organophosphate by dr sulman

Case presentationBy

Dr. Suleman Bashir

Patient Details

• Name- Ijaz

• Age/Gender- 30 years/Male

• Address- Kharian

• Maritial Status- Unmarried

• Education- Primary

• History taken from attendants

Presenting Complaints

• Loss of consciousness for 10 hours.

• Difficulty in breathing for 6 hours.

HOPI

• My patient a farmer by profession with no past medical history was found unconscious in the fields by his brother on the day of admission 2 hours after going to his farm. Patient had no symptoms preceding this event. There is no history of fever, headache, any drug or food intake from outside. There in no history of illicit drug abuse or addiction. There is no evidence of any vomiting at the scene.

HOPI contd

• Patient was taken to local hospital where he was given first aid and was referred to Mayo Hospital

• On his way to hospital, patient became tachypoenic and had difficulty in breathing with crackling sounds. There is also history of frothing from mouth. But there is no history of vomiting, fits, urinary or fecal incontinence or any weakness/focal deficit.

Systemic Inquiry

• No history of chronic headache,fits,visualdisturbances,blackouts,abnormal behavior, psychosis ,numbness or tingling sensations.

• No history of exertional dyspnoea,chestpain,body swelling, orthopnea,PND.

• No history of cough, plurisy, wheezing or nasal discharge

• There is no history of pain abdomen, vomiting, diarrhoea or food poisoning.

Past History

• NOT SIGNIFICANT

• NO HISTORY OF TUBERCULOSIS OR ANY CHRONIC SYSTEMIC ILLNESS

Family History

• There is no any significant history of TB, HTN, DM or any other illnesses in his family.

Drug History

• NO HISTORY OF USE OF ANY ILLICIT SUBSTANCE OR DRUG ADDICTION

• No known allergy to any drugs

Personal and social history

• LOW SOCIOECONOMIC STATUS

• UNMARRIED

• EDUCATION LEVEL(UPTO Primary)

Occupational History

• Farmer by profession.

Summary of History

• Altered Sensorium for 10 hours

• Difficulty in breathing with frothing from mouth

• No history of any drug intake

• No history of any food poisoning

• No history of headache, fits, vomiting or fever

• Farmer by profession.

• No history of any social conflict

Differential diagnosis

• Cerebro-vascular Accidents

• Poisoning/drug overdose

• Cardiac arrythmias with brain hypoxia

• Metabolic encephalopathy

• Meningoencephalitis

Physical Examination

• A young man lying in bed with respiratory distress, having cannulae in right hand with following vitals

• P/R- 100/min

• BP- 100/60 mm Hg

• T-98

• R/R- 28/min

• Pallor-• Icterus-• Edema-• Lymhadenopathy-• Cyanosis-• Bruises-• rash-• Thyroid not enlarged• Patechiae –• JVP not raised

CNS examination

• GCS- E2V2M5 - 9/15• HMF couldn’t be assessed• Speech couldn’t be assessed• CN- couldn’t be assessed• Pupils- B/L pinpoint• Sensory- Couldn’t be assesed• Motor

▫ Patient moving all 4 limbs but power couldn’t be assesed▫ Reflexes- all reflexes present ++▫ Tone- Seems to be normal▫ Plantar- B/L downgoing▫ Co-ordination couldn’t be assesed

• Cerebellar signs couldn’t be assesed• SOMI absent

Respiratory System

• On inspection-▫ Chest moving equally with respiratory rate of 28/min.▫ Abdomio-thoracic type of respiration▫ No chest deformity or scar marks noted

• Palpation▫ No tenderness or crepitus noted▫ Chest movement and expansion normal▫ Vocal fremitus absent

• Percussion▫ Normal

• Ascultation▫ B/L harsh vesicular breathing with b/l coarse crepts and

rhonci.

Systemic examination contd

• GIT- NAD

• CVS-NAD

History and examination summary

History Examination

• Altered Sensorium for 10 hours

• Difficulty in breathing with frothing from mouth

• No history of any drug intake

• No history of any food poisoning

• No history of headache, fits, vomiting or fever

• Farmer by profession.

• GCS- 9/15

• P/R- 100/min R/R- 28/Min

• Pin point pupil

• Frothing from mouth

• No focal deficit

• SOMI absent

• Plantar downgoing

• Chest- B/l coarse crepts with ronchi

Differentials

• Poisoning

▫ Organophosphate

▫ Opiod Poinosing/overdose

• Brainstem CVA (Pontine)

INVESTIGATIONS

• CBC

▫ Hb 11.1

▫ wbc 10.5

▫ plt 199

• RFT-N

• LFT-N

• S/E-N

• CARDIAC ENZYMES- N

• ABG-Respiratpry alkalosis

INVESTIGATIONS contnd.

• PT/APTT-N

• CT SCAN BRAIN-N

• ECG- INITIALLY SINUS TACHYCARDIA THEN SINUS BRADYCARDIA

FINAL DIAGNOSIS

• ORGANOPHOSPHATE POISONING

MANAGEMENT IN EMERGENCY

• Prop up with left lateral position

• IV Access obtained

• Cardiac monitor attached

• Ecg done

• Inj atropine 1cc given at interval of 2 to 3 mints till pts chest was dry and clear and Spo2 improved and pupils fully dilated.

• Inj pralidoxime 1gm in 100 cc N/SALINE given over ½ hour

Management

• Inj Ringer lactate IL GIVEN

• Inj Ulcerex + Marzine

• Inj C-Trox 1 gm stat

• All baselines with cardiac enzymes and ABGs sent

• Chest X-Ray and USG Abdomen were done

• CT Head Done

Treatment in Ward

• Cardiac Monitoring done

• Atropine chart maintained at regular intervals

• Inj Pralidoxime @ 200mg/ hr continousinfusion given

• IV fluids 3 Litres

• Antibiotics Inj sulzone 1 gm BD

• PPI

• NPO

Organoposphate Poisoning

• Organophosphate (OP) compounds are a diverse group of chemicals used in both domestic and industrial settings. Examples of organophosphates include insecticides (malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos, ethion), nerve gases (soman, sarin, tabun, VX), ophthalmic agents (echothiophate, isoflurophate), and antihelmintics (trichlorfon).

• Organophosphate compounds were first synthesized in the early 1800s when Lassaigne reacted alcohol with phosphoric acid.

• Nerve agents have also been used in battle, notably in Iraq in the 1980s. Additionally, chemical weapons still pose a very real concern in this age of terrorist activity.

• Exposure to organophosphates (OPs) is also possible via intentional or unintentional contamination of food sources. Although no clinical effects of chronic, low-level organophosphates (OPs) exposure from a food source have been shown, advancements in risk assessment and preparedness are ongoing.

Pathophysiology

• The primary mechanism of action of organophosphate pesticides is inhibition of carboxyl ester hydrolases, particularly acetylcholinesterase (AChE). AChE is an enzyme that degrades the neurotransmitter acetylcholine (ACh) into choline and acetic acid. ACh is found in the central and peripheral nervous system, neuromuscular junctions, and red blood cells (RBCs).

• Organophosphates inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of AChE. The phosphorylation occurs by loss of an organophosphate leaving group and establishment of a covalent bond with AChE.

• Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors. Clinical effects are manifested via activation of the autonomic and central nervous systems and at nicotinic receptors on skeletal muscle.

• Once an organophosphate binds to AChE, the enzyme can undergo one of the following:▫ Endogenous hydrolysis of the phosphorylated enzyme by

esterases or paraoxonases▫ Reactivation by a strong nucleophile such as pralidoxime

(2-PAM)▫ Irreversible binding and permanent enzyme inactivation

(aging)• Organophosphates can be absorbed cutaneously,

ingested, inhaled, or injected. Although most patients rapidly become symptomatic, the onset and severity of symptoms depend on the specific compound, amount, route of exposure, and rate of metabolic degradation.[3]

Clinical Presentation

•Signs and symptoms of organophosphate poisoning can be divided into 3 broad categories, including▫ (1) muscarinic effects, ▫ (2) nicotinic effects, and ▫ (3) CNS effects.

• Mnemonic devices used to remember the muscariniceffects of organophosphates are SLUDGE (salivation, lacrimation, urination, diarrhea, GI upset, emesis) and DUMBELS (diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, bronchorrhea; emesis; excess lacrimation; and salivation).

•

• Muscarinic effects by organ systems include the following:▫ Cardiovascular - Bradycardia, hypotension▫ Respiratory - Rhinorrhea, bronchorrhea,

bronchospasm, cough, severe respiratory distress▫ Gastrointestinal - Hypersalivation, nausea and

vomiting, abdominal pain, diarrhea, fecal incontinence

▫ Genitourinary - Incontinence▫ Ocular - Blurred vision, miosis▫ Glands - Increased lacrimation, diaphoresis

• Nicotinic signs and symptoms include muscle fasciculations, cramping, weakness, and diaphragmatic failure. Autonomic nicotinic effects include hypertension, tachycardia, mydriasis, and pallor.

• CNS effects include anxiety, emotional lability, restlessness, confusion, ataxia, tremors, seizures, and coma.

Physical Examination

• Clinical presentation may vary, depending on the specific agent, exposure route, and amount. Symptoms are due to both muscarinic and nicotinic effects.

• Vital signs: Depressed respirations, bradycardia, and hypotension are possible symptoms. Alternatively, tachypnea, hypertension, and tachycardia are possible. Hypoxia should be monitored for with continuous pulse oximetry.

• Paralysis▫ Type I: This condition is described as acute paralysis secondary to

continued depolarization at the neuromuscular junction▫ Type II (intermediate syndrome): Intermediate syndrome was

described in 1974 and is reported to develop 24-96 hours after resolution of acute organophosphate poisoning symptoms and manifests commonly as paralysis and respiratory distress. This syndrome involves weakness of proximal muscle groups, neck, and trunk, with relative sparing of distal muscle groups. Cranial nerve palsies can also be observed. Intermediate syndrome persists for 4-18 days, may require mechanical ventilation, and may be complicated by infections or cardiac arrhythmias. Although neuromuscular transmission defect and toxin-induced muscular instability were once thought to play a role, this syndrome may be due to suboptimal treatment.

Type III: Organophosphate-induced delayed polyneuropathy (OPIDP) occurs 2-3 weeks after exposure to large doses of certain organophosphates (OPs) and is due to inhibition of neuropathy target esterase. Distal muscle weakness with relative sparing of the neck muscles, cranial nerves, and proximal muscle groups characterizes OPIDP. Recovery can take up to 12 months.

• Neuropsychiatric effects: Impaired memory, confusion, irritability, lethargy, psychosis, and chronic organophosphate-induced neuropsychiatric disorders have been reported. The mechanism is not proven.

• Extrapyramidal effects: These are characterized by dystonia, cogwheel rigidity, and parkinsonian features (basal ganglia impairment after recovery from acute toxicity).

• Other neurological and/or psychological effects: Guillain-Barré–like syndrome and isolated bilateral recurrent laryngeal nerve palsy are possible.

• Ophthalmic effects: Optic neuropathy, retinal degeneration, defective vertical smooth pursuit, myopia, and miosis (due to direct ocular exposure to organophosphates) are possible.

• Ears: Ototoxicity is possible.

• Respiratory effects: Muscarinic, nicotinic, and central effects contribute to respiratory distress in acute and delayed organophosphate toxicity.

• Muscarinic effects: Bronchorrhea, bronchospasm, and laryngeal spasm, for instance, can lead to airway compromise. Respiratory failure is the most life-threatening effect and requires immediate intervention.

• Nicotiectsnic eff: These effects lead to weakness and paralysis of respiratory oropharyngeal muscles.

• Central effects: These effects can lead to respiratory paralysis.

• Rhythm abnormalities: Sinus tachycardia, sinus bradycardia, extrasystoles, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation (often a result of, or complicated by, severe hypoxia from respiratory distress) are possible.

• Other cardiovascular effects: Hypotension, hypertension, and noncardiogenic pulmonary edema are possible.

• GI manifestations: Nausea, vomiting, diarrhea, and abdominal pain may be some of the first symptoms to occur after organophosphate exposure.

• Genitourinary and/or endocrine effects: Urinary incontinence, hypoglycemia, or hyperglycemia is possible.

Differential Diagnoses

▫ Gastroenteritis, Viral

▫ Toxicity, Mushroom

Laboratory Studies

• Organophosphate (OP) toxicity is a clinical diagnosis. Confirmation of organophosphate poisoning is based on the measurement of cholinesterase activity; typically, these results are not readily available. Although RBC and plasma (pseudo) cholinesterase (PChE) levels can both be used, RBC cholinesterase correlates better with CNS acetylcholinesterase (AChE) and is, therefore, a more useful marker of organophosphate poisoning.

• The portable Test-mate ChE field test measures RBC AChE and PChE within 4 minutes.

• If possible, draw blood for measurement of RBC and plasma cholinesterase levels prior to treatment with pralidoxime (2-PAM). Monitoring serial levels can be used to determine a response to therapy.

• RBC AChE represents the AChE found on RBC membranes, similar to that found in neuronal tissue. Therefore, measurement more accurately reflects nervous system OP AChE inhibition.

• Plasma cholinesterase is a liver acute-phase protein that circulates in the blood plasma. It is found in CNS white matter, the pancreas, and the heart. It can be affected by many factors, including pregnancy, infection, and medical illness. Additionally, a patient's levels can vary up to 50% with repeated testing.

• RBC cholinesterase is the more accurate of the 2 measurements, but plasma cholinesterase is easier to assay and is more readily available.

• Cholinesterase levels do not always correlate with severity of clinical illness.

• Falsely depressed levels of RBC cholinesterase can be found in pernicious anemia, hemoglobinopathies, use of antimalarial drugs, and oxalate blood tubes.

• Falsely depressed levels of plasma cholinesterase are observed in liver dysfunction, low-protein conditions, neoplasia, hypersensitivity reactions, use of certain drugs (succinylcholine, codeine, morphine), pregnancy, and genetic deficiencies.

• Other laboratory findings include:

▫ leukocytosis

▫ Hemoconcentration

▫ metabolic and/or respiratory acidosis

▫ Hyperglycemia/hypoglycemia

▫ hypokalemia

▫ hypomagnesemia and

▫ elevated amylase and liver function studies

• ECG findings include prolonged QTc interval, elevated ST segments, and inverted T waves. Although sinus tachycardia is the most common finding in the poisoned patient, sinus bradycardia with PR prolongation can develop with increasing toxicity due to excessive parasympathetic activation.

• Procedures• Endotracheal intubation and mechanical ventilation

may be necessary in patients with organophosphate poisoning for airway protection and management of bronchorrhea and seizures.

• Central venous access and arterial lines may be needed to treat the patient with organophosphate toxicity who requires multiple medications and blood-gas measurements.

Treatment

• Medical Care• Airway control and adequate oxygenation are paramount in

organophosphate (OP) poisonings. Intubation may be necessary in cases of respiratory distress due to laryngospasm, bronchospasm, bronchorrhea, or seizures.

• Immediate aggressive use of atropine may eliminate the need for intubation. Succinylcholine should be avoided because it is degraded by plasma cholinesterase and may result in prolonged paralysis.

• Continuous cardiac monitoring and pulse oximetry should be established; an ECG should be performed. Torsades de Pointes should be treated in the standard manner. The use of intravenous magnesium sulfate has been reported as beneficial for organophosphate toxicity. The mechanism of action may involve acetylcholine antagonism or ventricular membrane stabilization.

• Remove all clothing and gently cleanse patients suspected of organophosphate exposure with soap and water because organophosphates are hydrolyzed readily in aqueous solutions with a high pH. Consider clothing as hazardous waste and discard accordingly.

• Health care providers must avoid contaminating themselves while handling patients. Use personal protective equipment, such as neoprene gloves and gowns, when decontaminating patients because hydrocarbons can penetrate nonpolarsubstances such as latex and vinyl. Use charcoal cartridge masks for respiratory protection when decontaminating patients who are significantly contaminated.

• Irrigate the eyes of patients who have had ocular exposure using isotonic sodium chloride solution or lactated Ringer's solution. Morgan lenses can be used for eye irrigation.

Medication Summary

• The mainstays of medical therapy in organophosphate (OP) poisoning include▫ atropine,▫ pralidoxime (2-PAM), and▫ benzodiazepines (eg, diazepam).

• Initial management must focus on adequate use of atropine. Optimizing oxygenation prior to the use of atropine is recommended to minimize the potential for dysrhythmias.

• A meta-analysis and review of the literature performed by Peter et al emphasized optimal supportive care along with discriminate use of 2-PAM, especially early in the course of treatment of moderately to severely OP poisoned patients, are the hallmarks of treatment. More prospective data are required.

• Intravenous glycopyrrolate or diphenhydraminemay provide an alternative centrally acting anticholinergic agent used to treat muscarinictoxicity if atropine is unavailable or in limited supply.

• In a single-center, randomized, single-blind study by Pajoumand et al found a benefit to magnesium therapy in addition to standard oxime and atropine therapy in reducing hospitalization days and mortality rate in patients with organophosphate poisoning.The mechanisms appear to be inhibition of acetylcholine (ACh) and organophosphate antagonism.

Anticholinergic agents

• Class Summary

• These agents act as competitive antagonists at the muscarinic cholinergic receptors in both the central and the peripheral nervous system. These agents do not affect nicotinic effects.

• Atropine IV/IM (Isopto, Atropair)

• Initiated in patients with OP toxicity who present with muscarinic symptoms.

• Competitive inhibitor at autonomic postganglionic cholinergic receptors, including receptors found in GI and pulmonary smooth muscle, exocrine glands, heart, and eye.

• The endpoint for atropinization is dried pulmonary secretions and adequate oxygenation. Tachycardia and mydriasis must not be used to limit or to stop subsequent doses of atropine. The main concern with OP toxicity is respiratory failure from excessive airway secretions.

• Glycopyrrolate (Robinul)

• Indicated for use as an antimuscarinic agent to reduce salivary, tracheobronchial, and pharyngeal secretions. Does not cross the blood-brain barrier. Can be considered in patients at risk for recurrent symptoms (after initial atropinization) but who are developing central anticholinergicdelirium or agitation.

• Since glycopyrrolate does not cross BBB, it is not expected to control central cholinergic toxicity. Bird et al suggested that atropine (rather than glycopyrrolate) was associated with lower, early OP-induced mortality

Antidotes

• Class Summary• These agents prevent aging of AChE and reverse muscle paralysis with OP poisoning.• Pralidoxime (2-PAM, Protopam)

• Nucleophilic agent that reactivates the phosphorylated AChE by binding to the OP molecule. Used as an antidote to reverse muscle paralysis resulting from OP AChEpesticide poisoning but is not effective once the OP compound has bound AChE irreversibly (aged). Current recommendation is administration within 48 h of OP poisoning. Because it does not significantly relieve depression of respiratory center or decrease muscarinic effects of AChE poisoning, administer atropine concomitantly to block these effects of OP poisoning.

• Signs of atropinization might occur earlier with addition of 2-PAM to treatment regimen. 2-PAM administration is not indicated for carbamate exposure since no aging occurs.

•

Benzodiazepines

• Class Summary

• These agents potentiate effects of gamma-aminobutyrate (GABA) and facilitate inhibitory GABA neurotransmission.

• Diazepam (Valium, Diastat, Diazemuls)

•

• For treatment of seizures. Depresses all levels of CNS (eg, limbic and reticular formation) by increasing activity of GABA.

Deterrence/Prevention

• Health care providers must avoid contaminating themselves while handling patients poisoned by organophosphates. The potential for cross-contamination is highest in treating patients after massive dermal exposure.Use personal protective equipment, such as neoprene or nitrile gloves and gowns, when decontaminating patients because hydrocarbons can penetrate nonpolar substances such as latex and vinyl.

• Use charcoal cartridge masks for respiratory protection when caring for patients with significant contamination.

Complications

• Complications include

▫ respiratory failure,

▫ seizures,

▫ aspiration pneumonia,

▫ delayed neuropathy, and

▫ death.

•THANK YOU