Literature review

Literature review Prepared by Dr.Saira PGR Medicine

Poisoning is a global issue occuring all over the world involving people of all ages and gender, from all ethnic and economic backgrounds

More than 700,000 deaths occur each year as a result of poisoning!!!

General approach to a patient with poisoning

Quickly asses the potential danger.Consider decontamination to prevent absorption.Treat complications if they occur.Observe the asymptomatic patients for appropriate interval.Asses the dangerThe drug to which person was exposedThe amount ingested/degree of exposureThe time since exposureThe presence of any sign or symptomsAny premorbidsSerum drug/toxin levels

In symptomatic patients,treatment of life threatening complications takes precedence over in-depth diagnostic evaluation1st and the foremost step is to stop the further exposure of the patient.Coma

Assesment and complicationsCausative agents includeAntihistaminesBezodiazepines Ethanol Opioids Anti-psychotic/anti-depressant drugsApproach Airway Breathing Circulation

..Drugs Dextrose In all comatose or convulsing patients give 50% dextrose(in our hospital 25% is available),50-100 ml IV bolus unless a rapid bedside blood sugar test is available.Thiamine In alcoholics/malnourished give thiamine 100mg IM/IV...Nalaxone 0.4-2mg is empirically given to any comatosed patient with depressed respiration.Nalmefene,a newer opioid antagonist has a duration of effect longer than nalaxone.

..Flumazenil 0.2-0.5mg IV repeated as needed upto a maximum of 3mg may reverse benzodiazepine induced coma.Its use is not commonly advised as the potential risks outweight its benefits

Hypothermia

..Hypothermia commomly accompanies coma due to hypoglycemic agents,opioids and other sedative-hypnotics.

It may cause or aggravate hypotension.

Gradual rewarming is usually preferred.Hypotension Agents causing hypotension include carbon mono-oxide,hydrogen sulphide,aluminium phosphide,arsenic and many sedative-hypnotics.

Empiric treatment with 200 ml boluses of 0.9% normal saline upto a total of 1-2 litres.

CVP guided fluids

Inotropes Hypertension Amphetamines,anti-cholinergics,cocaine

Treat hypertension if patient is symptomatic or diastolic BP >105-110 mmHg

Sodiumnitroprusside,labetalol,phentolamine intravenously can be used.Arrythmias Hypoxia,metabolic acidosis,or electrolyte imbalance may trigger an arrythmia.

Treatment includes removal of causative agent.If persists,amiodarone or lidocaine etc can be used.

Seizures May be caused by a number of drugs and metabolic disturbances.Administer 2-3mg lorazepam or 5-10mg diazepam over 1-2min.If IV acess is not immediately available 5-10mg midazolam can be given intramuscularly.For drug induced seizures phenobarbital is preferred over phenytoin.

Hyperthermia Amphetamines,anticholinergic agents,cocaine,salicylates,strychnine,TCA.

Malignant hyperthermia with general anesthetics and neuroleptic malignant syndrome with antipsychotics.

Remove clothings,spraying skin with cold water,and fanning.

Sedate,paralyze and place on mechanical ventilation.

Decontamination

Decontamination of the skin /eyesWash the affected areas with copious amounts of lukewarm water or normal saline

For oily substances use soap/shampoo for skin.

For warfare agents use diluted hypochlorite solution for skin.

Gastrointestinal decontaminationGastric lavage Activated charcoalWhole bowel irrigationIncreased drug removal Urinary manipulation(alkalinization)Hemodialysis Repeat dose charcoal(gut dialysis)

ANTIDOTESTOXINS AntidotesToxic agent Antidote

Acetaminophen N-acetylcysteineAnticholinergics Physostigmine Organophosphates Atropine and pralidoxime Benzodiazepines Flumazenil Carbon monoxideOxygen Cyanide Sodium nitriteDigitalis glycosidesDigoxin specific Fab antibodiesHeavy metals Chelating agents isoniazidPyridoxine Methanol Ethanol Opioids Nalaxone Snakebite Anti-snake venomDetails of all the chemicals and their antidotes can be seen in MERCK index

https://www.rsc.org/merck-index

Diagnosis of poisoning ..History may or may not be reliable.

Physical examination Blood pressure Pulse Temperature Pupils Sweating Peristaltic activity Sympathomimetic syndrome Blood pressure and pulse rate are elevatedTemperature is raised Sweating with dry mucus membranes Agitated,anxious or frankly psychotic

Sympatholytic syndrome Blood pressure and pulse rate are low.

Body temperature is reduced

Pupils constricted or pinpoint

Patient drowsy or comatosedCholinergic syndrome Bradycardia Miosis Sweating Bronchorrea Wheeze Excessive salivation Urinary incontinenceAgitated and anxious Anticholinergic syndrome Tachycardia Hypertension Raised body temperature Pupils widely dilated Skin hot flushed and dry Urinary retention Agitation/delirium

Laboratory tests Baselines Serum osmolality and osmol gap Electrolytes and anion gap BUNUrinalysis Electrocardiogram Abdominal radiographs Toxicology testing When to admit?

..The patient has features that are not expected to clear within 6-8 hours observation period.

Ingestion of delayed release preparations Continued administration of an antidote is required

Psychiatric or social services evaluation is needed for suicidal attempt or suspected drug abuse.Observe the patient Asymptomatic or mildly symptomatic patient should be observed for 4-6 hours.

Longer observation is indicated if the ingested substance is a sustained-release preparation or is known to slow the gastrointestinal motility or may cause a delayed onset of symptoms.Kala pathar intoxication

Introduction Paraphenylene diamine (PPD) has been used internationally as a key ingredient in different hair dye formulations to produce a variety of shades depending on its concentration.

PPD is used by women to color theirhair and as a dye when added to henna(Lawasonia alba) to color the palms and soles..

.. Poisoning with Paraphenylene Diamine (PPD) is emerging as an important means of intentional self harm in various developing countries of Asia and Africa.Mechanism of toxicityParaphenyleneDiamine(PPD) is a coal-tar derivative .

On oxidation produces Bondrowskis base having allergenic, mutagenic and highly toxic properties. Systemic poisoning Acute poisoning with PPD causes a characteristic:Severe oedema of the face and neck often requiring tracheostomy

Swollen dry hard tongue.

..

..Chocolate brown color of the urine

PPD intoxication is a multisystem poison and can cause :rhabdomyolysis,myoglobinuria and acute renal failure (ARF)..Asphyxia and respiratory failure are the immediate threats to life under such conditions.

Endotracheal intubation, emergency tracheostomy and ventilatory assistance are needed.

..Shock is another important clinical feature due to PPD

Myocarditis, hypovolemia and sepsis might be the underlying reasons for severe hypotension.

Myocardial injury and fatal cardiac arrhythmias form the basis of sudden cardiac death...Rhabdomyolysis and its consequences (ARF, hyperkalemia, hypocalcemia, hyperphosphatemia) are important parameters predictive of mortality in the syndrome of PPD intoxication.

ARF form the basis of hyperkalemia. Hyperkalemia, with its arrhythmogenic potential can also lead to sudden death.

.. Intensive supportive care is the corner stone of management.

.. Gastric lavage with saline and charcoal oxygen i/v fluids diuretics mannitol Antibiotics

.. Inotropes(if hemodynamically unstable) Steroids Calcium gluconate Sodium bicarbonate Cardiac monitoring Intake output monitoring Methylene blue Exchange transfusion..Consumption of amount, as low as 25ml results in hepatitis. As there is no specific antidote and the toxin is also non-dialyzable, aggressive management in collaboration with different specialties is needed. Formation of methaemoglobin

..

Use of methylene blue

Benzene poisoning

Introduction Benzene has been widely used as a multipurpose organic solvent. This use is now discouraged due to its high toxicity.

Present uses include benzene as a raw material in the synthesis of various plastics and detergents.

The tire industry and shoe factories use benzene extensively. ..Deaths from acute exposure to benzene are often related to physical exertion and release of epinephrine with subsequent cardiac failure.

Frequently, the person trying to rescue a collapsed victim will die during the effort of lifting the unconscious person ... Anesthesia may develop at concentrations above 3,000 ppm

At exposures of greater than 1,000 ppm CNS symptoms include giddiness, euphoria, nausea, and headaches; heightened cardiac sensitivity to epinephrine-induced arrhythmias may develop

.. Mild irritation to the eyes and mucous membranes.

Respiratory tract inflammation, pulmonary hemorrhages, renal congestion, and cerebral edema have been observed at autopsy in cases of acute benzene poisoning .

..People with existing hematologic disorders may be more sensitive to the acute toxicity of benzene to the bone-marrow.

Females may be more sensitive to benzene toxicity than males due to higher average body fat content, which serves as a storage reservoir for the chemical .Management OxygenGastric lavageNebulization Steroids PPISodium bicarbonateFluids IntubationMethylene blueExchange transfusions

Wheatpill(aluminium phosphide) poisoning

Introduction Wheat pill poisoning is a very serious but unfortunately under-reported and under-discussed problem.

These pills are used as grain preservatives. In wheat growing areas of Pakistan, these pills are easily available over the counter without any check or control on their sale.Easy availability and no antidote, makes it an ideal suicidal poison

...The spectrum of symptoms and signs and their severity depends upon the time lag between aluminium phosphide ingestion and hospitalisation.

The reported in-hospital mortality of aluminium phosphide poisoning is 55-90%.Mechanism of toxicityThey are available as tablets or powder. Wheat pills mostly contain aluminium phosphide 58% and inert ingredients 42%.

Phosphine is a very strong reducing agent that inhibits cellular enzymes involved in several metabolic processes

..It cause ARDS and denaturing of oxyhemoglobin.

Local inflammation can cause gastritis and esophagitis. .. Less than 25% of patients are able to reach a tertiary care hospitals.

only tip of the iceberg

Clinical presentation Patients with wheat pill poisoning present typically with epigastric pain, nausea, vomiting, cardiac arrhythmias and cardiogenic shock.

They worsen to develop severe refractory hypotension and metabolic acidosis.

Most deaths occur within first 12-24 hours after exposure and are cardiovascular in origin.

After 24 hours usual cause of death is liver failure.

..Most common symptom seen in patients is vomiting Most common sign is hypotension

Management As no antidote is available the management of wheat pill poisoning remains purely supportive.

Aluminium phosphide can be absorbed from exposed skin so exposed skin and hair should be flushed with water and then washed with soap.

Protocol for wheatpill poisoningThe protocol being mentioned here has been circulated to all DHQs and THQ s of Rawalpindi district by Principal RMC and Allied hospitals...Maintain double IV line.Keep NPO for 24-48 hours.Give fluids according to haemodynamic status.Perform gastric lavage with edible oil 1-2 litres alongwith activated charcoal.Inj.Omeprazole 40mg stat then odInj.mgs04 1gm iv stat then 1gm/hr for next 4 hours than 1 gm every 4 hourly for next 48-72 hours.

.Inj.hydrocortisone 250mg iv stat then 100mg tds.Inj calcium gluconate diluted iv stat then od.Inj.amiodarone (if arrythmia).Vitals monitoring.Monitor with ECG and baseline labs.ICU care.Attendants counselling.

Organophosphate poisoning

Introduction Poisoning with organophosphorus compounds (OP) is a global problem.

World Health Organization estimates that one million serious unintentional poisonings occur every year and an additional two million people are hospitalized for suicide attempts with pesticides.

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Clinical presentationMuscarinic manifestationsRespiratory: Increased bronchial secretions, bronchospasm, chest tightness, dyspnoea, cough

Eyes: Blurred vision, conjunctival injection, dimness of vision, miosisGastrointestinal: Cramping, diarrhea, nausea, vomiting

..Urinary: Incontinence

Cardiovascular: Bradycardia, hypotension

Exocrine glands: Increased salivation

..Nicotinic manifestations

Muscle fasciculation, cramping, weakness, diaphragmatic paralysis, respiratory failure, tachycardia, hypertension.

..Nausea and vomiting is the most common symptom reported by the patients while miosis is the most common sign observed

Management I/V line oxygenGastric lavage with normal saline and charcoal

Inj.Atropine every 5 minutes till signs of atropinization.Pralidoxime 1gm stat ;can be repeated as needed.PPIAntibioticsI/V fluid

Famous poison victims

SOCRATES died of hemlock

Cleopatra VII of Egypt

Napoleone di Buonaparte died of Arsenic

Bruce lee died of mixture of overdose of sedative hypnotics

Michael jackson died of mixed drug overdose

Scott Charles Bam Bam Bigelow died of multiple drugs overdose

Adolf Hitler died of cyanide

BURDEN OF POISONING AT DHQIn USAContact:American Association of Poison Control Centers at http://www.aapcc.org/Your local poison control centerPoison Prevention Week Council at http://www.poisonprevention.org/

In Uk UK National poisons information centres contact number 087 0600 6266PAKISTAN..????Toxicology Advisory center??Ordinance ???Legislation ???Protocol for wheatpill poisoningThe protocol being mentioned here has been circulated to all DHQs and THQ s of Rawalpindi district by Principal RMC and Allied hospitals...Maintain double IV line.Keep NPO for 24-48 hours.Give fluids according to haemodynamic status.Perform gastric lavage with edible oil 1-2 litres alongwith activated charcoal.Inj.Omeprazole 40mg stat then odInj.mgs04 1gm iv stat then 1gm/hr for next 4 hours than 1 gm every 4 hourly for next 48-72 hours..Inj.hydrocortisone 250mg iv stat then 100mg tds.Inj calcium gluconate diluted iv stat then od.Inj.amiodarone (if arrythmia).Vitals monitoring.Monitor with ECG and baseline labs.ICU care.Attendants counselling.THANK YOU