TREATMENT OF POISONING

TREATMENT OF POISONING

            Poisoning and deaths due to poisoning are on the rise over the years, despite advanced knowledge regarding their pharmacokinetics and pathology, and newer and better techniques being developed for the management of poisoning cases.

            The symptoms of poisoning can vary greatly depending on the type, length, quantity and age of the person involved.

            Poisoning occurs infrequently, but it is often life-threatening. So treatment of toxicity is very important to save the life of the animals. It should start as soon as possible because any delay may cause irreparable damage to the animal. Treatment of poisoning differs from treatment of other diseases, being all the cases as emergency cases. In addition to the replacement therapy, supportive therapy or symptomatic therapy, we have specific antidotes to the poisons. For majority of the poisoning cases treatment with an antidote is not possible. Instead, prompt medical intervention to improve the condition of the animal and ensure its survival. These practices focus on promoting the removal of the poison or neutralizing it, whilst maintaining the vital functions of the animal.

            The outcome of in vivo toxicity cases is dependent on two variables: The delivery of the toxicant to the site of action and the activity of the toxicant at the site of action. The delivery of the chemical to the site of action depends on the processes of absorption from the site of administration into the general circulation, and distribution via the blood to the site of action and body tissues. The toxic response is produced, if the toxicant is present above its threshold level at its site of action. The concentration present at the site of action and duration of exposure of a toxicant further depends on the rate of its elimination from the body.

            On the basis of various toxicodynamic and toxicokinetic parameters, treatment of toxicosis should be aimed at following points:

1. To decrease the absorption and distribution of toxicant.
2. To increase the threshold level of toxicity.
3. To increase the excretion of toxicant from the body.
4. To Decrease the Absorption and Distribution of Toxicant.

            By decreasing the absorption of a toxicant and its distribution in the body, we decrease its concentration in the body and delay its onset of action. Absorption and distribution of a toxicant in the body can be altered in following ways:

            The general principles of management of poisoning cases, as we know are:

1. Stabilization – which includes assessment and management of a) the airway and breathing, b) circulation and c) Depression of the CNS.
2. Evaluation, if the patient is already stable.
3. Decontamination – including skin / eye, gut, intestine, etc.
4. Poison elimination – dieresis, dialysis, haemoperfusion, etc.
5. Antidote administration – As of now, antidotes are available for < 5% poisons.
6. Nursing care.

By Influencing the Rate of Absorption of Toxicant

Non-specific treatment: By using some general or non-specific agents/measures, we can decrease the absorption of toxicant from its site of administration or application.

Emesis: Emesis is useful in recently ingested toxicant in monogastric animals. Emetics are useful in first 2 hours after ingestion of a toxicant and are of limited importance more than 4 hours after ingestion. Emetics should be used in non­corrosive poisoning only. These are contra-indicated for cor­rosive toxicants (caustics or hydrocarbons), in unconscious animals or with convulsions, coma or severe respiratory distress or where animals have ingested some sharp-edged objects. This avoids any secondary complications due to aspiration.

Locally acting emetics:

            Ipecac syrup (10%): 1-2 ml/kg body weight, orally in dogs; acts in 20-30 minutes.

            Hydrogen peroxide (3): 1-5 ml/kg, orally; Total dose should not exceed 50 ml in dog.

            Hypertonic Sodium chloride solution: 10-100 ml, orally.

            Copper sulphate solution: 10-60 ml, orally; It is not recommended as it is an irritant and facilitates the absorption of poisons.

Centrally acting emetics:

            Apomorphine hydrochloride: 0.04 mg/kg, LV. or I.M.; 0.08 mg/kg, S.C. in normal saline; contraindicated in cats and pigs; prompt effect, thorough, but does have central depressive effect and the possibility of cardiotoxicity (arrhythmias).

            Xylazine: 1.1 mg/kg, I.M. in cats; acts within 20-30 minutes.

Gastric lavage: It is possible in small animals where solution is drenched by stomach pipe and is pumped out again by suction pres­sure. Administration of lavage fluid must be gentle, preferably by gravity flow, to avoid potential injury to stomach. Process is repeated 15-25 times or until fluid is clear. Gastric lavage is useful when emesis is refused, contraindicated or when collection of gastric material is required. Lavage must be performed in an unconscious or anaesthetised animal. An endotracheal tube must be placed to prevent aspiration of stomach contents . Following agents may be used depending on the condition or type of toxicant.

            Tepid water or saline solution: 10 ml/kg body weight.

            Potassium permanganate solution (1:2000)

            Tincture iodine (1:250 of 5% solution).

            Tannic acid solution.

            Sodium bicarbonate solution.

            In ruminants, a large hose inserted in the rumen is used to introduce water gently until the abdomen expands slightly. The stomach tube is then lowered and allowed to discharge as much fluid as possible. This can be repeated several times. Enterogastric lavage (also called "through and through enema") is the combination of gastric lavage and a retrograde high enema given with the gastric tube and endotracheal tube still in place. Enema fluid is administered gently until fluid from the gastric tube flows, indicating nearly complete evacuation of the gastrointestinal tract. As enema fluid reaches the upper intes­tines, spontaneous vomiting may occur.

Neutralization of the poison within the GI tract

Adsorption therapy: Adsorption is the physical binding of a toxicant to an unabsorbable carrier which is eliminated in the faeces. Activated charcoal (Activated vegetable charcoal/Fine medicinal charcoal/BCK granules) is the most effective / highly polyvalent adsorbent for a wide variety of toxicants (especially large non-polar molecules) like alcohols, antimony, atropine, cocaine, digitalis, phenol, etc. Activated charcoal can be ad­ministered following emesis or gastric lavage, or administered when these procedures are contraindicated. Activated charcoal can be given at a dose rate of 2.5 g/kg body weight in a water slurry in which 1 g is suspended in 5 ml of water. Charcoal is usually administered with a cathartic such as sodium sulphate (250 mg/kg, orally) or 70% sorbitol (3 ml/kg, orally). This combination hastens removal of the toxicant­-charcoal complex and helps to prevent constipation that can occur from the charcoal.

Universal antidote (mixture of 2 parts activated charcoal, one part magnesium oxide and one part tannic acid for adsorption, catharsis and precipitation, respectively) is considered less efficient in some cases than activated charcoal alone because different ingredients in it, interfere with each other action. Egg white, milk and other demul­cents also act as adsorbents but are less effective than charcoal. Other adsorbents : Magnesium oxide (magnesia); kaolin.

General chemical antidotes:

Substances which form a complex or insoluble precipitate with poisons and neutralize them in GIT. The effects are often limited and debatable. This category includes:

Water-containing albumens (proteins ahich are capable of forming insoluble complexes with heavy metals and which neutralize acids and bases).

Tannins (these precipitate heavy metals, alkaloids, etc.).

Ferric hydrate.

Milk is commonly believed to act as the best general antidote; in fact, milk promotes the absorption of liposoluble poisons. A cardinal rule, therefore, is never administer milk.

Decontamination of the skin or hair: Some substances (hydrocarbons, acids, alkalis, agrochemicals, etc.) may, as a result of an accident or a spillage, contaminate the feathers or fur of animals. In general it is important that in such circumstances the following are under taken:

Epidermal structures (wings, nails, claws, feathers, fur) should all be cleaned with the greater care, paying particular attention to areas such as the ears, between toes, etc. The cleaning should be undertaken quickly to avoid licking and ingestion of poison, and to limit cutaneous absorption.

Use soapy water (preferably a soap with a low pH), rinsing with copious tepid water; repeat as often as necessary.

Dry carefully and thoroughly (e.g. with a hair dryer).

The following must never be used: organic solvents (alcohol, white spirit, etc.) or oily substances which may actually increase percutaneous absorption of the toxin.

Do not rub the area vigorously; cleaning and drying must be gentle but thorough.

Persons washing the animals should wear gloves and other protective garments.

Long and matted hair may be clipped, if necessary, for complete removal of toxicant residues.

Decontamination of eyes: For toxic ocular exposure, immediate flushing of eyes is advised. The eyes are gently flushed numerous times (20-30) with water or saline to enhance the decontamination.

Gastrotomy or rumenotomy: This may be necessary in situations that are refractory to emesis, lavage or activated charcoal. Foreign bodies, especially those containing toxic metals such as lead or zinc are in­dications for surgical intervention. An abdominal radiograph may be useful in detecting retained toxic metals. Persistent materials, i.e. toxic oils, tars, etc. also require surgical evacuation.

Specific treatment: Some agents specifically interact with or neutralize the toxicant, thus decreasing its absorption. Relatively few toxicants are neutralized in this way.

Complex formation: Antidote can interact with the toxicant to form a stable complex or form a product which is not toxic. This complex or product is then excreted from the body.

Toxicant	Antidote/Agent	Product/complex
Iron	Desferrioxamine	Iron-desferrioxamine complex
	Sodium bicarbonate	Ferrous carbonate
Silver nitrate	Sodium chloride	Silver chloride
Strychnine, nicotine, morphine	Potassium permanganate	Oxidized product
Fluoride	Calcium lactate	Calcium fluoride

By Influencing the Distribution of Toxicant to the Target Site

Non-specific treatment

Ion-trapping: Ion-trapping can be effective for acidic or basic compounds by blocking their distribution to target site or by inhibiting their reabsorption in the gastrointestinal tract or kid­ney tubules. Generally, acidic agents (i.e. aspirin, acetaminophen, barbiturates, phenoxy her­bicides) are ionized and excreted more effectively in alkaline urine, whereas, basic agents (amphetamine and most alkaloids) are ionized more effectively and readily excreted in acidified urine. Ion-trapping therapy is most suitable in acid-base im­balance conditions.

Alternate binding site: Distribution can also be affected by providing an alternate binding site to the toxicant. For example, infusion of albumin. Albumin provides a binding site for the toxicant which then fails to interact with the target site.

Specific treatment

Complex formation: Antidotes can complex with the toxicant making it unavailable to cross the cell membrane or interact with susceptible receptors. To be effective, the complex must be both inactive and stable until excreted.

Toxicant	Antidote/Agent	Mechanism of action
Methanol	Ethanol	Competitive inhibition
Fluoroacetate	Acetate or monoacetin	Competitive inhibition
Heparin	Protamine	Complex formation
Venom	Antivenin	Complex formation

Metabolic conversion: Some antidotes enhance metabolic con­version, i.e. detoxification of the toxicant to a less toxic product. For example, nitrite interacts with haemoglobin and cyanide to form cyanmethaemoglobin, which is less toxic than cyanide and decreases cyanide's access to the cytochrome oxidase system. Thiosulphate provides sulphur, which interacts with cyanide to form thiocyanate.

To Increase the Threshold of Toxicity (Additional treatment measures)

            These vary widely according to the symptoms observed, but one of the main preoccupations of the practitioner will be to support vital functions (respiration and circulation). By using various agents, the threshold level of toxicity can be increased so that more concentration of toxicant is required to produce intoxica­tion. This can be achieved by using specific antidote or appropriate emergency supportive and symptomatic therapy. Thus more concentration of toxicant is required to produce a toxic effect.

Non-specific treatment: Appropriate emergency supportive therapy is often the most valuable part of early treatment for toxicosis. It provides clinical support to the vital functions of body. Major life threatening effects of toxicants need to be assessed and appropriate therapy started.

Respiratory depression: In case of respiratory depression or failure following measures are usually helpful: A patent airway should be established with a cuffed en­dotracheal tube to prevent aspiration of vomitus in a comatose or anaesthetized animal.

Mechanical ventilation or oxygen should be used if needed for apnoea, anoxia or severe anaemia.

Respiratory stimulants, i.e. Nikethamide, Doxapram (1-2 mglkg, I.V.), should be used only if necessary.

Caffeine and theophylline: cardiovascular and respiratory stimulants, which also have a diuretic action.

Heptaminol – a cardiac stimulant; Heptaminol acephyllinate combines Heptaminol and theophylline.

Cardiac arrhythmias: In case of cardiac arrhythmias, appropriate antiarrhythmic drugs should be employed.

Shock: Shock may occur due to toxicants causing excessive fluid loss, vomiting, diarrhoea, blood loss or cadiomyopathy. Use of plasma volume expander, fluid therapy or whole blood administra­tion may be followed,

Acid-base disturbance and electrolyte imbalance: These should be monitored closely and appropriate fluid and electrolyte therapy is administered, Metabolic acidosis is the most common toxicant associated acid-base imbalance. It can initially be treated with either sodium bicarbonate (0.5-2.0 mEq/kg, every 4 hour by I.V. route) or sodium lactate (0.17 molar concentration given at 16-32 mg/kg, I.V.).

CNS dysfunctions: Central nervous system stimulation or depres­sion is a common result of toxicosis. Use of appropriate drugs to counteract it may be necessary.

CNS seizures: Seizures can be controlled by using diazepam (0.5 mg/kg, I.V., repeated after 20 minutes for 3-4 times, if required). Diazepam is the drug of choice for acute seizures of unknown aetiology.

Phenobarbitone (6 mg/kg, I.V.) is used if diazepam is ineffec­tive or prolonged seizure control is needed. Pentobarbitone and other CNS depressants can also be used.

CNS depression: Analeptics such as doxapram (1-2 mg/kg, I.V.) have been used to treat CNS depression, especially when respiratory depresion is more severe.

Hypothermia or hyperthermia: Hypothermia or hyperthermia may also occur during toxicosis. Seizures may be accompanied by hyperthermia, whereas the anaesthesia used to control seizures can promote hypothermia.

Hyperthermia: Hyperthermia is treated with cold baths, ice packs or cooled intravenous fluid. Usually antipyretics are of little help in such conditions.

Hypothermia: It may be prevented through the use of blankets, warm water bottles and heating pads. Warming surroundings of the animal is safer than directly applying heat to the body.  Anuresis: To maintain adequate renal flow and to reduce cerebral oedema, osmotic diuretics like mannitol (1-2 g/kg, I.V.) may be used.

Specific treatment: Use of specific pharmacological antidotes produce an effect that neutralizes or antagonises the effect of toxicant. Antidotes are generally administered after exposure to toxicants often in response to clinical toxicosis. Some antidotes may be toxic, if used in higher dose or if used for long duration. As many antidotes are specific to toxicants, so if given in absence of the particular toxicant they may produce their own adverse effects. So, correct diagnosis is important prior to the use of antidote. General decontamination and use of supportive therapy often help in the effectiveness of antidote treatment.

Toxicant	Antidote	Mechanism of action
Morphine	Naloxone	Receptor antagonism
Organophosphorus and carbamate insecticides	Atropine	Receptor antagonism
Carbon monoxide	Oxygen	Antagonism
Warfarin	Vitamin K	Antagonism
Curare	Neostigmine	Antagonism
5-Fluorouracil	Thymidine	Altcruut« pathway

To Increase the Elimination of Toxicant from the Body

            Elimination of a toxicant from the body may be increased by using therapeutic agents. It is achieved by increasing the rate of excretion of the compound from the body via the kidneys or lungs or other physiological mechanisms.

Non-specific treatment

Catharsis: Catharsis is indicated for removal of unabsorbed toxicants especially those that have passed into intestine. Mineral oil or oil based cathartics are not recommended in poisoning as they may increase the absorption of toxicant. Preferred agents are osmotic saline purgatives (magnesium sulphate, sodium sulphate) and sorbitol. Cathartics may be used with or without activated charcoal. If used with charcoal, then cathartic may be given 30 min after administration of activated charcoal. Cathartic is not recommended if animal has diarrhoea.

Never use irritant purgatives.

Don’t use oil-based purgatives as they facilitate absorption.

Sodium sulphate: 250 mg/kg, orally.

Sorbitol (70%): 3 ml/kg, orally.

Dialysis: Haemodialysis, peritoneal dialysis and haemoperfusion are possible in sophisticated hospitals. Haemodialysis involves passage of blood from an artery through dialysis membrane which is then returned to the body via a vein. In peritoneal dialysis, an essentially isotonic solution is introduced into the peritoneal cavity and later withdrawn. Here, the peritoneum itself serves as the dialysis membrane. Haemoperfusion involves passage through charcoal or some other chambers. These are useful when patient is in comatose condition, or in situations of renal failure, anuria, hypotension, fluid and electrolyte imbalance, and hepatic failure.

However, peritoneal dialysis procedure has limited value for the management of some poisonings and fluid may need frequent change. Dialysis is useful in intoxication by digitoxin, methanol, lithium, phenobarbitone, etc.

Renal elimination:

Increase glomerular filteration:

Diuresis: Institute a forced diuresis. Forced diuresis with excessive fluid administration may result in com­plications including cerebral oedema, pulmonary oedema and dis­turbance in acid-base or electrolytes status.

5% glucose solution, by slow i.v. infusion: Large animals: 2-5 ml/kg per 24 h; Small animals: 5-20 ml/kg per 24 h.

10% glucose solution, slow i.v. infusion: Large animals: 0.5-1 ml/kg per 24 h; Small animals: 1-2 ml/kg per 24 h.

10% mannitol solution, by i.v. infusion: Large animals: 1-2 ml/kg per 24 h; Small animals: 2 ml/kg per 24 h.

Diuresis to promote rapid renal filtration of toxicants may be of limited value. For this, toxicant must be present at high concentration in an unbound form. Often a substantial portion of filtered toxicant is reabsorbed by the renal tubules. However, diuretics may be useful in oedema due to complications of poisoning, i.e. heart failure, ascites from liver failure, pulmonary oedema, acute renal failure, etc. Strong diuretics are contraindicated.

Furosemide: small animals - 2-4 mg/kg, twice a day by I.V. or I.M. route; large animals – 0.5-1 mg/kg.

Reduce tubular reabsorption by modifying urinary pH:

Forced acid dieresis to eliminate weak bases:

Urinary acidifier Ammonium chloride: 100 mg/kg body weight, given in divided doses daily by oral route or 20-40 g to large animals; 2-5 g to small animals. It has been known to cause vomiting. Arginine chloride: i.m. or i.v.; large animals – 7-10 g; small animals – 0.1-0.2 g/kg.

Ascorbic  acid: i.v.; all species: 40 mg/kg.

Forced alkaline dieresis to eliminate weak acids:

Urinary alkaliniser

Sodium bicarbonate:   0.5-2.0 mEq/kg, every 4 hours by I.V. route.

                                    1.4% by i.v. infusion; large animals – 2-4 ml/kg 24 h; small animals –                                      by regular monitoring of the acid-base balance (No. of ml to perfuse = base                                             deficit (in mmol) x 0.6 x body weight in kg)

Ringer’s lactate, by iv infusion: all species – 5-10 ml/kg per h.

Trometamol: 3.66% solution by iv infusion: dogs: 1-4 ml/kg per 24 h.

Use a diuretic such as acetazolamide.  

Specific treatment: Specific antidotes enhance excretion of the toxicant or form a complex with it which is less toxic and which is rapidly excreted from the body.

Toxicant	Antidote	Mechanism of action
Bromide	Chloride	Enhance renal excretion
Copper	D-penicillamine	Chelation
Lead	Calcium disodium EDT A	Chelation
Arsenic	Dimercaprol (British anti- Lewisite)	Chelation

 MANAGEMENT OF POISONING

In addition to the treatment of poisoning as discussed above, certain management practices also help in the therapy. When poisoning has occurred or is occurring, further exposure to the toxicant should be avoided. In case of livestock, changing pastures or feedlots may prevent further exposure. Shifting of pets from area of exposure to another site may also be helpful. Changing of feed and water source prevents further potential ingestion of toxicant. Intoxicated animal should be kept at a place which is free from ex­cessive noise and other disturbances. Convulsive seizures usually in­crease in intensity with external stimuli. If animal has been fastened with a chain or a rope, its removal is required otherwise animal may strangulate itself or may get hurt. Vicinity of intoxicated animal should be free of sharp objects and obstacles. This helps in decreasing injury to the intoxicated animal.

Toxidromes

            These are a collection of symptoms and signs that consistently occur after ingestion of a particular poison / toxin and drug and can often be identified with a basic history and physical examination. Various signs and symptoms of the poisons are grouped into different toxidromes as the rapid identification of the toxidrome saves time in evaluating and managing a poisoned patient. The various toxidromes are anticholinergic, cholinergic, sympathomimetic (adrenergic), opioid and sedative-hypnotic. Each of these toxidromes has specific signs and symptoms and requires a set pattern of management. Hence even if the poison cannot be identified, it can be classified into one of the above syndromes based on the signs and symptoms exhibited and appropriate treatment can be initiated.