- Email: [email protected]
Intravenous Morphine Sulfate versus Intravenous Tramadol for Acute Pain in the Afghan National Security Forces
P H A R M / T O X C O R N E R
INTRAVENOUS MORPHINE SULFATE VERSUS INTRAVENOUS TRAMADOL FOR ACUTE PAIN IN THE AFGHAN NATIONAL SECURITY FORCES Authors: Andrew E. Gawlikowski, PharmD, Alice E. Barsoumian, MD, FACP, Beth M. Baykan, MSN, BSN, RN, NP, and Joseph L. Taylor, MHA, BSN, RN, FACHE, Travis Air Force Base, CA, Fort Sam Houston, TX, and Tyndall Air Force Base and Pensacola, FL Section Editor: Allison A. Muller, PharmD, D.ABAT
Earn Up to 8.0 CE Hours. See page 543. hile serving as a medical advisor in a regional military hospital in Afghanistan, you observe a 28-year-old male Afghan National Police (ANP) officer being brought into the emergency department with a right lower extremity blast injury resulting from exposure to an improvised explosive device. You note that a tourniquet was successfully placed at the scene. The patient reports having no medical history, takes no medications, and has no known drug allergies. His initial vital signs are as follows: blood pressure, 100/58 mm Hg; heart rate, 120 beats per minute; and respiratory rate, 24 breaths per minute. On a numeric rating scale, he reports a pain level of 10 out of 10. The attending Afghan physician writes an order for tramadol, 100 mg, to be administered intravenously every 4 hours as needed for pain. Why not morphine? Will tramadol be as efficacious? Will the patient still be in pain? As part of a deployment to Afghanistan, our team provided medical advice to the ANP and Afghan National
Army and made frequent trips to their Kabul-based flagship hospitals (Kabul National Military and ANP Hospitals). In this role, we noted a relatively low use of morphine sulfate by these 2 facilities compared with our Western medicine standards. We also noticed a significant amount of tramadol in intravenous (IV) form being dispensed from their pharmacies. After discussing this observation with the Afghan staff, we were told that many providers prefer to use IV tramadol rather than IV morphine sulfate for acute pain. As service members from the United States, where IV tramadol is not available, we were intrigued. Why would tramadol rather than morphine sulfate be preferred for acute pain? In this review we intend to look at Afghanistan culture, examine tramadol and morphine sulfate pharmacology, and discuss the history of both agents and their use in combat-related injuries.
Andrew E. Gawlikowski is Chief of Outpatient Pharmacy Operations, David Grant Medical Center, Travis Air Force Base, CA.
Afghanistan’s history in recent years has been marked by the toppling of the Taliban, the establishment of a new constitution, and ongoing insurgency. Although much attention has been focused on the international casualties associated with this ongoing conflict, the majority of casualties are incurred by the Afghan security institutions, especially the ANP. The Afghan National Security Force sustains major injuries and causalities from improvised explosive devices and small arms fire, with 13,729 service members killed and 16,511 wounded from 2001 to February 2014. 1 Thus combat trauma is a large part of practice in Afghan medicine. The opium trade has been a part of the country’s history and has increased in recent years 2; additionally, the use of opiates as a drug of abuse is on the rise in Afghanistan. 3 In this context, the use of opiates as painkillers is highly regulated, with restrictions for patients and providers. 4 In addition, Islam is the dominant religion
W
Alice E. Barsoumian is a staff physician in the Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX. Beth M. Baykan is Chief Nurse, 325th Medical Group, Tyndall Air Force Base, FL. Joseph L. Taylor, Member, Northwest Florida Chapter, is Associate Director of Medical Services, Naval Hospital, Pensacola, FL. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the U.S. Department of the Air Force, U.S. Department of the Navy, U.S. Department of Defense, or U.S. Government. This work was prepared as part of the author's official duties, and, as such, there is no copyright to be transferred. For correspondence, write: Andrew Gawlikowski, PharmD, David Grant Medical Center, Travis Air Force Base, 3458 Neely Road, Joint Base McGuire-DixLakehurst, NJ 08641; E-mail: [email protected]. J Emerg Nurs 2015;41:533-5. Available online 28 September 2015 0099-1767 Published by Elsevier Inc. on behalf Emergency Nurses Association. http://dx.doi.org/10.1016/j.jen.2015.08.014
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PHARM/TOX CORNER/Gawlikowski et al
in Afghanistan, with 99% of the population identified as Muslim, 5 and Islamic views describe the endurance of pain as virtuous; it is believed that through its endurance sins can be forgiven. However, Islamic bioethicists also state that every patient has a right to alleviate pain through treatment. 6 It is also notable that Islam forbids the use of substances that alter consciousness, although the use of opiate pain medications is seen as allowable out of necessity. 6 The literature describes both the enduring of pain and the acceptance of pain treatment by observant Muslim patients. 7,8
Morphine Use for Trauma: Overview
Morphine sulfate is a natural, pure opiate agonist binding to mu, kappa, and delta receptors in the hypothalamus. 9 The onset of action is 5 to 10 minutes when administered intravenously. Morphine is available in IV, subcutaneous, rectal, and oral forms, and because of its quick onset and euphoric effects, it is a good baseline option to treat acute pain caused by combat-related injuries. The use of morphine sulfate for pain was first documented in 1804. 10 Extracted from opium sap, it was originally thought to be a miracle drug, until addiction was noted to be a prominent adverse effect. Morphine is the standard for most combat trauma pain management situations, although it is contraindicated if head trauma is suspected, because parenteral forms can cause increased intracranial pressure. 9 Caution is also required when using any opiates in patients with hemorrhagic shock, because this class of drugs leads to reduced vasoconstriction. 9
Tramadol for Use in Trauma: Overview
Developed in Germany in 1962, tramadol began to be used as an analgesic for mild to moderate pain in the mid 1970s in Europe. Approved by the U.S. Food and Drug Administration in 1995, the oral form (Ultram, Janssen Pharmaceuticals, Titusville, NJ) was considered a viable pain control option to avoid use of a pure opiate, and Ultram is used throughout the United States. When tramadol is administered parenterally, it bypasses first-pass metabolism, negating its opiate qualities 11 and reducing its usefulness for treating severe or trauma-induced pain. However, when tramadol is taken by mouth, it is converted to O-desmethyltramadol through first-pass metabolism. This has opiate receptor activity and increases the likelihood of abuse potential. In 2014 the Food and Drug
534
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Administration reclassified tramadol as a schedule IV controlled substance because of its abuse potential. 12 Tramadol is a synthetic weak opiate agonist with receptor activity at mu, serotonin, and norepinephrine receptors. Structurally, tramadol is similar to codeine, and once it is metabolized through the liver, its metabolite has stronger mu agonist activity. 12 When administered intravenously, tramadol peak plasma concentration is reached at about 45 minutes. 11 Tramadol is available in intramuscular, IV, intranasal, and rectal forms outside the United States. Major adverse effects with IV tramadol include flushing and nausea. Respiratory depression, which is associated with morphine, is not common at therapeutic levels of tramadol. 11 See the Table for a comparison of the adverse effects of the 2 drugs.
IV Morphine versus IV Tramadol
A comprehensive literature review revealed few studies that compared the efficacy between morphine and tramadol. The existing studies, although few in number, demonstrate a relatively similar level of pain control between the medications for trauma and surgical patients. One randomized controlled trial evaluated IV tramadol versus IV morphine with respect to posttraumatic pain in a hospital setting. 13 In this trial, 105 patients were randomized to receive tramadol or morphine, and it was found that the analgesic effect was similar between the 2 groups when measured on a 4-point rating scale. Sedation scores were similar among groups, and the authors reported tramadol to be an acceptable alternative to morphine. A second study, conducted in Malaysia, compared patient-controlled analgesia (PCA) with morphine and tramadol. 14 This double-blind study with 160 postsurgical patients randomized patients to PCA with morphine or tramadol. Appropriate loading and infusion doses of each
TABLE
Comparison of the adverse effect profile of intravenous morphine versus tramadol, in order of frequency Morphine adverse effects
Tramadol adverse effects
Drowsiness Flushing Respiratory depression Pruritus Physical dependence
Dizziness Nausea Fatigue
Data from references 9 and
11
.
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drug were used. No significant differences in pain or sedation scores were noted between the 2 groups. Adverse events, including sedation, were the same in each group. The authors report that PCA with tramadol is equally effective as PCA with morphine for patients after major surgery. Conclusion
Although not many of us will experience the challenges and rewards of practicing medicine in Afghanistan, we will be confronted by patients afflicted with pain wherever we provide care. Delivering culturally sensitive care is always a challenge, and thus understanding the medication utilization preferences of non-Western health care providers is imperative when we are given the opportunity to participate in humanitarian relief efforts and educational exchange programs or, as in this article, when we engage in military service with international partners. This review describes an alternative pain medicine viewpoint, examining the pharmacology, history, and use of morphine and tramadol in trauma-related injuries, and briefly explores the historical and cultural considerations of treating pain in Afghan patients. Noting the Afghan preference for tramadol rather than morphine for combat-related injuries in Afghanistan poses a unique scenario unfamiliar to Western audiences and leads to other potential research questions—primarily, what are the reasons for this preference? Are the reasons for this preference specific to this unique country, its laws, and its history, or are they more generalizable? How successful is the pain control delivered with tramadol for the trauma patients who receive it? More information must be gathered to answer these questions. Although some data regarding the equivalency of pain control between IV forms of both morphine and tramadol exist, additional studies would be useful in medical decision making when both drugs are available. REFERENCES 1. The Brookings Institution. The Afghanistan Index. http://brookings. edu/afghanistanindex. Published 2014. Accessed December 3, 2014. 2. Islamic Republic of Afghanistan Ministry of Counter Narcotics. Afghanistan Opium Survey 2014. http://mcn.gov.af/Content/files/
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Afghan%20opium%20survey%202014%20cultivation%20and%20 production.pdf. Published 2014. Accessed September 4, 2015. 3. Islamic Republic of Afghanistan Ministry of Counter Narcotics. Afghanistan Drug Report 2012. http://mcn.gov.af/Content/files/13_11_07__English% 20Afghanistan%20Drug%20Report%202012(1).pdf. Published 2012. Accessed September 4, 2015. 4. Cleary J, Radbruch L, Torode J, Cherny NI. Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Asia: a report from the Global Opioid Policy Initiative (GOPI). Ann Oncol. 2013;24(Suppl 11):xi51-xi59. 5. Central Intelligence Agency. The World Factbook: South Asia: Afghanistan. https://www.cia.gov/library/publications/the-world-factbook/geos/af.html. Updated September 1, 2015. Accessed September 4, 2015. 6. Brandon S, Broeckaert B. Necessary interventions: Muslim views on pain and symptom control in English Sunni e-Fatwas. Ethical Perspect. 2010;17:626-651. 7. Baider L. Cultural diversity: family path through terminal illness. Ann Oncol. 2012;23(Suppl 3):62-65. 8. Silbermann M, Arnaout M, Daher M, et al. Palliative cancer care in Middle Eastern countries: accomplishments and challenges. Ann Oncol. 2012;23(Suppl 3):15-28. 9. Morphine Sulfate Injection Higlhlights of Prescribing Information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/ 202515s000lbl.pdf. Accessed September 11,2015. 10. Drug Enforcement Agency. Cannabis, coca, and poppy: nature’s addictive plants. http://www.deamuseum.org/ccp/opium/history.html. Accessed September 4, 2015. 11. Tramadol Summary of Product Characteristics. https://www.medicines. org.uk/emc/medicine/22344. Accessed September 11, 2015. 12. Expert Committee on Drug Dependence, World Health Organization. Tramadol Update Review Report. http://www.who.int/medicines/areas/ quality_safety/6_1_Update.pdf?ua=1. Published June 2014. Accessed September 4, 2015. 13. Vergnion M, Degesves S, Garcet L, Magotteaux V. Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation. Anesth Analg. 2001;92(6):1543-1546. 14. Hadi MA, Kamaruljan HS, Saedah A, Abdullah NM. A comparative study of intravenous patient-controlled analgesia morphine and tramadol in patients undergoing major operation. Med J Malaysia. 2006;61(5):570-576.
Submissions to this column are encouraged and may be sent to Allison A. Muller, PharmD, D.ABAT [email protected]
WWW.JENONLINE.ORG
535
INTRAVENOUS MORPHINE SULFATE VERSUS INTRAVENOUS TRAMADOL FOR ACUTE PAIN IN THE AFGHAN NATIONAL SECURITY FORCES Authors: Andrew E. Gawlikowski, PharmD, Alice E. Barsoumian, MD, FACP, Beth M. Baykan, MSN, BSN, RN, NP, and Joseph L. Taylor, MHA, BSN, RN, FACHE, Travis Air Force Base, CA, Fort Sam Houston, TX, and Tyndall Air Force Base and Pensacola, FL Section Editor: Allison A. Muller, PharmD, D.ABAT
Earn Up to 8.0 CE Hours. See page 543. hile serving as a medical advisor in a regional military hospital in Afghanistan, you observe a 28-year-old male Afghan National Police (ANP) officer being brought into the emergency department with a right lower extremity blast injury resulting from exposure to an improvised explosive device. You note that a tourniquet was successfully placed at the scene. The patient reports having no medical history, takes no medications, and has no known drug allergies. His initial vital signs are as follows: blood pressure, 100/58 mm Hg; heart rate, 120 beats per minute; and respiratory rate, 24 breaths per minute. On a numeric rating scale, he reports a pain level of 10 out of 10. The attending Afghan physician writes an order for tramadol, 100 mg, to be administered intravenously every 4 hours as needed for pain. Why not morphine? Will tramadol be as efficacious? Will the patient still be in pain? As part of a deployment to Afghanistan, our team provided medical advice to the ANP and Afghan National
Army and made frequent trips to their Kabul-based flagship hospitals (Kabul National Military and ANP Hospitals). In this role, we noted a relatively low use of morphine sulfate by these 2 facilities compared with our Western medicine standards. We also noticed a significant amount of tramadol in intravenous (IV) form being dispensed from their pharmacies. After discussing this observation with the Afghan staff, we were told that many providers prefer to use IV tramadol rather than IV morphine sulfate for acute pain. As service members from the United States, where IV tramadol is not available, we were intrigued. Why would tramadol rather than morphine sulfate be preferred for acute pain? In this review we intend to look at Afghanistan culture, examine tramadol and morphine sulfate pharmacology, and discuss the history of both agents and their use in combat-related injuries.
Andrew E. Gawlikowski is Chief of Outpatient Pharmacy Operations, David Grant Medical Center, Travis Air Force Base, CA.
Afghanistan’s history in recent years has been marked by the toppling of the Taliban, the establishment of a new constitution, and ongoing insurgency. Although much attention has been focused on the international casualties associated with this ongoing conflict, the majority of casualties are incurred by the Afghan security institutions, especially the ANP. The Afghan National Security Force sustains major injuries and causalities from improvised explosive devices and small arms fire, with 13,729 service members killed and 16,511 wounded from 2001 to February 2014. 1 Thus combat trauma is a large part of practice in Afghan medicine. The opium trade has been a part of the country’s history and has increased in recent years 2; additionally, the use of opiates as a drug of abuse is on the rise in Afghanistan. 3 In this context, the use of opiates as painkillers is highly regulated, with restrictions for patients and providers. 4 In addition, Islam is the dominant religion
W
Alice E. Barsoumian is a staff physician in the Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX. Beth M. Baykan is Chief Nurse, 325th Medical Group, Tyndall Air Force Base, FL. Joseph L. Taylor, Member, Northwest Florida Chapter, is Associate Director of Medical Services, Naval Hospital, Pensacola, FL. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the U.S. Department of the Air Force, U.S. Department of the Navy, U.S. Department of Defense, or U.S. Government. This work was prepared as part of the author's official duties, and, as such, there is no copyright to be transferred. For correspondence, write: Andrew Gawlikowski, PharmD, David Grant Medical Center, Travis Air Force Base, 3458 Neely Road, Joint Base McGuire-DixLakehurst, NJ 08641; E-mail: [email protected]. J Emerg Nurs 2015;41:533-5. Available online 28 September 2015 0099-1767 Published by Elsevier Inc. on behalf Emergency Nurses Association. http://dx.doi.org/10.1016/j.jen.2015.08.014
November 2015
VOLUME 41 • ISSUE 6
Afghanistan: Historical and Cultural Considerations
WWW.JENONLINE.ORG
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PHARM/TOX CORNER/Gawlikowski et al
in Afghanistan, with 99% of the population identified as Muslim, 5 and Islamic views describe the endurance of pain as virtuous; it is believed that through its endurance sins can be forgiven. However, Islamic bioethicists also state that every patient has a right to alleviate pain through treatment. 6 It is also notable that Islam forbids the use of substances that alter consciousness, although the use of opiate pain medications is seen as allowable out of necessity. 6 The literature describes both the enduring of pain and the acceptance of pain treatment by observant Muslim patients. 7,8
Morphine Use for Trauma: Overview
Morphine sulfate is a natural, pure opiate agonist binding to mu, kappa, and delta receptors in the hypothalamus. 9 The onset of action is 5 to 10 minutes when administered intravenously. Morphine is available in IV, subcutaneous, rectal, and oral forms, and because of its quick onset and euphoric effects, it is a good baseline option to treat acute pain caused by combat-related injuries. The use of morphine sulfate for pain was first documented in 1804. 10 Extracted from opium sap, it was originally thought to be a miracle drug, until addiction was noted to be a prominent adverse effect. Morphine is the standard for most combat trauma pain management situations, although it is contraindicated if head trauma is suspected, because parenteral forms can cause increased intracranial pressure. 9 Caution is also required when using any opiates in patients with hemorrhagic shock, because this class of drugs leads to reduced vasoconstriction. 9
Tramadol for Use in Trauma: Overview
Developed in Germany in 1962, tramadol began to be used as an analgesic for mild to moderate pain in the mid 1970s in Europe. Approved by the U.S. Food and Drug Administration in 1995, the oral form (Ultram, Janssen Pharmaceuticals, Titusville, NJ) was considered a viable pain control option to avoid use of a pure opiate, and Ultram is used throughout the United States. When tramadol is administered parenterally, it bypasses first-pass metabolism, negating its opiate qualities 11 and reducing its usefulness for treating severe or trauma-induced pain. However, when tramadol is taken by mouth, it is converted to O-desmethyltramadol through first-pass metabolism. This has opiate receptor activity and increases the likelihood of abuse potential. In 2014 the Food and Drug
534
JOURNAL OF EMERGENCY NURSING
Administration reclassified tramadol as a schedule IV controlled substance because of its abuse potential. 12 Tramadol is a synthetic weak opiate agonist with receptor activity at mu, serotonin, and norepinephrine receptors. Structurally, tramadol is similar to codeine, and once it is metabolized through the liver, its metabolite has stronger mu agonist activity. 12 When administered intravenously, tramadol peak plasma concentration is reached at about 45 minutes. 11 Tramadol is available in intramuscular, IV, intranasal, and rectal forms outside the United States. Major adverse effects with IV tramadol include flushing and nausea. Respiratory depression, which is associated with morphine, is not common at therapeutic levels of tramadol. 11 See the Table for a comparison of the adverse effects of the 2 drugs.
IV Morphine versus IV Tramadol
A comprehensive literature review revealed few studies that compared the efficacy between morphine and tramadol. The existing studies, although few in number, demonstrate a relatively similar level of pain control between the medications for trauma and surgical patients. One randomized controlled trial evaluated IV tramadol versus IV morphine with respect to posttraumatic pain in a hospital setting. 13 In this trial, 105 patients were randomized to receive tramadol or morphine, and it was found that the analgesic effect was similar between the 2 groups when measured on a 4-point rating scale. Sedation scores were similar among groups, and the authors reported tramadol to be an acceptable alternative to morphine. A second study, conducted in Malaysia, compared patient-controlled analgesia (PCA) with morphine and tramadol. 14 This double-blind study with 160 postsurgical patients randomized patients to PCA with morphine or tramadol. Appropriate loading and infusion doses of each
TABLE
Comparison of the adverse effect profile of intravenous morphine versus tramadol, in order of frequency Morphine adverse effects
Tramadol adverse effects
Drowsiness Flushing Respiratory depression Pruritus Physical dependence
Dizziness Nausea Fatigue
Data from references 9 and
11
.
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Gawlikowski et al/PHARM/TOX CORNER
drug were used. No significant differences in pain or sedation scores were noted between the 2 groups. Adverse events, including sedation, were the same in each group. The authors report that PCA with tramadol is equally effective as PCA with morphine for patients after major surgery. Conclusion
Although not many of us will experience the challenges and rewards of practicing medicine in Afghanistan, we will be confronted by patients afflicted with pain wherever we provide care. Delivering culturally sensitive care is always a challenge, and thus understanding the medication utilization preferences of non-Western health care providers is imperative when we are given the opportunity to participate in humanitarian relief efforts and educational exchange programs or, as in this article, when we engage in military service with international partners. This review describes an alternative pain medicine viewpoint, examining the pharmacology, history, and use of morphine and tramadol in trauma-related injuries, and briefly explores the historical and cultural considerations of treating pain in Afghan patients. Noting the Afghan preference for tramadol rather than morphine for combat-related injuries in Afghanistan poses a unique scenario unfamiliar to Western audiences and leads to other potential research questions—primarily, what are the reasons for this preference? Are the reasons for this preference specific to this unique country, its laws, and its history, or are they more generalizable? How successful is the pain control delivered with tramadol for the trauma patients who receive it? More information must be gathered to answer these questions. Although some data regarding the equivalency of pain control between IV forms of both morphine and tramadol exist, additional studies would be useful in medical decision making when both drugs are available. REFERENCES 1. The Brookings Institution. The Afghanistan Index. http://brookings. edu/afghanistanindex. Published 2014. Accessed December 3, 2014. 2. Islamic Republic of Afghanistan Ministry of Counter Narcotics. Afghanistan Opium Survey 2014. http://mcn.gov.af/Content/files/
November 2015
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Afghan%20opium%20survey%202014%20cultivation%20and%20 production.pdf. Published 2014. Accessed September 4, 2015. 3. Islamic Republic of Afghanistan Ministry of Counter Narcotics. Afghanistan Drug Report 2012. http://mcn.gov.af/Content/files/13_11_07__English% 20Afghanistan%20Drug%20Report%202012(1).pdf. Published 2012. Accessed September 4, 2015. 4. Cleary J, Radbruch L, Torode J, Cherny NI. Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Asia: a report from the Global Opioid Policy Initiative (GOPI). Ann Oncol. 2013;24(Suppl 11):xi51-xi59. 5. Central Intelligence Agency. The World Factbook: South Asia: Afghanistan. https://www.cia.gov/library/publications/the-world-factbook/geos/af.html. Updated September 1, 2015. Accessed September 4, 2015. 6. Brandon S, Broeckaert B. Necessary interventions: Muslim views on pain and symptom control in English Sunni e-Fatwas. Ethical Perspect. 2010;17:626-651. 7. Baider L. Cultural diversity: family path through terminal illness. Ann Oncol. 2012;23(Suppl 3):62-65. 8. Silbermann M, Arnaout M, Daher M, et al. Palliative cancer care in Middle Eastern countries: accomplishments and challenges. Ann Oncol. 2012;23(Suppl 3):15-28. 9. Morphine Sulfate Injection Higlhlights of Prescribing Information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/ 202515s000lbl.pdf. Accessed September 11,2015. 10. Drug Enforcement Agency. Cannabis, coca, and poppy: nature’s addictive plants. http://www.deamuseum.org/ccp/opium/history.html. Accessed September 4, 2015. 11. Tramadol Summary of Product Characteristics. https://www.medicines. org.uk/emc/medicine/22344. Accessed September 11, 2015. 12. Expert Committee on Drug Dependence, World Health Organization. Tramadol Update Review Report. http://www.who.int/medicines/areas/ quality_safety/6_1_Update.pdf?ua=1. Published June 2014. Accessed September 4, 2015. 13. Vergnion M, Degesves S, Garcet L, Magotteaux V. Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation. Anesth Analg. 2001;92(6):1543-1546. 14. Hadi MA, Kamaruljan HS, Saedah A, Abdullah NM. A comparative study of intravenous patient-controlled analgesia morphine and tramadol in patients undergoing major operation. Med J Malaysia. 2006;61(5):570-576.
Submissions to this column are encouraged and may be sent to Allison A. Muller, PharmD, D.ABAT [email protected]
WWW.JENONLINE.ORG
535