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Comparing Adverse Effects of Analgesic Strategies For Comparing Adverse Effects daily and weekly time during which higher than that of the only ATC opi- their pain interfered with their mood oids group and 17 times higher than of Analgesic Strategies for or activities, and they indicated the that of the only PRN opioids group. Chronic Cancer Pain amount of relief they received from Source: J Pain Symptom Manage. 2007;33(1):67–77. their pain medicine in the previ- Nausea, vomiting, drowsiness, lack ous week. They also completed the of energy, urinary retention—some- Karnofsky Performance Status (KPS), Clopidogrel: Best Results times the adverse effects of the anal- which measures patients’ ability to per- Pre- or Post-PCI? gesic medication are enough to derail form activities of daily living and their pain management for patients with need for caregiver assistance. When is the best time to give the anti- cancer. It would help to understand There were no significant differ- platelet clopidogrel to patients sched- the relationships between the type of ences between any of the four groups uled for diagnostic coronary angiogra- analgesic prescription and the preva- in terms of pain intensity or amount of phy—before ad hoc coronary stenting lence and severity of adverse effects. time spent in pain. Total pain interfer- or immediately after? Researchers from But not much information is available, ence scores, however, were significantly University of Debrecen, Debrecen, say researchers from the University higher in the ATC plus PRN opioids Hungary and Medical University of of California, San Francisco; the Uni- group than in the no opioids group. Vienna and Wilhelminenhospital, both versity of Nebraska, Omaha; and the The ATC plus PRN opioids group in Vienna, Austria say starting treat- University of Texas Southwestern Med- also had significantly lower functional ment before percutaneous coronary ical Center, Dallas. They conducted scores on the KPS than the no opioids intervention (PCI) has several benefits. a descriptive, correlational study of and the only PRN opioids groups, sug- The researchers assigned 4,160 174 patients with bone metastasis—as gesting that the former patients may patients with suspected coronary artery part of a larger clinical trial evaluating have been grappling with more exten- disease to receive a loading dose of the PRO-SELF Pain Control Program sive, painful disease. The percentage clopidogrel 300 mg either six to 24 (University of California Regents, of pain relief was significantly lower in hours before stenting (n = 1,481) or Oakland, CA)—and found that adverse the no opioids group than in the only immediately afterward (n = 2,679). effects were particularly prevalent with PRN opioids group. At 30 days, the composite primary either around-the-clock (ATC) opioids The prevalence of most adverse endpoint of acute myocardial infarc- alone or ATC opioids in combination effects ranged from about 25% to tion (AMI), urgent repeat target vessel with as-needed (PRN) opioids. 80%—which is consistent with rates revascularization (TVR), or all-cause The study participants, adult out- reported previously in the medical death was nearly twice as common in patients from several sites in Northern literature. Notably, mean severity rat- the patients who received post-PCI California (including a VA facility and a ings for most adverse effects were in treatment (4.47%) than in those who military hospital), had been prescribed the mild to moderate range, regardless received pre-PCI treatment (2.77%). one of four analgesic strategies: no opi- of analgesic strategy. The researchers When the endpoint components were oids (11%), only PRN opioids (42%), speculate that the patients may have considered individually, there remained only ATC opioids (18%), or ATC plus learned to tolerate or use strategies to a significant reduction in AMIs with PRN opioids (29%). The most com- manage some of the adverse effects. pre-PCI treatment, although the differ- mon short-acting opioid products used The highest prevalence rates and ences in TVR and all-cause death were were acetaminophen with codeine and severity ratings for most adverse effects nonsignificant. acetaminophen with hydrocodone. were found in the only ATC opioids The post-PCI treatment group The most common long-acting opioids and ATC plus PRN opioids groups. also was significantly more likely to were controlled-release morphine and A higher total opioid dose increased have stent thrombosis. Pre-PCI treat- transdermal fentanyl. the risk of many of the adverse effects ment was associated with more major Patients kept a pain management studied. The total opioid dose taken bleeding: 1.35% versus 0.41% in the diary and a checklist of 11 adverse by patients in the ATC plus PRN opi- post-PCI group. The researchers note, effects. They rated the amount of oids group was more than three times however, that major bleeding occurred Continued on page 31 APRIL 2007 • FEDERAL PRACTITIONER • 29 DRUG MONITOR Continued from page 29 less frequently than either AMI or the placed the patient on a nonrebreather trial. Study medications were titrated composite endpoint. face mask, and administered 4 mg of slowly to the full dosages by the end This study’s findings were consistent naloxone but observed no response of week five and maintained through with previous research showing the from the patient. week 10. risk of acute and subacute stent throm- At the ED, the staff administered Patients in all three study groups bosis to be highest within the first few another 4 mg of naloxone. After his were predominantly young, white men. postimplantation days. The benefit Glasgow Coma Scale score dropped During weeks six through 10, the pro- of giving clopidogrel more than six from 7 (on ED arrival) to 3, the staff portion of cocaine free urine samples hours before the planned PCI, say the decided to intubate him. They preoxy- was significantly greater in the tiaga- researchers, may be in preventing acute genated him with a bag valve mask and bine group (43%) than in the gabapen- thrombotic occlusion during the first gave him etomidate 30 mg IV followed tin and placebo groups (31% and 35%, two to six hours after stenting. They by succinylcholine 1.5 mg/kg. Two respectively). Between the first and last explain that, within this timeframe, intubation attempts, however, were weeks, cocaine free urine samples and the full dose of unfractionated heparin impeded by an inability to open his abstinent rates increased substantially applied during PCI has mostly an anti- mouth fully. Suspecting MMR, the staff in the tiagabine group: from 27% to coagulant effect and only a moderate gave the patient vecuronium 10 mg, 48% and from 13% to 35%, respec- influence on platelet activity. They also which relieved the masseter rigidity tively. By contrast, these rates rose less note that increased platelet reactiv- and allowed successful intubation. dramatically in the placebo group— ity has been documented in patients Typically, the authors say, MMR and remained virtually unchanged in undergoing PCI. is managed by stopping the paralytic the gabapentin group. Source: Am J Heart. 2007;153(2):289–295. agent and rescheduling the proce- The gabapentin group had signifi- doi:10.1016/j.ahj.2006.10.030. dure after an evaluation for malignant cantly lower treatment retention (65%) hyperthermia. But this isn’t a practical compared with the tiagabine and When Succinylcholine option when an intubation is urgent, as placebo groups (80% and 92%, res- is often the case in the ED. In this situ- pectively). The only adverse effect at- Inhibits Urgent Intubation ation, early detection and rapid man- tributed to the study medication was agement are key. headache in one patient taking tiaga- With a rapid onset and short duration Source: Am J Emerg Med. 2007;25(1):102–104. bine. Generally, tiagabine was well toler- of action, the depolarizing neuromus- doi:10.1006.j.ajem.2006.05.032. ated, with no evidence of oversedation, cular blocker succinylcholine is an seizures, or other significant adverse emergency department (ED) standby Tiagabine vs. Gabapentin for reactions. The researchers suggest initi- for rapid sequence intubation. On rare ating tiagabine at night, then increasing occasions, though, it can cause mas- Cocaine Dependency the dose on a twice daily schedule until seter muscle rigidity (MMR), which reaching the target dosage. can complicate intubation and be life It came as a bit of a surprise, but Although the researchers are not threatening. Physicians from Carl R. tiagabine proved much better than clear about why gabapentin did Darnall Army Medical Center, Fort gabapentin for reducing cocaine use not increase cocaine free urine sam- Hood, TX report a case of succinyl- among patients with cocaine depen- ples, they propose a few possibilities. choline-induced MMR that illustrates dency who were receiving methadone One is that tiagabine increases gamma- why clinicians need to be ready with a treatment, say researchers at Yale aminobutryric acid (GABA) levels to prompt response. University, New Haven, CT; the VA brain areas directly related to reinforc- The patient, a 36-year-old man, Connecticut Healthcare System, West ing the effects of cocaine. While gaba- had taken an overdose of clonidine Haven; and the University of Arkansas, pentin also increases GABA levels in a and consumed an unknown quantity Little Rock. dose dependent fashion, the areas in the of alcohol approximately three hours The researchers randomly assigned brain it affects are not fully understood. before he was medically evaluated. 76 patients, all of whom were seeking Therefore, gabapentin not only may When he was found, he was unre- help for cocaine and opioid depen- fail to reduce cocaine reinforcement in sponsive to verbal or painful stimuli. dency, to receive tiagabine 24 mg/d, certain areas but also may trigger brain Emergency medical services inserted gabapentin 2,400 mg/d, or placebo— areas that prompt cocaine use.
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