Toxicology Lecture Script PDF

Toxicology Lecture Script Slide 1 Toxicology Slide 2 The objectives of the lecture are to: ▪ Discuss of general concepts for toxicology, lab evaluation and treatment. ▪ Discuss of alcohol intoxication and withdrawal evaluation, and treatment. ▪ Discuss the clinical presentation, diagnosis and treatm...

Toxicology Lecture Script Slide 1 Toxicology Slide 2 The objectives of the lecture are to: ▪ Discuss of general concepts for toxicology, lab evaluation and treatment. ▪ Discuss of alcohol intoxication and withdrawal evaluation, and treatment. ▪ Discuss the clinical presentation, diagnosis and treatment of opioid toxicity and withdrawal. ▪ Discuss the clinical presentation, diagnosis and treatment of salicylate toxicity. ▪ Discuss snakebites diagnosis and management. Slide 3 Toxicology Background and Epidemiology The American Association of Poison Control reported approximately 2.5 million human toxic exposures in 2018. This number is relatively consistent with previous report years. In 2018, approximately 1350 fatalities occurred as a result of exposure. This is total number of fatalities accounting for all age groups. 90% exposures happened in the individual’s residence. In adults equal to or greater than 20 years, exposures were higher in women than men. The number of fatalities in adults 20 years or older represented ~1260 with the rates in men and women being fairly similar. Human exposure includes unintentional, intentional, and adverse reactions. This includes drug overdose with antidepressants, illicit drugs, household cleaning products, etc. Accidental exposure such as bites or stings, and unforeseen drug interactions or inappropriate drug dosing. The most frequently involved substances were analgesics, sedative/hypnotics/antipsychotics, and antidepressants. The most common route for exposure was ingestion, followed by dermal, and then inhalation/nasal. As the clinician you need to be aware of the classic features that could constitute as a drug overdose. Slide 4 Initial Care. Efforts should focus on confirming intoxication and initiating targeted therapy. ABCDs are imperative and you must identify any life-threatening problems first. A & B or airway and breathing. How is the patient’s respiratory status? Always be aware of possible facial injuries from patient’s falling due to altered mental status as result of ingestion. Is their airway patent? Are they able to protect their airway if they are altered? Patients who have substantial snoring, oxygen desaturations, etc. are unlikely able to protect their airway in this situation especially if they are lethargic, somnolent, or obtunded. C or circulation. What is their heart rate? Or their heart rhythm? Some intoxications may cause bradycardia or rhythm changes such as an atrioventricular blocks or hypotension, but also as the provider, you must recognize that some intoxications cause severe tachycardia or hypertension. As the clinician it is important that you are able to obtain a thorough history and physical; however, this may not be possible in all cases. In some cases, you may have to obtain information from other sources. The HPI can help identify the causative agent or aid with potential differential diagnoses. Ultimately, this allows the clinician to appropriately treat the patient. Rapid assessment of the mental status, temperature, pupil size, muscle tone, reflexes, and skin should be next. Slide 5 Case Study. A 31-year-old WF presents to the ED with suspected indigestion of an unknown substance. Initially, she was agitated but became lethargic approximately 1.5 hours after arrival. You are the AG-ACNP, what labs would you order for further assessment? CMP  allows you to assess the electrolytes, renal and liver function, and glucose. Usually, this will not provide the etiology for intoxication; however, it will provide information about the side effects as a result of the intoxication. It may also rule out another differential diagnosis. CBC  This will not provide the etiology of intoxication as well; however, it may provide information about potential side effects of intoxication. Additionally, it may rule out another differential diagnosis. Toxicology screen  traditionally, this assesses for opiates, amphetamines, benzodiazepines, cocaine, THC, and PCP. This varies on the institution. Some institutions may have more extensive screening. Ethanol level  assessing for ingested alcohol levels. In the clinical setting, this is usually reported in mg/dL. This varies from the blood alcohol level that is reported in g/dL. Ethanol levels greater than 80 will demonstrate coordination impairment with levels greater than 300 causing grave concern for severe intoxication that result in respiratory compromise. ABG  provides information resulting from intoxication, withdrawal, etc. Salicylate level  important to assess if concern for indigestion. Pending the level will dictate the type of care and what side effects may result from ingestion. Acetaminophen level  important to assess if concern for indigestion. Pending the level will dictate the type of care and what side effects may result from ingestion. Additionally, some people are not aware of the amount acetaminophen in other substances. CK level  this will not provide any insight into intoxication; however, it can be elevated with certain intoxications. The resulting elevation can be detrimental to the body especially the kidneys. In this particular patient, we also want to get a urine pregnancy. While not a lab, another beneficial diagnostic to get is an ECG for assessment of the QTc interval. A prolonged QTc can result in dangerous arrhythmias such as Vtach but more specifically torsades. Slide 6 Laboratory Evaluation. Laboratory evaluation may include the assessment of the 3 gaps of toxicology which are the anion gap, osmol gap, and arterial oxygen saturation gap. The anion gap measures the difference between measured anions and cations. The anion gap is commonly performed in patients who present with altered mental status, unknown exposures/ingestions, renal failure, and acute illnesses. The most common cause of an elevated anion gap is an increased in unmeasured anions and this includes lactic acidosis, uremia, ketoacidosis, rhabdomyolysis and any sort of toxic ingestions. The osmol gap is the measured osmolality minus the calculated osmolarity. A “normal” osmol gap ranges from -10 to 10. Depending on the book or reference, it may be upward to 12-14. However, an osmol gap approaching or over 20 and most certainly 25 should be cause for concern of a toxic alcohol ingestion such as methanol or ethylene glycol. You may see an increase in some disease processes such as chronic kidney disease, lactic acidosis and ketoacidosis; however, it’s not to the extent of a toxic alcohol level. The arterial oxygen saturation gap is the difference between the oxygen saturation measured on pulse oximetry and the oxygen saturation calculated based on ABG results. The arterial oxygen saturation gap is typically seen in carbon monoxide poisoning. If the gap is greater than 5%, then it may represent carbon monoxide poisoning or methemoglobinemia. Unexplained widening of these gaps should raise the possibility of drug overdose or toxic ingestion. Under normal circumstances in the clinical setting, if an etiology for gap elevation or widening is quickly identified, then the assessment of the other gaps is unnecessary, especially if the gap improves with the treatment of the identified etiology. Slide 7 Toxicology: General Treatment. Notifying poison control is strongly advised. Poison control can help identify the appropriate laboratory testing, patient disposition and treatment including the need for a specific antidote or method to enhance drug elimination. Detoxification: Gastric emptying includes the syrup of ipecac and gastric lavage. The syrup of ipecac has no role in the hospitalized setting because literature has indicated it has no proven efficacy. Gastric lavage – the risk associated with gastric lavage typically excludes its use in most patients. These risks are aspiration, arrhythmias, and stomach perforation. However, it may be indicated for indigestion of highly toxic substances in which no reliable alternative therapy is available. And this is typically for indigestions within 60 minutes or less of hospital arrival. Gastric lavage is performed by instilling 200ml of warm tap water at a time until there is clearing of aspirated fluid. Activated charcoal binds drugs and interferes with their absorption. This should be given within a timely fashion typically up to 4 hours after indigestion and generally given in a single dose based on weight. However, you can consider multi-dose therapy in life-threatening indigestion of certain drugs. Overall activated charcoal increases drug elimination but has not shown to reduce morbidity or mortality in controlled trials. Bowel irrigation. Routine use is not recommended; however, it can potentially be useful for fatal or highly-toxic sustained release or enteric coated drugs OR indigestion of large amounts of iron OR body packers. A body packer is someone who ingests or packs a large amount of illicit drug packets via their rectum. Forced diuresis and urinary pH manipulations. Forced diuresis is not recommended. It has the potential to cause pulmonary edema, volume overload, and hypernatremia with minimal to no literature to suggest it as an efficacious therapy. Urine pH manipulation or alkalization is typically reserved for salicylate poisoning. It has the potential to cause alkalemia, volume overload, hypernatremia, and hypokalemia. In these specific patients, avoid Diamox to induce alkaline diuresis because the therapy can lead to metabolic acidosis which can exacerbate the toxicity of certain drugs such as salicylates. Lastly, is hemodialysis which is indicated when severe electrolyte disturbances or acid-base imbalances are present. Additionally, it’s usually reserved when no other alternative is present. Slide 8 Alcohol. Slide 9 Epidemiology. More than 38 million adults report binge drinking an average of 4x a month. Approximately 6% of adults have an Alcohol Use Disorder (AUS). Alcohol is responsible for over 600,000 ED visits each year in the US. There are more than 2,200 deaths from alcohol poisoning each year. Alcohol-driving fatalities account for 30% of all driving fatalities. Nearly 88,000 people die from alcohol-related causes each year with more than 2/3 being men. Slide 10 Clinical Presentation: Alcohol Intoxication. Signs and symptoms of alcohol toxicity depends on the serum concentration and the frequency of alcohol ingestion. If the individual consumes alcohol daily, then a higher serum concentration typically needs to occur for signs and symptoms of alcohol intoxication. Remember that ethanol is rapidly absorbed from the gastric mucosa and the small intestines. As the individual becomes more intoxicated symptoms typically progress. Initially the patient may prevent with mild symptoms of impairment. Signs and symptoms of alcohol toxicity are… Disinhibition of normal social functioning. Euphoria which is typically exhibited as excessive talking or showing off. Ataxia which is typically exhibited as uncoordinated gait. Poor judgment Loss of memory Slurred speech Worsening ataxia Vomiting Confusion/disorientation Progressive lethargy and coma And then patients can also have seizures and respiratory depression especially with severe alcohol intoxication or typically referred to as alcohol poisoning. Slide 11 Case Study. Mrs. S is a 45-year-old AAF who presents to the ED with alcohol intoxication, what lab tests or diagnostics would you include in the work-up? Prior to working-up this patient (if able) get a thorough history and physical. How much alcohol has the patient consumed? Over what time period? Has the patient sustained any sort of injuries as a result of alcohol intoxication? Does the patient chronically use alcohol? If so, how much and how often? Is there a possibility of co-ingestions? This information may impact care delivery. The work partly depends on the H&P. Labs include: CMP  Specifically focus on the patient’s glucose level and hypoglycemia. Ideally, individuals should eat with alcohol consumption; however, this may not be the case with binge drinking or chronic alcoholism. Alcohol prevents the liver from releasing stored glucose into the bloodstream, essentially preventing gluconeogenesis. In turn, this leads to hypoglycemia. In addition to the glucose, you want to elevate the electrolytes such as the Na and Mg levels, especially in the setting of chronic alcoholism. CBC  Will likely not provide much information; however, it may demonstrate a macrocytosis due to the direct toxicity of alcohol of the marrow and/or the result of B12 or folate deficiency. Macrocytosis can be evident without an anemia. Additionally, you would anticipate macrocytosis in someone with regular or chronic use of alcohol. Blood alcohol concentration (BAC) and/or ethanol level  This may not be necessary pending on the patient’s history. Providers tend to treat patient symptoms and not the actual alcohol level. Symptoms are highly variable pending the chronicity of the patient’s use. However, if the values are available, 80 mg/dL is defined as overtly impaired with levels 100-150 mg/dL as intoxicated, levels 250-300 mg/dL as passing out/unconscious, and levels >300 mg/dL at risk for fatal respiratory depression. Tox Screen or Urine Drug Screen  Especially if you are concerned about co-indigestion. Diagnostics may include imaging to evaluate for injuries if the patient has fallen, hit their head, etc. Additional testing may be warranted pending the patient’s presentation, physical exam, and history. Slide 12 Treatment. Treatment is primarily supportive care. If profoundly lethargic/obtunded and concern for airway compromise, then proceed with ABCs. Some patients may require intubation and mechanical ventilation for respiratory support. D50 for hypoglycemia. Why can’t you use glucagon for hypoglycemia in alcohol poisoning? Glucagon is ineffective because it tells the liver to break down glycogen to glucose. Remember, in alcohol poisoning, gluconeogenesis is essentially inhibited especially with decreased food consumption over a couple of days. IVF hydration may or may not be necessary. It is dependent on the patient and whether they exhibit signs of dehydration. Electrolyte replacements if needed. Anti-emetics If a patient has chronic alcoholism, then the patient: May have significant electrolyte deficiencies requiring electrolyte replacement May need monitoring for withdrawal May need folate, thiamine, and multi-vitamins (“Banana Bag”) replacement Will need cessation counseling and/or rehab. Slide 13 Alcohol Withdrawal Slide 14 Epidemiology. Approximately 14.4 million Americans have an Alcohol Use Disorder There are 1.2 million hospital admissions for problems related to alcohol abuse annually. As many as 5% of these individuals will develop delirium tremens (DTs). Historically, mortality from DTs has been as high as 20% if untreated. Currently, the mortality from DTs ranges from 5-15% despite modern medical mgmt. Alcohol withdrawal is more common in men than women. Slide 15 Clinical Presentation. If able, you always want to start with a thorough history and physical whether being admitted for alcohol withdrawal or for a different reason but noted to consume alcohol regularly. If the patient does drink alcohol, the provider needs to investigate what they’re drinking, how often, how much, time of last ingestion, history of prior alcohol withdrawal, and if they use any other substances in combination with alcohol use. Withdrawal will typically present in those who abuse alcohol daily for at least a period of 3 months or those who have consumed large quantities (binge drinking) for at least 1 week. Symptoms typically appear within 6-12 hours after cessation of alcohol; however, this may vary after cessation of alcohol. Hallmark of withdrawal is a continuum of signs and symptoms ranging from tremors to DTs. Patients can have mild, moderate, or severe signs and symptoms of withdrawal. Mild withdrawal usually occurs within 24 hours of the last drink. Signs and symptoms are typically tremors, insomnia, anxiety, diaphoresis, and autonomic hyperactivity such as tachycardia, hyperthermia, and hypertension. Patients can also have GI upset. Moderate withdrawal usually occurs within 24-36 hours of the last drink. Signs and symptoms are typically worsening tremors, intense anxiety, insomnia, and excessive adrenergic symptoms which are typically seen as worsening hypertension and tachycardia. Severe withdrawal usually occurs >48 hours after the last drink. Signs and symptoms usually include disorientation, agitation, hallucinations, tremors, tachycardia, hypertension, hyperthermia, diaphoresis, and tachypnea. Approximately 25-30% with significant alcohol withdrawal have withdrawal seizures. The seizures tend to be brief, generalized, and occur in clusters. A withdrawal can be the first sign of alcohol withdrawal. Approximately 30-40% of patients who have seizures, DTs follow. Slide 16 Delirium Tremens (DTs). Most intense sign of alcohol withdrawal. Typically occurs 48-72 hours after the last drink; however, can occur up to 3-10 days after last drink. It’s a medical emergency and should be treated promptly. It’s characterized by global confusion, hallucinations, agitation, disorientation, fever, HTN, diaphoresis, and tachycardia. Treatment is supportive. The CIWA-Ar (revised) is the most objective and best validated tool to assess the severity of alcohol withdrawal. It looks at nausea and vomiting, tactile/auditory/visual disturbances, tremors, paroxysmal sweats, headache, anxiety, agitation, and orientation. Slide 17 Diagnostics. CMP  with a focus on sodium, potassium, magnesium, chloride, bicarbonate, renal function, liver function, and glucose. These may all be impaired especially in the setting of chronic alcohol use. CBC  Long term alcohol abuse can lead to myelosuppression which is often noted in the platelet count so these patients may be thrombocytopenic. It’s also important to note that blood loss from the GI tract and nutritional deficiencies can lead to anemias. Most commonly B12 and folate deficiencies which present as a megaloblastic anemia. CK level  the CK level can be elevated as a result of rhabdomyolysis due to significant adrenergic hyperactivity or seizure activity. An amylase and lipase level especially in the setting of chronic alcohol abuse + sign/symptoms consistent with pancreatitis UA  evaluation of ketones Consider serum osmolality to calculate an osmol gap Drug screen if suspect co-ingestion. If suspect injury or new-onset seizures, then CT Brain would be warranted Possibly an ECG pending the medication mgmt. chosen for the patient. Some antipsychotics may predispose the patient to QTc prolongation. Slide 18 Treatment. Treatment focuses on stabilization and prevention of syndrome progression. IV resuscitation and replete electrolytes. Treat hypoglycemia. Give folate and multi-vitamins. You want to administer thiamine. Thiamine has no effect on alcohol withdrawal. It’s used is to prevent Wernicke encephalopathy or syndrome. You want to administer benzodiazepines. Typically, Ativan is administered because it has less hepatic metabolism. Additionally, it can be given IV and has a short half-life. It’s usually given in bolus dosing. Alternative options are Librium and Valium. Administer anti-hypertensives such as Clonidine. And of course, supportive interventions such as airway and breathing to treatment of coexisting diseases. Slide 19 Benzodiazepine Overdose. Slide 20 Epidemiology. The percentage of adults filling a benzodiazepine prescription has steadily increased. In 2016, approximately 27,000 benzodiazepine exposures were reported to poison control with 1.3% resulting in a major toxicity and less than 1% resulting in death. Not uncommon to be co-ingested with alcohol and opioids. Benzodiazepines are relatively safe in overdose when used alone; however, in combination with opioids, they can produce significant respiratory depression and at times are fatal. Slide 21 Clinical Presentation. Ms. A is a 20-year-old HF who presented to the ED secondary to a suicide attempt. Her mother reports she took 20 alprazolam. As the AG-ACNP, what symptoms do anticipate as result of a benzodiazepine overdose? Symptoms may include dizziness, confusion, drowsiness, blurred vision, anxiety, agitation, unresponsiveness, or coma. Patients may have hallucinations, slurred speech, nystagmus, hypotonia, impaired cognition, weakness, respiratory depression, and hypotension. The provider should focus their physical exam on vital signs, cardiorespiratory, and neurological functioning first. Classic isolated benzodiazepine overdose presents with normal vital signs but unresponsiveness. It’s very important you identify when the medication was indigested, how many, and any possible co-ingestion. Additionally, note if the patient uses benzodiazepines as a result of a medical condition. Slide 22 Diagnostics and Treatment. Diagnostics are similar to those previously discussed under alcohol toxicity. However, it’s important the clinician test for co-ingestants that could complicate care such as alcohol, acetaminophen, or other analgesics. If significant respiratory depression, then an ABG is warranted. Additionally, an ECG may be warranted if concern for certain co-ingestants such as tricyclic antidepressants. Treatment should always focus on ABCs first and then supportive care. Activated charcoal is not routinely recommended. Romazicon can be considered. It is the antidote for benzodiazepine overdose; however, it’s useful in reversing sedation or coma but has no effect on respiratory depression. Romazicon use is controversial. You need to ensure benzodiazepines were not prescribed as a result of a life-threatening condition prior to administration. In long-term benzodiazepine users it may precipitate withdrawal, seizures, and potentially exacerbate the reason for which the benzodiazepine was initially prescribed. The ideal use for Romazicon is utilization in a patient with an isolated benzodiazepine overdose or benzodiazepine naïve patients. If you have a patient presenting with respiratory depression especially severe respiratory depression, then start considering co-ingestants such as opioids. In those patients, you want to administer Narcan. Slide 23 Opioid Toxicity. Slide 24 Epidemiology. Opiate or opioids can be naturally, synthetic or semisynthetic drugs. The term opiate denotes natural and refers to morphine and codeine. Synthetic drugs are Methadone, Fentanyl, and Demerol. Semisynthetic drugs are Oxycodone, Diluadid, and Hydrocodone. Overdose deaths have increased almost 6-fold since 1999. Additionally, opioids have accounted for 2/3 of deaths in the drug overdose epidemic making it the leading cause of all drug overdose deaths. From 2016-2017, prescription opioid and heroin deaths remained stable; however, synthetic opioids such as Fentanyl have continued to rise. In fact, overdose deaths involving synthetic opioids increased by 45%. Fentanyl 50-100x more potent than morphine Not uncommon for it to be mixed with other drugs such as heroin and cocaine Is responsible for much of the increase in synthetic opioid overdoses Slide 25 Clinical Presentation. As always, the history is an important component to the clinical presentation. Where there any bystanders, family, pill bottoms, drug paraphernalia? Ingestion time? Possible quantity? Coingestions? Prior or known use? Track marks? Opioids cause generalized central nervous system depression which can range from: Lethargy Agitation, paranoia, hallucinations Respiratory depression/respiratory arrest. Hypotension Bradycardia Slowed respiratory rate Decreased gut motility can cause transient GI upset Seizures: most notably to occur with Demerol Noncardiogenic pulmonary edema: most notably occurs with heroin Miosis The clinical triad for opioid toxicity/overdose includes central nervous system depression, respiratory depression, and miosis. Slide 26 Diagnostics. History is a major component for diagnosis. Combination of GCS score