- Email: [email protected]
Anticholinergic Syndrome
PHARM/TOX CORNER
Anticholinergic Syndrome
Author: David A. Kemmerer, RN, BSN, Portland, Maine Section Editor: Allison A. Muller, PharmD, D.ABAT
David A. Kemmerer is a Certified Specialist in Poison Information (CSPI), Northern New England Poison Center, Maine Medical Center, Portland, Maine. For correspondence, write: David A. Kemmerer, RN, BSN, Northern New England Poison Center, 22 Bramhall Street, Portland, ME 04102; E-mail: [email protected]. J Emerg Nurs 2007;33:76-8. 0099-1767/$32.00 Copyright n 2007 by the Emergency Nurses Association. doi: 10.1016/j.jen.2006.10.013
76
Earn Up to 9.5 CE Hours. See page 90. Red as a Beet Dry as a Bone Blind as a Bat Mad as a Hatter Hot as Hades 1
O
ne fall evening a 17-year-old man presented to the emergency department after he reportedly ingested some tea made from the plant Jimsom Weed. His presentation was classic for anticholinergic syndrome. He was very agitated with hallucinations and was making picking movements in the air. His pupils were dilated and his skin was hot and f lushed. An EKG revealed a sinus tachycardia with a rate of 130 beats per minute. He was mildly hypertensive. He had vomited prior to admission and was noted to have hypoactive bowel sounds. Additionally, he had urinary retention. Toxicology panels were sent for drugs of abuse, acetaminophen, salicylates, and tricyclic antidepressants, and all returned negative. His care included cardiac monitoring, intravenous f luids, insertion of a urinary catheter, and lorazepam given as often as needed to control his agitation. Treatment with lorazepam helped to control the agitation as well as the hypertension and tachycardia. Repeat dosing was required, and over the course of several hours, his symptoms resolved. Compared with ED admissions for the abuse of alcohol, opiates, and anxiolytics, drugs that cause anticholinergic effects are some of the most frequently encountered overdoses in emergency departments.2 The list of drugs and plants that have anticholinergic properties is lengthy, and rarely do anticholinergic poisonings require more than observation and supportive care. Patient management becomes more complicated with drugs or plants that have both anticholinergic properties and affect other neurotransmitters.
JOURNAL OF EMERGENCY NURSING
33:1
February 2007
PHARM/TOX CORNER/Kemmerer
In northern New England, the most frequently encountered drugs with anticholinergic properties that result in evaluation in emergency departments are antihistamines, tricyclic antidepressants, phenothiazines, antipsychotics, neuroleptics, and cyclobenzaprine. Most frequently, the patient encounter is due to abuse or overdose. Occasionally the patient encounter is the result of accidental supratherapeutic dosing, as in a childhood poisoning. Other drug classes that have anticholinergic properties are antiparkinson drugs, belladonna alkaloids, cycloplegics, and gastrointestinal and genitourinary antispasmodics. Numerous plants with anticholinergic properties can be abused or accidentally ingested. The short list includes Jimsom Weed (Datura stramonium), Salvia divinorum, Angel’s Trumpet (Datura sauveolens), Deadly Nightshade (Atropa belladonna) and Black Henbane (Hyoscyamus niger). Anticholinergic syndrome is a constellation of signs and symptoms that may be present in whole or in part in the poisoned patient. Central effects are dose-dependent and agent-dependent and include drowsiness, agitation, picking motions with the hands, hallucinations to seizures, and coma. Peripheral effects that are common to anticholinergic agents include mydriasis with cycloplegia, dry mucous membranes, hyperref lexia, f lushed skin, diminished bowel sounds or ileus, urinary retention, tachycardia, and hypertension or hypotension.
The list of drugs and plants that have anticholinergic properties is lengthy, and rarely do anticholinergic poisonings require more than observation and supportive care. These symptoms may be difficult to distinguish from other drug-induced and non–drug-induced syndromes. A differential list for anticholinergic syndrome should include viral encephalitis, Reye’s syndrome, head trauma, postictal state, neuroleptic malignant syndrome, acute psychiatric disorder, withdrawal from alcohol or sedativehypnotics, and drugs that cause serotonin syndrome. Key symptoms differentiating anticholinergic syndrome are diminished bowel sounds, urine retention, and mydriasis with sluggish or nonreactive pupils.
February 2007
33:1
The primary toxicologic mechanism of substances with anticholinergic properties is to competitively antagonize acetylcholine at neuroreceptor sites. The resultant central and peripheral effects are relatively easily managed with supportive care. However, anticholinergic syndrome may only account for a portion of the entire toxicologic syndrome in certain overdoses.3-5
Numerous plants with anticholinergic properties can be abused or accidentally ingested. It is not uncommon for a patient with a drug overdose to present with a mixed syndrome, or toxidrome. Drugs that affect other neurotransmitters must be investigated as causative agents. Take, as examples, diphenhydramine, tricyclic antidepressants, and quetiapine. Diphenhydramine, a first-generation antihistamine, in addition to its anticholinergic effects, also blocks sodium and potassium channels, potentially causing QRS widening and QT prolongation. Tricyclic antidepressant overdoses may present with anticholinergic symptoms but also cause a blockade of sodium and potassium channels, potentially leading to tachyarrhythmias and lowering of the seizure threshold. Atypical antipsychotic agents, such as quetiapine, also give a mixed toxidrome with anticholinergic, serotonergic, and dopaminergic characteristics. Quetiapine also affects sodium and potassium channels. Agents that affect multiple sites often require other therapies in conjunction with those needed for solely anticholinergic effects, for example, sodium bicarbonate if the agent is causing sodium channel blockade with widened QRS. Lidocaine may be required if the poisoning has caused refractory ventricular fibrillation/ventricular tachycardia and sufficient bicarbonate therapy is unsuccessful.3-5 The treatment of anticholinergic syndrome is largely symptomatic and supportive; it may include airway support, intravenous fluids, urinary catheterization, and sedation and should include cardiac monitoring. Activated charcoal should be used with attention to protecting the patient’s airway if central nervous system depression occurs. Prior to activated charcoal administration, one must ensure that the patient has bowel sounds. There is no proven benefit to
JOURNAL OF EMERGENCY NURSING
77
PHARM/TOX CORNER/Kemmerer
multidose activated charcoal in patients with anticholinergic syndrome.
Patient disposition is largely dependent on clinical signs and the agent or agents ingested. Cathartics may cause nausea and vomiting, especially in the hypoactive gut, and increase the risk of aspiration. Benzodiazepines are the preferred initial treatment for agitation and tachycardia. Certain medications should be avoided, such as haloperidol, phenytoin, and class IA, C, and III antiarrhythmics. Seizures generally respond to benzodiazepines. Phenobarbital can be used if necessary. If intubation is necessary, propofol is a good choice of a titratable sedative that may be used for induction and sedation because it also elevates seizure threshold. The use of physostigmine is reserved for the treatment of severe anticholinergic symptoms (eg, profound tachycardia, severe hyperthermia, and unmanageable agitation) and should be used with caution because it has the potential to cause seizures, atrioventricular block, and asystole, especially in the patient with a tricyclic antidepressant overdose. Physostigmine also can potentiate the action of depolarizing neuromuscular blocking agents such as succinylcholine.1,3-5 Patient disposition is largely dependent on clinical signs and the agent or agents ingested. If the patient has taken a purely anticholinergic agent and is observed to have only minor symptoms with no arrhythmias, then generally a 4- to 6-hour observation time is sufficient. Mental status should be clearing, tachycardia should be resolving, and the patient should have urinated and have active bowel sounds. If the agent (such as diphenhydramine or tricyclic antidepressants or other agents that affect multiple receptors) is causing or has the potential to cause more severe symptoms (eg, arrhythmias and seizures), the patient should be admitted to the ICU.3-5 What is probably most challenging is to determine the disposition of the patient who is having persistent minor to moderate symptoms without tachyarrhythmias or significant agitation. For these patients, keep in mind that anticholinergics slow the gut and prolong drug absorption.
78
A longer ED observation time with cardiac monitoring may be sufficient to determine the course of symptomology. Again, most patients with anticholinergic poisoning do well with close observation and good supportive care. REFERENCES 1. Tintinalli J, Kelen G, Stapcznski JS. Emergency medicine: a comprehensive study guide. 6th ed. New York: McGraw-Hill; 2004. p. 1143Q6. 2. Drug Abuse Warning Network. National estimate of drugrelated emergency department visits. U.S. Department of Health and Human Services, Substance Abuse and Mental Health Service Administration; 2004. 3. Brent J, Wallace K, Burkhart K, Phillips S, Donovan JW. Critical care toxicology: diagnosis and management of the critically poisoned patient. 1st ed. Philadelphia: Mosby; 2005. p. 449Q56. 4. Olson K. Poisoning and drug overdose. 4th ed. New York: McGraw-Hill; 2004. p. 436Q7. 5. Flomenbaum N, Goldfrank L, Hoffman R, Howland R, Lewin N, Nelson N. Goldfrank’s toxicological emergencies. 8th ed. New York: McGraw-Hill; 2006. p. 261Q9.
Submissions to this column are welcomed and encouraged. Submissions may be sent to: Allison A. Muller, PharmD, D.ABAT The Children’s Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104 215 590-2004 . [email protected]
JOURNAL OF EMERGENCY NURSING
33:1
February 2007
Anticholinergic Syndrome
Author: David A. Kemmerer, RN, BSN, Portland, Maine Section Editor: Allison A. Muller, PharmD, D.ABAT
David A. Kemmerer is a Certified Specialist in Poison Information (CSPI), Northern New England Poison Center, Maine Medical Center, Portland, Maine. For correspondence, write: David A. Kemmerer, RN, BSN, Northern New England Poison Center, 22 Bramhall Street, Portland, ME 04102; E-mail: [email protected]. J Emerg Nurs 2007;33:76-8. 0099-1767/$32.00 Copyright n 2007 by the Emergency Nurses Association. doi: 10.1016/j.jen.2006.10.013
76
Earn Up to 9.5 CE Hours. See page 90. Red as a Beet Dry as a Bone Blind as a Bat Mad as a Hatter Hot as Hades 1
O
ne fall evening a 17-year-old man presented to the emergency department after he reportedly ingested some tea made from the plant Jimsom Weed. His presentation was classic for anticholinergic syndrome. He was very agitated with hallucinations and was making picking movements in the air. His pupils were dilated and his skin was hot and f lushed. An EKG revealed a sinus tachycardia with a rate of 130 beats per minute. He was mildly hypertensive. He had vomited prior to admission and was noted to have hypoactive bowel sounds. Additionally, he had urinary retention. Toxicology panels were sent for drugs of abuse, acetaminophen, salicylates, and tricyclic antidepressants, and all returned negative. His care included cardiac monitoring, intravenous f luids, insertion of a urinary catheter, and lorazepam given as often as needed to control his agitation. Treatment with lorazepam helped to control the agitation as well as the hypertension and tachycardia. Repeat dosing was required, and over the course of several hours, his symptoms resolved. Compared with ED admissions for the abuse of alcohol, opiates, and anxiolytics, drugs that cause anticholinergic effects are some of the most frequently encountered overdoses in emergency departments.2 The list of drugs and plants that have anticholinergic properties is lengthy, and rarely do anticholinergic poisonings require more than observation and supportive care. Patient management becomes more complicated with drugs or plants that have both anticholinergic properties and affect other neurotransmitters.
JOURNAL OF EMERGENCY NURSING
33:1
February 2007
PHARM/TOX CORNER/Kemmerer
In northern New England, the most frequently encountered drugs with anticholinergic properties that result in evaluation in emergency departments are antihistamines, tricyclic antidepressants, phenothiazines, antipsychotics, neuroleptics, and cyclobenzaprine. Most frequently, the patient encounter is due to abuse or overdose. Occasionally the patient encounter is the result of accidental supratherapeutic dosing, as in a childhood poisoning. Other drug classes that have anticholinergic properties are antiparkinson drugs, belladonna alkaloids, cycloplegics, and gastrointestinal and genitourinary antispasmodics. Numerous plants with anticholinergic properties can be abused or accidentally ingested. The short list includes Jimsom Weed (Datura stramonium), Salvia divinorum, Angel’s Trumpet (Datura sauveolens), Deadly Nightshade (Atropa belladonna) and Black Henbane (Hyoscyamus niger). Anticholinergic syndrome is a constellation of signs and symptoms that may be present in whole or in part in the poisoned patient. Central effects are dose-dependent and agent-dependent and include drowsiness, agitation, picking motions with the hands, hallucinations to seizures, and coma. Peripheral effects that are common to anticholinergic agents include mydriasis with cycloplegia, dry mucous membranes, hyperref lexia, f lushed skin, diminished bowel sounds or ileus, urinary retention, tachycardia, and hypertension or hypotension.
The list of drugs and plants that have anticholinergic properties is lengthy, and rarely do anticholinergic poisonings require more than observation and supportive care. These symptoms may be difficult to distinguish from other drug-induced and non–drug-induced syndromes. A differential list for anticholinergic syndrome should include viral encephalitis, Reye’s syndrome, head trauma, postictal state, neuroleptic malignant syndrome, acute psychiatric disorder, withdrawal from alcohol or sedativehypnotics, and drugs that cause serotonin syndrome. Key symptoms differentiating anticholinergic syndrome are diminished bowel sounds, urine retention, and mydriasis with sluggish or nonreactive pupils.
February 2007
33:1
The primary toxicologic mechanism of substances with anticholinergic properties is to competitively antagonize acetylcholine at neuroreceptor sites. The resultant central and peripheral effects are relatively easily managed with supportive care. However, anticholinergic syndrome may only account for a portion of the entire toxicologic syndrome in certain overdoses.3-5
Numerous plants with anticholinergic properties can be abused or accidentally ingested. It is not uncommon for a patient with a drug overdose to present with a mixed syndrome, or toxidrome. Drugs that affect other neurotransmitters must be investigated as causative agents. Take, as examples, diphenhydramine, tricyclic antidepressants, and quetiapine. Diphenhydramine, a first-generation antihistamine, in addition to its anticholinergic effects, also blocks sodium and potassium channels, potentially causing QRS widening and QT prolongation. Tricyclic antidepressant overdoses may present with anticholinergic symptoms but also cause a blockade of sodium and potassium channels, potentially leading to tachyarrhythmias and lowering of the seizure threshold. Atypical antipsychotic agents, such as quetiapine, also give a mixed toxidrome with anticholinergic, serotonergic, and dopaminergic characteristics. Quetiapine also affects sodium and potassium channels. Agents that affect multiple sites often require other therapies in conjunction with those needed for solely anticholinergic effects, for example, sodium bicarbonate if the agent is causing sodium channel blockade with widened QRS. Lidocaine may be required if the poisoning has caused refractory ventricular fibrillation/ventricular tachycardia and sufficient bicarbonate therapy is unsuccessful.3-5 The treatment of anticholinergic syndrome is largely symptomatic and supportive; it may include airway support, intravenous fluids, urinary catheterization, and sedation and should include cardiac monitoring. Activated charcoal should be used with attention to protecting the patient’s airway if central nervous system depression occurs. Prior to activated charcoal administration, one must ensure that the patient has bowel sounds. There is no proven benefit to
JOURNAL OF EMERGENCY NURSING
77
PHARM/TOX CORNER/Kemmerer
multidose activated charcoal in patients with anticholinergic syndrome.
Patient disposition is largely dependent on clinical signs and the agent or agents ingested. Cathartics may cause nausea and vomiting, especially in the hypoactive gut, and increase the risk of aspiration. Benzodiazepines are the preferred initial treatment for agitation and tachycardia. Certain medications should be avoided, such as haloperidol, phenytoin, and class IA, C, and III antiarrhythmics. Seizures generally respond to benzodiazepines. Phenobarbital can be used if necessary. If intubation is necessary, propofol is a good choice of a titratable sedative that may be used for induction and sedation because it also elevates seizure threshold. The use of physostigmine is reserved for the treatment of severe anticholinergic symptoms (eg, profound tachycardia, severe hyperthermia, and unmanageable agitation) and should be used with caution because it has the potential to cause seizures, atrioventricular block, and asystole, especially in the patient with a tricyclic antidepressant overdose. Physostigmine also can potentiate the action of depolarizing neuromuscular blocking agents such as succinylcholine.1,3-5 Patient disposition is largely dependent on clinical signs and the agent or agents ingested. If the patient has taken a purely anticholinergic agent and is observed to have only minor symptoms with no arrhythmias, then generally a 4- to 6-hour observation time is sufficient. Mental status should be clearing, tachycardia should be resolving, and the patient should have urinated and have active bowel sounds. If the agent (such as diphenhydramine or tricyclic antidepressants or other agents that affect multiple receptors) is causing or has the potential to cause more severe symptoms (eg, arrhythmias and seizures), the patient should be admitted to the ICU.3-5 What is probably most challenging is to determine the disposition of the patient who is having persistent minor to moderate symptoms without tachyarrhythmias or significant agitation. For these patients, keep in mind that anticholinergics slow the gut and prolong drug absorption.
78
A longer ED observation time with cardiac monitoring may be sufficient to determine the course of symptomology. Again, most patients with anticholinergic poisoning do well with close observation and good supportive care. REFERENCES 1. Tintinalli J, Kelen G, Stapcznski JS. Emergency medicine: a comprehensive study guide. 6th ed. New York: McGraw-Hill; 2004. p. 1143Q6. 2. Drug Abuse Warning Network. National estimate of drugrelated emergency department visits. U.S. Department of Health and Human Services, Substance Abuse and Mental Health Service Administration; 2004. 3. Brent J, Wallace K, Burkhart K, Phillips S, Donovan JW. Critical care toxicology: diagnosis and management of the critically poisoned patient. 1st ed. Philadelphia: Mosby; 2005. p. 449Q56. 4. Olson K. Poisoning and drug overdose. 4th ed. New York: McGraw-Hill; 2004. p. 436Q7. 5. Flomenbaum N, Goldfrank L, Hoffman R, Howland R, Lewin N, Nelson N. Goldfrank’s toxicological emergencies. 8th ed. New York: McGraw-Hill; 2006. p. 261Q9.
Submissions to this column are welcomed and encouraged. Submissions may be sent to: Allison A. Muller, PharmD, D.ABAT The Children’s Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104 215 590-2004 . [email protected]
JOURNAL OF EMERGENCY NURSING
33:1
February 2007