Highlights From the American Pain Society Meeting
Traditionally, the American Pain Society's (APS) annual meeting mixes science and clinical practice in a milieu of educational workshops, with original research abstracts presented in a relatively small poster session. But as scientific and clinical advances in pain medicine expand, the amount and variety of original research presented at the annual meeting of the APS has grown in breadth and depth. The following discussion highlights key research in basic science and new treatments, as well as treatment-related complications presented in poster sessions at the 22nd Annual Scientific Meeting of the APS.
Oxycodone-Related Deaths. Oxycodone has received considerable notoriety in the media recently. In an attempt to clarify factors involved in deaths related to oxycodone abuse, Haddox and colleagues from Purdue Pharma, Stamford, Connecticut, examined the deaths using a Drug Abuse Warning Network (DAWN)-based classification system. They assembled an Oxycodone Postmortem Database comprising 1243 cases that consisted of solicited submissions from medical examiner and coroner offices in 23 states during a 29-month period ending in January 2002. Of the 1014 evaluable cases involving oxycodone, 921 (90.8%) were found to be related to drug abuse, and 93 (9.2%) were categorized as not involving drug abuse. In total, 31 (3.4%) of the cases in which drug abuse was implicated reported oxycodone as a single entity used. Investigators reported that 96.6% of the deaths involved multiple drugs in which there was at least 1 other possible contributory drug in addition to oxycodone. Most prevalent drug combinations were oxycodone in combination with: benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants. These findings are important from a medical-legal standpoint and as a key analysis in the field of pain medicine.
Sex Differences in Morphine Metabolism. Pain is difficult to measure during the acute postoperative period, which limits our ability to analyze these states and renders their management more challenging. Few high-quality, randomized, prospective, controlled trials have compared agents and their metabolites. Now, a study from Idaho State University, Pocatello, Idaho, by Ratka and associates has shown sex differences in pharmacokinetics of morphine glucuronides in the elderly.
Investigators administered a single oral dose of morphine (0.5 mg/kg) to elderly men and women (over 60 years) and then measured concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G). Plasma profiles of morphine did not differ significantly between men and women but the time required to reach the maximum concentration of M3G was significantly longer (1.7-fold) in women than men. However, for the initial 2-3 hours, levels of M6G were higher in men than women. The clearance of M3G and M6G was significantly lower in women compared with men. The M3G clearance was about 2 times lower than the clearance of M6G. These investigators concluded that among the elderly, there are sex differences in the pharmacokinetics of morphine glucuronides but not morphine. The results indicate that with repeated doses of morphine, M3G may accumulate to a greater extent in elderly women than elderly men. It is hoped that, as more studies are performed, we will be able to define more clinical end points, and develop newer drugs with rapid onset and offset, no active metabolites, and reduced morbidity and mortality for our patients.
CSF Chemistry and Chronic Intrathecal Morphine. Despite widespread use of intrathecal morphine for controlling chronic cancer-related pain, no studies have examined the long-term effects of chronic intrathecal morphine infusions on CSF chemistry (protein, glucose, WBC). This is particularly important for patients who are being evaluated for possible CSF infection during chronic spinal drug delivery. Furthermore, granuloma formation on the catheter tip is a potential complication, and knowing the baseline CSF chemistry compared with subsequent measurements may help determine whether any of these substances add to the risk for granuloma formation.
Wallace and Yaksh from the University of California, San Diego, obtained CSF samples from 17 patients receiving chronic intrathecal morphine via implanted infusion pump. Samples were assayed for protein, glucose, and white and red blood cells. The investigators used fluoroscopy to check the integrity and location of the catheter tip. They found no correlation between morphine concentrations and CSF protein, glucose, WBC, or RBC levels. Likewise, they found no correlation between morphine daily dose and levels of CSF protein, glucose, WBC, or RBC. Thus, chronic intrathecal morphine infusions do not cause abnormalities in CSF protein, glucose, or red or white blood cells, and therefore are likely not a risk factor for CSF infection or granuloma formation.
Until we find markers for granuloma formation in such cases, it is probably prudent that all patients receiving long-term intrathecal analgesia undergo periodic radiographic surveillance to further define their risk for developing occult catheter-associated masses and to allow intervention before neurologic injury can develop.
Traditionally, the American Pain Society's (APS) annual meeting mixes science and clinical practice in a milieu of educational workshops, with original research abstracts presented in a relatively small poster session. But as scientific and clinical advances in pain medicine expand, the amount and variety of original research presented at the annual meeting of the APS has grown in breadth and depth. The following discussion highlights key research in basic science and new treatments, as well as treatment-related complications presented in poster sessions at the 22nd Annual Scientific Meeting of the APS.
Oxycodone-Related Deaths. Oxycodone has received considerable notoriety in the media recently. In an attempt to clarify factors involved in deaths related to oxycodone abuse, Haddox and colleagues from Purdue Pharma, Stamford, Connecticut, examined the deaths using a Drug Abuse Warning Network (DAWN)-based classification system. They assembled an Oxycodone Postmortem Database comprising 1243 cases that consisted of solicited submissions from medical examiner and coroner offices in 23 states during a 29-month period ending in January 2002. Of the 1014 evaluable cases involving oxycodone, 921 (90.8%) were found to be related to drug abuse, and 93 (9.2%) were categorized as not involving drug abuse. In total, 31 (3.4%) of the cases in which drug abuse was implicated reported oxycodone as a single entity used. Investigators reported that 96.6% of the deaths involved multiple drugs in which there was at least 1 other possible contributory drug in addition to oxycodone. Most prevalent drug combinations were oxycodone in combination with: benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants. These findings are important from a medical-legal standpoint and as a key analysis in the field of pain medicine.
Sex Differences in Morphine Metabolism. Pain is difficult to measure during the acute postoperative period, which limits our ability to analyze these states and renders their management more challenging. Few high-quality, randomized, prospective, controlled trials have compared agents and their metabolites. Now, a study from Idaho State University, Pocatello, Idaho, by Ratka and associates has shown sex differences in pharmacokinetics of morphine glucuronides in the elderly.
Investigators administered a single oral dose of morphine (0.5 mg/kg) to elderly men and women (over 60 years) and then measured concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G). Plasma profiles of morphine did not differ significantly between men and women but the time required to reach the maximum concentration of M3G was significantly longer (1.7-fold) in women than men. However, for the initial 2-3 hours, levels of M6G were higher in men than women. The clearance of M3G and M6G was significantly lower in women compared with men. The M3G clearance was about 2 times lower than the clearance of M6G. These investigators concluded that among the elderly, there are sex differences in the pharmacokinetics of morphine glucuronides but not morphine. The results indicate that with repeated doses of morphine, M3G may accumulate to a greater extent in elderly women than elderly men. It is hoped that, as more studies are performed, we will be able to define more clinical end points, and develop newer drugs with rapid onset and offset, no active metabolites, and reduced morbidity and mortality for our patients.
CSF Chemistry and Chronic Intrathecal Morphine. Despite widespread use of intrathecal morphine for controlling chronic cancer-related pain, no studies have examined the long-term effects of chronic intrathecal morphine infusions on CSF chemistry (protein, glucose, WBC). This is particularly important for patients who are being evaluated for possible CSF infection during chronic spinal drug delivery. Furthermore, granuloma formation on the catheter tip is a potential complication, and knowing the baseline CSF chemistry compared with subsequent measurements may help determine whether any of these substances add to the risk for granuloma formation.
Wallace and Yaksh from the University of California, San Diego, obtained CSF samples from 17 patients receiving chronic intrathecal morphine via implanted infusion pump. Samples were assayed for protein, glucose, and white and red blood cells. The investigators used fluoroscopy to check the integrity and location of the catheter tip. They found no correlation between morphine concentrations and CSF protein, glucose, WBC, or RBC levels. Likewise, they found no correlation between morphine daily dose and levels of CSF protein, glucose, WBC, or RBC. Thus, chronic intrathecal morphine infusions do not cause abnormalities in CSF protein, glucose, or red or white blood cells, and therefore are likely not a risk factor for CSF infection or granuloma formation.
Until we find markers for granuloma formation in such cases, it is probably prudent that all patients receiving long-term intrathecal analgesia undergo periodic radiographic surveillance to further define their risk for developing occult catheter-associated masses and to allow intervention before neurologic injury can develop.
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