1. GASTRIC DECONTAMINATION ( PREVENTION OF ABSORPTION )

2. General Aspects Most controversial issue in medical toxicology Initial management of the orally poisoned patient The focus is on determining which decontamination technique or combination of techniques is preferred Only few GI decontamination studies provide guidance based on meaningful clinical endpoints

3. Modes Modes of decontamination are Gastric emptying  Gastric lavage  Emesis Activated charcoal Whole bowel irrigation

4. Gastric Emptying Principle theory is simple: “if a portion of xenobiotic can be removed prior to absorption, its potentially toxic effect should either be prevented or minimized”. Time is an important consideration- preferably within 60mins of ingestion. Choose between the 2 methods: syrup of ipecac or orogastric lavage.

5. Risk assessment: When to consider Gastric Emptying Gastric Emptying is usually not indicated if Gastric Emptying May be indicated if The xenobiotic has limited toxicity at any dose Although the xenobiotic ingested is potentially toxic, the dose ingested is less than that expected to produce significant illness The ingested xenobiotic is well adsorbed by activated charcoal, and the amount ingested is not expected to exceed the adsorptive capacity of activated charcoal Significant spontaneous emesis has occurred The patient presents many hours post ingestion and has minimal signs or symptoms of poisoning The ingested xenobiotic has a highly efficient antidote (such as acetaminophen) Given the time of ingestion, a significant amount of the ingested xenobiotic is still present in the stomach The ingested xenobiotic is also known to produce serious toxicity or the patient has obvious signs or symptoms of life-threatening toxicity The ingested xenobiotic is not adsorbed by activated charcoal Although the ingested xenobiotic is adsorbed by activated charcoal, the amount ingested exceeds the activated charcoal-to-xenobiotic ratio of 10:1 even with a double-standard dose of activated charcoal The patient has not had spontaneous emesis No highly effective specific antidote exists or alternate therapies (such as hemodialysis) pose a significant risk to the patient

6. Orogastric lavage To be considered when patient has ingested a potentially life-threatening amount of xenobiotic and the procedure can be undertaken within 60mins of ingestion. Indications  The patient meets criteria for gastric emptying  The benefits of gastric emptying outweigh the risks

7. Contraindications  The patient does not meet criteria for gastric emptying  The patient has lost or will likely lose his/her airway protective reflexes and has not been intubated.  Ingestion of an alkaline caustic  Ingestion of a foreign body (such as a drug packet)  Ingestion of a xenobiotic with a high aspiration potential (such as a hydrocarbon) in the absence of endotracheal intubation  The patient is at risk of haemorrhage or gastrointestinal perforation because of underlying pathology, recent surgery, or other medical condition that could be further compromised by the use of orogastric lavage  Ingestion of a xenobiotic in a form known to be too large to fit into the lumen of the lavage tube (such as many modified-release preparations).

8. The Technique of performing Orogastric Lavage Select the correct tube size Adults/adolescents: 36-40 French Children: 22-28 French PROCEDURE 1. If there is potential airway compromise, endotrachael or nastrotrachael intubation should precede orogastric lavage 2. The patient should be kept in the left-lateral decubitus position. Because the pylorus points upward in this orientation, this position theoritically helps prevent the xenobiotic from passing through the pylorus during the procedure. 3. Prior to the insertion, the proper length of tubing to be passed should be measured and marked on the tube.

9. Procedure contd… 4. After the tube is inserted, it is essential to confirm that the distal end of the tube is in the stomach. 5. Withdraw any material present in the stomach and consider the immediate instillation of activated charcoal for large ingestions of xenobiotics known to be adsorbed by activated charcoal. 6. Via a funnel (or a lavage syringe) instil in an adult 250ml aliquots of a room- temperature saline lavage solution. In children, aliquots should be 10-15 mL/kg to a maximum of 250mL. 7. Orogastric lavage should continue for at least several litres in an adult and for at least 0.5-1L in a child or until no particulate matter returns and the effluent lavage solution is clear. 8. Following orogastric lavage, the same tube should be used to instil activated charcoal if indicated. COMPLICATIONS Aspiration pneumonitis, mechanical injury to airway oesophagus and stomach, electrolyte imbalance (severe hypernatremia)

10. Emesis Using syrup of ipecac (a derivative of the plant alkaloid emetine). Dosage For adults 30 ml of syrup with 16 oz of fluid (Repeat in 20 mins if no emesis) For children(1-12 years of age) 15 ml of syrup with 6-8 oz of fluid For infants(6-12 months of age) 10 ml of syrup with 4 oz of fluid This dosage is 100% effective in producing emesis.

11. Contd… However, 100% rate of emesis is not equitable to 100% rate of removal of toxin. Ideally, only 30-40% removal can be achieved within 1-2 hrs of post ingestion. Significant higher removal rates if emesis induced within 30 mins of post ingestion. Usage of this mode in hospital setting is virtually zero: Most poisoning in children are benign Rapid development of altered mental status with many adult overdose Ipecac induced vomiting may be delayed/persistent

12. Activated charcoal Its use has had a resurgence over the past 10 yrs. Recommended to administer within 1 hr of ingestion. Factors like food, sustained release formulation and co-ingestion of anticholinergic or opioid properties which slow the rate of absorption, increase the time frame for possible adsorption to activated charcoal Charcoal is prepared from vegetable matter usually peat, coal, wood, coconut shell or petroleum and is activated by heating at a high temperature in a stream of oxidising gas (steam, co 2,air) or with an activating agent such a phosphoric acid or zinc chloride or by a combination of both. Process of activation creates highly developed internal pore structure and thereby increase the surface area from 2-4 m 2 /g to an area in excess of 1500 m 2 /g. This inert, non-toxic adsorbent with a surface area as high as 3000m 2 /g, is quite effective in binding high molecular weight compounds due to inter-molecular attraction( van der waals forces).

13. Contd… Action By reducing systemic adsorption Enhancing elimination through interruption of either enterohepatic or enteroentric recirculation Dosage depending upon patient’s weight and the quantity of xenobiotic ingested 0.5-1 g/kg in children 25-100 g in adults (can be instilled through Ewald tube) Mixing it with juice, chocolate syrup, jam and ice-cream bring a higher acceptance rate in children. Tablet forms should not be used for gastric decontamination.

14. Contd… This had been traditionally administered in conjunction with a cathartic to facilitate evacuation of toxic substances. Commonly used cathartics are Magnesium sulphate(15-20 g in 10% solution) Magnesium citrate(200-300 ml) Sodium sulphate Sorbitol(100-150 ml in a 70% solution or 0.5-3ml/kg up to 50g in children) This cathartics account for additional 30% drug elimination. Side-effects of activated charcoal: vomiting, constipation, diarrhoea, peritonitis, intestinal obstruction, pulmonary aspiration and hypermagnesimia.

15. Indications and Contraindications for Single-Dose Activated Charcoal Therapy Without Gastric Emptying IndicationsContraindications  The patient does not meet criteria for gastric emptying or gastric emptying is likely to be harmful  Ingestion of a toxic amount of a xenobiotic that is known to be adsorbed by activated charcoal (aspirin, acetaminophin, barbiturates, phenytoin, theophylline, cyclic antidepressants etc.)  This ingestion has occurred within a time frame amenable to adsorption by activated charcoal or clinical factors are present that suggest that not all of the xenobiotic has already been systemically adsorbed  Activated charcoal is known not to adsorb a clinically meaningful amount of ingested xenobiotic  Airway protective reflexes are absent or expected to be lost and the patient is not intubated  Gastrointestinal perforation is likely as in cases of caustic ingestions  Therapy may increase the risk and severity of aspiration, such as in the presence of hydrocarbons with a high aspiration potential  Endoscopy will be an essential diagnostic modality (acid or alkaline caustics).

16. Multiple-Dose activated charcoal Def: More than 2 sequential doses of activated charcoal Action To prevent the absorption of xenobiotics that are slowly absorbed from the GI tract (sustained release, enteric coated) To enhance the elimination of xenobiotics that have already been absorbed Larger doses in shorter intervals should be used for patients with more severe toxicity Complications also same as single-dose activated charcoal

17. Indication and Contraindications of Multiple-Dose Activated Charcoal Therapy IndicationsContraindications  Ingestion of a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline  Ingestion of a significant amount of any slowly released xenobiotic, or of a xenobiotic known to form concretions or bezoars  Any contraindication to single-dose activated charcoal  The presence of an ileus or other causes of diminished peristalsis

18. Technique of administering Multiple-Dose Activated charcoal Therapy Initial dose orally or via orogastric or nasogastric tube Adults and children: 1g/kg of body weight or a 10:1 ratio of activated charcoal-to-xenobiotic, whichever is greater. Following massive ingestions, 2g/kg of body weight might be indicated, if such a large dose can be easily administered and tolerated. Repeat doses orally or via orogastric or nasogastric tube Adults and children:0.25-0.5g/kg of bodyweight every 1-6hrs (larger doses or shorter dosing intervals may occasionally be indicated).

19. Procedure 1. Add 8 parts of water to the selected amount of powdered form. All formulations, including prepacked slurries, should be shaken well for at least 1 min to form a transiently stable suspension prior to drinking or instillation via orogastric or nasogastric tube 2. Activated charcoal can be administered with a cathartic, for the first dose only, when indicated, but cathartics should never be administered routinely and never be repeated with subsequent doses of activated charcoal 3. If the patient vomits the dose of activated charcoal, it should be repeated. Smaller, more frequent doses or continuous nasogastric administration may be better tolerated. An antiemetic may be needed. 4. If a nasogastric or orogastric tube is used for MDAC administration, time should be allowed for the last dose to pass through the stomach before removing the tube. Suctioning the tube itself prior to removal may prevent subsequent charcoal aspiration.

20. Whole bowel irrigation Oro or nasogastric administration of large amounts of osmotically balanced PolyEthylene Glycol Electrolyte Lavage Solution (PEG-ELS) to flush the GI tract in an attempt to prevent further absorption of xenobiotics Whole body irrigation should not be coupled with activated charcoal.

21. Indications and Contraindications for Whole- Bowel Irrigation IndicationsContraindications  Potentially toxic ingestions of sustained-release drugs  Ingestion of a toxic amount of a xenobiotic that is not adsorbed to activated charcoal when other methods of gastrointestinal decontamination are not possible or not efficacious  Removal of packets of illicit drugs (e.g., from body-packers)  Airway protective reflexes are absent or expected to become so in a patient who has not been intubated  Gastrointestinal tract is not intact  Signs of ileus obstruction, significant gastrointestinal haemorrhage, or hemodynamic instability that might compromise gastrointestinal motility  Persistent vomiting  Signs of leakage from illicit cocaine packets (indication for surgical removal)

22. Other treatments Surgery and Endoscopy If signs of leakage or mechanical bowel obstruction Combination treatments Orogastric lavage followed by activated charcoal Activated charcoal prior to whole-bowel irrigation

23. Conclusion Approach needs to be more individualized. No decontamination method is completely free of risk. Indications for each patient must be well defined and the method of choice must depend largely on the time, amount and the type of xenobiotic ingested. By available evidences today, activated charcoal must be the first choice, only accompanied by orogastric lavage when the desirable ratio of activated charcoal to xenobiotic cannot be achieved and the xenobiotic is still thought to be in the stomach.

24. Contd… Advancement of medical toxicology is dependent on well designed clinical studies that concentrate on measuring the effect of gastrointestinal decontamination using sound and relevant clinical endpoints. It is recommended that some form of GI decontamination be considered in every patient with potentially life-threatening toxicity regardless of the time since ingestion, as long as no absolute contraindications exist.