Oral poisoning: an update

Transcription

1 : an update Catherine Ward MBBS BSc Hons FRCA Mark Sair PhD MRCP FRCA Key points The mainstay treatment of poisoning is resuscitation and supportive care. Poisoning should be considered in any patient exhibiting bizarre behaviour, a reduced conscious level, or unexplained physiological instability. Ipecac is no longer recommended in the treatment of acute poisoning. Activated charcoal should be given within 60 min of ingestion of poison but may have an effect for up to 2 h or longer post-ingestion. Acetaminophen levels are mandatory in all cases of adult overdose. Catherine Ward MBBS BSc Hons FRCA Specialist Registrar Derriford Hospital Plymouth The Anaesthetic Department Level 5, Torbay District General Hospital Lawes Bridge Torquay TQ2 7AA Tel: þ Fax: þ caf.ward@btinternet.com (for correspondence) Mark Sair PhD MRCP FRCA Consultant in Intensive Care Medicine and Anaesthesia Derriford Hospital Plymouth Department of Anaesthesia Level 9 Plymouth Hospitals NHS Trust Plymouth Devon PL6 8DH 6 Oral poisoning: an update Acute poisoning accounts for hospital admissions per year in the with in excess of 4000 deaths reported in England and Wales per annum. Although the majority of poison-related deaths occur in the community, reduction of in-hospital morbidity and mortality remains an important challenge. The largest proportion of enquiries to the National Poisons Information Service (NPIS) and Guy s and St Thomas Poisons Unit (GTPU) are concerning pre-school children. 1 A recent report indicated that 85% of poisonings occur in the home. Drugs accounted for the majority, but industrial chemicals and household products were involved in a significant number. Only one-third of cases were deliberate. The medications most commonly taken were acetaminophen, non-steroidal analgesics, and antidepressants. 2 The NPIS was commissioned by the Health Protection Agency and consists of five regional centres that operate a 24 h information service to health-care staff on the diagnosis, treatment, and management of poisoning. GTPU ceased to be a provider to NPIS in November 2005 and operates independently with support from Guy s and St Thomas Foundation Trust. Toxbase, the online toxicology database, was established in 1998 and NPIS recommends it as the first point of contact for registered health-care professionals. The website provides easily accessible information on acute poisoning and its management. 3 Initial approach to the poisoned patient Poisoning should be considered in any patient exhibiting bizarre behaviour, a reduced conscious level, or unexplained metabolic, cardiovascular, or respiratory instability. All cases are managed as acute medical emergencies using an ABC approach regardless of the agent used. Rare exceptions include patients poisoned with organophosphates, where health-care workers first need to protect themselves from the agent, and cyanide poisoning, where the antidote for cyanide is immediately required. All cases require: resuscitation; risk assessment; substance identification; specific treatment (if available); a period of observation. A focused and detailed poisoning history and examination are required to identify specific physical signs of poisoning followed by the selective use of antidotes and laboratory tests (Table 1). Most poisoned patients require supportive treatment only. A risk assessment should be performed by obtaining specific information from ambulance personnel or witnesses regarding the nature, timing, and amount of drug or poison. One-third of cases involve more than one toxin and alcohol is a common contributing factor. The patient s clothing should be checked for notes or blister packets, which may give a clue to quantity and type of drug ingested. In cases of deliberate self-harm, there may be previous hospital admissions to aid diagnosis. The patient s general practitioner should be contacted for previous history as family or witness sources are often unreliable. Supportive care and monitoring Patients suspected of being exposed to a poison or drug should be monitored in an appropriate clinical environment. Where coma is inevitable, patients should be intubated pre-emptively or at the first sign of deterioration in level of consciousness. Tracheal intubation will protect the airway and allow early administration of activated charcoal (AC) via a nasogastric tube if required. Patients who are at risk of cardiac instability and acidosis should have continuous ECG and invasive arterial pressure monitoring with regular blood gas analysis. Body temperature and serum glucose should be checked and i.v. dextrose administered if required. doi: /bjaceaccp/mkp039 Advance Access publication 15 December, 2009 Continuing Education in Anaesthesia, Critical Care & Pain Volume 10 Number & The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please journals.permissions@oxfordjournal.org

2 Table 1 Specific signs in poisoning and overdose Toxidrome Drug Common Findings Other signs and symptoms Potential Treatments Anticholinergic Scopolamine, atropine Altered mental status, dilated pupils, urinary retention, hyperthermia, dry mucous membranes Cholinergic Investigations Acetaminophen levels are considered mandatory in all cases of adult overdose and should be taken 4 h post-exposure. Salicylate levels are not recommended in the asymptomatic patient. Screening for substances of abuse can be achieved quickly with readily available commercial urine kits. Other laboratory tests include full blood count, urea and electrolytes, lactate, liver function tests, and coagulation studies. Where poisoning is caused by specific agents, for example, methanol or carbamazepine plasma levels are taken 4 hourly to allow refinement of risk assessment and to gauge the response to enhanced elimination techniques. A chest radiograph may indicate pulmonary oedema, which is suggestive of poisoning with narcotics or salicylates. Abdominal radiographs can identify packets of drugs smuggled in body packers. Radiological investigations are otherwise rarely required in the setting of acute poisoning. Gastric decontamination There is much debate regarding the use of the so-called decontamination triangle of forced emesis, gastric lavage, and single-dose AC. Decontamination strategies are not without side-effects and the risk:benefit ratio should be considered before administration. The American Academy of Clinical Toxicology and European Association of Poisons Centres state that gastrointestinal decontamination should not be administered routinely. Induced emesis Organophosphates; carbamates Salivation, lacrimation, sweating, nausea, vomiting, urination, defaecation, muscle weakness, bronchorrhoea Ipecac induces vomiting by both direct gastrointestinal effects and central nervous system actions. It is administered at a dose of 30 ml in adults followed by water 240 ml. Emesis typically occurs within 20 min and persists for min. Several studies have compared ipecac with single-dose AC. Ipecac conveys no benefit, whether given alone or combined with AC. 4 Side-effects include Seizures, dysrrhythmias, rhabdomyolysis Bradycardia, dilated or constricted pupils, seizures, respiratory failure, paralysis Opioid Heroin, morphine CNS and respiratory depression, small pupils Hypothermia, bradycardia, respiratory arrest, acute lung injury Salicylates Aspirin Altered mental status, respiratory alkalosis, Low-grade fever, ketonuria, acute lung metabolic acidosis, tinnitus, hyperpnoea, injury tachycardia, sweating Serotonin Meperidine; MAOI, Altered mental status, increased muscle tone, Intermittent whole body tremor Syndrome SSRI, TCA hyperreflexia, hyperthermia Sympathomimetic Cocaine; amphetamine Agitation, dilated pupils, excessive sweating, tachycardia, hypertension, hyperthermia Seizures, rhabdomyolysis, myocardial infarction, cardiac arrest, hyperthermia prolonged time in the Accident and Emergency Department and increased incidence of aspiration pneumonitis. Its use is no longer recommended. 5 Gastric lavage Gastric lavage is performed by placing a large-bore orogastric tube (30 40 F), instilling and re-aspirating several litres of water to wash out the stomach contents. This is continued until no more pill fragments are identified in gastric contents. 6 Patients must be able to protect their own airway. Drug absorption is not reduced if lavage is commenced 1 h or more after drug ingestion. Paradoxically, one study suggested that gastric lavage promotes post-pyloric transfer of poison into the small intestine where it is more rapidly absorbed. There are no data demonstrating improved clinical outcome with gastric lavage and its use is associated with significant morbidity and mortality. Complications include gastrointestinal tract perforation and aspiration. Activated charcoal Physostigmine; sedation with benzodiazepines, cooling, supportive management Airway protection and IPPV, atropine, pralidoxime Airway protection, IPPV naloxone Multi-dose AC, alkalinization of urine, K þ repletion, haemodialysis, hydration Cooling, benzodiazepines Cooling, sedation with benzodiazepines, hydration Most drugs and chemicals are absorbed by AC. It creates weak van der Waals forces that bind with the substance in the gastrointestinal tract. The numerous charcoal particles provide a large enough surface area to prevent further absorption. AC should be administered orally or nasogastrically via a 16 F tube in the intubated patient. The charcoal to toxin ratio is 10:1 with a usual dose of g or 1 g kg 21 in a child. This dose should be given within 1 h of poison ingestion. 7 Its efficacy is time-dependent, with nearly 90% reduction in absorption 30 min after drug ingestion decreasing to 30% at 1 h. 8 It has been shown to reduce acetaminophen absorption up to 2 h after ingestion. AC is unpalatable and can cause vomiting, thus in children it can be mixed with ice cream. Patients should also be warned that it will make their stools black. It is not recommended in poisoning with lithium, iron, alcohol, methanol, ethylene glycol, petroleum distillates, Continuing Education in Anaesthesia, Critical Care & Pain j Volume 10 Number

3 corrosives, acids, or alkalis. Repeated doses of 25 g per 4 6 hourly can be of benefit for poisoning with slow release formulations, for example, salicylate, barbiturates, theophylline, quinine, digoxin, carbamazepine, phenytoin, and dapsone. Multiple doses interrupt the enterohepatic circulation of the drug, reducing the plasma levels, and there are data that this reduces the duration of toxicity. A major but rare adverse effect from repeat doses is acute bowel obstruction from charcoal concretions, which is particularly likely in the presence of an anticholinergic ileus. Whole bowel irrigation Whole bowel irrigation (WBI) aims to reduce the time for ingested substances to be absorbed. It requires the administration of polyethylene glycol (PEG) litres solution per hour and is best administered through a 12 F feeding tube. The head of the bed should be elevated to 45º to prevent aspiration. If emesis occurs, then the infusion should be discontinued for 30 min and restarted at half the normal rate. Metoclopramide can be helpful as an antiemetic due to its prokinetic effects. Current recommendations are that the PEG is administered until the effluent is clear. The technique is not used routinely but may be considered where poisoning includes sustained release or enteric coated tablets. 9 It may also be used for drugs for which charcoal is known to be ineffective, for example, alcohols, boric acid, cyanide, iron, lithium, hydrocarbons, acids, and alkalis. It has been used with some success in the treatment of body packers, heavy metal, and battery ingestion. WBI is contraindicated in patients with an unprotected airway, haemodynamic instability, bowel obstruction, bowel perforation, or an ileus. Increased elimination Alkaline diuresis enhances the elimination of weak acids such as salicylates and some herbicides. Sodium bicarbonate is administered and the ph of the urine measured to keep the urinary ph Weak acids become charged in alkaline urine resulting in a concentration gradient drawing more toxin into the renal tubular system. Hypokalaemia can result from this technique and should be corrected aggressively. Alkaline diuresis should be used with caution in patients with renal impairment or cardiac disease. Treatment for specific poisons Acetaminophen Acetaminophen is responsible for hospital admissions a year and results in 345 deaths per annum. It is often one component of a mixed overdose. Acetaminophen produces the toxic metabolite N-acetyl-p-benzoqinone imine (NAPQI) which is neutralized by glutathione (Fig. 1). Depletion of glutathione results in NAPQI toxicity to hepatocytes. Patients particularly at risk are chronic alcoholics, those taking antiepileptic drugs, for example, carbamazepine and phenytoin (i.e. enzyme inducers) and patients receiving anti-tuberculous treatment, since they produce more NAPQI. Other patients at risk include those who have reduced glutathione stores due to such conditions as HIV, malnutrition, or terminal malignancy. A recent Cochrane review concluded that AC was more effective than gastric lavage or ipecac in reducing acetaminophen absorption. N-acetylcysteine (NAC) should be given, but the optimum dosing regimen remains uncertain. NAC may reduce the mortality of patients with fulminant liver failure. The superiority of NAC over methionine is unproven and 5% of patients receiving it will develop anaphylactoid reactions. Current advice from Toxbase is that high-risk patients should receive NAC at lower plasma acetaminophen concentrations (Fig. 2). Patients who develop fulminant liver failure may be offered life-saving liver transplantation, but the selection criteria are in need of refinement based on long-term outcome data. 11 Haemodialysis Haemodialysis is helpful in ethylene glycol, methanol, lithium, theophylline, and salicylate poisoning. The usefulness of this technique depends on the pharmacological properties of the ingested drug. The drug or poison should have a low volume of distribution (,1 litre kg 21 ), a low molecular weight (,500 Da), low protein binding, and low water solubility. 10 Fig 1 Acetaminophen metabolism. 8 Continuing Education in Anaesthesia, Critical Care & Pain j Volume 10 Number

4 Fig 2 Acetaminophen nomogram (permission from Prof. P.A. Routledge, Therapeutics and Toxicology Centre, Cardiff University). Salicylates Patients with salicylate poisoning may present with tinnitus, deafness, hyperventilation, epigastric pain, vomiting, hyperthermia, sweating, dehydration, respiratory alkalosis, metabolic acidosis, and electrolyte disturbances. Agitation and confusion may indicate the development of cerebral oedema which can be fatal. Treatment includes rehydration, treatment of acid base disturbance, and close monitoring of plasma levels. AC should be administered as soon as possible even in delayed presentations. The use of multidose AC is debatable, but should be considered if the plasma salicylate level continues to increase or if a slow release preparation has been taken. Alkalinization of the urine may increase the elimination of salicylate and should be considered in patients with signs of toxicity or in patients with plasma levels more than 300 mg litre 21. In patients with levels more than 700 mg litre 21, haemodialysis should be considered. Benzodiazepines Deaths associated with benzodiazepine overdose are due to mixed overdoses, especially alcohol and other drugs. Clinical manifestations are associated with drowsiness, respiratory depression, Table 2 Common antidotes Indicated in poisoning with Benzodiazepines Ethylene glycol, methanol Organophosphates Warfarin Cyanide Digoxin b-blockers Methaemoglobinaemia Acetaminophen Opiate Antidote Flumazenil Fomepizole and ethanol (10% for i.v. use) Atropine Factor II, VII, IX, X concentrate Dicobalt edetate, hydroxycobalamin Digibind Glucagon Methylene blue N-acetylcysteine Naloxone dysarthria, and ataxia. Coma is not common but is most often seen in the elderly or patients who have ingested alcohol or other drugs. Treatment is supportive. The use of flumazenil is controversial as it has many side-effects and is rarely indicated. Adverse effects include ventricular tachycardia, raising intracranial pressure, withdrawal in chronic abusers, and seizures if used in the presence of tricyclic antidepressants. It can be used to reverse benzodiazepine coma so as to avoid intubation, but this should be limited to situations of benzodiazepine overdose where no other drugs have been taken (Table 2). Continuing Education in Anaesthesia, Critical Care & Pain j Volume 10 Number

5 Opiates Increasing doses of opioids progressively produce euphoria, pinpoint pupils, sedation, respiratory depression, and apnoea. Complications include hypotension, convulsions, non-cardiogenic pulmonary oedema, and compartment syndrome from prolonged immobility. Where this is suspected, serum CK and urinary myoglobin should be measured to look for evidence of rhabdomyolysis. Naloxone should be given in 100 mg boluses i.v. to a maximum of 2 mg with the aim of reversing the opiate effect and reversing respiratory depression. This antidote can precipitate an acute agitated withdrawal state and when giving it staff should be mindful of their own safety. Naloxone can be administered i.v., i.m., s.c., or via the tracheal route. It has a short half-life (20 min if given i.v.) and therefore may be needed as an infusion since respiratory depression may reoccur. It can rarely cause ventricular dysrhythmias and hypertension and drowsiness at very high doses. Tricyclic antidepressants Tricyclic antidepressants cause 250 fatalities each year in the. The predominant cause of death is cardiac depression by sodium channel blockade with resultant decrease in cardiac output. Overdose presents with a sinus tachycardia, mydriasis, coma, hyperreflexia, convulsions, ECG changes, and hypotension. A QRS interval of.120 ms indicates cardiac toxicity and is predictive of ventricular arrhythmias and seizures. Treatment includes prevention of absorption using AC. Sodium bicarbonate is given as a loading dose (8.4% 1 2 ml kg 21 ) followed by an infusion or intermittent bolus. Sodium bicarbonate should be administered even in the absence of a significant metabolic acidosis as it helps to stabilize the Na channels in the myocardium and prevent cardiotoxicity. Convulsions can be treated with benzodiazepines initially, but anaesthesia with propofol may be required. Phenytoin is the anti-arrhythmic of choice and glucagon can be helpful if there is evidence of myocardial depression. Selective serotonin reuptake inhibitors These drugs include citalopram, fluoxetine, flovoxamine, paroxetine, and sertraline. Nausea, vomiting, agitation, tremor, nystagmus, drowsiness, dysrhythmias, and mild hypertension are the most common features of overdose. Convulsions have been reported up to 10 h post-ingestion. If administered with other drugs like cocaine, tricyclics MAOIs, or MDMA which release serotonin or affect its reuptake, this may result in serotonin syndrome. Serotonin syndrome consists of a triad of altered mental status, neuromuscular hyperactivity, and autonomic instability, similar in presentation to neuroleptic malignant syndrome hyperpyrexia, acidosis, arrythmias, and rhabdomyolysis are seen. Treatment is supportive but should include AC up to 1 h post-ingestion. Convulsions should be treated with benzodiazepines and phenytoin. Cryoheptadine and chlorpromazine are 5HT-2A antagonists and have successfully been used to treat serotonin syndrome, but there are no controlled trials to support the use of either agent. If rhabdomyolysis is suspected, urinary alkalinization and volume replacement may be helpful to reduce renal failure. Fluid resuscitation including 225 mmol of 8.4% sodium bicarbonate over 2 h is administered to increase urine ph to.7. If renal failure occurs, haemodialysis or haemofiltration is required. Methanol and ethylene glycol Methanol and ethylene glycol poisoning results in a severe high anion gap metabolic acidosis. Both are metabolized via the enzyme alcohol dehydrogenase resulting in formation of acids (formic, glycolic, and oxalic, respectively) which accumulate in the body and are responsible for neurological damage and death. Overdose with these agents can be treated with oral or nasogastric ethanol because of its greater affinity for alcohol dehydrogenase. However, maintaining plasma alcohol levels in the correct range is difficult and time-consuming, particularly if the patient is undergoing dialysis. Fomepizole blocks the metabolism of methanol and ethanol and can be injected 12 hourly. It is expensive and not widely available. Folate deficiency in primates is predictive of poor outcome in methanol toxicity and it is suggested that folate be given in a dose of 1 mg kg 21 day 21 for 48 h. 12 Summary Acute poisoning is relatively common and is the cause of significant morbidity and mortality. NPIS and Toxbase provide a 24 h information service for all aspects of poisoning. Treatment of poisoning remains largely supportive. Few drugs have antidotes and therefore treatment is aimed at reducing further absorption of the drug, increasing its elimination, and treating the side-effects. Gastric decontamination with AC is time-dependent, but can significantly reduce drug absorption. Forced emesis and gastric lavage are no longer recommended. References 1. Greene SL, Dargan PI, Jones AL. Acute poisoning: understanding 90% of case in a nutshell. Postgrad Med J 2005; 81: Jones A, Dargan P, Greene S et al. Guy s and St Thomas Poisons Unit Annual Report Good AM, Bateman DN. National Poisons Information Service Annual Report, 2005/ Heard K. The changing indications of the gastrointestinal decontamination in poisonings. Clin Lab Med 2006; 26: Krenzelok EP, McGuigan M, Lheur P. Position Paper: Ipecac Syrup American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Clin Toxicol 2004; 42: Vale JA. Position statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35: Chyka PA, Seger D. Position statement: single dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin 1997; 35: Continuing Education in Anaesthesia, Critical Care & Pain j Volume 10 Number

6 8. Green R, Grierson R, Sitar DS, Tenenbein M. How long after drug ingestion is activated charcoal still effective? J Toxicol Clin Toxicol 2001; 39: Lapatto-Reiniluoto O, Kivisto KT, Neuvonen PJ. Activated charcoal alone and followed by whole bowel irrigation in preventing the absorption of sustained release drugs. Clin Pharmacol Ther 2001; 70: Jones LO. Poisoning. Anaesth Intensive Care Med 2006; 7: Brok J, Buckley N, Gluud C. Interventions for Paracetamol (Acetaminophen) Overdose (Review), The Cochrane Library, Issue 3, Wiley, 2008; Brent J, Mcmartin K, Philips S, Aaron C, Kulig K. Fomepizole in the treatment of methanol poisoning. N Engl J Med 2001; 344: 24 2 Please see multiple choice questions 5 7 Continuing Education in Anaesthesia, Critical Care & Pain j Volume 10 Number