OP POISONING – ICU MANAGEMENTIs it straightforward ??

Dr.Vaidyanathan RConsultant Anaesthesiologist and Intensivist

INCIDENCE

3 million cases per year worldwide

12% of all ICU admissions in india 30% of patients reqiring ventilatory support.

75% of all admissions due to poisonings.

THE NEUROMUSCULAR JUNCTION

• Acetylcholine is the neurotransmitter released by the terminal nerve endings of all postganglionic parasympathetic nerves and in both sympathetic and parasympathetic ganglia.

• It is also released at the skeletal myoneural junctions and serves as a neurotransmitter in the central nervous system.

• Acetylcholinesterase is present in two forms: true cholinesterase which is found primarily in the nervous tissue and erythrocytes and pseudocholinesterase which is found in the serum and liver.

• OPs bind to the active serine residue of acetyl cholinesterase irreversibly and convert the enzyme into an inactive protein complex, resulting in the accumulation of acetylcholine at the receptors.

• This leads to overstimulation and subsequent disruption of nerve impulse transmission in both the peripheral and central nervous systems.

Pathophysiology of OP Poisoning

CLINICAL MANIFESTATIONS

• It is useful to remember the toxidrome in terms of the 3 clinical effects on nerve endings:

1.Nicotinic effects at neuromuscular junctions and autonomic ganglia

2. Muscarinic effects

3. CNS effects,.

The “SLUDGE”• SLUDGE / BBB - mnemonic

– S = Salivation – L = Lacrimation – U = Urination – D = Defecation – G = GI symptoms – E = Emesis

– B = Bronchorrhea – B = Bronchospasm – B = Bradycardia

DUMBELS!• DUMBELS - mnemonic

– D = Diarrhea and diaphoresis – U = Urination – M = Miosis – B = Bronchorrhea, bronchospasm, and bradycardia – E = Emesis – L = Lacrimation – S = Salivation

Symtoms

Nicotinic effects • Nicotinic signs and symptoms include weakness, fasciculations and

paralysis.

• CNS effects may lead to seizures and CNS depression

Muscuranic Effects

Cardiovascular: Bradycardia, hypotension.

Respiratory: Rhinorrhea, bronchorrhea, bronchospasm, cough.

cont’d – muscarinic effectss

• Gastrointestinal : Increased salivation, nausea and vomiting, abdominal pain, diarrhea, fecal incontinence.

• Genitourinary : Urinary incontinence.

• Ocular : Blurred vision, increased lacrimation, miosis.

• Dermatologic : Excessive sweating.

 

CNS EFFECTS • Anxiety, restlessness, ataxia, absent reflexes,

convulsions, insomnia, tremors, dysarthria, coma, hyperreflexia

• Cheyne Stokes breathing, respiratory depression, and circulatory collapse can occur.

• The end-result may be multisystem manifestations involving GIT, respiratory system, CVS, CNS, skeletal muscles, as well as metabolic effects such as hypo- or hyperglycemia.

Neurological manifestations are the most important sequel of OP poisoning

• A large number of patients with acute OP poisoning develop neuromuscular weakness requiring prolonged ventilation.

• Three types of paralyses are recognized based on the time of occurrence and differ in their pathophysiology.

 

Neurological Manifestations in OP Poisoning 

Type-I Paralysis or Acute Paralysis

Type-I paralysis occurs with the initial cholinergic crisis.

• Develops within 24-48 h.

• Due to persistent depolarization at NMJ

• Features include muscle fasciculations, cramps, twitching, and weakness.

Cont’d• Manifestations respond to atropine although it may not fully

block the nicotinic effects.

• Muscle weakness may have upper motor neuron manifestations.

• Muscle paralysis involve the respiratory muscles leading to respiratory failure requiring ventilation.

• This may be further compounded by severe bronchorrhea.

• Acute respiratory failure has been observed in 33% of patients who presented with OP poisoning.

Type-II Paralysis or Intermediate Syndrome

• First described by Wadia as Type-II paralysis subsequently described and termed intermediate syndrome by Senanayake.

• Develops after the acute cholinergic crisis, 24-96 h after the poisoning

• In the majority of patients, respiratory insufficiency heralds onset of the syndrome.

• Needs ventilatory support for 14-21 days.• Cranial nerve palsies and proximal muscle weaknes with relative

sparing of the distal muscle groups. • The reported incidence of this syndrome varies between 8% and

49%

Type-III Paralysis or OP-Induced Delayed Polyneuropathy

• OP-induced delayed polyneuropathy (OPIDP) is a sensory-motor distal axonopathy

• Usually occurs after the ingestion of large doses of certain OP insecticides or after chronic exposure.

• Two distinct clinical entities have been described -I. A Pure motor polyneuropathyII.OPIDP with mild sensory component with a more prominent

motor component.

• A pure sensory neuropathy has not been observed in either single or repeated acute OP poisoning.

Cont’d

• Usually occurs 2-3 weeks after the acute poisoning episode.

• Characterized by distal muscle weakness

• Sparing of neck muscles • Cranial nerves and proximal muscles are spared.

Other Neurologic Manifestations Neuropsychiatric manifestations • Termed as chronic OP-induced neuropsychiatric disorder • Includes impaired memory, confusion, irritability, lethargy, and

psychosis. • Manifestations are usually temporary.

Extrapyramidal manifestations • Develops 4-40 days following poisoning and lasts for approx 1-4

weeks including dystonias, resting tremor, cog-wheel rigidity and choreoathetosis.

Neuro-ophthalmological sequlae • Optic atrophy, degeneration of retina, defective vertical smooth

pursuit movements, myopia owing to spasm or paresis of accommodation.

Cadiovascular Manifestations

• Cardiac manifestations are often the cause of serious complications or fatality

• Wide variety of cardiac manifestations possible.

• Karki et al(1992) reported of cardiac complications in 62.2% of patients.

Cont’d Electrocardiographic Manifestations• These include prolonged Q-T corrected (QTc) interval

(67%); elevated ST segment (24%); inverted T-waves (17%); prolonged PR interval (9%)

• Rhythm abnormalities such as sinus tachycardia (35%), sinus bradycardia (28%),extra systoles (6%), atrial fibrillation (9%) and ventricular tachycardia (4%)

• Other manifestations reported were noncardiogenic pulmonary edema (43%), hypertension (22%), and hypotension (17%).

Cont’d• Ludomirsky et al.described three phases of cardiac toxicity.

Phase 1: A brief period of increased sympathetic tone.

Phase 2: Prolonged period of increased parasympathetic activity, including atrioventricular block.

Phase 3: QT prolongation followed by torsade de points , ventricular tachycardia, and development of ventricular fibrillation.

Laboratory Studies• The most common tests to determine OP and carbamate

poisoning are measurements of serum cholinesterase and RBC AChE activity

• RBC AChE is more specific.

• In the ideal case, the diagnosis is confirmed with a decrease in enzyme activity from baseline (50% for RBC cholinesterase activity), though a baseline, preexposure enzyme level is not available for most patients.

 Management

General Measures : Decontamination

• Decontamination of the skin is very important and done thoroughly.

• Gastric decontamination should be done by forced emesis if the patient is fully awake or through a gastric lavage.

• All patients should also receive 0.5-1 g/kg activated charcoal every 4 h. Sodium sulfate or sorbitol can be used as a cathartic.

Airway and Respiration• The airway should be secured and adequate oxygenation should

be ensured.

• Atropine can precipitate ventricular arrhythmia in hypoxic patients.

• Early use of atropine will reduce respiratory secretions, improve

muscle weakness, and thereby improve oxygenation.

• Careful observation of the respiratory status is required as these patients are prone to respiratory failure during the acute phase and intermediate syndrome.

MONITORING DURING TREATMENT

Parameters monitored during treatment

• Neck muscle weakness• Respiratory rate• Tidal volume or vital capacity• Single breath count• Symptoms of ocular muscle involvement (eg:ptosis or

diplopia)• Arterial blood gas estimation and pulse oximetry.

 Specific Therapy

Anticholinergic Agents

• Anticholinergics are still the mainstay of treatment and should be started as soon as the airway has been secured.

• Atropine can be started initially as a 2.4mg IV bolus and

then repeated at doses of 2-5 mg IV bolus every 5-15 min until atropinization is achieved.

• Most commonly used regimen is 0.2mg/kg/hour titrated to desired effect

Target end-points of Atropine therapy

• Heart rate > 80/ min• Dilated pupils• Dry axillae• Systolic blood pressure >80• Chest clear of secretions and crepts.• Drying of all secretions…….

Oximes

• PRALIDOXIME (2-PAM). – OPCs bind and phosphorylate one of the active sites of

AChE and inhibit the functionality of this enzyme.– Oximes bind to the OP causing the compound to break its

bond with AChE – REACTIVATION.– AGEING IS A CONCERN.

• The main therapeutic effect of pralidoxime is due to recovery of N-M transmission at nicotinic synapses.

• However, oximes also enhance cholinesterase activity at muscarinic sites decreasing the requirement for atropine.

• Multitude of studies have been conducted.

• Johnson et al compared pralidoxime 1 g as a bolus, with pralidoxime 12 g as an infusion (no bolus) over 4 days.

• Mortality rates, need for ventilation, and rates of intermediate syndrome were higher with the infusion group than with the bolus group.

• Another study by Cherian et al compared pralidoxime 12 g given over 3 days with placebo.

• Results were similar in both groups in terms of rates of mortality, ventilatory support, and intermediate syndrome

Cont’d,• Oxime therapy and outcomes in human organophosphate poisoning: an

evaluation using meta-analytic techniques.Peter JV, Moran JL, Graham P 2006 Feb;34(2):502-critical care medicine

• Oximes in acute organophosphorus pesticide poisoning: a systematic review of clinical trials M. Eddleston, L. Szinicz P. Eyer and N. Buckley QJM (2002) 95 (5): 275-283.

• RCT s and meta analysis of the available trials either show null effect or even harmful effect with use of PAM .

• Overall analysis of all available evidence show either a null effect or no harm.

WHO GUIDELINES• Both the 1-g bolus dose and the 12-g infusion dose fall short of

WHO-recommended dosing for adults• A bolus of at least 30 mg/kg followed by an infusion of at least 8

mg/kg/h. • Pediatric dosing is a 25-50 mg/kg bolus given over 30 minutes

then an infusion of 10-20 mg/kg/h.

1) None of the oximes (pralidoxime, obidoxime, Hl6 or Hlo7) are universal reactivators

2) Oximes useless once ageing has occurred.

Dimethyl pesticides presenting to hospital 3 h after ingestion, about 50% of the acetylcholinesterase will already be aged and unresponsive to oximes.12 h later 94% aged acetylcholinesterase and therefore be unresponsive to oximes.

Diethyl pesticides since it takes 33 h for 50% inhibition and oximes can be effective for up to 5 days after ingestion.

Ageing occurs much early less than 1hr in atypical compounds.

Pitfalls of oximes…

Galantamine and Huperzine A A reversible acetylcholinesterase inhibitor that crosses the blood - brain

barrier used in Alzheimers…

• Has anticonvulsant properties

• Prevents neurodegeneration,which is a hallmark of OP poisoning • The therapeutically effective dose is about 3 -12 mg.

• Galantamine is administered by intranasal ,oral administration,im or sc injection

• Lot of interest during gulf war and war aginst terror used in combination with atropine.

• Huperzine-A – studied extensively in animal studies.

MISCELLANEOUS:

• Infections:Respiratory infections should be anticipated and treated

vigorously.

• Benzodiazepines: Seizures are an uncommon complication of OP

poisoning. When they occur, they represent severe toxicity.

As with most seizures of toxicologic etiology, benzodiazepines are the preferred medication

Novel therapies• Magnesium and clonidine have shown promising results. Both reduces Ach synthesis and reduces its release from pre synaptic

terminals

• NaHCo3 has been used in place of oximes in Iran & Brazil.Increasing PH to 7.55 been claimed to increase survival.

• Haemoperfusion and haemodialysis.

• BuChE and recombinant bacterial phosphotriesterases and hydrolases like Oph and OpdA.

FAST HUG ME

• Feeeding - EEN• Analgesia & Sedation• Thromboprophylaxis• Head –up position• Ulcer prophylaxis• Glycemic control• Monitoring • Evaluation

SHOULDN’T THAT BE STRAIGHT FORWARD ???

• BUT WATCH OUT-----

PAEDIATRIC PT S

• 6 patients less than 12 yrs.

• Youngest of them was 4 yrs!!.ventilated for 72 hrs

• Usually accidental.

• Diagnosis is often challenging

• Treated as seizure disorders, acute abdomen, acute GE.

Paediatric Differential diagnosis

• Intussusception• Reactive Airway Disease• Respiratory Distress Syndrome• Seizure disorders.• Bacteremia and Sepsis• Gastroenteritis• Dehydration

ALWAYS WATCH OUT FOR PUPILS

HOW LONG DOCTOR ???

PREGNANT PATIENTS

• Pregnant patients who have ingested OP insecticides during the second or third trimester of pregnancy have

been treated successfully with atropine and pralidoxime and later delivered healthy newborns with no significant abnormalities.

• However, foetal distress is a possiblity both due to poisonoing and its treatment.

• Pregnant women should receive the same treatment as that given to other adults.

Cont’d• 6 pregnant pt.s got admitted with consumption of OP

compound. 3 were on ventilator. One delivered a healthy baby,while the other had to be induced MTP.

• 2 other patients continued their pregnancies and 1 patient had to be induced MTPs during subsequent admissions.

• Both atropine and pralidoxime are pregnancy class C drugs.

• In the Tokyo subway attacks, 5 pregnant women were mildly poisoned, and all had normal babies without complications.

• 2 patients miscarried in a similar series from lucknow.

Geriatric and COPD• 24 patients out of 215

patients were more than 65 yrs.

• 10 of them had COPD. The eldest of them was @ 85 yrs.

• All made good recovery with mean duration of ventilation being 7.2 days.

• NIV used during weaning for 4 of them.

THE OLDEST OF `EM ALL

COPD

Cardiac disease - IHD• 8 of our patients had pre existing cardiac disease / IHD

• 5 of them severely low EF – 30% and less.

• Often go for weaning failures.

• Require prolonged ventilatory support, tracheostomy and NIV.

• Emotionally and physically draining… • All of them walked home ultimately with mean duration of

ventilation of 9.2 days

ALCOHOL AND OP COMPOUND• Often close friends – go hand in hand!!

• More than 50% of our pts had consumed alcohol with op compound.

• Severe alcohlic liver disease was seen in 6 of the patients.

• Alcohol withdrawal syndromes and delirium tremens seen in quite a significant number of patients.

• Thiamine to be used very liberally..

Sample spectrum of op poisoning

MISCELLANEOUS• Mixed compounds

• Severe anaemia – in our own series more than 5 patients required transfusions before extubations

• Infections - 8 pts had VAP ( OUT OF 215). 2 of them had severe sepsis.

• 4 of them had ARDS. All recovered.

• One had severe pancreatitis.• Severe coaugulopathy and upper GI bleed in one pt each.

• Iv op injections….

JIST vol 008.Issue 001 Jan-Jun 2012

Management of organophosphorous compound poisoning–A one year experience in a tertiary care hospital –Vaidyanathan R,Ashoka HG,Pramodkumar

•Male preponderance with 73:18 for males : females•Maximum pts seen in the most productive age group of 21 - 40yrs.(64%)• Out of 91 patients , 39 required ventilatory support (about 42%).•2 patients died while being on ventilator bringing the overall mortality to 2.1%. Mean duration of ICU stay was 4.2 days for pts not requiring ventilator and 8.6 for those requiring ventilator.•Mean duration of mechanical ventilation was 7 days. (max – 21 days)•Mean serum cholineesterase levels were 2100 ( 2181 and 3443)•The mean time elapsed since consumption was 5.4 hrs and 8.1 hrs for patients requiring ventilatory support.

• Commonest compound of consumption was Dimethoate (Rogar) -14 • Methyl parathion & chlorpyriphos 3 each • Carbamates in 2 cases. 12 were unknown compound.• Out of 39 patients , 6 had intermediate syn (15.38%).

• Mean APACHE II score was 8.9 and that for pts requiring ventilatory support was 11.5.

• Mean SOFA score was 1.01 and 1.84 for pts on ventilator.• SOFA score,APACHE II score and the time since ingestion of

compound were significantly associated with pt.s requiring ventilatory support (p<0.05)

• With logistic regression analysis none of these three factors predicted need for ventilation or mortality independently.

Observation and results

2009-2014

537 out of 2756 total ICU ADMISSIONS - 20%

537 out of total 791 admissions due to acute poisoning – 70%

215 out of 768 pt s requiring venttilatory suopport - 30%

5 patients died during course – overall mortality < 1%

Occupying almost 40% of all ICU DAYS…