William G. Brose

Subcutaneous lidocaine for treatment of neuropathic cancer pain

Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient.

Morphine and hydromorphone epidural analgesia. A prospective, randomized comparison.

Because evidence from uncontrolled, unblinded studies suggested fewer side effects from epidural hydromorphone than from epidural morphine, we employed a randomized, blinded study design to compare the side effects of lumbar epidural morphine and hydromorphone in 55 adult, non-obstetric patients undergoing major surgical procedures. A bolus dose of epidural study drug was given at least 1 h prior to the conclusion of surgery, followed by a continuous infusion of the same drug for two postoperative days. Infusions were titrated to patient comfort. Visual analog scale (VAS) pain scores, VAS sedation scores, and subjective ratings of nausea and pruritus were assessed twice daily. The two treatments provided equivalent analgesia. Sedation scores and prevalence of nausea did not differ significantly between groups. Prevalence of pruritus, however, differed significantly on postoperative day 1, with moderate to severe pruritus reported by 44.4% of patients in the morphine group versus 11.5% in the hydromorphone group (P < .01). On post-operative day 2, reports of pruritus by patients receiving morphine remained higher than those among the hydromorphone-treated subjects, although this difference was no longer statistically significant (32% vs. 16.7%, P = .18). We conclude that lumbar epidural morphine and hydromorphone afford comparable analgesia, but the occurrence of moderate to severe pruritus on the first postoperative day is reduced by the use of hydromorphone.

CSF and blood pharmacokinetics of hydromorphone and morphine following lumbar epidural administration

&NA; Sixteen consenting patients scheduled for elective thoracotomy were enrolled into a randomized trial of epidural morphine and hydromorphone. Each patient had a lumbar epidural catheter placed preoperatively for the purpose of post‐thoracotomy analgesia. Shortly before the end of the operative procedure each patient received 5 mg of morphine and 0.75 mg of hydromorphone via the epidural catheter. Blood was sampled at regular intervals following the opiate administration and patients were randomized to 1 of 7 cervical CSF sampling times. Blood and CSF samples were assayed for morphine and hydromorphone concentration to determine blood and CSF pharmaco‐kinetic profiles. A maximum blood morphine concentration of 60 ± 25 ng/ml (mean ± S.D.) was obtained at 11 ± 6 min (mean ± S.D.). The blood hydromorphone peak of 14 ± 13 ng/ml (mean ± S.D.) occurred 8 ± 6 min The mean peak CSF opioid concentrations of 1581 ng/ml for morphine and 309 ng/ml for hydromorphone occurred 60 min after epidural administration. The blood and CSF pharmacokinetic profiles for morphine and hydromorphone are presented. These profiles are similar for the two drugs after lumbar epidural administration.

Derivation and cross-validation of pharmacokinetic parameters for computer-controlled infusion of lidocaine in pain therapy

Background Lidocaine administered intravenously is efficacious in treating neuropathic pain at doses that do not cause sedation or other side effects. Using a computer-controlled infusion pump (CCIP), it is possible to maintain the plasma lidocaine concentration to allow drug equilibration between the plasma and the site of drug effect. Pharmacokinetic parameters were derived for CCIP administration of lidocaine in patients with chronic pain. Methods Thirteen patients (mean age 45 yr, mean weight 66 kg) were studied. Eight subjects received a computer-controlled infusion, targeting four increasing lidocaine concentrations (1-7 micro gram *symbol* ml sup -1) for 30 min each, based on published kinetic parameters in which venous samples were obtained infrequently after bolus administration. From the observations in these eight patients, new lidocaine pharmacokinetic parameters were estimated. These were prospectively tested in five additional patients. From the complete data set (13 patients), final structural parameters were estimated using a pooled analysis approach. The interindividual variability was determined with a mixed-effects model, with the structural model parameters fixed at the values obtained from the pooled analysis. Internal cross-validation was used to estimate the residual error in the final pharmacokinetic model. Results The lidocaine administration based on the published parameters consistently produced higher concentrations than desired, resulting in acute lidocaine toxicity in most of the first eight patients. The highest measured plasma concentration was 15.3 micro gram *symbol* ml sup -1. The pharmacokinetic parameters estimated from these eight patients differed from the initial estimates and included a central volume one-sixth of the initial estimate. In the subsequent prospective test in five subjects, the new parameters resulted in concentrations evenly distributed around the target concentration. None of the second group of subjects had evidence of acute lidocaine toxicity. The final parameters (+/-population variability expressed as %CV) were estimated as follows: V1 0.101+/-53% 1 *symbol* kg sup -1, V2 0.452 +/-33% l *symbol* kg sup -1, Cl1 0.0215+/-25% l *symbol* kg sup -1 *symbol* min sup -1, and Cl2 0.0589+/-35% l *symbol* kg sup -1 *symbol* min sup -1. The median error measured by internal cross-validation was +1.9%, and the median absolute error was 14%. Conclusions Pharmacokinetic parameters for lidocaine were derived and administration was prospectively tested via computer-controlled infusion pumps for patients with chronic neuropathic pain. The estimated parameters performed well when tested prospectively. A second estimation step further refined the parameters and improved performance, as measured using internal cross-validation.

Continuous epidural hydromorphone for postthoracotomy pain relief

Abstract Forty-four patients were treated with a continuous infusion of lumbar epidural hydromorphone (0.05%) after thoracic operations. Postoperatively, visual analog pain scores were obtained. On postoperative day 1 and 2, more than 90% of the patients experienced either no pain (visual analog pain scale=0) or mild pain (visual analog pain score=1 to 3) at rest. The incidence of side effects (hypoventilation, pruritis, and nausea) was less than reported with other epidurally administered opioids. Continuous infusion of lumbar epidural hydromorphone produced safe, predictable analgesia after thoracotomy.

Pharmacokinetics of intravenous dynorphin A(1–13) in opioid-naive and opioid-treated human volunteers*

Dynorphin A(1–13) is a fragment of the endogenous opioid neuropeptide dynorphin A. Previous research suggested that intravenously administered dynorphin A(1–13) has the ability to modulate morphine‐induced analgesia. We designed this study to characterize the disposition of intravenous dynorphin immunoreactivity in humans and to determine whether concomitant long‐term opioid therapy influenced the pharmacokinetics or side‐effects profile of dynorphin A(1–13).

IASP taxonomy: Questions and controversies

AIM OF INVFsTlliBILQhl The IASP subcommittee on Taxonomy proposed a pain taxonomy in 1888 to further the evaluation and treatment of patients with pain problems. This project was designed to evaluate the utilll of the IASP Pain Taxonomy1 in clinical practice. METHODS: The Pain Management Unit of the Flinders Medical Centre introduced the IASP taxonomy into clinical use for the coding of all patients evaluated in the clinic beginning December, 1987. The IASP five digit code was determined for each patient following the initial interviews and entered into a computer&J relational data base for subsequent analysis. Codes were determined in accordance with the rules provided by the Committee on Taxonomy, by a single medical doctor who was responsible for each individual patient. EigM different doctors from four english speaking countries assigned codes for their respective patients. RESULTS: IASP coding information was obtained on 1,558 patients over 18 consecuttve months. The data were reviewed and each axis of the five diift code was broken down into component values. Frequency distrtbutiins charts were generated for each axis. These frequency distribution charts were reviewed by members of the Pain Management Unit in order to clarify controversies in patient coding. Coding data for axes 1 (region), 2 (system) and 5 (etiology) were compared with written text diagnoses to indicate areas where coding inconsistencies occurred. Axis three (temporal characteristics of pain: pattern of occurence) was reviewed and found to provide inadequate descrimination of the most common presenting symptom. CONCLUSION: The IASP taxonomy represents an important first step in providing better communications in the field of pain management. Continued improvements of the pain taxonomy are necessary to devebp a useful tool. This presentation will summarize the clinical use of the taxonomy, point out controversies in coding pain-related data, and suggest alterations and evaluation strategies to improve the taxonomy. REFERENCES: 1. International Association for the Study of Pain. Subcommittee on Taxonomy, Classification of chronic pain; description of pain terms, Merskey H (ed) Pain supplement 3 (1988) Sl-S225.

IV Methadone Titration: Significant Difference in Lag Times to Peak Analesia and Sedation

Clinical Pharmacology & Therapeutics (1996) 59, 131–131; doi: 10.1038/sj.clpt.1996.22

Continuous Epidural Hydromorphone for Postthoracotomy Pain Relief

Forty-four patients were treated with a continuous infusion of lumbar epidural hydromorphone (0.05%) after thoracic operations. Postoperatively, visual analog pain scores were obtained. On postoperative day 1 and 2, more than 90% of the patients experienced either no pain (visual analog pain scale = 0) or mild pain (visual analog pain score = 1 to 3) at rest. The incidence of side effects (hypoventilation, pruritus, and nausea) was less than reported with other epidurally administered opioids. Continuous infusion of lumbar epidural hydromorphone produced safe, predictable analgesia after thoracotomy.

Comparison of morphine and hydromorphone for postoperative epidural opioid analgesia

AIMS OF mHGAHON: This study aimed to document the required dose of morphine and incidence of complications when morphine is administered epidurally via an implanted portal of the Pharmacia Port-A-Cath s tern for control of pain in cancer atients. S: Over x e last six years we have iIIIQbUIt edQ Port-A-Caths for the epidural administration of morphine in 287 patients with cancer. These patrents remained under the treatment of our Unit and were regularly assessed, providing 6: ood ongoin P documentation. Patients’ records were reviewed to obtain data about morphine dose an incidence o complications. pEsULTI’