01Approach to the Critical Patient/attcp75

Immediate priorities

›Airway and decontamination threats

›Oropharyngeal caustic injury severity

›Mucosal ulceration and tongue swelling

›Airway compromise from edema

›If airway compromise, early intubation before edema progresses

›Rapid sequence intubation with video laryngoscopy

›Airway edema may preclude delayed intubation

›GI decontamination window

›Activated charcoal 1 g/kg PO or NG only if within 1 to 2 hours and airway protected

›Fuller's earth 1 to 2 g/kg as alternative adsorbent if available

›Gastric lavage contraindicated due to caustic injury risk

›Circulation and organ failure

›Hemodynamic instability markers

›SBP < 90 mmHg

›MAP < 65 mmHg

›Tachycardia with poor perfusion

›Urine output monitoring

›Target > 0.5 mL/kg/hour to promote paraquat excretion

›Oliguria or anuria as acute kidney injury marker

›Metabolic acidosis recognition

›Serum bicarbonate < 18 mmol/l as early warning

›Mixed metabolic and respiratory acidosis in 80% of severe cases

›Oxygen restriction

›Supplemental oxygen potentiates paraquat oxidative lung injury

›Avoid supplemental O2 unless SpO2 < 90% on room air

›If required, use lowest FiO2 to maintain SpO2 88 to 92%

›Do not target normoxia in early course

02History/hx79

Exposure characterization

›Route and substance identity

›Oral ingestion

›Most common and most lethal route

›Product name and concentration

›Dermal or inhalational exposure

›Occupational spray without PPE

›Skin contact duration and surface area

›Product verification

›Container label or photograph

›Commercial concentrate 20 to 24% versus dilute formulation

›Dose and timing

›Volume ingested

›Even 10 to 15 mL of 20% concentrate can be fatal

›Estimated paraquat ion dose in mg/kg

›Time since ingestion

›Drives decontamination urgency

›Paraquat largely excreted in urine within 12 to 24 hours

›Co-ingestants

›Alcohol ingestion influence on absorption

›Other herbicides or pesticides

Presenting symptoms

›GI symptoms

›Nausea and vomiting

›Present in 93% of cases

›Early onset within minutes to hours

›Oropharyngeal pain

›Mouth and throat burning in 85% of cases

03Physical Exam/exam71

Vital signs and general assessment

›Hemodynamic snapshot

›Blood pressure

›Hypotension in fulminant poisoning

›SBP < 90 mmHg as severity marker

›Heart rate

›Tachycardia common

›Sinus tachycardia most frequent ECG finding

›Respiratory rate

›Tachypnea correlates with pulmonary injury

›Rising rate signals worsening fibrosis

›Temperature

›May be normal or mildly elevated

›High fever rare unless secondary infection

›SpO2

›May be falsely reassuring early

›Normal initial saturation does not exclude lethal ingestion

Oropharyngeal and GI examination

›Mouth and throat findings

›Mucosal erythema and ulceration

›Hallmark of significant ingestion

›White pseudomembranes

›Tongue swelling

›Airway risk indicator

›Progressive edema possible

›Oropharyngeal burns

›Extent correlates with dose

›Esophageal injury implied

04Differential Diagnosis/ddx50

Toxicologic mimics

›Other herbicide poisonings

›Diquat poisoning

›ICD-10 T60.3 toxic effect of herbicides

›Closely related bipyridyl compound

›Causes renal failure and GI injury but less pulmonary fibrosis

›Distinguished by less prominent lung involvement

›Glyphosate poisoning

›Surfactant-mediated toxicity

›Generally lower mortality than paraquat

›Less pulmonary fibrosis pattern

›Organophosphate poisoning

›ICD-10 T60.0

›Cholinergic toxidrome

›SLUDGE and miosis distinguish from paraquat

›Other ingested toxins

›Caustic ingestion

›ICD-10 T54 series

›Similar oropharyngeal burns

›Different systemic toxicity without pulmonary fibrosis

›Iron poisoning

›ICD-10 T45.4

›GI hemorrhage and metabolic acidosis

›Hepatic failure

›Methanol or ethylene glycol

›High anion gap metabolic acidosis

›Different clinical trajectory without pulmonary fibrosis

›Mushroom poisoning Amanita species

05Laboratory Tests/lt69

Confirmatory toxicology

›Urine dithionite test

›Bedside qualitative rapid screen

›Add sodium dithionite and sodium hydroxide to urine sample

›Blue or green color change confirms paraquat presence

›Available within minutes

›Negative result does not exclude if levels are very low

›Plasma paraquat concentration

›Quantitative and prognostic

›Level > 2 mg/L at 4 hours post-ingestion predicts death

›Level > 0.2 mg/L at 24 hours predicts death

›Plot against Proudfoot-Dougall nomogram for time-adjusted prognosis

›Reference laboratory turnaround may delay results

Organ function assessment

›Renal panel

›Serum creatinine

›Independent predictor of mortality

›Median 532 umol/l (6 mg/dL equivalent) in non-survivors

›Median 168 umol/l (1.9 mg/dL equivalent) in survivors

›Serial monitoring every 4 to 6 hours initially

›Electrolytes

›Potassium elevation with AKI

›Bicarbonate low with metabolic acidosis

›Urine protein

›Independently predicts death in prospective series

›Included in composite prognostic index

›Hepatic panel

›AST and ALT

06Diagnostic Tests/dt71

Scoring Systems

›Severity classification by ingested dose

›Dose-based stratification

›Low dose < 20 mg/kg paraquat ion

›Moderate dose 20 to 40 mg/kg

›Fulminant dose > 40 mg/kg

›Clinical utility

›Guides aggressiveness of immunosuppression

›Informs prognosis discussions

›APACHE II score

›Prognostic utility

›Higher scores in non-survivors

›Median 15.5 in non-survivors versus 7 in survivors

›Useful for ICU triage and resource allocation

›IPCS Poisoning Severity Score

›Graded severity classification

›Increasing grade correlates with increasing mortality

›Standardized cross-center comparability

›Proudfoot-Dougall nomogram

›Time-adjusted plasma level interpretation

›Plot plasma paraquat level against hours post-ingestion

›Survival zone versus predicted death zone

›Guides intensity of treatment and goals of care discussion

›ACEP Level C recommendation for prognostication

MRI

›MRI chest role in paraquat poisoning

›Acute phase utility

›Limited role due to availability constraints

07Disposition/dispo47

Admission indications

›All oral paraquat ingestions require admission

›Monitoring requirement

›No safe outpatient monitoring exists for oral ingestion

›Delayed pulmonary fibrosis onset up to 2 weeks

›Decontamination window

›GI decontamination most effective within hours

›IV hydration to promote renal excretion

›Psychiatric risk

›Intentional ingestion requires inpatient psychiatric assessment

›ICU indications

›Fulminant poisoning signs

›Dose > 40 mg/kg

›Hemodynamic instability

›Multi-organ failure

›Respiratory compromise

›Dyspnea at presentation

›Supplemental oxygen requirement

›Metabolic derangement

›Severe metabolic acidosis

›Rising creatinine with anuria

›Immunosuppressive therapy initiation

›Requires close monitoring for complications

Transfer considerations

›Transfer to higher level center

›Hemodialysis or hemoperfusion capability required

›If AKI develops beyond local capacity

›Toxicology expertise

08Treatment/t118

GI decontamination

›Activated charcoal

›Dosing

›1 g/kg PO or via NG tube

›Additional dose may be given for paraquat due to prolonged GI transit

›Maximum individual dose 50 g

›Timing

›Most effective within 1 to 2 hours of ingestion

›May be considered up to 4 hours if large ingestion

›Precautions

›Airway must be protected before administration

›Caustic injury may limit tolerability

›Evidence

›Activated charcoal with magnesium citrate superior survival in animal models

›Fuller's earth

›Alternative adsorbent

›1 to 2 g/kg orally

›Comparable efficacy to activated charcoal

›Less widely available than activated charcoal

›Mechanism

›Clay-based adsorbent with high paraquat binding affinity

›Contraindicated interventions

›Gastric lavage

›Contraindicated due to caustic injury risk

›Unlikely to add benefit beyond emesis

›Induced emesis

›Contraindicated with caustic oropharyngeal injury

Immunosuppressive therapy

›Combination pulse immunosuppression

›Rationale

›Targets inflammatory and fibrotic cascade

›Most widely used pharmacologic regimen

›Meta-analysis suggests reduced mortality 60.4% versus 85.3% in controls

›Methylprednisolone

›1 g IV daily for 3 days pulse

›Followed by tapering oral prednisolone

›Prednisolone 125 mg daily declining over several weeks

›Cyclophosphamide

›15 mg/kg IV daily for 2 days

›WBC monitoring every 3 to 7 days

›Hold if WBC < 3.0 x 10^9/L

›Mesna given concurrently for bladder protection

›Dexamethasone adjunct

›5 mg IV twice daily for 14 days in some protocols

›Taiwanese cohort (n=1811) combination with methylprednisolone and cyclophosphamide associated with highest survival (48%)

›Evidence level

›Observational and meta-analytic data

›No high-quality RCT available

›ACEP Level C recommendation

Antioxidant and supportive pharmacotherapy

›N-acetylcysteine

›Dosing

›150 mg/kg IV over 15 to 60 minutes loading dose

›Followed by 50 mg/kg IV over 4 hours

›Then 100 mg/kg IV over 16 hours

›Mechanism

›Free radical scavenging

›NF-kB inhibition

›Glutathione replenishment

›Evidence

›Favorable case reports

›No RCT data available

›Reasonable adjunct given low risk profile

›Deferoxamine

›Iron chelation with antioxidant properties

›Used in case of massive ingestion with survival reported

›Mechanism: iron chelation reduces hydroxyl radical generation

›Not standard first-line therapy

›Dosing

›15 mg/kg/hour IV to maximum 6 g per day

›Pirfenidone

›Anti-fibrotic agent

›Used in pediatric case to prevent pulmonary fibrosis

›Good outcome at 6-month follow-up reported

›801 mg PO three times daily in adults

›Emerging adjunct, limited evidence base

Renal replacement and elimination

›Hemodialysis

›Indications

›AKI with fluid overload or hyperkalemia

›Uremia management

›May provide some paraquat removal

›Timing

›Early initiation if creatinine rising rapidly

›Does not substitute for immunosuppression

›Hemoperfusion

›Role

›Activated charcoal or resin hemoperfusion for paraquat removal

›Most effective within 4 hours of ingestion

›Efficacy declines with time as paraquat redistributes to tissues

›Evidence

›No consistent mortality benefit demonstrated in trials

›May be considered in early massive ingestion

›ACEP Level C recommendation

Supportive care

›IV fluid management

›Aggressive hydration

›Normal saline 1 to 2 L initial bolus

›Titrate to urine output > 0.5 mL/kg/hour

›Promotes paraquat renal excretion

›Caution with fluid overload

›Monitor lung status carefully

›Pulmonary edema risk with AKI

›Oxygen management

›Restrictive oxygen strategy

›Avoid supplemental O2 unless SpO2 < 90%

›If required, lowest FiO2 to maintain SpO2 88 to 92%

›Hyperoxia accelerates paraquat-mediated lung destruction

›Ventilator strategy if intubated

›Low tidal volume 6 mL/kg ideal body weight

›Permissive hypercapnia acceptable

›Minimize FiO2 aggressively

›Nutritional support

›NPO initially if oropharyngeal injury

›Nasogastric route when swallowing impaired

›Parenteral nutrition if extensive mucosal damage

›Enteral nutrition when feasible

›Early gut nutrition improves outcomes

›Pain management

›Oral mucosal and esophageal pain

›Viscous lidocaine rinses for mucosal pain

›Systemic analgesia titrated carefully

›Opioids with caution given aspiration risk

09Special Populations/sp64

Pregnancy

›Pregnancy-specific considerations

›Maternal toxicity dominates management

›Fetal mortality expected with significant maternal poisoning

›Maternal stabilization takes priority

›Immunosuppressive therapy risks

›Cyclophosphamide teratogenic

›First trimester exposure carries highest teratogenicity risk

›Risk-benefit discussion with obstetrics essential

›Methylprednisolone in pregnancy

›Category C but generally preferred over cyclophosphamide

›Fetal adrenal suppression risk with prolonged use

›N-acetylcysteine in pregnancy

›Safe, preferred antioxidant adjunct

›Hepatoprotective benefit in other maternal toxicologies

›Oxygen restriction

›Fetal oxygenation depends on maternal SpO2

›Balance paraquat oxygen potentiation against fetal oxygen needs

›Target SpO2 > 92% if gestation viable

›Fetal monitoring

›Continuous if viable gestation

›Obstetric consultation mandatory

›Delivery consideration if maternal condition critical

Geriatric

›Geriatric population features

›Reduced physiologic reserve

›Pulmonary fibrosis progression faster on reduced baseline

›Lower creatinine may mask significant AKI

10Background/b89

Epidemiology

›Global burden

›One of the most lethal herbicides worldwide

›Case fatality rate 60 to 90% following oral ingestion

›No specific antidote exists

›Geographic distribution

›Highest incidence in South and Southeast Asia

›Pacific Islands and parts of Latin America

›Countries without regulatory bans have higher rates

›Sri Lanka paraquat ban associated with significant mortality reduction

›Demographics

›Mean age approximately 30 years in large series

›Approximately 70% male

›Agricultural and rural communities predominate

›Mechanism of poisoning

›Intentional self-harm predominant in most settings

›Highly lethal agent makes it attractive for suicide

›Regulatory access is key prevention target

›Occupational exposure

›Chronic low-level dermal exposure agricultural workers

›Inhalational exposure during spraying

›Accidental ingestion

›Pediatric cases

›Mislabeled beverage containers

Pathophysiology

›Mechanisms of toxicity

›Redox cycling as primary mechanism

›Paraquat accepts electrons from NADPH

›Regenerates via reduction of molecular oxygen

›Produces superoxide and hydrogen peroxide continuously

›Reactive oxygen species generation

›Lipid peroxidation of cell membranes

›Mitochondrial damage

›Severe inflammation cascade

›Pulmonary selective toxicity

›Lung cells actively uptake paraquat against concentration gradient

›Polyamine transport system concentrates paraquat in type I and II pneumocytes

›Lungs are primary target organ

›Temporal injury pattern

›Phase 1: Oropharyngeal and GI injury

›Caustic burns of mucosa within hours

›Nausea, vomiting, dysphagia

›Phase 2: Multi-organ injury

›Days 1 to 5

›Acute kidney and hepatic injury

›Cardiac and neurological involvement in fulminant cases

›Phase 3: Pulmonary fibrosis

›Days 5 to 14 and beyond

›Progressive irreversible fibrosis

›Death from respiratory failure weeks after ingestion

›Fulminant pattern

›High dose > 40 mg/kg

›Multi-organ failure within 24 to 48 hours

›ARDS, cardiovascular collapse, death

›Absorption and elimination

›Rapid GI absorption

›Peak plasma levels within 1 to 2 hours

›Largely eliminated in urine within 12 to 24 hours

›Tissue distribution

›Concentrates in lungs, kidneys, liver, muscles

›Tissue-bound fraction not amenable to dialysis

Therapeutic Considerations

›Oxygen restriction rationale

›Core therapeutic principle

›Oxygen serves as electron acceptor in paraquat redox cycling

›Hyperoxia dramatically accelerates free radical generation

›Restricting oxygen breaks the oxidative cycle

›Clinical evidence

›Normoxic or hypoxic conditions associated with better survival

›Avoid routine oxygen even in early course

›Immunosuppression rationale

›Inflammatory component of lung injury

›Oxidative stress triggers inflammatory cascade

›Steroids suppress inflammatory amplification

›Cyclophosphamide reduces fibroblast proliferation

›Evidence base

›Meta-analyses suggest 25% relative reduction in mortality

›Taiwanese cohort with combination therapy: 48% survival versus historical controls

›Evidence quality low due to lack of RCTs

›Antioxidant strategy rationale

›Reducing oxidative damage

›N-acetylcysteine replenishes glutathione

›Deferoxamine chelates iron reducing hydroxyl radical production

›Combination may have additive benefit

›Prevention of fibrosis

›Pirfenidone inhibits TGF-beta mediated fibrosis

›Anti-fibrotic therapy emerging as adjunct

›Futility and goals of care

›Prognosis communication

›Fulminant poisoning with dose > 40 mg/kg near universally fatal

›Early goals of care discussion appropriate

›Palliative care involvement for severe cases

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Paraquat poisoning discharge care

›Strict compliance with follow-up appointments

›Lung function testing as scheduled

›Kidney function blood tests as ordered

›No gardening or agricultural chemical exposure

›Avoid all herbicide contact

›Use full PPE if occupational exposure unavoidable

›Medications as prescribed

›Complete all tapering steroid doses as directed

›Do not stop medications without speaking to your doctor

›Warning signs to return to emergency immediately

›Shortness of breath or breathing difficulty

›Even mild breathlessness requires evaluation

›Lung injury can worsen days to weeks after exposure

›Chest tightness or pain

›Decreased urine output or no urine

›Yellow skin or eyes (jaundice)

›Severe mouth or throat pain worsening

›Confusion, extreme weakness, or fainting

›Coughing up blood

›Mental health support

›Psychiatric follow-up appointment

›If the ingestion was intentional

›Contact mental health crisis line if thoughts of self-harm return

›Safe storage of all chemicals

›Remove access to herbicides and pesticides from home

›Involve family or support person in safety plan

12References/r17

Guidelines and key sources

›Toxicology and poison control references

›WHO paraquat poisoning management guidelines

›UpToDate: Paraquat and diquat poisoning clinical review

›Proudfoot AT, Stewart MS et al: Paraquat poisoning: significance of plasma-paraquat concentrations. Lancet 1979

›Key clinical studies

›Lin JL, Liu L et al: Pulse therapy with cyclophosphamide and methylprednisolone in paraquat poisoning. Taiwan series n=1811 demonstrating 48% survival with combination protocol

›Lin NC et al: Prognostic index for paraquat poisoning: AUC 0.921 for six-variable composite score predicting death

›Lee SY et al: Serial CT lung volume fraction ratio as prognostic marker with ratio < 0.3 universally fatal and > 0.8 all survived

›Pharmacologic evidence

›Meta-analysis of immunosuppressive therapy in paraquat poisoning: 60.4% versus 85.3% mortality controls

›N-acetylcysteine case reports with favorable outcomes in paraquat poisoning

›Pirfenidone pediatric case report with 6-month follow-up survival

›Coding standards

›ICD-10 T60.3 toxic effect of herbicides and fungicides

›ICD-10 J70.2 acute drug-induced interstitial pneumonitis (pulmonary complications)

›ICD-10 N17.9 acute kidney failure unspecified (renal complications)

›SNOMED CT paraquat poisoning disorder concept

Evidence & Review