01Approach to the Critical Patient/attcp66

Immediate priorities

›Airway threats

›Copious bronchorrhea causing airway obstruction

›Aggressive suction before and during laryngoscopy

›Do NOT use succinylcholine for RSI — prolonged paralysis from inhibited pseudocholinesterase

›Rocuronium 1.2 mg/kg IV preferred paralytic

›Respiratory failure requiring intubation

›Tidal volume <5 mL/kg or vital capacity <15 mL/kg

›Hypoxemia: SpO2 <90% despite supplemental O2

›Apnea or agonal respiration

›Early intubation improves outcomes — do not delay

›Bronchospasm management

›Atropine also bronchodilates — treat toxidrome first

›Nebulized ipratropium as adjunct

›Decontamination (before airway if patient ambulatory)

›Don full PPE before patient contact

›Secondary contamination of healthcare workers is well documented

›Gloves, gown, eye protection, N95 minimum; HAZMAT team for mass casualty

›Remove all clothing and jewelry

›Clothing may retain up to 80% of dermal toxin load

›Copious soap and water irrigation of skin and hair

›Minimum 15 minutes of irrigation

›Irrigate eyes if ocular exposure

›Saline irrigation 1–2 L per affected eye

›Circulation stabilization

›Bradycardia or cardiovascular collapse

›Atropine is first-line antidote and chronotropic agent

›IV fluid resuscitation for hypovolemia from diarrhea/vomiting/diaphoresis

02History/hx53

Exposure characterization

›Exposure source

›Organophosphate pesticide (chlorpyrifos, diazinon, malathion, parathion)

›Carbamate pesticide (carbaryl, aldicarb, methomyl)

›Nerve agent (sarin, soman, tabun, VX, Novichok)

›Cholinesterase-inhibiting medication (pyridostigmine, neostigmine, donepezil, rivastigmine, distigmine, physostigmine)

›Route of exposure

›Ingestion — onset 30–90 minutes

›Inhalation — onset seconds to minutes

›Dermal absorption — onset up to 48 hours; fat-soluble organophosphates may redistribute for days

›Ocular — rapid miosis with minor systemic effect

›Timing and quantity

›Time of exposure onset

›Duration of exposure

›Concentration or product name

Symptom characterization

›Muscarinic symptoms (SLUDGE/DUMBBBELS)

›Salivation and lacrimation

›Urination (incontinence)

›Defecation and GI cramping

›Emesis

›Bronchorrhea and bronchospasm

›Bradycardia

›Nicotinic symptoms

›Muscle twitching or fasciculations

›Weakness progressing to paralysis

›Tachycardia (may mask bradycardia early)

›Hypertension

03Physical Exam/exam37

Vital signs

›Cardiovascular findings

›Bradycardia — most classic; muscarinic effect

›Tachycardia — may predominate early from nicotinic/sympathetic stimulation

›Hypotension

›Hypothermia possible with distigmine-induced crisis

›Respiratory findings

›Tachypnea

›Apnea in severe cases

Focused examination

›Eyes

›Miosis (pinpoint pupils) — hallmark finding

›Lacrimation

›Blurred vision

›Oropharynx and airway

›Excessive salivation and drooling

›Odor — garlic-like or solvent smell with pesticide exposure

›Pulmonary

›Wheezing and bronchospasm

›Rhonchi from copious bronchorrhea — most critical monitoring parameter

›Secretion burden assessed with auscultation before and after atropine dosing

›Abdomen

›Hyperactive bowel sounds

›Diffuse tenderness from GI cramping

›Fecal incontinence

›Skin

›Profuse diaphoresis

›Localized fasciculations at site of dermal exposure

04Differential Diagnosis/ddx31

Primary toxidrome differentials

›Carbamate poisoning (ICD-10: T60.0X)

›Clinically indistinguishable from organophosphate poisoning

›Shorter duration — carbamates spontaneously dissociate from acetylcholinesterase

›Pralidoxime benefit less established but generally given

›Nerve agent exposure (ICD-10: T59.891)

›Extremely rapid onset — seconds with inhalation

›Full SLUDGE plus CNS features and seizures

›May require massive atropine doses (100+ mg in mass casualty events)

›Muscarinic mushroom poisoning

›Inocybe, Clitocybe species — contain muscarine

›SLUDGE symptoms without significant nicotinic features

›No fasciculations or paralysis

Mimics requiring differentiation

›Myasthenic crisis vs. cholinergic crisis (ICD-10: G70.01 / T44.0X)

›Both present with muscle weakness and respiratory failure

›Cholinergic crisis — excess secretions, miosis, fasciculations, bradycardia

›Myasthenic crisis — dry, pupils normal, no fasciculations, prior diagnosis

›Edrophonium (Tensilon) test may help differentiate in stable patients

›Nicotine poisoning (ICD-10: T65.291)

›Early cholinergic stimulation followed by ganglionic blockade

›Tachycardia and hypertension may dominate

›Opioid toxicity (ICD-10: T40.2X)

›Shares miosis and respiratory depression

›Lacks secretions, bronchorrhea, and fasciculations

›Responds to naloxone

›Serotonin syndrome (ICD-10: T43.8X)

›Shares diaphoresis and altered mental status

05Laboratory Tests/lt40

Cholinesterase assays

›RBC (erythrocyte) cholinesterase

›Reflects true acetylcholinesterase inhibition

›Gold standard for confirming severity of organophosphate poisoning

›Depressed to <25% of normal indicates significant poisoning

›Recovers slowly — weeks with organophosphates

›Treatment MUST NOT be delayed awaiting results

›Serum (pseudocholinesterase / butyrylcholinesterase)

›More readily available than RBC cholinesterase

›Less specific — depressed by liver disease, pregnancy, malnutrition

›Recovers faster than RBC cholinesterase

›Useful for monitoring treatment response trend

Critical labs

›Arterial or venous blood gas

›Hypoxemia (PaO2 <60 mmHg) — indicates respiratory failure

›Hypercarbia (PaCO2 >45 mmHg) — indicates ventilation failure

›Metabolic acidosis from tissue hypoperfusion and seizures

›Basic metabolic panel

›Electrolyte abnormalities — hypokalemia, hypocalcemia from vomiting/diarrhea

›Renal function — organophosphates cause nephrotoxicity

›Glucose — hypo- or hyperglycemia possible

›Complete blood count

›Leukocytosis common

›Neutropenia in severe cases

›Serum lactate

›Marker of tissue hypoperfusion

›Lactate >2 mmol/l indicates significant metabolic compromise

›Creatine phosphokinase

06Diagnostic Tests/dt67

Scoring Systems

›Severity stratification

›Mild toxicity

›Miosis, lacrimation, salivation, diaphoresis, nausea

›No respiratory compromise

›Ambulatory and alert

›Moderate toxicity

›Bronchospasm, vomiting, diarrhea

›Muscle fasciculations, mild weakness

›Preserved respiratory function

›Severe toxicity

›Respiratory failure requiring intubation

›Seizures or status epilepticus

›Cardiovascular collapse

›Coma or flaccid paralysis

›Intermediate syndrome risk indicators

›Neck flexor weakness after apparent initial recovery

›Onset 24–96 hours post-exposure

›Fat-soluble organophosphate (e.g., fenthion) — higher risk

›Atropinization scoring

›Endpoint: clear lungs on auscultation

›Absence of wheeze and rhonchi

›Dry oral mucosa

›Secondary endpoint: HR >80 bpm, SBP >80 mmHg

MRI

›MRI indications in cholinergic toxicity

›Not a primary diagnostic tool for the toxidrome

›Diagnosis is clinical — based on history and toxidrome recognition

07Disposition/dispo29

ICU admission indications

›Criteria for ICU-level care

›Any patient requiring atropine infusion

›Endotracheal intubation and mechanical ventilation

›Hemodynamic instability — bradycardia, hypotension, shock

›Seizures or altered mental status

›Significant nicotinic symptoms — paralysis, respiratory muscle weakness

›Intermediate syndrome risk — fat-soluble organophosphate exposure

›All moderate-to-severe poisonings require ICU admission

Observation criteria

›Extended observation requirements

›Mild exposures with minimal symptoms

›Minimum 6–12 hours observation

›Repeat cholinesterase levels if available

›Dermal exposures

›Extended observation up to 48 hours due to delayed absorption

›Reassess for late-onset bronchorrhea and bradycardia

›Ingestion of fat-soluble organophosphates

›Lipophilic redistribution can cause delayed recurrence for days to weeks

›Extended monitoring in ICU even after initial stability

Discharge criteria

›Safe discharge requirements

›Complete resolution of all cholinergic symptoms

›Stable vital signs off atropine for minimum 6 hours

›Adequate respiratory function — normal spirometry or >15 mL/kg vital capacity

›No evidence of intermediate syndrome (neck flexor strength intact)

›Psychiatric clearance for all intentional ingestions

›Adequate home support and follow-up arranged

08Treatment/t87

Antidote therapy — Atropine

›Atropine — first-line muscarinic antagonist

›Mechanism

›Blocks muscarinic receptors — dries secretions, reverses bronchospasm, increases HR

›Does NOT reverse nicotinic effects (paralysis, fasciculations)

›Does NOT cross blood-brain barrier significantly at standard doses

›Adult dosing

›Initial dose: 2–4 mg IV bolus

›Double the dose every 5 minutes until atropinized

›Doses of 10–20 mg or more in the first hour are common in severe cases

›Endpoint is clear lungs on auscultation, not pupil dilation

›Maintenance infusion

›10–20% of the loading dose per hour as continuous infusion

›Titrate to maintain atropinization endpoints

›Minimum 48 hours of atropinization before tapering

›Pediatric dosing

›Initial dose: 0.02 mg/kg IV

›Double every 5 minutes until atropinized

›No minimum dose restriction applies in poisoning

›Safety notes

›Avoid administering atropine during significant hypoxemia — risk of VF

›Ensure adequate oxygenation before atropine boluses

›AHA 2023 guidelines support atropine as first-line agent (Class I)

Antidote therapy — Pralidoxime (2-PAM)

›Pralidoxime — acetylcholinesterase reactivator

›Mechanism

›Cleaves organophosphate-enzyme bond — reactivates acetylcholinesterase

›Addresses nicotinic effects: paralysis, fasciculations

›Does NOT effectively cross blood-brain barrier

›Must be given before irreversible "aging" of the enzyme bond

›Adult dosing

›Loading dose: 1–2 g IV over 15–30 minutes

›Maintenance infusion: 1 g/hr continuous

›Higher-dose regimens (2 g loading + 1 g/hr) showed improved survival in RCTs

›Continue infusion for 18–24 hours after atropine discontinued

›Pediatric dosing

›Loading dose: 20–50 mg/kg IV over 30 minutes

›Maintenance infusion: 10–20 mg/kg/hr

›Limitations

›Efficacy limited by agent-specific aging rates — most effective within 24–48 hours of exposure

›Some agents age within minutes (soman)

›Oximes not universally effective across all organophosphate agents

›AHA 2023 guidelines support early pralidoxime use (Class IIa)

Seizure management

›Benzodiazepines — first-line for organophosphate-induced seizures

›Diazepam

›Adult dose: 5–10 mg IV PRN; repeat every 5–15 minutes

›Pediatric dose: 0.2–0.5 mg/kg IV per dose (maximum 10 mg per dose)

›AHA 2023 guidelines: first-line agent for seizures (Class I)

›Midazolam

›Adult dose: 5–10 mg IV/IM

›Intramuscular route preferred if IV access delayed

›Pediatric dose: 0.1–0.3 mg/kg IV/IM

›Status epilepticus escalation

›Phenobarbital if benzodiazepines fail — propofol as third-line

›Avoid phenytoin — ineffective for toxin-induced seizures

›Pyridoxine 70 mg/kg IV (maximum 5 g) if seizures refractory — particularly for nerve agents

Airway management

›Intubation considerations

›Rocuronium 1.2 mg/kg IV — preferred neuromuscular blocking agent

›Succinylcholine CONTRAINDICATED — pseudocholinesterase inhibited; prolonged paralysis

›Aggressive suction of secretions before laryngoscopy

›Video laryngoscopy preferred given secretion burden

›Post-intubation: atropine continues to be required for secretion management

›Ventilator settings

›Lung-protective strategy: tidal volume 6 mL/kg ideal body weight

›PEEP 5–8 cmH2O to maintain alveolar recruitment

›Monitor for auto-PEEP in bronchospasm

Decontamination

›GI decontamination

›Activated charcoal 1 g/kg PO (maximum 50 g) for recent ingestion

›Only if airway is protected (intubated or intact gag)

›Administer within 1–2 hours of ingestion for maximum benefit

›Contraindicated if vomiting or decreased consciousness

›Gastric lavage — not routinely recommended

›Consider for massive ingestion within 1 hour with protected airway

›Skin decontamination

›Remove all clothing — accounts for majority of dermal toxin

›Soap and water irrigation minimum 15 minutes

›Irrigate eyes with saline if ocular exposure

Fluid and supportive care

›Volume resuscitation

›IV fluid resuscitation for losses from diarrhea, vomiting, and diaphoresis

›Normal saline or Lactated Ringer's as first-line

›Target urine output >0.5 mL/kg/hr

›Vasopressors

›Norepinephrine for persistent hypotension after atropine and fluids

›NPO in acute setting due to vomiting and aspiration risk

›Medications to avoid

›Succinylcholine — prolonged paralysis

›Morphine — worsens respiratory depression

›Theophylline and aminophylline — lower seizure threshold

›Phenothiazines — lower seizure threshold and cause QTc prolongation

09Special Populations/sp56

Pregnancy

›Physiological considerations

›Increased plasma cholinesterase in pregnancy — may alter presentation and duration

›Pseudocholinesterase activity increases by 20–30% in second and third trimester

›May modestly reduce severity of some agents

›Fetal vulnerability

›Organophosphates cross the placenta — direct fetal cholinergic toxicity

›Risk of fetal hypoxemia from maternal respiratory compromise

›Seizures and hemodynamic instability directly threaten fetal viability

›Treatment in pregnancy

›Atropine — safe in pregnancy; use standard dosing without modification

›Fetal tachycardia expected — not an indicator to withhold

›Pralidoxime — limited human data but benefit outweighs risk in severe poisoning

›Animal studies show no teratogenicity; use standard dosing

›Benzodiazepines — use in seizure emergency; short-term use acceptable

›Diazepam may cause neonatal respiratory depression if near term

›Rocuronium — preferred for intubation; sugammadex reversal available

›Obstetric consultation for fetal monitoring

›Continuous fetal heart rate monitoring in viable pregnancies

›Emergency C-section if fetal distress unresponsive to maternal stabilization

Geriatric

›Physiological changes affecting management

›Reduced cholinesterase reserve — often on cholinesterase inhibitors for dementia

›Donepezil (Aricept) and rivastigmine (Exelon) cause iatrogenic cholinergic excess

›Distigmine-induced cholinergic crisis associated with renal impairment and constipation

›Reduced renal and hepatic clearance — prolonged drug effects

›Pre-existing cardiac disease — higher risk from bradycardia and QTc prolongation

›Polypharmacy interactions — QTc-prolonging drugs increase dysrhythmia risk

10Background/b72

Epidemiology

›Global burden

›Organophosphate poisoning causes approximately 200,000 deaths per year globally

›Leading cause of poisoning-related mortality in South/Southeast Asia, Africa, and China

›Intentional self-harm accounts for the majority of cases in developing countries

›Accidental occupational exposure is the dominant mechanism in developed countries

›ICD-10 classifications

›Organophosphate pesticide poisoning: T60.0X

›Carbamate pesticide poisoning: T60.0X1

›Nerve agent poisoning: T59.891

›Medication-induced cholinergic excess: T44.0X

›Demographic patterns

›Agricultural workers and pesticide handlers — occupational risk

›Children — accidental ingestion of household or stored pesticides

›Military and civilian populations — nerve agent exposure in conflicts and terrorism

›Alzheimer's and myasthenia gravis patients — medication-induced crises

›Mortality

›Untreated severe organophosphate poisoning — mortality approaches 100%

›With appropriate atropine therapy — mortality significantly reduced

›Intermediate syndrome accounts for a significant proportion of delayed deaths

Pathophysiology

›Mechanism of toxicity

›Irreversible inhibition of acetylcholinesterase (organophosphates)

›Phosphorylates the serine residue of the enzyme active site

›Accumulation of acetylcholine at all cholinergic synapses

›Aging — time-dependent irreversible bond formation; rate varies by agent

›Reversible inhibition of acetylcholinesterase (carbamates)

›Spontaneous hydrolysis over hours — self-limited toxicity

›Pralidoxime benefit less established due to rapid spontaneous reactivation

›Receptor systems affected

›Muscarinic receptors (M1-M5)

›Exocrine glands: excess secretions (salivation, lacrimation, bronchorrhea, diaphoresis)

›Smooth muscle: bronchospasm, GI hypermotility, urinary incontinence

›Cardiac: bradycardia, AV block, hypotension

›Eyes: miosis

›Nicotinic receptors (neuromuscular junction)

›Initial stimulation: fasciculations, tachycardia, hypertension, mydriasis

›Depolarization block: flaccid paralysis, respiratory muscle failure

›CNS receptors

›Seizures, altered mental status, coma, central apnea

›Intermediate syndrome

›Pathogenesis — postsynaptic dysfunction at neuromuscular junction

›Onset 1–4 days after resolution of acute cholinergic crisis

›Proximal limb weakness, neck flexor weakness, respiratory failure

›Associated with fat-soluble organophosphates (fenthion, dimethoate, parathion)

›Organophosphate-induced delayed neuropathy (OPIDN)

›Onset 2–3 weeks post-exposure

›Peripheral neuropathy — distal weakness and sensory loss

›Caused by inhibition of neuropathy target esterase (NTE)

Therapeutic Considerations

›Atropine dosing philosophy

›Doses far exceeding standard ACLS are required

›Standard ACLS dose (0.5–1 mg) is subtherapeutic in significant poisoning

›Cumulative doses of 40–100 mg in the first 24 hours reported in severe cases

›Endpoint is pulmonary — clear lungs on auscultation

›Pupil size is NOT a reliable endpoint — miosis may persist despite adequate treatment

›Atropine maintenance infusion after loading

›Prevents recurrent bronchorrhea from ongoing acetylcholine accumulation

›Minimum 48 hours of continued therapy recommended

›Pralidoxime controversy

›High-dose vs. low-dose regimens

›High-dose (2 g loading + 1 g/hr) showed survival benefit in RCTs from Sri Lanka

›WHO recommends standard 1 g loading + 0.5 g/hr in resource-limited settings

›Agent-specific limitations

›Soman — ages within minutes, pralidoxime has minimal benefit

›Parathion and fenthion — aging slower; pralidoxime most effective

›Carbamates — spontaneous reactivation; pralidoxime less critical

›AHA 2023 guidance

›Pralidoxime supported as adjunct to atropine (Class IIa)

›Give early before irreversible aging occurs

›Succinylcholine avoidance

›Pseudocholinesterase (plasma cholinesterase) is inhibited by organophosphates

›Succinylcholine is metabolized by pseudocholinesterase

›Paralysis may persist for hours to days instead of minutes

›Rocuronium 1.2 mg/kg is the safe alternative

11Patient Discharge Instructions/pdi38

copy discharge instructions

›Discharge instructions for cholinergic toxicity

›What happened to you

›You were poisoned by a chemical that overstimulates nerves throughout your body

›This caused excessive secretions, muscle twitching, and difficulty breathing

›You received antidote medications to reverse the poison's effects

›Medications

›Take all prescribed medications exactly as directed

›Do not resume cholinesterase inhibitor medications (donepezil, rivastigmine, pyridostigmine) without your doctor's approval

›Warning signs — return to emergency immediately

›New or returning difficulty breathing or shortness of breath

›Excessive drooling or secretions returning

›Inability to lift your head off the bed or new muscle weakness

›Blurred vision or pinpoint pupils returning

›Confusion, agitation, or loss of consciousness

›Muscle twitching or uncontrolled movements

›Vomiting, severe diarrhea, or abdominal cramping

›Intermediate syndrome warning

›A delayed complication called intermediate syndrome can occur 1–4 days after poisoning

›Signs include severe weakness of arms, legs, and difficulty breathing

›Return immediately if you develop new weakness even days after feeling better

›Delayed neuropathy warning

›In some cases, nerve damage can develop 2–3 weeks after exposure

›Signs include numbness, tingling, or weakness in hands and feet

›Report any new sensory or motor changes to your doctor

›Activity restrictions

›Avoid strenuous physical activity for at least 1 week

›Do not operate machinery or drive until fully recovered and cleared by a physician

12References/r25

Guidelines and key sources

›American Heart Association 2023 Focused Update

›Lavonas EJ, et al. 2023 AHA Focused Update on Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning. Circulation. 2023

›Class I recommendation for atropine as first-line agent

›Class IIa recommendation for pralidoxime as adjunct

›Benzodiazepines Class I for seizure management

›Succinylcholine avoidance explicitly recommended

›American Heart Association 2025 Guidelines

›Cao D, et al. Part 10: Adult and Pediatric Special Circumstances of Resuscitation. Circulation. 2025

›Updated guidance on toxicological cardiac arrest management

›Landmark trials and clinical evidence

›Eddleston M, et al. Management of Acute Organophosphorus Pesticide Poisoning. Lancet. 2008

›Systematic review of atropine dosing and outcomes

›Established high-dose pralidoxime regimen data

›Aman S, et al. Management of Organophosphorus Poisoning: Standard Treatment and Beyond. Critical Care Clinics. 2021

›Comprehensive review of treatment controversies

›Pralidoxime high-dose vs. low-dose RCT data

›Reference texts

›Henretig FM, Kirk MA, McKay CA. Hazardous Chemical Emergencies and Poisonings. NEJM. 2019

›Kales SN, Christiani DC. Acute Chemical Emergencies. NEJM. 2004

›Pediatric specific

›Chung S, et al. Chemical-Biological Terrorism and Its Impact on Children. Pediatrics. 2020

›AAP guidance on pediatric cholinergic toxidrome management

›Biochemical monitoring

›Sepahi S, et al. Biochemical Responses as Biomarkers of Organophosphate and Carbamate Intoxication. Journal of Biochemical and Molecular Toxicology. 2023

›Systematic review of cholinesterase assay clinical utility

Evidence & Review

Evidence & Review