12 Toxicology

SECTION 12

Toxicology 63.

Management of Snake Bite - An Update Joseph K Joseph, Manoj P Jose, Jaideep Menon

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Unknown Poisoning Viny Rampal, Vinod Mitla, SS Jamwal

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C H A P T E R

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Management of Snake Bite An Update Joseph K Joseph, Manoj P Jose, Jaideep Menon

India is estimated to have the highest snake bite mortality in the world with WHO estimates placing the number between 15,000 to 30,000 per annum. The oftquoted figure till recently was around 50,000. Conservative estimates put the deaths related to snakebite in between 35,00050,000 per year in India alone. It is quite unfortunate that most of the deaths in our country are due to fright and wrong line of treatment.

The first thing to be verified is whether it is a snake bite at all. And if so whether it was a venomous snake bite.

The victim may be shown a chart with photographs of venomous snakes in the area to help identification.

Symptoms of pain out of proportion to the extent of injury are typical of envenomation. If the pain seems proportional to the injury seen, it may not be a snake bite at all and could be an injury from other causes.

The species identification does not really change the medically management at present, as the ASV we use is polyvalent i.e ASV which neutralizes the venom of all the “Big Four”. The currently used polyvalent ASV would not cover king cobra bites, sea snake bites and would have nil or very minimal benefit in pit viper bite.

and malena, chemosis, macular bleed, excessive menstrual bleed, bleeding from bite site or the canula, bleeding into muscles, bleeding from gingival sulci, epistaxis. Bleeding into skin & mucous membrane may show evidence of petichiae, purpura, epistaxis.

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Hypotension resulting from hypovolemia or direct vasodilatation.

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Low back pain, loin pain indicative of an early renal failure or retroperitoneal bleeding. The passing of reddish or dark brown urine or declining or no urine output.

• Lateralising neurological symptoms and asymmetrical pupils maybe indicative of intracranial bleeding

GENERAL SIGNS AND SYMPTOMS OF ELAPID ENVENAMATION

Swelling and local pain (Cobra). Local necrosis and or blistering (Cobra)

PATIENT ASSESSMENT PHASE ON ARRIVAL

Descending paralysis, initially of muscles innervated by the cranial nerves, commencing with ptosis, diplopia or ophthalmoplegia. The patient complains of difficulty in focusing and the eye lids feel heavy.

DIAGNOSIS PHASE – SYMPTOMS

Dysphagia, dysguesia involvement of sense of smell, diaphoresis. Circum oral pallor and paraesthesia, profound thirst, miosis, abdominal pain, vomiting, painful lymphadenopathy, palpitation, breathlessness, chest pain, Paralysis of jaw and tongue may lead to upper air way obstruction and aspiration of pooled secretions because of the patients inability to swallow.

Deal with any life threatening symptoms on presentation i.e. Airway, breathing and circulation. If there is evidence of a bite, where the skin has been broken, give Tetanus toxoid.

Hemostatic abnormalities are prima facie evidence of a viper bite. Cobras & Krait do not cause haemostatic disturbances. All the vipers can cause renal failure.

Russell’s Viper can also manifest neurotoxic symptoms in a wide area of India, especially southern India. This can sometimes cause confusion and further work is necessary to establish how wide this area might be. The neurotoxic symptoms of Russell’s Viper are believed to be presynaptic or krait like in nature.

GENERAL SIGNS & SYMPTOMS OF VIPERIDAE ENVENOMATION

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Local pain & swelling and erythema over bitten part., Tender enlargement of local lymph nodes, Local necrosis and or blistering, Vomiting, abdominal pain The victim may bleed from any orifice or organ, hemoptysis, epistaxis, hematuria, hematemesis

Bulbar paralysis and respiratory failure. Paradoxical respiration, as a result of the intercostal muscles becoming paralysed is a frequent sign.

Hypoxia due to inadequate ventilation can cause cyanosis, altered sensorium and coma.

Stomach pain which may suggest haemorrhage in the stomach (Krait).

submucosal

Krait bite often present in the early morning with paralysis that can be mistaken for a stroke.

LATE ONSET ENVENOMING

The patient should be kept under close observation for at least 24 hours. Many species, particularly, the Krait and the Hump nosed pit viper are known for the length of

TOXICOLOGY

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Fig. 1 : 20 min Whole blood clotting test (20 min WBCT) time it can take for symptoms to manifest. Often this can take between 6 to 12 hours. Late onset envenoming is a well documented occurance.

This is also particularly pertinent at the start of the rainy season when snakes generally give birth to their young.

Juvenile snakes 8 to 10 inches long, tend to bite the victim lower down on the foot in the hard tissue area and thus any signs of envenomation can take much longer to appear.

In the case of a cobra bite there is very little pain at the bite site immediately after bite. But if a lethal dose has been injected, slight local pain develops after about eight to 30 minutes. There may be very little swelling at the bite site.

BITE BY SEA SNAKE

The bite is usually painless and may go unnoticed. There is minimal or no local swelling and involvement of local lymph node is unusual. Generalised rhabdomyolysis is the dominant effect of envenoming by these snakes. Early symptoms include headache, a thick feeling of the tongue, thirst, sweating and vomiting, generalised aching,trismus, stiffness and tenderness of the muscles become noticeable between 30 minutes to 3½ hours after the bite. progressive flaccid paralysis with ptosis occur. The patient remains conscious until the respiratory muscles are sufficiently affected to cause respiratory failure.

Myoglobinemia and myoglobinuria develop 3 to 8 hours after the bite. Myoglobin and potassium released from damaged skeletal muscles may cause acute kidney injury.

INVESTIGATION

clotting mechanism. The use of plastic bottles, tubes or syringes will give false readings and should not be used.

The glass vessel should be left undisturbed for 20 minutes and then gently tilted, not shaken. If the blood is still liquid then the patient has incoagulable blood. The test tube must not have been washed with detergent as this will inhibit the contact element of the clotting mechanism.

The test should be carried out every 30 minutes from admission for three hours. If everything is normal, repeated at one hour interval till six hours after bite and twice more at 3 hour intervals the next 6 hours. If all reports are normal, no further triage would be needed. A normal 20 WBCT and clot lysis would exclude viperidae species. But it occasionally happens that the parameters become abnormal only 24 hours after the bite especially in pit viper bites.

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Simultaneously, a single breath counting test is done in suspected elapidae bites and the same is repeated at 15 minutes interval over the first 2 hours.

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The onset of symptoms and sudden progression are more common with Elapidae bite rather than viperidae. Most sea snake, krait and cobra bite would show symptoms within the first 6 hours, the shortest time frame being for the sea snakes.

Similarly, the mortality due to elapidae bites are mostly in the first 24 hours. The likelihood of a “dry bite” from among the “big four” is most with a cobra.

OTHER USEFUL TESTS

20 minute whole blood clotting test (20 WBCT) considered the most reliable test of coagulation in hematotoxic bite and can be carried out at the bedside without special training. It is significantly superior to the capillary tube method (Figure 1).

Haematological: Hemoglobin, PCV, TLC, DLC, ESR, Peripheral smear (Figure 2). Platelet count- which is repeated 6 hourly the first 24 hours in viperidae bite.

A few milliliters of fresh venous blood is placed in a new, clean, dry glass test tube and left at ambient temperature for 20 minutes. It is important that the tube is clean, glass and dry as the mechanism under review is the contact

DIC Work up: D. Dimer, FDP, Fibrinogen which are repeated on the third day.

Coagulation Work up: CT, BT, APTT >1.5 ULN, PT >1.5 ULN

Renal function: Blood urea, Serum creatinine

ANTI-SNAKE VENOM (ASV)

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Anti Snake Venom (ASV) is the mainstay of treatment.

The ASV available in India is polyvalent i.e it is effective against all the four common species; Russells viper common cobra, common krait and saw scaled viper.

There are known species such as the Hump-nosed pit viper (hypnale hypnale) where polyvalent ASV is known to be ineffective. In addition there are regionally specific species such as sachureki’ saw scaled viper (Echis carinatus Sachureki) in Rajasthan, where the effectiveness of polyvalent ASV may be questionable.

Fig. 2: Peripheral smear showing schistocytes and burr cells in a patient with hemotoxic snake bite Liver function Tests Muscle Enzymes: Creatinine phosphokinase (CPK) Biochemistry: Na, K and Blood Sugar Urine: Checked for myoglobin, Haemoglobin & Protein Blood group : ABO, Rh (at the earliest as blood doesn’t clot later)

1.

Evidence of Systemic Envenoming

Evidence of coagulopathy: Primarily detected by 20 minute WBCT[whole blood clotting test] PT &APPT or visible spontaneous systemic bleeding from gums etc.

Evidence of Neurotoxicity: Ptosis, external ophthalmoplegia, muscle paralysis, inability to lift head –broken neck sign.

Oxygen saturation/BP/Postural Blood Pressure/PR/RR Arterial Blood gases.

The same may have to be repeated depending on the clinical course of the patient.

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The tests repeated on a daily basis are : Hb, PCV, CBC, urea, creatinine, platelets and urine protein.

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The coagulation work up usually normalizes within 24 to 48 hours of treatment. Exceptions are in cases of certain pit viper species, where it may take up to 2-3 weeks to normalize.

A peripheral smear is also sent for in which crenated RBC, schistocytes (fragmented red cells/ “helmet”cell ) or burr cells are looked for. These suggest systemic envenomation and along with thrombocytopenia are markers for MAHA (microangiopathic haemolytic anaemia).

SNAKE BITE TREATMENT PROTOCOL – TREATMENT PHASE

1.

Managing Pain

Snake bite can often cause severe pain at the bite etc. This can be treated with pain killers such as paracetamol. Mild opiates like Ketorolol 50 mg. can be used orally for relief of severe pain. In cases of severe pain, ketorolol can be given IV.

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Handling tourniquets

Sudden removal can lead to a massive surge of venom leading to neurological paralysis, hypotension due to vasodilation, etc.

* Before removal of the tourniquet, check for the presence of pulse distal to the tourniquet.

OTHER DETERMINANTS ARE

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Cardiovascular abnormalities, hypotension, shock cardiac arrythmia, abnormal ECG.

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Persistent and severe vomiting or abdominal pain.

PREVENTION OF ASV REACTIONS - PROPHYLACTIC REGIME

0.25 – 0.3 mg adrenaline 1 : 1000 given subcutaneously & (deep IM) If the victim has a known sensitivity to ASV pre-medication with adrenaline, hydrocotisone and anti histamine may be advisable, in order to prevent severe reactions.

TEST DOSE OF ASV

Test dose have been shown to have no predictive value in detecting anaphylactoid or late serum reaction and should not be used. These reactions are not IgE mediated but complement activated. They may also pre-sensitise the patient and thereby create greater risk.

ASV DOSAGE

Symptoms and signs being not a useful guide for deciding the degree of envenomation and having no diagnostic methods to determine the level of Venom in blood or tissue, any ASV regimen adopted could only be an estimate.

1 ml. of ASV neutralizes 0.6 mg. of Russel Viper venom, 0.6 mg. of Cobra venom, 0.45 mg. of krait venom, & 0.45 mg. of saw-scaled viper venom.

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ASV ADMINISTRATION CRITERIA

ASV is a scarce, costly commodity and should only be administered when there are definite signs of envenomation. Unbound, free flowing venom, can only be neutralized when it is in the blood stream or tissue fluid. In addition, Anti Snake Venom carries risks of anaphylactic reactions and should not therefore be used unnecessarily.

RUSSELL VIPER

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Russell’s Viper injects on an average 63 mg. (5 to 147 mg. + 7) of venom.

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1 ml. of ASV neutralizes 0.6 mg. of Russells Viper Venom.

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1 vial i.e 10 ml. of ASV neutralises 6 mg. of Russells viper venom.

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The total required dose will be between 100 ml (10 Vial) to 250 ml. Starting with 10 vial ensures sufficient neutralizing power., Starting with 10 vials ensures that there is sufficient neutralizing power to neutralize the average amount of venom injected and during the next 12 hours to neutralize any remaining free flowing venom.

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Start IV Normal Saline with wide bore needle.

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Begin with 10 vials of ASV in 100 ml of Normal Saline and to start with 10-15 drops per minutes for 15 minutes and watch for reactions. If the patient is not having signs and symptoms of anaphylactic shock continue the ASV. All ASV are to be administered over 1 hour period at constant speed.

Continue to monitor the vital signs at 5 minutes interval for first 30 minutes and then at 15 minutes interval for 2 hours.

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REPEAT DOSE IN HAEMATOTOXIC ENVENOMATION

As already explained, initial blood test reveals coagulation abnormality 10 vials of ASV given. No additional ASV until next 6 hours (Liver unable to replace clotting factors in under 6 hours). After initial 6 hours, another 20 WBCT is done. If there is evidence of abnormality of 20 WBCT (continued coagulation disturbance) another 8-10 vials of ASV administered in one hour time. Repeat 20 WBCT and repeat ASV 6 hourly until coagulation is restored, unless a species is identified as one against which polyvalent ASV is not effective. (Usually in majority of cases 20 vial ASV is enough).

NEUROTOXIC ENVENOMATION

Neostigmine is an anti cholinesterase that prolongs the life of acetylcholine and can therefore reverse respiratory failure and neurotoxic symptoms. It is particularly effective for post synaptic neurotoxins such as those of the Cobra. There is some doubt over its usefulness against pre-synaptic neurotoxin such as those of the Krait and the Russells Viper. However it is worth trying in these cases.

NEOSTIGMINE TEST

In the case of neurotoxic envenomation the “Neostigmine Test” will be administered. This test involves administration of 1.5 to 2 mg. of neostigmine IM together with 0.6 mg. of atropine IV. The paediatric neostigmine dose is 0.04 mg/kg IM and the dose of atropine is 0.05 mg/ kg.

The patient should be closely observed for 1 hour to determine if the neostigmine is effective. The following measures are useful objective methods to assess this.

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Single breath count, mm of Iris uncovered (amount covered by the descending eye lid), Inter incisor distance (measured distance between the upper & lower incisors), Length of time upward gaze can be maintained.

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FEV1 or FVC

For example, if single breath count or inter incisor distance is selected, the breath count or distance between the upper and lower incisors are measured and recorded. Every 10 minutes the measurement is repeated. The average blood plasma time for neostigmine is 20 minutes, so by 30 minutes any improvement should be visible by an improvement in the measure.

ASV IN NEUROTOXIC ENVENOMATION:

Treat the patient with 10 vial of ASV initially as in the case of hematotoxic envenomation. If the Neostigmine test is positive, 0.5 mg of Neostigmine IM and 0.6 mg. Atropine IV at half hourly intervals for 5 injection, followed by repeating the same dose at increasing intervals of 2 to12 hours. If there is no improvements in symptoms after 1 hour, Neostigmine should be stopped.

The ASV regime relating to neurotoxic envenomation has caused considerable confusion. If the initial dose has been unsuccessful in reducing the symptoms, or if the symptoms have worsened or if the patient has gone into respiratory failure, then a further dose should be administered, after 1-2 hours. At this point the patient should be re-assessed.

REPEAT DOSE – NEUROTOXIC ENVENOMATION

Initial dose of 10 vials given and if symptoms persist or worsen or in respiratory failure repeat 10 more vials of ASV after 1-2 hours as a second dose and discontinue ASV. 20 vials is the maximum dose of ASV that should be given to a neurotoxically envenomed patient.

Once the patient in respiratory failure, has received 20 vials of ASV and is supported on a ventilator, ASV therapy should be stopped. This recommendation is due to the assumption that all circulating venom would have been neutralized by this point. Therefore, further ASV serves no useful purpose.

Evidence suggests that “reversibility” of post synaptic neurotoxic envenoming is only possible in the first few hours. After that the body recovers by using its own mechanism. Large doses of ASV, over long period, have no benefit in reversing envenomatio No further doses of ASV are required, unless a proven recurrence of envenomation is established. Additional vials to prevent recurrence is not necessary.

ASV IN CHILDREN

Children receive the same ASV dosage as adults. The ASV is targeted at neutrlising the venom. Snake inject the same amount of venom into adults and children.

RECOVERY SIGNS

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RECURRENT ENVENOMATION

In case of neurotoxic envenoming where the victim is evidencing symptoms such as ptosis, respiratory failure etc, it is probably wise to administer one dose of 8 to 10 vials of ASV to ensure that no unbound venom is present.

ASV REACTIONS

If anyaphylaxis is evident, then

When coagulation has been restored no further ASV should be administered, unless proven recurrence of a coagulation abnormality is established. Indian ASV a F(ab)2 product and has a half life of 90 hours and therefore is not required in a prophylactic dose to prevent re envenomation.

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ASV will be discontinued temporarily. 0.5 mg of 1 :1000 adrenaline to be given IM in adults. Children are given 0.01 mg/kg adrenalin IM .

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There is better patient outcome if adrenaline is used early

ANTI HEAMOSTATIC MAXIMUM ASV DOSAGE GUIDANCE

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The normal guidelines are to administer ASV every 6 hours until coagulation has been restored. However, what should the clinician do after say, 30 vials have been administered and the coagulation abnormally persists?

There are a number of questions that should be considered. Firstly, is the envenoming species one for which polyvalent ASV is effective? For example it has been established that envenomation by the Hump nosed Pit Viper (Hypnale Hypnale) does not respond to normal ASV[joseph et al 2007]. This may be a cause as, in the case of Hypnale, coagulopathy can continue upto 3 weeks

ASV IN SPECIAL SITUATION

Victims Requiring Life Saving Surgery

In very rare cases, symptoms may develop which indicate that life saving surgery is required in order to save the victim. An example would be a patient who presents with signs of an intracranial bleed. Before surgery can take place, coagulation must be restored in the victim in order to avoid catastrophic bleeding. In such cases a higher initial dose of ASV is justified (upto 25 vials) solely on the basis on guaranteeing a restoration of coagulation after 6 hours.

POOR PROGNOSTIC INDICATORS IN VIPER BITE

VICTIMS WHO ARRIVE LATE

A frequent problem witnessed in our country is victims who arrive late after the bite, often after several days,

Low Platelets < 20,000/mm3, Polymorphonuclear leucolytosis with presence of band form, crenated RBC, Haemo concentration at presentation – indirectly denotes capillary leak, Raised D – Dimer, low fibrinogen, Low serum protein and albumin, haemoglobinuria, bilateral parotid swelling “Viper Head” appearance, Giddiness, syncope immediately following a snake bite, agitated behaviour – cerebral anoxia, profound thirst.

COMPLICATIONS

Capillary leak syndrome occurs in Viperidae bites due to heamorrhagins degrading the compact proteins of basement membranes, shifting fluid from intravascular to interstitial space.

Hypotension ARDS, acute kidney injury, pitutary insufficiency cardiac and neurological complications and, locked in syndrome in elapid bites are are the important complications.

REFERENCES

1.

Punde DP. Management of snakebite in rural Maharashtra : a 10 year experience. Natl Med J India 2005; 18:71-5.

2.

Mohapatra B, Warrell DA, SuraweeraW, Bhatia P, Dhingra N, Jotkar RM, Rodriguez PS, Mishra K, Whitaker R, Jha P. Million Death Study Collaborators. Snakebite mortality in India: a nationally representative mortality survey. PLoS Negl Trop Dis 2011; 5:e1018.

SNAKE BITE IN PREGNANCY

There is very little definitive data published on the effects of snake bite during pregnancy. Pregnant women are treated in exactly the same way as other victims.

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3. Joseph K Joseph; Viperidae envenomation in IndiaHandbook of Toxinology, Springer 2014.

4.

Joseph J K, Simpson ID et al, First Authenticated cases of life threatening envenoming by humpnosed pit viper in India- Trans R . Soc Trop Med Hyg 2007; 101:85-90.

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Spontaneous systemic bleeding such as gum bleeding, bleeding from venepuncture sites etc. usually stops within 15 to 30 minutes. Blood coagulability is usually restored in 6 hours. Postsynaptic neurotoxic envenoming such as the Cobra may begin to improve as early as 30 minutes after ASV. Pre-synaptic neurotoxic envenoming such as the krait usually takes a considerable time to improve. Active hemolysis and Rhabdomyolysis may cease within few hours and urine return to its normal colour. In patient with shock, blood pressure may increase after 30 minutes.

usually with acute renal failure. The key determining factor to decide on ASV treatment is to look for signs of current venom activity venom can only be neutralized if it is unattached. Perform a 20 WBCT and determine if any coagulatopathy is present. If coagulopathy is present administer ASV. If no coagulopathy is evident treat renal failure.

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One of the boons of modern civilisation is Stress, physical, mental, emotional or financial. Chinese, though competing with U.S.A in all fields have incurred a tenfold increase in rate of mental illnesses & suicides, equating with Japanese in the latter. Similarly around2 million poison exposure cases occurred in USA in 1995 with children less than 6years accounting for 53% of these, although with only 2.8% of fatalities. In adults more often than not the poisoning is intentional(homicidal or suicidal) hence always accompanied by a larger dose and delayed information to attendants with an increased mortality in contrast to children where it is unintentional/accidental hence. with reduced mortality.1 Even in pregnant females there are more than 7000 poisoning exposures yearly.

In our Indian set-up also suicidal poisoning a domain of females in the past is equally increasing in young adolescents1 & past middle-aged males. The means &ways of poison ingestion have also undergone a sea of change from copper sulphate3(the blue Vitriol), ratti, cannabis, organophosphates & Cellphos4 as the common suicidal varieties and marking nut, dhatura and alcohol5 mixed with barbiturates as the common homicidal varieties to opiates, benzodiazepines, cyclic antidepressants, Hashish, heroin& calcium channel blockers to insulins.

The word Poison is derived from Fr. Gr. “Potion” that is a substance that produces harmful, toxic effects in one draught only i.e. in minimal amounts, because we know that ”in excess every good thing is bad” There is reference of poisoning in B.C. era (300 B.C) of poisoning in Greece. There have been reports of wide spread use of opium smoking in China and near East, causing harm for centuries.

In the United States of America even today the 0.14% annual prevalence of heroin dependence is only 1/3rd the rate of prescription opiate abuse, representing only the tip of an Iceberg. Similarly the 2% role of morphine dependence in South East and South West Asia represents only a partial data and though apparently low as compared to other abused substances their disease burden is substantial, with high rates of morbidity and mortality, disease transmission, increased healthcare, crime and law enforcement cost and less tangible cost of family disturbances and loss of productivity. The fashion today is one of polydrug use involving alcohol, sedatives, opiates, cannabinoids and stimulants, by way of smoking, oral ingestion, I/v ingestion, inhalation or skin patches thereby increasing the chance of transmission of diseases like hepatitis B, AIDS and other communicable diseases.

Unknown Poisoning Viny Rampal, Vinod Mitla, S S Jamwal

At the same time these produce complications like meningitis, osteomyelitis and abscesses in various organs, which are dangerous and difficult and costly to treat2.

In India usually a patient of poisoning is brought to hospital after all the means of self treatment, ranging from whodwho, Ojha, local quack have been exhausted (from fear of police and society) hence rarely is the victim in original shape of poisoning or conscious enough to narrate the reality, hence more often than not, most of the cases present as one of unknown poisoning putting to test your clinical acumen, general knowledge about the patient and the area he is from and the condition of his attendants. In some of the cases the emanating odour, the physical signs and the history given by the attendants may give a partial lead. Our approach in managing a patient of suspected toxic Ingestion has always been to give an immediate physical assessment and to address the ABC of resuscitation (airway,breathing and respiration) without delay and to concentrate on the History under following “Five Ws”: !)who ----- the patients age, -weight, relationship to others present and gender; !!)what ----the name and dosage of medication (s) or substances of abuse, coingestants and amount ingested;!!!) when --- the time and date of ingestion; !v) where ---both the route of poisoning (e.g., ingestion or injection) and the geographic location where the poisoning occurred, and V) why ---whether intentional or unintentional, and associated details. In addition, a detailed past medical history should be obtained, including previous poisonings, medical conditions and concurrent medications that might affect the patent’s response to and metabolism or elimination of ingestants, psychiatric history and history of substance abuse. Particular attention should be devoted to eliciting a history of alcoholism, and renal or hepatic disease.

Clinicians should attempt to obtain this information in all cases, even for apparently minor ingestions5,6.

ASSESSMENT AND STABILIZATION

Emergency Assessment

A brief physical assessment should be performed immediately in all patients to determine the effects of toxin (s) and other conditions that might be present.

Particular attention should be directed to adequacy of the airway and ventilation, level of mental status and cardiac function. Unstable patients should be placed on a cardiac monitor, with measurement of vital signs every five to 15 minutes until the patent is stabilized to the point that monitoring is no longer necessary.

INITIAL STABILIZATION PROCEDURES

Stabilisation of the patient is the first priority in managing toxic ingestions and is performed simultaneously with the initial physical assessment. Treatment should address the “ABCs” (airway, breathing, circulation) without delay. Also, the potential for rapid changes in the patent’s condition should be considered in making decisions about airway and ventilatory support. Treatment with naloxone (Narca), dextrose and thiamine should be considered in patients with altered mental status naloxone is a competitive antagonist at opiate receptors and can reverse narcotic-induced symptoms when given intravenously, intramuscularly, endotracheally, subcutaneously or intralingually. Successful submental administration of naloxone has also been reported. 5 Naloxone can safely be given to patients with respiratory and/or CNS depression who have a low likelihood of opioid addiction. Because of concern about withdrawal symptoms and/or unmasking symptoms from coingestants, caution is indicated in cases of suspected opioid addiction and multi- drug poisonings-3. Naloxone is administered to adults for treatment of respiratory depression in a dosage of 2.0 mg initially, repeated every two minutes as needed up to a total of 10 mg; in narcotic dependent patients or those with non-life threatening symptoms, the dosage is 0.1 mg initially, doubled every two minutes up to a total of 10 mg; in children older than five years of age or weighing more than 20 kg, the dosage is 2.0 mg initially for patients with respiratory depression and 0.1 to 0.8 mg if respiratory depression is not present, in neonates and young children, the initial dosage is 0.1 mg per kg2,6.

Symptoms of hypoglycemia (e,g, altered mental status, cool, clammy skin, coma) are rapidly reversed with administration of hypertonic dextrose. Patients with altered mental status, absent focal neurologic signs and low or borderline hypoglycemia (blood sugar less than 80 mg per dL on rapid reagent testing) should receive intravenous dextrose (adults: 50 mL of 50% dextrose; children: 4 mL per kg of 25% dextrose; neonates: 5 mL per kg of 10% dextrose) Dextrose may be administered empirically if rapid reagent testing is not available. The safety of hypertonic dextrose in settings of cerebral ischemia has been questioned and, whenever feasible, bedside documentation of hypoglycemia should be obtained before administering dextrose.

In case where intravenous access is difficult, glucagon 1.0 mg intramuscularly, may be given as a temporizing measure. Intravenous thiamine (vitamin B1) should be given to patients treated with hypertonic dextrose (adults: 100 mg; children: 10 to 25 mg), theoretically before the dextrose is administered, to prevent Wernicke’s encephalopathy6.

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DETERMINATION OF INGESTED SUBSTANCE

Physical findings may suggest the type of toxin (s) ingested but, more often, a detailed history, examination of medication containers or toxocologic analysis reveals the answer. Physical findings, however, often enable the clinician to determine if the toxin is a physiologic stimulant or a depressant, and which common poisons should be considered in the initial management of the patient.

Physical signs following ingestion of stimulants often include mydriasis (dilated pupils), tremor, tachycardia, irritability, diaphoresis, mania, convulsions and tachyarrhythmias. Commonly ingested stimulants include cocaine, amphetamine caffeine, theophylline, tricyclic antidepressants (early symptoms after overdose), antihistaminics and hallucinogens.

Physical findings produced by physiologic depressants include lethargy, decreased responsiveness to verbal and physical stimulation, miosis (constricted pupils), hypothermia and coma. Common sedative-hypnotics include alcohol, benzodiazepines, barbiturates, opiates, muscle relaxants and chloral hydrate.

Cardiovascular agents include antihypotensive agents (angiotensin-converting enzyme inhibitors, beta blockers, calcium channel blockers and centrally acting agents), digitalis, nitrites and antiarrhythmic agents.

LABORATORY EVALUATION

Laboratory evaluation is indicated in most symptomatic patients, when ingested substances are unknown, if the poison has the potential to produce moderate to severe toxicity and if the ingestion was intentional. Routine studies should include a complete blood cell count, determination of serum electrolyte and glucose levels, a chemical screen with hepatic and renal function studies (e.g., calcium, aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, lactate dehydrogenase, prothrombin time, blood urea nitrogen, creatinine) and urinalysis. Measurement of serum osmolarity may be helpful if poisoning with methanol, ethylene glycol or isopropanol is suspected.

Drug screening has limited value because care in most cases of toxic ingestion is supportive and not affected by identification of the ingestant. However, drug screening is a common practice in many medical settings where poisonings are managed and can provide useful information. Qualitative toxicology screening is most useful when the ingested toxin in unknown, in cases of multiple ingestion and when symptoms and physical findings are not compatible with the history. Quantitative

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The initial assessment is especially important in patients with decreased responsiveness and unstable vital signs because, for example, head trauma or penetrating body trauma can masquerade as an overdose. Evidence of head injury, penetrating wounds or chemical burns of the mouth and face mandate specific valuation and management strategies and should not be missed.

Focal neurologic signs are suggestive of central nervous system (CNS) vascular events, including cerebrovascular accidents, neurotoxic snake bite poisoning and subdural hematoma. A more detailed physical assessment should be performed after the patient’s cardiopulmonary status has been stabilized2,6.

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toxicology screening is useful when knowledge of drug serum levels may affect patient management; examples include ingestions of acetaminophen, salicylates, ethanol, ethylene glycol, isopropyl alcohol, digoxin, iron, lithium, theophylline, anticonvulsants and methanol.

TOXICOLOGY

ANCILLARY TESTS

An electrocardiogram should be performed in patients with arrhythmias and/or suspected ingestion of cardiotoxic drugs. Chest radiographs should be obtained in patients with suspected aspiration, coma or ingestion of medications (salicylates, narcotics, paraquat, sedativehypnotics) than can produce noncardiogenic pulmonary edema. Abdominal radiographs may detect abnormal densities in patients who have ingested drug packets, salicylates, calcium salts, heavy metals (e.g., iron tablets) or radiopaque foreign bodies. Ingested hydrocarbons may be visualized as a “layer” between gastric fluid and the gastric air bubble.

Ancillary tests such as electrocardiograms, chest radiographs and plain abdominal films need not be routinely ordered but, when appropriate, can provide the clinician with additional useful information.

DECONTAMINATION

is indicated after ingestion of hydrocarbon products containing benzene, toluene, camphor, halogenated hydrocarbon pesticides or heavy metals, or if the ingestion was greater than 4 to 5 mL per kg); patients with depressed gag reflexes who are not intubated and clinically insignificant ingestions. Complications include aspiration, and perforation of the esophageus or bronchus.

A 28- to 36-in French tube is suitable for use in children; a 36- to 40-in French tube is suitable for use in adults.

Gastric lavage is accomplished in children using normal saline or tap water in 15 Ml per kg aliquots until clear.

Lavage in adults uses 300 ml aliquots until clear, up to 10 to 20 L, if necessary. Administration of activated charcoal through the lavage tube before and after lavage may be beneficial in patients with potential fatal ingestions.

IPECAC

Ipecac continues to be useful in management of alert patients unable to travel to a health care facility within one hour of ingestion. It has been shown that ipecac used at home by experienced hospital staff treating paediatric poisonings following ingestions identified as not being “high-risk” decreases paediatric emergency department visits without jeopardizing safety.

Following evaluation and stabilization of the poisoned patient, attention is directed toward decontamination, i.e., decreasing absorption of the ingested poison from the gastrointestinal tract. This can be accomplished by emptying the stomach via gastric lavage, administration of activated charcoal within the gut lumen and use of methods for increasing transit of the toxic substances through the gastrointestinal tract.

Syrup of ipecac is administered in the following dosages: in infants six months to one year of age, 10 mL; in children one to 12 years age, 15 mL; in adolescents over 12 years of age, 30 mL. Water is given immediately after ipecac to enhance the efficacy of gastric emptying with emesis; adults should receive 8 to 16 oz; children should receive 4 to 8 oz; children less than one year of age should receive 5 to 15 mL per /kg body weight.

Gastric emptying should not routinely be used in all oral poisoning cases because it is ineffective when used at a late stage, may delay more effective interventions and can cause needless complications, such as aspiration. However, it is often beneficial when used early in the treatment of potentially severe poisonings. Gastric emptying is most effective when used within one hour of the ingestion and cannot be justified beyond four hours following the ingestion except in patients with concretions, massive ingestions or ingestions of substances that markedly decrease gastric motility. The stomach may be emptied by gastric lavage or by inducing emesis with syrup of ipecac.

Ipecac should not be given children who are less than six months of age, patients who are already vomiting, patients with altered mental state or impaired gag reflexes, and patients who have ingested medications that cause seizures or decreased responsiveness. Use of ipecac should be avoided following ingestion of corrosive (acids or alkalis), sharp objects, most hydrocarbons (similar to gastric lavage) or when treatment with activated charcoal is anticipated within 60 to 90 minutes.

GASTRIC LAVAGE

In most situations, gastric lavage is preferable to administration of ipecac, particularly in emergency departments where prolonged ipecac induced vomiting may delay treatment with activated charcoal. Indications for lavage include ingestion of highly toxic substances (large ingestions or substances associated with high morbidity and mortality); substances not well adsorbed by activated charcoal (i.e., lithium, iron, lead, and methanol) and in patients with the potential for a jeopardized airway (e.g., altered alertness).

Contraindications to gastric lavage include ingestion of corrosives and most hydrocarbons (gastric emptying

ACTIVATED CHARCOAL

Activated charcoal forms the mainstay of gastric decontamination and is effective for most oral poisonings when given alone or following gastric emptying.

Exceptions include ingestions of caustic acids and alkalis, alcohols, lithium and heavy metals (e.g., iron, arsenic). Activated charcoal is inert and remains within the gastrointestinal tract, offering a large surface area for adsorption of ingested toxins. In addition activated charcoal may decrease the absorption of drugs that undergo enterogastric or enterohepatic circulation.

The usual dosage is 1 to 2 g per kg for children and adults, usually given as a single dose combined with a cathartic.

The charcoal is mixed with water in a ratio of 1:4 to 1:8 (1 part charcoal to 4 or 8 parts water) to form a slurry; small quantities of fruit juice or chocolate powder can improve

the taste. Multiple dosing (1 g per kg every two to six hours) had been shown to be effective for poisonings with phenobarbital, phenytoin, carbamazepine. Salicylates, digitalis, theophylline and dapsone. When multiple dosing is used, a cathartic can be given with the first dose but should not be administered with subsequent doses to prevent serious fluid and electrolyte imbalances.Use of activated charcoal is contraindicated in mechanical obstruction and ileus.6,7

WHOLE BOWEL IRRIGATION

METHANOL POISONING

Also known as wood alcohol poisoning,moonshine and Hooch-poisoning is a very common type of tragedy usually occuring in slums, rural areas and in places of illicit distillation.The poisoning is almost entirely to its ingestion as a substitute for ethanol or to the drinking of denatured ethyl alcohol. Methanol is oxidized in the body to formaldehyde and formic acid and the enzyme alcohol dehydrogenase appears to be responsible for first step in oxidation. The accumulation of toxic metabolites of methanol damage the optic nerve and retina. Accumulation of formic acid as also the inhibitory effect of formate on oxidation of carbohydrates, results in severe acidosis, manifestations of poisoning, usually occuring 12-24 hrs after ingestion usually include nausea, vomiting, severe abdominal pain,vasomotor disturbances, CNS depression, respiratory failure and visual disturbances,ranging from mild blurring of vision to total blindness,due to toxic optic neuropathy, which may progress to optic atrophy. Serious poisoning also causes severe acidosis with a wide anion gap. For efficient management of acute poisoning gastric lavage is useful only if performed within first hour or two. The specific treatment involve alcohol dehydrogenases, institution of a saline or osmotic diuresis, thiamine and pyridoxine supplements, fomepizole or ethanol and hemodialysis The intravenous administration of alcohol dehydrogenase inhibitor fomepizole (15mg/kg as a loading dose) or ethanol intravenously to achieve a level of 22mmol /L (100mg/dL serves to lessen the toxicity by competing with methanol for metabolism by alcohol dehydrogenase. I/V methyl prednisolone and retrobulbar triamcinolone have shown recovery in visual salvage. Fomepizole though costly is a better agent as it does not produce excessive obtundation caused by ethanol. 5,910

Commonly used both in peace and war as euphoric, analgesics and somniferent since ages. The hero of Odyssey also used Nepenthe free from sorrow) during war. In U.S.A alone around 9,000 adolescents become opiate abusers everyday and not through drug dealers but through the family members the most common presenting poisonings symptoms include shallow and slow respiration, pupillary miosis, bradycardia, hypothermia and stupor and coma. Usually the patients is a chronic addict belonging to all strata of society and usually a history is elicited which is. helpful inmanaging the patient. The specific treatment in addition to ABC (vide-supra) involves.

Naloxone (an opiate antagonist) 0.4—2 mg IV Or IM, with an expected response within 1 to 2 minutes and if the overdose is due to buprenorphine 10 mg or more naloxnie and if this does thus not produce the desired effect then another cause of toxicity, poly drug ingestion should be suspected, like benzodiazepines and an additional dose of flumazenil at 0.2 mg/ minute can be given to a maximum of 3gm/hr, but it may precipitate seizures and increase inctranial pressure. Like naloxone, administration for a prolonged period in usually required since most bezodiazepines remain active for considerably longer than flumazenil. Support of vital functions includes oxygen and positive pressure breathing, IV fluids, pressor agents for hypotension and cardiac monitoring to detect QT prolongation, which might require treatment.

1.

For detoxification of opiate withdrawal methadone dose tapering regimens (from 60 to 70 mg daily, usually even upto 150 mg daily) range from 2 to 3 weeks to as long as 180 days. Buprenorphine, a partial agonist of morphine allows a shorter detoxification period compared to methadone and is superior to alpha – 2 –adrenergic agonist clonidine.

2.

Medication- free- treatment, these may be carried out in inpatient, residential or outpatient setting but 1 to 5 years outcome are very poor and involve the coordination of physician, a counsellor and detoxification expert.7,11

COCAINE AND OTHER PSYCHO- STIMULANT DRUGS

Derived from the leaves of coca plant (Erythroxylon coca) cocaine is a stimulant and a local anaesthetic with potent vasoconstrictor properties and produces physiologic and behavioural effects when administered orally, intranasally, intravenously are via inhalation during smoking (pyrolysis) the reinforcing effects appear to be related to activation of dopaminergic neurons in the mesolimbic system. It is widely abuse all the world over and in all strata of society commonly abused as a polydrug. Cocaine produces abrief dose related stimulation & enhancement of mood and an increase in cardia rate and blood pressure,there is significant rise in body temperature and high doses are associated with lethal pyrexia or hypertension. In addition to

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Since most often the patient is brought in an unconscious state and in most of the poisonings the laboratory assessment may not come to our rescue hence again it is only the clinical knowledge which will be beneficial in light of the signs and symptoms of the patients. The involvement of various systems will be a pointer to the poison involved e.g. unconsciousness, stupor or convulsions in case of opiate poisoning are cannabis poisonings and tachycarhia, hypertension, arrhythmias and pulmonary edemia in cases of stimulants like amphetamine etc. Hence a brief description of signs and symptoms along with management is rendered as below.

OPIATE POISONINGS

TOXICOLOGY

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generalized seizures neurologic complications may include headache, ischemic or hemorrhagic stroke, or subarachnoid hemorrhage with death from respiratory depression cardiac arrhythmias and convulsions. Hepatic necrosis may also occur along with paranoid ideation and visual and auditory hallucinations that resemble alcoholic hallucinosis. The disorders of cerebral blood flow and perfusion in these patients can be detected with magnetic resonance spectroscopy studies. Coca-ethylene a metabolite of cocaine can be detected in blood and urine. Although people may use it for euphoria and as an aphrodiasic, its long term use is associated with loss of libido, impotence and gynecomastia in males and in females derangement of menstrual cycle, galactorrhea, amenorrhea and infertility. In pregnant women cocaine abuse is instrumental in producing congenital malformations in the foetus and perinatal cardiovascular and cerebrovascular disease in the mother9,11. Treatment of cocaine overdose characterised by an hyper adrenergic state (vide-supra) is an emergency, to be managed in an intensive care unit. For control of seizures I/V diazepam in doses upto 0.5mg/kg administered over an 8 hr period has proven to be effective and for ventricular arrhythmias o.5 to 1mg of propanolol has shown success. In case the desired response is still not achieved a multydrug toxicity should be suspected, especially heroin and managed accordlngly.treatment of chronic cocaine abuse is a long process,requiring the coordination of a physician, a psychiatrist and a psychosocial care taker2,13.

Marijuana and cannabis compounds: In India these are obtained from cannabis indica (Bhang) which in addition to the psycho active substance,delta-9tetrahydrocannibanol (THC) contains many other toxic compounds. Marijuana is obtained from the concentrate of its leaves and flowering tops. Hashish is prepared from concentrated resin of C.indica and contains a THC concentration of between 8-12mgm% by wt. Smoking is the most common route of use as marijuana and being cheap is most popular among adolescents. Acute intoxication produces a feeling of relaxation and euphoria akin to alcohol intoxication and is accompanied by some impairment in thinking, concentration and perceptual and psychomotor function. Physical effects primarily include conjunctival injection and tachycardia, but angina may be precipitated in patients with a history of coronary insufficiency. Decreased sperm count and motility besides other morphological abnormalities of spermatozoa have been detected in chronic marijuana smokers in addition to chronic bronchial irritation. Therapeutic uses in the form of synthetic oral cannabinol (dronabinol) include as anti-emetic in patients of chemotherapy as an appetiser in AIDS patients for reduction of intraocular pressure in glaucoma and for reduction of spasticity in multiple sclerosis and other neurologic disorders13,14.

Methamphetamine: Famous as Meth, Speed, Chalk, Crank, Ice, Glass or Crystal is second only to cocaine abuse as threat to the society involving young adults (1825 years). It is consumed in the form of smoking, snorting, I/V injections or oral administration, resulting in euphoria

and decreased fatigue. Adverse effects include, headache, difficulty in concentrating, diminished apetite, abdominal pain, vomiting or diarrhoea, disordered sleep, paranoid or aggressive behaviour and psychosis.

Severe toxicity involves, hypertension, cardiac arrhythimias, or cardiac failure, sub-arachnoid hemmorrhage, ischemic stroke, intracerebral hemmorrhage, convulsions or coma. The magnetic resonance spectroscopic studies show neuronal damage in the frontal areas and basal ganglia.

The treatment is symptomatic involving use of ammonium chloride for acidification of urine and to enhance clearance of the drug. For hypertension sodium nitroprusside or a-adrenergic antagonists are used. Sedatives may be used for reduction of agitation and other signs of central nervous system hyperactivity. Chronic dependence may be treated similar to those described for cocaine abuse. Ecstasy or MDMA (3,4-methylenedioxymethamphetamine) is a derivative of methamphetamine, usually taken orally but may be injected or inhaled. Its effects last for 3 to 6 hrs. and in addition to amphetamine like effects it can induce hyperthermia and vivid hallucinations and other perceptual distortions6,13.

Lysergic Acid Diethylmide (LSD) : A very potent hallucinogen, even in 20 micro gm oral doses induces profound psychological and physiologic effects, within minutes tachycardia, hypertension pupillary dilation, tremor and hyperpyrexia occur. A variety of bizarre and often conflicting perceptual and mood changes, including visual illusions, synesthesias and extreme lability of mood, usually occur within 30 minutes after LSD in take and may last for 12 to 18 hrs. Even though the half life of the drug is only three hours.

The most frequent acute medical emergency caused by LSD use is a panic episode (the “ Bad trip” which may persist up to 24 hrs and is best managed by supportive reassurance (“talking down”) and if need be by administration of small doses of anxiolytic drugs. Its chronic use makes one prone towards enhanced risk for schizophreniform psychosis and derangements in memory function, problem solving and abstract thinking.

All these are amenable to psychiatric treatment.

Phencyclidine (PCP) : A cyclohexylamine derivative, widely used in veterinary medicine to briefly immobilize large animals is also sometimes used as a dissociative anesthetic. It is easily synthesized and primarily young people and polydrug users are its ictims. It is used orally, by smoking, by snorting or by IV injection, and also as an adulterant in THC, LSD, amphetamine or cocaine, the commonest street preparation is “angeldust”. Low doses (5 mg) produce agitation, excitement, impaired motor coordination, dysarthria and analgesia. However toxicity produces horizontal or vertical nystagmus, flushing, diaphoresis and hyperacusis. The behavioural changes include distortions of body image, disorganization of thinking and feelings of estrangement. Higher doses of PCP (5 to 10 mg) may produce salivation, vomiting,

myoclonus, fever, stuper, or coma. Still higher doses of ten mg or more case convulsions, opisthotonos, and decerebrate posturing which may be followed by prolonged coma.

REFERENCES

1.

Johnston LD et al: Monitoring the Future: National Results on adolescent Drug Use: Overview of Key Findings 2008.

Bethesda, Maryland, National Institute on Drug Abuse, 2008.

2.

Lowinson JH et al (eds): Substance Abuse: A comprehensive Textbook. Baltimore, Williams & Wilkins, 2005

3.

Wahal P.K. and Mahashwar B.B. “Common poisonings in India” in Ahuja M.M.S. editor Progress in Clinical Medicine in India series four Arnold Heinemann publishers New Delhi India 1994 591-624.

Singh Surjeet in Aluminium phosphide poisoning Agarwal A.K. editor Medicine Update 2009 Part-I published by association of physicians of India. 444-447

5.

Shah Sandip, Pandey, Vikas, Thakore Nilay, Mehta Nellesh.

Study of 63 cases of Methyl Alcohol Poisoning (Hooch Tragedy in Ahmedabad) Journal Association physicians of India 2012; 60:34-37.

6.

Larsen Lars C. in Oral Poisonings: Guidelines for Initial Evaluation and Treatment. A Treatise on poisoning, East Carolina university School of Medicine, Greenville.

7. Principles of drug addiction Treatment: A Reserch- Based Guide, 2nd ed. National Institute on Drug Abuse, NIH publication No. 09-4180, US. Department of Health and Human Services, 2009.

8. Ries R et al (eds): Principles of Addiction Medicine, 4th addition Philadelphia, Lippincott Williams & Wilkins, 2009.

9. Dubose,Thomas D,Jr. Acidosis and Alkalosis:Kasper Dennis L, Fauci Anthony S, Hauser Stephen L, Longo Dan L, Jameson J Larry and Loscalzo Joseph editors.Harrisons Principles of Internal Medicine 19thy Edition, New York :Mcgraw Hill 2016.

10.

Shukla M, Shiroh I,Saleem A:Intravenous Methylprednisolone could salvage vision in Methylalcohol Poisoning. Indian J Opthalmol 2006; 54:68-69 11. Brady DT et al (eds): Women & Addiction: A comprehencive handbook. New York, Gilford Press, 2009.

12. Kosten Thomas R. in Opioid Drug Abuse and Dependence in Longo Dan L., Kasper Dennis L., Jameson J. Larry, Fauci Anthony S. et.al,editors. Harrison’s principles of intenal medicine 18th Edition New York : McGraw Hill, 2012.

13. Mello Nancy K. and Mendelson Jack H. Cocaine and other commonly abused drugs : Longo Dan L., Kasper Dennis L., Jameson J. Larry, Fauci Anthony S. et.al,editors. Harrison’s principles of intenal medicine 18th Edition New York : McGraw Hill, 2012.

14. Mello NK, Mendelson JH: Cocaine, hormones and behaviour: Clinical and preclinical studies, in Hormones, Brain and Behavior, 2nd ed, DW Pfaff et al (eds). San Diego, Academic Press 2009, pp 3081-3139.

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Since the initial symptoms of PCP overdose (anxiety, paranoia, delusions, hallucinations) may mimic an acute schizophrenic reaction hence the clinical diagnosis is difficult however it can be confirmed by determination of PCP levels in serum or urine because it remains in urine for 1 to 5 days following high dose in take. The treatment requires life support measures, including treatment of coma convulsions and respiratory depression in an intensive care unit. Although there is no specific antidote for PCP, its excretion from the body can be enhanced by gastric labage and acidification of urine (vide-supra). Death usually occurs because of aspiration, hyperthermia, respiratory depression, severe hypertension, seizures, hypertensive encephalopathy and intracerebral hemorrhage. Acute psychosis because of PSP is a psychiatric emergency, because the patient may be at a high risk for suicide or violence towards others and is successfully managed by haloperidol (5mg IM) on an hourly basis to induce suppression of psychotic behaviour. Chronic PCP use induces insomnia, anorexia, severe social and behavioural changes and even chronic schizophrenia7,13.

4.