Lecture_Prof. Lukšić.pptx

Lecture – Acute poisoning and first aid Common Causes of Poisoning: Etiology, Diagnosis and Treatment Prof. Boris Lukšić, MD., PhD. Clinical Department of Infectious Diseases University Hospital of Split Split, Croatia Introduction  Poisoning has always been a part of human life.  The cause...

Lecture – Acute poisoning and first aid Common Causes of Poisoning: Etiology, Diagnosis and Treatment Prof. Boris Lukšić, MD., PhD. Clinical Department of Infectious Diseases University Hospital of Split Split, Croatia Introduction  Poisoning has always been a part of human life.  The causes and scientific understanding of poisoning change over time, and with them the opportunities for its correct diagnosis and treatment.  In earlier times, poisoning was thought of as a single clinical entity that could be prevented, or treated, in practically the same way for all agents: ◦ Standard “detoxifying measures” were used, and supposed universal antidotes such as mithridate and theriac were held to be able to counteract the effects of any and all poisons. Introduction  Today, modern analytical toxicology and the rapid accessibility of support from poison information centers enable treating physicians to address each case individually, with much more accurate poisoning risk assessment.  The specific treatment to be provided depends on the toxic substance and dose involved. Clinical epidemiology  Health problems caused by longstanding tobacco and ethanol consumption can be thought of as types of chronic poisoning.  The causes of acute poisoning change over time.  Some substances that were once very common causes of poisoning are now only rarely so.  These include barbiturates, older types of rodenticide (thallium compounds), and alkyl phosphate insecticides such as parathion (Figure 1). Clinical epidemiology  Newer medications, illegal drugs, technical products such as cleaning agents and cosmetics, and new consuming habits (both intentional and unintentional) have also changed the overall picture substantially.  The official cause-of-death statistics for Germany in the year 2011 included 1987 deaths (0.23% of all deaths) ◦ that were classified under the ICD-10 codes T36–50 (medications, illegal drugs, biologically active substances) ◦ and 1296 (0.15%) that were classified under codes T51–65 (substances of non-medical use). Clinical epidemiology  1410 deaths were classified as intentional self-intoxication with medications (X60–X64).  The German hospital diagnosis statistics for the year 2011 included 205 121 cases of treatment for acute intoxication: ◦ 43 675 in-hospital treatments with the main diagnosis of poisoning with medications, illegal drugs, and biologically active substances (T36–50); ◦ 29 927 treatments for the toxic effects of substances of mainly non-medical use (T51–65); ◦ 131 519 treatments for mental and behavioral disturbances caused by acute intoxication with psychotropic substances (F10.0–19.0). Clinical epidemiology  Acute alcohol poisoning was classified under the ICD-10 code T51 in a small minority of cases (2858 cases, Figure 1) and under the code F10.0 in most cases (116 517 cases, Figure 2).  Substances affecting the central nervous system were involved in most intoxications with medications (Figure 2). Clinical epidemiology  The substances of non-medical use that were most commonly involved in intoxications were the following: ◦ alcohols, mainly ethanol; ◦ carbon monoxide and other gases and vapors, as well as other kinds of smoke and harmful substances; ◦ substances ingested with food, including plants and mushrooms; ◦ substances derived from contact with poisonous animals (insect bites in the vast majority of cases). Clinical epidemiology  The statistics compiled by the German poison information centers (Giftinformationszentren, GIZ) are based on a more detailed classification and thus enable a finer analysis.  About half of all inquiries to the GIZ-Nord Poisons Center (the responsible center for the four northwestern states of Germany, i.e. Bremen, Hamburg, Lower Saxony and Schleswig-Holstein) come from doctors in a full range of outpatient and inpatient treatment settings ◦ hospitals, practices, emergency medical services; ◦ the other half come from persons who had been exposed or thought they had been exposed to a toxic substance. Clinical epidemiology  The approximately 456 173 inquiries that were received from 1996 to 2011 most commonly dealt with real or potential intoxication with medications, chemical products, plants, food items (especially products containing alcohol), or cosmetics.  Data were collected in accordance with European legislation.  The severity of poisoning was initially documented in terms of estimated risk with the Poisoning Severity Score and was followed up in cases of severe poisoning. Clinical epidemiology  Manifest intoxications often arose after the ingestion of medications, illegal drugs, and chemical products.  In contrast, the ingestion of cosmetics or plants led to manifest intoxication in only a small percentage of exposures.  There were only a few cases of severe poisoning from plants indigenous to Germany, including, for example, death cap mushrooms (Amanita phalloides) and wolfsbane (Aconitum napellus). Clinical epidemiology  One of the tasks of poison information centers is to detect poisoning arising from any new medication by observing the increasing incidence of poisoning with it as the prescription frequency rises (pharmacovigilance) (Figure 3).  The poison information centers in Germany maintain an information-sharing system so that cases of poisoning from various centers can be evaluated as a group.  This enables rapid risk assessment for products that have recently appeared on the market. : The treatment of poisoning: general aspects  Clinical trials in toxicology are often hard to carry out.  The framework conditions are hardly ever the same from one case of poisoning to another, and, as a result, the assessment of any particular intervention may be problematic.  The available data on various types of treatment have been taken into consideration in the position papers issued by the medical societies.  Pre-hospital measures for persons suffering from an intoxication generally consist of the usual emergency measures for securing vital bodily functions. The treatment of poisoning: general aspects  It is essential to take a detailed history from the patient and any other involved persons and to obtain samples of medications (and their packages), food remnants, vomitus, and any products that may have caused the intoxication.  In particular, the samples obtained at the outset may turn out to be of major forensic importance.  When intoxication occurs in the workplace, safety data sheets may yield clues to the presence of toxic residues in the products that are used there. The treatment of poisoning: general aspects  Even for patients with no or only mild symptoms the situation may become life-threatening.  Medical observation is therefore necessary until such a situation can be excluded by a reliable risk assessment based on clinical diagnosis and, where appropriate, additional laboratory testing.  Long latencies are characteristic of, for example, poisoning by mushrooms of the Cortinarius species (e.g., the fool’s webcap Cortinarius orellanus), death cap mushrooms, or paracetamol.  There may be an oligo symptomatic interval lasting several days before life-threatening manifestations arise. The treatment of poisoning: general aspects  Poison information centers have comprehensive information about active substances and products and can help with the identification of the toxic substance and with an assessment of the risks and probable course of the episode.  The poison information centers offer assistance with the proper choice of laboratory tests, the selection and transport of samples (urine and serum samples taken early on in the patient’s course), determination of a laboratory that can perform the necessary tests at once, and logistical support so that the case can be dealt with rapidly. The treatment of poisoning: general aspects  Patients who have been exposed to poisonous substances in doses that are so small as to be clearly nontoxic need no further work-up or treatment.  All other patients are initially treated with symptom-oriented management.  Treatments that lower absorption or enhance elimination are only rarely indicated; the same is true of pre-hospital treatment with antidote (i.e., at the site of poisoning). The treatment of poisoning: general aspects  For patients who have ingested corrosive substances (e.g., acids or bases), rapid irrigation of the mucous membranes is indicated, while induced vomiting and the use of activated charcoal are contraindicated.  The administration of milk to poisoning victims is hardly ever useful, despite a persistent traditional notion to this effect. The treatment of poisoning: specific treatments  Treatments that lower absorption ◦ Early administration of a single dose of activated charcoal ◦ Gastric lavage (“stomach pumping”) and provoked vomiting, once common measures for lowering the absorption of ingested poisons, have been largely abandoned in favor of the administration of activated charcoal in aqueous suspension. ◦ This method of lowering absorption is markedly less invasive and considerably less dangerous when performed for the proper indications. ◦ Nonetheless, one should not administer activated charcoal before knowing the adsorptive properties of the ingested substance. ◦ Activated charcoal adsorbs many medications, alkaloids, and vitamin K antagonists well, but many other substances are not adsorbed to any useful extent. The treatment of poisoning: specific treatments  Treatments that lower absorption ◦ Early administration of a single dose of activated charcoal ◦ Activated charcoal administration is contraindicated after the ingestion of corrosive substances (e.g., inorganic acids), surfactants, or liquid hydrocarbons, and whenever the respiratory tract has not been protected (by intubation). ◦ The main risk associated with the administration of an activated charcoal suspension is aspiration. ◦ Experience in poison information centers has shown that activated charcoal is often given in an insufficient dose; 0.5–1 g/kg body weight is recommended. ◦ Suspension in adequate amounts of fluid is necessary to avoid provoking ileus. The treatment of poisoning: specific treatments  Treatments that lower absorption ◦ Gastric lavage ◦ The putative clinical benefit of gastric lavage has never been unequivocally demonstrated; on the other hand, the severe complications that have been observed in controlled trials include aspiration, hypoxia, pneumonia, perforation, and laryngospasm. ◦ As a result, after extensive discussion in specialty societies for clinical toxicology, the indications for gastric lavage as a means of reducing the absorption of poisonous substances have been substantially restricted. ◦ As a rule, this method should only be considered in life-threatening cases within 60 minute of the ingestion. ◦ Contraindications include corrosive injuries with acids or bases, ingestions of liquid hydrocarbons of low viscosity such as gasoline, and loss of the protective airway reflexes (in patients who are not intubated). The treatment of poisoning: specific treatments  Treatments that lower absorption ◦ Induced vomiting ◦ Ipecac syrup was used for many years to provoke vomiting in children after toxic ingestions; this is no longer considered an appropriate routine measure. ◦ Another historic method of inducing vomiting was with intramuscularly administered apomorphine. ◦ The administration of sodium chloride solution to induce vomiting is, likewise, an obsolete treatment, particularly in children, this can cause hypernatremia if the patient, against expectation, does not vomit. ◦ 3 grams of sodium chloride per kilogram of body weight is stated to be a lethal dose. The treatment of poisoning: specific treatments  Treatments that lower absorption ◦ Anterograde intestinal lavage ◦ Anterograde intestinal lavage is used in only a few kinds of poisoning, in which rapid removal of the intestinal contents is necessary to prevent the absorption of potentially lethal amounts of the toxic substance (e.g., overdoses of timed-release medications, or of illegal drugs transported within the gut in plastic bags or similar containers). ◦ Laxatives ◦ Laxatives such as sorbitol or, more commonly, sodium sulfate were given in earlier years to treat acute poisoning, but their use is no longer recommended. ◦ The simultaneous administration of laxatives and activated charcoal lowers the efficacy of both. The treatment of poisoning: specific treatments    Treatments that enhance elimination Various methods can be used to enhance the elimination of toxic substances with a long half-life. The preferred method depends on the substance to be eliminated. ◦ ◦ ◦ ◦ ◦ Repeated administration of activated charcoal Urine alkalinization Hemodialysis Hemoperfusion Antidotes The treatment of poisoning: specific treatments  The “Bremen List” is a proposal for a minimal antidote kit, which was intended to serve as the basis for further discussions of this topic (Box). New treatments for specific types of poisoning  Insulin therapy has not yet become established as a treatment for beta-blocker and calcium-antagonist poisoning because of the insufficient clinical experience to date.  Life-threatening poisoning with local anesthetics has been treated successfully with the administration of lipid emulsions, so-called lipid rescue therapy. Selected individual types of poisoning       Psychotropic drugs Tricyclic antidepressants and sedating neuroleptic drugs such as phenothiazines are often ingested with suicidal intent. When taken accidentally by a child, the normal therapeutic daily dose for an adult may suffice to cause overt signs of poisoning. The main clinical manifestations are those of the anticholinergic syndrome. When a potentially lethal dose has been taken, the treatment consists of gastric lavage as soon as possible, or else a single administration of activated charcoal within an hour of ingestion. If sedation has already set in, activated charcoal administration is contraindicated because of the risk of aspiration. Selected individual types of poisoning      Psychotropic drugs Attempts to enhance the elimination of tricyclic anti -depressants are unlikely to succeed because of their large volume of distribution and their extensive binding to plasma proteins. Raising the blood pH with sodium bicarbonate lowers the free active substance concentration and simultaneously raises the serum sodium concentration, making cardiac arrhythmia less likely. Flumazenil is now considered to be contraindicated for patients who are intoxicated with psychotropic drugs. The same is true of physostigmine, which was once commonly recommended as an antidote for the anticholinergic symptoms of tricyclic antidepressant overdose. Selected individual types of poisoning       Psychotropic drugs The newer antidepressants (selective serotonin re-uptake inhibitors, SSRI) are less cardiotoxic. Their effects can be potentiated, however, by simultaneous administration with other drugs that have a similar mechanism of action, such as appetite suppressants; the serotonin syndrome may result. A further group of substances often involved in poisoning consists of opium, diamorphine (heroin), other opioids such as methadone, other synthetic narcotics, cocaine, and other (hallucinogenic) drugs. Now as in the past, treatment with an opioid antagonist (naloxone) is indicated to treat poisoning due to any substance that acts at the opiate receptor. Poisoning with other types of substances is best treated symptomatically. Selected individual types of poisoning      Novel psychoactive substances Alongside substances that have been in use since the 1930s, such as metamphetamine (INN: metamfetamine), currently popular designer drugs (newer amphetamine and cathinone derivatives) are offered for sale over the Internet, often deliberately mislabeled as “bath salts,” “plant food,” or “research chemicals.” Some act mainly as stimulants, others mainly as hallucinogens. “Spice,” a substance that recently appeared on the market in Germany, was touted as a mixture of exotic plants that are little known here. Extensive toxicological analysis revealed that the plant material was doped with synthetic cannabinoid receptor agonists. Selected individual types of poisoning       Novel psychoactive substances These designer compounds evade detection by the rapid tests for traditional illegal drugs that have been in common use up to the present. Now that the analytical identification of the offending substance has become possible in individual clinical cases, toxic side effects have been found to occur more commonly after the consumption of synthetic cannabinoids than after the consumption of tetrahydrocannabinol. Drug dependence has also been described. The figures in current drug reports reveal a marked rise in the consumption of designer drugs. The most prominent effects of such substances are often their sympathomimetic effects, which are especially evident in overdoses (Figure 4). Selected individual types of poisoning    Novel psychoactive substances Because of the way they are manufactured, illegal drugs may contain neurotoxic by-products that can induce parkinsonism. An analysis of substances being offered for sale over the Internet revealed a group of legal drugs of botanical origin that are commonly touted as “legal highs” and can be obtained without any difficulty: ◦ diviner’s sage (Salvia divinorum, salvinorin A); ◦ hallucinogenic mushrooms (ibotenic acid, muscimol); ◦ kratom (Mitragyna speciosa, mitragynin), a botanical drug with an opiate receptor-agonist effect that is cultivated and consumed in a number of Asian and African countries despite being prohibited there; ◦ Hawaiian baby woodrose (Argyreia nervosa, syn. Argyreia speciosa [L. f.], lysergic acid amide).  The hallucinogenic effect of these substances is treated purely symptomatically, if treatment is needed. Selected individual types of poisoning     Analgetics Among the non-opioid analgesics, paracetamol (= acetaminophen) is now taken less commonly with suicidal intent than was previously the case. The induction of cytochrome P450 isoenzyme 2E1 by alcohol or, less commonly, by prescription drugs potentiates the toxic effect of paracetamol by promoting the generation of toxic metabolites. Acetylcysteine is a well-tolerated antidote whose main effect is to promote glutathione synthesis and thereby accelerate the inactivation of the toxic paracetamol metabolite N-acetyl-p-benzoquinone imine. Poisoning with substances of mainly nonmedical use       Alcohols In recent years, the contamination of alcoholic drinks with methanol has repeatedly led to episodes of mass poisoning with lethal outcomes. A major problem in such cases is the delayed initiation of specific treatment, nearly always because of delayed diagnosis. Toxic products arise as a result of metabolism through the action of the enzyme alcohol dehydrogenase. On the other hand, patients treated early with fomepizole or with hemodialysis have a good prognosis. Rapid and reliable clinical diagnosis is now available by means of toxicological analysis. Poisoning with substances of mainly nonmedical use       Alcohols Ethylene glycol poisoning is often a suspected diagnosis in children. Swallowing even a single mouthful of antifreeze (which is often stored in beverage bottles) can produce overt signs of poisoning. Here, too, the treatment consists of early administration of fomepizole, and possibly hemodialysis if treatment is initiated late and the patient is already suffering from marked acidosis. The last few years have seen a marked rise in the number of cases of severe ethanol intoxication among adolescents in Germany (cf. the German Drogensuchtbericht [Drug Addiction Report] for 2012, [34]). Ethanol accounts for about 60% of all hospital admissions for acute intoxication. Poisoning with substances of mainly nonmedical use     Gamma-hydroxybutyric acid (GHB), 1,4-butanediol, Gammabutyrolactone (liquid ecstasy) The consumption of gamma-hydroxybutyric acid (GHB, liquid ecstasy) has risen in recent years. This substance is approved as an intravenous anesthetic, and its sodium salt is approved for the symptomatic treatment of narcolepsy with cataplexy; it is covered by the German Law on Narcotics. In contrast, there are few if any legal restrictions on the sale and consumption of two toxicologically related substances, the common solvent gammabutyrolactone and the chemical intermediate product 1,4-butanediol, both of which are metabolized to GHB in the body (Figure 5). : Poisoning with substances of mainly nonmedical use     Gamma-hydroxybutyric acid (GHB), 1,4-butanediol, Gammabutyrolactone (liquid ecstasy) GHB is sold on the black market with powerfully associative advertising (e.g., as a putative “cattle anesthetic”) and taken by users with the intention of elevating mood; as it has no recognizable taste, it is also sometimes given surreptitiously to unsuspecting persons as a “date-rape” drug or knock-out preparation. It causes sudden loss of consciousness with amnesia afterward; its use can be highly dangerous, particularly in an overdose or in mixed intoxications. Exogenous GHB can be detected in the blood or urine for only about 6 (resp. 12) hours after ingestion, as the substance is rapidly metabolized and is also normally synthesized in the body in small amounts. Poisoning with substances of mainly nonmedical use        Carbon monoxide Carbon monoxide poisoning due to the use of coal gas now belongs to the realm of history. At present, domestic carbon monoxide poisoning can result from the improper use of wood-charcoal grills, from defective heaters, or from smoke inhalation. Carbon monoxide poisoning is also an important topic in occupational medicine surveys. It is treated by the administration of oxygen at normobaric pressure, or at hyperbaric pressure for severe cases in order to transport more physically dissolved oxygen. The indications for hyperbaric oxygenation differ from one country to another. Poisoning with substances of mainly nonmedical use      Gases, smoke Exposures to airborne particulate matter are associated with many diseases that can be considered types of chronic poisoning (tobacco smoke, exhaust fumes, fiber dust). Smoke inhalation is a common cause of acute poisoning. Its victims may have inhaled not only carbon monoxide, but also other toxic substances, such as hydrogen cyanide. These two gases work synergistically, on the one hand lowering the oxygen-transporting capacity of hemoglobin by forming carboxyhemoglobin, and on the other hand impairing electron transport by forming cyanide complexes with the trivalent iron atom of cytochrome oxidase. Poisoning with substances of mainly nonmedical use     Gases, smoke Treating hydrogen cyanide poisoning with 4-dimethylaminophenol (4-DMAP) is contraindicated when the patient has been simultaneously exposed to carbon monoxide. The methemoglobin formation induced by 4-DMAP would additionally impair the oxygen-transporting capacity of the blood. In such cases, hydroxocobalamin can be used as an antidote. Conclusion  Most intoxications can be treated symptomatically and with intensive-care measures as needed.  Specific, effective measures directed against the particular offending substance can be used to treat only a small minority of patients.  Poison information centers can help with therapeutic decisionmaking and planning in individual cases. Conclusion  These centers have extensive data on many types of products, offer advice, and can help organize suitable toxicological testing if necessary.  The ongoing collection of data by poison information centers is useful for the refinement of surveillance measures and also serves as a point of departure for research projects whose findings can be incorporated into future treatment recommendations. Thank You for Your attention