PHARM/TOX CORNER
MY TRAUMA PATIENT TAKES METHADONE: HOW DO I MANAGE HIS PAIN? Authors: Charlann Staab, MSN, RN CFRN, CHC, CHPC, Phoenix, AZ Section Editor: Allison A. Muller, PharmD, D.ABAT
Earn Up to 9.0 CE Hours. See page 519.
ou are 7 hours into your ED shift, and an emergency aircraft is 5 minutes out. The charge nurse relays the report of a single-vehicle crash on a rural highway. The patient is an unrestrained driver of a full-size older-model van who left the roadway and impacted a guardrail, reportedly traveling at 55 mph (88 km/h). The flight crew describes a starred windshield on the driver’s side, a bent steering wheel, and an intrusion of 8 to 12 inches of the bumper into the engine compartment. The patient reports that he took his eyes off the road briefly after dropping his cigarette on the floor. He denies a loss of consciousness, is complaining of chest discomfort with noted chest bruising, and has multiple abrasions and contusions to his lower legs. He volunteers a medication list that includes methadone and has no known drug allergies. When asked about pain, he reports a pain level of 6 to 8 on a scale of 10. The initial vital signs are as follows: blood pressure, 148/76 mm Hg; heart rate, 108 beats/min; and respiratory rate, 14–16 breaths/min. A patient’s medication list can help identify medical conditions; however, a basic list may not be enough. What comes to mind when the patient says he or she is taking methadone? Past heroin use? Other opioid use? Acute pain? Chronic pain? Does methadone work like disulfiram? Can you medicate a patient for acute pain if he or she is taking methadone? If so, what medications are good choices? Are there any specific dosage considerations? As patient advocates, nurses must recognize that pain management is a priority because pain is considered a valuable assessment parameter and it has been suggested that pain is the fifth vital sign. A pain level of 6 to 8 surely deserves consideration of analgesia. How does concurrent methadone use affect the management of acute pain?
Y
Charlann Staab, Member, Arizona State Council, is Manager, Clinical Services, PHI Air Medical, Phoenix, AZ. For correspondence, write: Charlann Staab, MSN, RN CFRN, CHC-C, CHPC, 1146 N Melody Cir, Chandler, AZ 8522; E-mail: [email protected]. J Emerg Nurs 2014;40:509-11. 0099-1767 Copyright © 2014 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jen.2014.05.008
September 2014
VOLUME 40 • ISSUE 5
Methadone Use: Past and Present
Methadone is not a new medication; it was developed in Germany in 1937 and introduced to the United States in 1947 with Federal Drug Administration approval as an analgesic for severe pain and an antitussive. 1 Over the past 40 years, methadone has been used in palliative care, in the management of neuropathic pain, and as a long-acting opioid analgesic alternative. 2 Results from the 2010 National Survey on Drug Use and Health suggested an estimated 22.8 million Americans aged 12 years or older, or 8.9%, were involved in illicit drug use. 3 Methadone use in the United States alone has risen 1,293% (1997–2007), and some authorities suggest that prescriptions will increase due to an increase in heroin use. 3
Background of Methadone
Methadone is a legal potent synthetic narcotic drug successfully used as a treatment for the addiction of heroin and related opioid narcotics. 4 When taken orally on a daily basis, methadone prevents opioid withdrawal symptoms and suppresses “drug hunger.” 5 Methadone appears in the bloodstream within 30 minutes of oral administration, reaching peak levels within 2 to 4 hours. Methadone does not cause euphoria, and the body does not develop a physiological tolerance, unlike with heroin and opioids. However, just like the substances it replaces, methadone is addictive and reportedly has a high risk of abuse with a half-life of 24 hours or more. 6 The half-life is typically extended and unpredictable in patients with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. There are a number of drugs that can interact with methadone resulting in somnolence, itching, hypotension, respiratory depression, prolonged QTc (possibly leading to torsades de pointes), and death. 7 Methadone is metabolized in the liver and excreted through the urine and bile, and any illness causing liver or kidney damage can increase the serum level and, in turn, yield an increased risk of toxicity. Mortality and morbidity rates associated with methadone treatment have increased dramatically in recent years, largely in
WWW.JENONLINE.ORG
509
PHARM/TOX CORNER/Staab
TABLE 1
TABLE 2
Associated drugs and conditions that may increase risk of prolonged QTc with methadone a Haloperidol Diazepam Ciprofloxacin Droperidol Levofloxacin Moxifloxacin Hypomagnesemia Hypokalemia
Medications and foods that increase methadone plasma levels a Amiodarone Ciprofloxacin Clarithromycin Erythromycin Diltiazem Ketoconazole Nefazodone Ritonavir Monoamine oxidase inhibitors Selective serotonin reuptake inhibitors Central nervous system depressants Ethanol Grapefruit juice
a Data from Armstrong, Wynn, Sanderson1; Paulozzi, Logan, Hall6; and Kuryshev, BruejingWright, Brown.7
the population prescribed methadone for pain control rather than addiction maintenance. 6 Inadvertent drug overdose has been reported, and methadone’s interaction history should be a concern. 4,8 When the drug is used to treat acute pain, the analgesic effect lasts only 4 to 6 hours, yet methadone has a very long and variable plasma half-life, averaging 24 to 36 hours, possibly as long as 55 hours. 9 Methadone’s prolonged and cumulative distribution in body tissues and slow elimination create a risk of drug interactions even after the analgesic effects wear off, as well as extended toxicity. 2 One should compare this with morphine sulfate, which is an effective analgesic but with a half-life of only 2 to 3 hours. Methadone can block nerve conduction through membranestabilizing activity (sodium channels) and lead to cardiovascular collapse or cardiac dysrhythmias especially in the presence of alcohol, opiates, benzodiazepines, or barbiturates. The primary cardiac dysrhythmias reported are ventricular tachycardia, prolonged QT interval, and torsades de pointes. 4, 5 In 2006 the Federal Drug Administration added a black-box warning for methadone addressing the potential risks of using this drug for pain management.
a
Data from Lipman4 and Corkey, Schifano, Ghodse.9
Trauma patients who present with an altered level of consciousness and are administered analgesia may be at increased risk of aspiration because of the emetic effects of methadone and the depressive effects on the cough/gag reflex. Just as some substances and medications produce an additive relationship to methadone, there are also substances that inhibit intended metabolism, enhancing the risk of overdose, as listed in Table 2. 9 In contrast, there are a significant number of medications that can increase the metabolism of methadone (Table 3), decreasing its concentration and inducing the onset of withdrawal symptoms affecting several body systems (ie, cardiovascular, respiratory, neurologic, psychosocial, and metabolic). A summary of the withdrawal symptoms is shown in Table 4. 9
Other Considerations in Methadone Patients Toxicity
There is a narrow margin between therapeutic and toxic blood levels of methadone, with a number of substances and drugs that can intensify or prolong the effects of methadone. Table 1 lists some substances, medications, and conditions that may increase the risk of toxicity. Signs of methadone toxicity are not dose specific and are similar to those of other opioids: respiratory depression, pinpoint pupils, hypotension, circulatory failure, pulmonary edema, and coma. Most deaths involving methadone result from respiratory depression in combination with other drugs such as ethanol, other opiates, or benzodiazepines. 9
510
JOURNAL OF EMERGENCY NURSING
Patients newly prescribed methadone are commonly involved in vehicle collisions; however, isolating the cause as purely related TABLE 3
Medications or substances that decrease methadone plasma levels a Phenytoin Carbamazepine Rifampin Fluconazole a
Data from Corkey, Schifano, Ghodse.9
VOLUME 40 • ISSUE 5
September 2014
Staab/PHARM/TOX CORNER
TABLE 4
Methadone withdrawal signs and symptoms a
a
Gastrointestinal
Neurologic
Cardiovascular
Psychosocial
Metabolic
Nausea Vomiting Diarrhea
Tremors Prolonged insomnia Seizures
Tachycardia Hypertension
Irritability Hallucinations Panic Delusions Delirium Depression
Fever/chills
Data from Lipman.9
to drug administration is complex because the methadone population has multiple comorbidities and impairments, such as chronic pain, behavioral health concerns, and alcohol abuse. 4 Does the patient have any known history of HIV, hepatitis B, or hepatitis C suggesting poor metabolism of methadone? 4 A patient taking methadone for heroin or other opiate addictions may not know his or her HIV or hepatitis status. Diligent use of personal protection devices is warranted because all patients should be considered infectious.
4. Lipman JJ. The methadone poisoning “epidemic”. Forensic Exam. 2008;17(2):38-46.
Conclusion
5. Magnelli F, Biondi L, Calabria R. Safety and efficacy of buprenorphine/ naloxone in opioid-dependent patients: an Italian observational study. Clin Drug Investig. 2010;30(Suppl. 1):21-6.
In the scenario presented, the flight crew chose not to medicate the patient based on physiological parameters and a short 20minute transport. ED staff slowly introduced oral analgesia while monitoring end-tidal carbon dioxide levels. The patient was monitored for 24 hours with a diagnosis of a cardiac contusion and was then released with encouragement to follow up with his pain specialist. Proper history inquiry, conservative but effective analgesia administration, and close monitoring (ongoing respiratory assessment, end-tidal carbon dioxide level, and hemodynamic monitoring) provided a safe approach to this patient.
Acknowledgment
The author acknowledges Carole Rush for her assistance with this article.
September 2014
VOLUME 40 • ISSUE 5
REFERENCES 1. Armstrong SC, Wynn GH, Sanderson NB. Pharmacokinetic drug interactions of synthetic opiate analgesics. Psychomatics. 2009;50(2):169-76. 2. Lipman AG. Methadone: effective analgesia, confusion and risk [editorial]. J Pain Palliat Care Pharmacother. 2005;19(2):3-5. 3. Manchikanti L, Helm SII, Fellows B. Opioid epidemic in the United States. Pain Physician. 2012;15(3 Suppl.):ES29-38.
6. Paulozzi LG, Logan JE, Hall AJ. A comparison of drug overdose deaths involving methadone and other opioid analgesics in West Virginia. Addiction. 2009;104(9):1541-8. 7. Kuryshev YA, Bruejing-Wright A, Brown AM. Increased cardiac risk in concomitant methadone and diazepam treatment: pharmacodynamic Interactions in cardiac ion channels. J Cardiovasc Pharmacol. 2010;56(4):420-30. 8. McCance-Katz EF, Mandell TW. Drug interactions of clinical importance in the methadone and buprenorphine. Am J Addict. 2010;19(1):2-3. 9. Corkey JM, Schifano F, Ghodse AH. The effects of methadone and its role in fatalities. Hum Psychopharmacol. 2004;19(8):565-76.
Submissions to this column are encouraged and may be sent to Allison A. Muller, PharmD, D.ABAT [email protected]
WWW.JENONLINE.ORG
511
MY TRAUMA PATIENT TAKES METHADONE: HOW DO I MANAGE HIS PAIN? Authors: Charlann Staab, MSN, RN CFRN, CHC, CHPC, Phoenix, AZ Section Editor: Allison A. Muller, PharmD, D.ABAT
Earn Up to 9.0 CE Hours. See page 519.
ou are 7 hours into your ED shift, and an emergency aircraft is 5 minutes out. The charge nurse relays the report of a single-vehicle crash on a rural highway. The patient is an unrestrained driver of a full-size older-model van who left the roadway and impacted a guardrail, reportedly traveling at 55 mph (88 km/h). The flight crew describes a starred windshield on the driver’s side, a bent steering wheel, and an intrusion of 8 to 12 inches of the bumper into the engine compartment. The patient reports that he took his eyes off the road briefly after dropping his cigarette on the floor. He denies a loss of consciousness, is complaining of chest discomfort with noted chest bruising, and has multiple abrasions and contusions to his lower legs. He volunteers a medication list that includes methadone and has no known drug allergies. When asked about pain, he reports a pain level of 6 to 8 on a scale of 10. The initial vital signs are as follows: blood pressure, 148/76 mm Hg; heart rate, 108 beats/min; and respiratory rate, 14–16 breaths/min. A patient’s medication list can help identify medical conditions; however, a basic list may not be enough. What comes to mind when the patient says he or she is taking methadone? Past heroin use? Other opioid use? Acute pain? Chronic pain? Does methadone work like disulfiram? Can you medicate a patient for acute pain if he or she is taking methadone? If so, what medications are good choices? Are there any specific dosage considerations? As patient advocates, nurses must recognize that pain management is a priority because pain is considered a valuable assessment parameter and it has been suggested that pain is the fifth vital sign. A pain level of 6 to 8 surely deserves consideration of analgesia. How does concurrent methadone use affect the management of acute pain?
Y
Charlann Staab, Member, Arizona State Council, is Manager, Clinical Services, PHI Air Medical, Phoenix, AZ. For correspondence, write: Charlann Staab, MSN, RN CFRN, CHC-C, CHPC, 1146 N Melody Cir, Chandler, AZ 8522; E-mail: [email protected]. J Emerg Nurs 2014;40:509-11. 0099-1767 Copyright © 2014 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jen.2014.05.008
September 2014
VOLUME 40 • ISSUE 5
Methadone Use: Past and Present
Methadone is not a new medication; it was developed in Germany in 1937 and introduced to the United States in 1947 with Federal Drug Administration approval as an analgesic for severe pain and an antitussive. 1 Over the past 40 years, methadone has been used in palliative care, in the management of neuropathic pain, and as a long-acting opioid analgesic alternative. 2 Results from the 2010 National Survey on Drug Use and Health suggested an estimated 22.8 million Americans aged 12 years or older, or 8.9%, were involved in illicit drug use. 3 Methadone use in the United States alone has risen 1,293% (1997–2007), and some authorities suggest that prescriptions will increase due to an increase in heroin use. 3
Background of Methadone
Methadone is a legal potent synthetic narcotic drug successfully used as a treatment for the addiction of heroin and related opioid narcotics. 4 When taken orally on a daily basis, methadone prevents opioid withdrawal symptoms and suppresses “drug hunger.” 5 Methadone appears in the bloodstream within 30 minutes of oral administration, reaching peak levels within 2 to 4 hours. Methadone does not cause euphoria, and the body does not develop a physiological tolerance, unlike with heroin and opioids. However, just like the substances it replaces, methadone is addictive and reportedly has a high risk of abuse with a half-life of 24 hours or more. 6 The half-life is typically extended and unpredictable in patients with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. There are a number of drugs that can interact with methadone resulting in somnolence, itching, hypotension, respiratory depression, prolonged QTc (possibly leading to torsades de pointes), and death. 7 Methadone is metabolized in the liver and excreted through the urine and bile, and any illness causing liver or kidney damage can increase the serum level and, in turn, yield an increased risk of toxicity. Mortality and morbidity rates associated with methadone treatment have increased dramatically in recent years, largely in
WWW.JENONLINE.ORG
509
PHARM/TOX CORNER/Staab
TABLE 1
TABLE 2
Associated drugs and conditions that may increase risk of prolonged QTc with methadone a Haloperidol Diazepam Ciprofloxacin Droperidol Levofloxacin Moxifloxacin Hypomagnesemia Hypokalemia
Medications and foods that increase methadone plasma levels a Amiodarone Ciprofloxacin Clarithromycin Erythromycin Diltiazem Ketoconazole Nefazodone Ritonavir Monoamine oxidase inhibitors Selective serotonin reuptake inhibitors Central nervous system depressants Ethanol Grapefruit juice
a Data from Armstrong, Wynn, Sanderson1; Paulozzi, Logan, Hall6; and Kuryshev, BruejingWright, Brown.7
the population prescribed methadone for pain control rather than addiction maintenance. 6 Inadvertent drug overdose has been reported, and methadone’s interaction history should be a concern. 4,8 When the drug is used to treat acute pain, the analgesic effect lasts only 4 to 6 hours, yet methadone has a very long and variable plasma half-life, averaging 24 to 36 hours, possibly as long as 55 hours. 9 Methadone’s prolonged and cumulative distribution in body tissues and slow elimination create a risk of drug interactions even after the analgesic effects wear off, as well as extended toxicity. 2 One should compare this with morphine sulfate, which is an effective analgesic but with a half-life of only 2 to 3 hours. Methadone can block nerve conduction through membranestabilizing activity (sodium channels) and lead to cardiovascular collapse or cardiac dysrhythmias especially in the presence of alcohol, opiates, benzodiazepines, or barbiturates. The primary cardiac dysrhythmias reported are ventricular tachycardia, prolonged QT interval, and torsades de pointes. 4, 5 In 2006 the Federal Drug Administration added a black-box warning for methadone addressing the potential risks of using this drug for pain management.
a
Data from Lipman4 and Corkey, Schifano, Ghodse.9
Trauma patients who present with an altered level of consciousness and are administered analgesia may be at increased risk of aspiration because of the emetic effects of methadone and the depressive effects on the cough/gag reflex. Just as some substances and medications produce an additive relationship to methadone, there are also substances that inhibit intended metabolism, enhancing the risk of overdose, as listed in Table 2. 9 In contrast, there are a significant number of medications that can increase the metabolism of methadone (Table 3), decreasing its concentration and inducing the onset of withdrawal symptoms affecting several body systems (ie, cardiovascular, respiratory, neurologic, psychosocial, and metabolic). A summary of the withdrawal symptoms is shown in Table 4. 9
Other Considerations in Methadone Patients Toxicity
There is a narrow margin between therapeutic and toxic blood levels of methadone, with a number of substances and drugs that can intensify or prolong the effects of methadone. Table 1 lists some substances, medications, and conditions that may increase the risk of toxicity. Signs of methadone toxicity are not dose specific and are similar to those of other opioids: respiratory depression, pinpoint pupils, hypotension, circulatory failure, pulmonary edema, and coma. Most deaths involving methadone result from respiratory depression in combination with other drugs such as ethanol, other opiates, or benzodiazepines. 9
510
JOURNAL OF EMERGENCY NURSING
Patients newly prescribed methadone are commonly involved in vehicle collisions; however, isolating the cause as purely related TABLE 3
Medications or substances that decrease methadone plasma levels a Phenytoin Carbamazepine Rifampin Fluconazole a
Data from Corkey, Schifano, Ghodse.9
VOLUME 40 • ISSUE 5
September 2014
Staab/PHARM/TOX CORNER
TABLE 4
Methadone withdrawal signs and symptoms a
a
Gastrointestinal
Neurologic
Cardiovascular
Psychosocial
Metabolic
Nausea Vomiting Diarrhea
Tremors Prolonged insomnia Seizures
Tachycardia Hypertension
Irritability Hallucinations Panic Delusions Delirium Depression
Fever/chills
Data from Lipman.9
to drug administration is complex because the methadone population has multiple comorbidities and impairments, such as chronic pain, behavioral health concerns, and alcohol abuse. 4 Does the patient have any known history of HIV, hepatitis B, or hepatitis C suggesting poor metabolism of methadone? 4 A patient taking methadone for heroin or other opiate addictions may not know his or her HIV or hepatitis status. Diligent use of personal protection devices is warranted because all patients should be considered infectious.
4. Lipman JJ. The methadone poisoning “epidemic”. Forensic Exam. 2008;17(2):38-46.
Conclusion
5. Magnelli F, Biondi L, Calabria R. Safety and efficacy of buprenorphine/ naloxone in opioid-dependent patients: an Italian observational study. Clin Drug Investig. 2010;30(Suppl. 1):21-6.
In the scenario presented, the flight crew chose not to medicate the patient based on physiological parameters and a short 20minute transport. ED staff slowly introduced oral analgesia while monitoring end-tidal carbon dioxide levels. The patient was monitored for 24 hours with a diagnosis of a cardiac contusion and was then released with encouragement to follow up with his pain specialist. Proper history inquiry, conservative but effective analgesia administration, and close monitoring (ongoing respiratory assessment, end-tidal carbon dioxide level, and hemodynamic monitoring) provided a safe approach to this patient.
Acknowledgment
The author acknowledges Carole Rush for her assistance with this article.
September 2014
VOLUME 40 • ISSUE 5
REFERENCES 1. Armstrong SC, Wynn GH, Sanderson NB. Pharmacokinetic drug interactions of synthetic opiate analgesics. Psychomatics. 2009;50(2):169-76. 2. Lipman AG. Methadone: effective analgesia, confusion and risk [editorial]. J Pain Palliat Care Pharmacother. 2005;19(2):3-5. 3. Manchikanti L, Helm SII, Fellows B. Opioid epidemic in the United States. Pain Physician. 2012;15(3 Suppl.):ES29-38.
6. Paulozzi LG, Logan JE, Hall AJ. A comparison of drug overdose deaths involving methadone and other opioid analgesics in West Virginia. Addiction. 2009;104(9):1541-8. 7. Kuryshev YA, Bruejing-Wright A, Brown AM. Increased cardiac risk in concomitant methadone and diazepam treatment: pharmacodynamic Interactions in cardiac ion channels. J Cardiovasc Pharmacol. 2010;56(4):420-30. 8. McCance-Katz EF, Mandell TW. Drug interactions of clinical importance in the methadone and buprenorphine. Am J Addict. 2010;19(1):2-3. 9. Corkey JM, Schifano F, Ghodse AH. The effects of methadone and its role in fatalities. Hum Psychopharmacol. 2004;19(8):565-76.
Submissions to this column are encouraged and may be sent to Allison A. Muller, PharmD, D.ABAT [email protected]
WWW.JENONLINE.ORG
511
