Low-dose amitriptyline as an adjunct to opioids for postoperative orthopedic pain: a placebo-controlled trial.

Tricyclic antidepressants (TCAs) have been found to be useful in the management of a variety of chronic pain conditions, although there is little published regarding the potential efficacy of this class of drug as an adjunct for the control of acute postoperative pain and related symptoms. Twenty-eight patients undergoing total hip or knee arthroplasty completed a randomized, placebo-controlled, double-blinded trial of 50 mg of amitriptyline p.o. HS on postoperative days 1, 2 and 3 while using patient-controlled morphine or meperidine analgesia (PCA). Visual analog (VAS) and numerical verbal (NVS) pain ratings, sedation scores, sleep quantity/quality scores, and sense of well-being scores were assessed twice daily on each of the days succeeding amitriptyline/placebo use. Hourly opioid use was recorded and transcribed from the memory of the PCA devices in use. Mean scores in the amitriptyline group for pain NVS were greater (P < 0.05) (higher score = greater pain) on day 1 and greater on day 2 for the pain VAS. Mean scores for sense of well-being were greater (P < 0.05) (higher score = better sense of well-being) for the placebo group on days 1 and 2. On days 2 and 3, sleep scale variable mean scores were worse in the placebo group (P < 0.025). There were no other statistically significant differences between the control and active drug groups for any of the outcome variables measured. We conclude that amitriptyline at the dose prescribed is no different than placebo in altering the majority of postoperative symptom variables studied in the sample study population but caused no significant adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat.

Preliminary reports have demonstrated that the application of local heat to the transdermal fentanyl patch significantly increased systemic delivery of fentanyl. The objective of this study was to further evaluate the pharmacokinetic effect of local heat administration on fentanyl drug delivery through the transdermal fentanyl patch delivery system in volunteers. In addition, the study was intended to document the effect of heat on steady-state transdermal fentanyl delivery. This was an open, 3-period, crossover study that evaluated the pharmacokinetics and safety of 25 microg/h transdermal fentanyl administered with and without local heat. During Sessions A and B, subjects received transdermal fentanyl for a 30-hour period. During Session A, heat was applied for 1 hour at the 24-hour time point during the 30-hour period. During Session B, heat was applied for the first 4 hours and then again for 1 hour at the 24-hour time point during the 30-hour period. The order of Sessions A and B was randomized, and a minimum of 2 weeks separated the sessions. Five of the 10 subjects returned to participate in Session C. During Session C, subjects received transdermal fentanyl 25 microg/h for 18 hours. Heat was applied during the first 4 hours of administration and then again for 15-minute periods at the 12- and 16-hour time points. Arterial blood samples for determination of serum fentanyl concentration were collected. Maximum concentration (C(max)), time to maximum concentration (t(max)), and area under the curve (AUC) were determined for each treatment period. Sedation, vital signs, oxygen saturation, and adverse events were recorded. During a period of 36 hours, there were no significant differences in C(max), AUC, or T(max) between transdermal fentanyl delivery with no heat and heat. However, significant differences were seen during the first 4 hours, with C(max) and AUC values almost 3 times higher for the heated administrations than for the administrations without heat. With heat, the mean C(max) was 0.63 ng/mL compared with a C(max) of 0.24 ng/mL without heat (P =.007). With early heat, the mean AUC was 1.22 ng/mL. h compared with 0.42 ng/mL. h without heat (P =.003). There was no statistically significant difference between the median times to achieve peak values (T(max)) during the first 4 hours. The addition of heat at 24 hours resulted in rapid increases in serum fentanyl concentrations for both groups and higher serum fentanyl concentrations for the administration that did not receive heat previously. Applying heat for 15 minutes at the 12-hour and 16-hour time points produced a rapid but short duration increase in serum fentanyl concentrations. The results suggest controlled heat might be used to significantly shorten the time needed to reach clinically important fentanyl concentrations. Controlled heat might be useful to produce rapid increases in serum concentrations for the rapid treatment of breakthrough pain.

Systemic exposure to lidocaine and tetracaine is low after an application of a lidocaine 7%-tetracaine 7% peel in adults.

BACKGROUND: The lidocaine 7%-tetracaine 7% (LT) peel has been demonstrated to be useful for a variety of dermatologic applications, including cosmetic, laser, and vascular access procedures. Aim To measure and evaluate the detectable plasma levels and safety of lidocaine and tetracaine in adult volunteers after a single application of an LT peel, a novel method of topical anesthesia that does not require occlusion. METHODS: A randomized, factorial design study was used to evaluate the pharmacokinetic profile of lidocaine and tetracaine after a single application of the LT peel in adult volunteers (n = 36; mean age, 26.6 years). The LT peel was applied to the anterior surface of the left or right thigh of volunteers for 30, 60, or 90 min over a 50-, 100-, or 200-cm(2) area. Venous blood samples were collected at 0, 30, 60, 90, 120, 150, 180, 210, 300, and 420 min after the initial application of the LT peel. RESULTS: At all time points, plasma concentrations of lidocaine and tetracaine were below the limits of quantification for the assay: 100 ng/mL and 5 ng/mL, respectively. Because of the lack of concentrations above the limit of quantification, it was not possible to determine the pharmacokinetic parameters, other than the maximum concentrations of < 100 ng/mL for lidocaine and < 5 ng/mL for tetracaine. A single application of the LT peel was well tolerated, and no study subject reported an adverse event. CONCLUSIONS: A single application of LT peel to up to 200 cm(2) of anterior thigh in adults with a duration of up to 90 min produces systemic levels of lidocaine and tetracaine that are of no clinical significance at all time points measured up to 420 min after the initial application.

Pharmacologic management of neuropathic pain.

The mechanisms underlying the pathogenesis of neuropathic pain are complex but are gradually coming to light. Agents that have been found effective in a variety of neuropathic pain conditions include drugs that act to modulate (a) sodium or calcium channels, (b) N-methyl-D-aspartate receptors, (c) norepinephrine or serotonin reuptake, (d) opioid receptors, and (e) other cellular processes. Clinical trials have primarily evaluated these treatments for postherpetic neuralgia and painful diabetic neuropathy, the two most common types of neuropathic pain. Nonetheless, the identification of effective treatment regimens remains challenging, often because multiple mechanisms may be operating in a given patient giving rise to the same symptom. Alternatively, a single mechanism may be responsible for multiple symptoms. Currently available diagnostic tools are inadequate to determine the best treatment using a mechanism-based model. Clinically, drug treatment of neuropathic pain is often a matter of treatment trials. This article presents a summary of available clinical information on first-line and lesser-known treatments for neuropathic pain.