetal tachycardia may occur

›OB consultation emergently

›Pralidoxime safety

›Limited human data — use in life-threatening poisoning

›Category C — animal data reassuring, no major teratogenicity

›Benzodiazepines

›Diazepam crosses placenta freely

›Neonatal respiratory depression possible if near delivery

›Midazolam shorter acting — preferred near term

›Succinylcholine contraindicated as per standard protocol

›Rocuronium or vecuronium for RSI

Geriatric

›Older adult risk factors

›Higher case fatality rate

›Mean age non-survivors 47 years vs survivors 29 years

›Reduced physiologic reserve

›Comorbidity interaction

›Baseline cardiac disease increases arrhythmia risk

10Background/b91

Epidemiology

›Global burden

›Approximately 200,000 deaths per year globally from pesticide poisoning

›OP compounds responsible for largest proportion

›WHO lists OP poisoning as major global health problem

›Geographic distribution

›Highest burden in South Asia, Southeast Asia, Pacific rim, sub-Saharan Africa

›Access to highly toxic OP compounds drives mortality disparity

›Intent distribution

›Intentional self-harm most common mechanism globally

›Accidental occupational exposure second most common

›Case fatality rate

›Ranges from 4–30% depending on compound and healthcare access

›Higher fatality with highly toxic compounds (WHO class I and II)

›Mortality predictors

›Fasciculations at presentation (90% of non-survivors)

›Acidosis, elevated lactate, hypokalemia in non-survivors

Pathophysiology

›Core mechanism

›Irreversible phosphorylation of acetylcholinesterase (AChE)

›AChE normally breaks down acetylcholine (ACh) at synapses

›ACh accumulates at muscarinic, nicotinic, and CNS synapses

›Muscarinic effects (parasympathetic end organs)

›Bronchospasm and bronchorrhea

›Bradycardia and hypotension

›GI hypermotility (SLUDGE)

›Miosis

›Urinary incontinence

›Nicotinic effects (neuromuscular junction and sympathetic ganglia)

›Muscle fasciculations

›Paralysis from depolarization block

›Tachycardia and hypertension (early)

›Respiratory muscle failure

›CNS effects

›Seizures from excessive ACh stimulation of CNS receptors

›Altered mental status

›Central apnea

›Aging phenomenon

›Irreversible conformational change of AChE-OP complex over time

›Aging rate determines oxime therapy window

›Soman ages within minutes, chlorpyrifos within hours to days

›After aging, AChE cannot be reactivated by pralidoxime

›New enzyme synthesis required — takes days to weeks

›Intermediate syndrome

›Distinct from acute cholinergic crisis

›Onset 24–96 hours after cholinergic crisis resolves

›Mechanism: persistent nicotinic receptor dysfunction

›Clinical features

›Proximal limb weakness

›Respiratory muscle weakness requiring reintubation

›Cranial nerve palsies (neck flexors, extraocular muscles)

›Duration

›Resolves in 2–3 weeks typically

›Ventilatory support may be prolonged

›Cardiac toxicity

›Direct muscarinic and nicotinic stimulation of cardiac tissue

›QTc prolongation from autonomic imbalance

›Reversible LV dysfunction — EF falling to approximately 42% acutely

›Cardiac injury biomarkers

›Troponin elevated in approximately 34% of severe cases

›Recovery of cardiac function expected with systemic recovery

Therapeutic Considerations

›Antidote pharmacology

›Atropine as muscarinic antagonist

›Competes with ACh at muscarinic receptors

›Does not reverse nicotinic effects (paralysis, fasciculations)

›Does not regenerate AChE

›Pralidoxime as oxime nucleophile

›Cleaves OP-AChE bond before aging to regenerate active enzyme

›Active at both muscarinic and nicotinic synapses

›Controversies persist regarding mortality benefit in large trials

›Benzodiazepines for GABAergic support

›Directly reduce neuronal excitability

›Effective even when muscarinic seizures do not respond fully to atropine

›Decontamination principles

›Removes ongoing source of toxin absorption

›Skin decontamination reduces total absorbed dose

›Particularly important for dermal exposure route

›Provider safety during decontamination

›Secondary contamination events documented in emergency settings

›Barrier precautions mandatory

›Monitoring strategy

›Serial lung exam as primary atropine efficacy marker

›QTc trend for arrhythmia risk

›Lactate and urine output for perfusion

›Intermediate syndrome surveillance

›Daily grip strength and respiratory muscle assessment

›Negative inspiratory force (NIF) monitoring in intubated patients

›Evidence gaps

›Optimal pralidoxime dosing regimen remains debated

›WHO IPPF trial standard dose did not show mortality benefit

›High-dose protocols used empirically at toxicology centers

›No mortality benefit proven for activated charcoal in large trials

›Airway protection remains prerequisite

11Patient Discharge Instructions/pdi42

copy discharge instructions

›Organophosphate poisoning discharge instructions

›What happened

›You were treated for poisoning by an organophosphate compound

›These chemicals affect the nervous system and can be life-threatening

›You were treated with antidotes including atropine and pralidoxime

›Full recovery from mild poisoning is expected

›Some weakness may persist for several weeks

›Activity

›Rest at home for at least 1 week

›No driving until cleared by your doctor — reaction time may be impaired

›No return to agricultural or pesticide work until cleared by occupational health

›Warning signs — return to the emergency department immediately

›Difficulty breathing or shortness of breath

›Even mild breathlessness warrants return

›New muscle weakness especially in arms or neck

›Weakness that develops days after discharge may be intermediate syndrome

›Blurred vision or severe eye pain

›Excessive saliva, tearing, or sweating returning

›Seizures or loss of consciousness

›Confusion or unusual behavior

›Chest pain or palpitations

›Vomiting that prevents fluids or medications

›Follow-up instructions

›Return to clinic or GP within 2–3 days

›Weakness assessment at follow-up visit

›Repeat blood tests may be ordered

›Psychiatry or counselling appointment

12References/r23

Guidelines and key sources

›Major guidelines and societies

›WHO guidelines on management of pesticide poisoning

›Atropine and pralidoxime protocols

›Decontamination standards

›American Academy of Clinical Toxicology position statements

›GI decontamination after poisoning

›Oxime use in OP poisoning

›ACEP clinical policies for toxicological emergencies

›Landmark trials and studies

›WHO IPPF pralidoxime trial

›Standard-dose pralidoxime did not reduce mortality vs placebo

›Informs ongoing dosing controversy

›Prospective studies on OP mortality predictors

›Fasciculations, acidosis, and lactate as non-survivor markers

›Mean age differences between survivors and non-survivors

›Cardiac manifestations studies

›QTc prolongation prevalence 56–67%

›Troponin elevation in 34% of severe cases

›Reversible LV dysfunction with EF recovery

›Coding references

›ICD-10 T60.0 toxic effects of organophosphate and carbamate insecticides

›ICD-10 T60.0X1A intentional self-harm

›SNOMED CT organophosphate poisoning concept

Evidence & Review