Winston C. V. Parris

Intrapleural analgesia for postthoracotomy pain and blood levels of bupivacaine following intrapleural injection

An epidural type catheter was placed in the pleural space under direct vision before the closure of the chest in 24 patients who underwent thoracotomy for various types of lung or aortic surgery. All patients received intrapleural injections of 20 ml of 0.5 per cent bupivacaine with or without epinephrine as initial pain therapy. Patients also received subsequent doses of a similar volume of 0.375 per cent bupivacaine with epinephrine 1:200,000 up to four times a day for a maximum duration of seven days. Good pain relief was achieved in patients who underwent lateral and posterior thoracotomies. No pain relief was achieved in patients who underwent anterior thoracotomy or in patients in whom there was excessive bleeding in the pleural space. Bupivacaine blood concentrations were measured in 11 patients following the initial dose of 20 ml of 0.5 per cent bupivacaine (with epinephrine 1:200,000 in five of the 11 patients). The mean peak plasma concentration of bupivacaine when used with epinephrine was 0.32 ± 0.02 μg·ml-1. The mean peak plasma concentrations of bupivacaine when used without epinephrine was 1.28 ± 0.48 μg·ml-1. Our present data show that intrapleural analgesia is useful in the management of postoperative pain in patients who undergo thoracotomy. Our data also show that there is a significant decrease in peak plasma concentrations of bupivacaine when epinephrine is added to the solution (P < 0.05).RésuméChez 24 patients, lors ďune thoracotomie pour chirurgie aortique ou pulmonaire, nous avons laissé un cathéter de type épidural dans la cavité pleurale. A titre ďanalgésique, nous y avons ďabord injecté 20 ml de bupivacaine 0.5 pour cent avec ou sans adrénaline 1.200,000. Nous avons poursuivi la thérapie à raison de doses de 20 ml de bupivacaine 0.375 pour cent avec adrénaline 1:200,000 injectées jusqu’à quatre fois par jour durant un maximum ďune semaine. Ľanalgésie s’est avérée adéquate dans les cas de thoracotomies postérieures ou latérales mais insuffisante pour les thoracotomies antérieures ou en présence ďhémorragie intrapleurale. Après la première dose de 20 ml de bupivacaine 0.5 pour cent, nous en avons mesuré les taux sériques chez 11 patients (dont cinq avaient de ľadrénaline 1:200,000 mélangée à ľanesthésique local). Administrée seule, la bupivacaine atteignait un taux sérique maximal moyen de 1.28 ± 0.48 μg·ml-1 alors que ľadjonction ďadrénaline réduisait cette valeur à 0.32 ± 0.02 μg·ml-1 (P < 0.05). En postopératoire ďune thoracotomie, ľanalgésie intra-pleurale s’avàre utile et ľaddition ďadrénaline à la bupivacaine en réduit le taux sérique maximal.

Comparison of controlled-release and immediate-release oxycodone tablets in patients with cancer pain.

PURPOSE This study compared the clinical efficacy of oxycodone hydrochloride controlled-release (CR) tablets administered every 12 hours with immediate-release (IR) oxycodone tablets administered four times daily in patients with cancer-related pain. PATIENTS AND METHODS Cancer patients who required therapy for moderate to severe pain were randomized to CR oxycodone every 12 hours (n=81) or IR oxycodone four times daily (n=83) for 5 days in a multicenter, double-blind study. Pain intensity was assessed four times daily (categorical scale of none, slight, moderate, and severe); acceptability of therapy was assessed twice daily (categorical scale of very poor, poor, fair, good, and excellent). RESULTS Pain intensity remained slight during the study, with mean oxycodone doses of 114 mg/d (range, 20 to 400 mg/d) for CR and 127 mg/d (range, 40 to 640 mg/d) for IR. Acceptability of therapy was fair to good with both treatments. While standard conversion ratios provided an acceptable dose for many patients, a protocol amendment that allowed initial titration and use of rescue medication reduced the discontinuation rate for lack of acceptable pain control (from 34% to 4% with CR and from 31% to 19% with IR before and after amendment, respectively) without increasing the discontinuation rate for adverse events (from 8% to 7% with CR and from 13% to 11% with IR). Fewer adverse events were reported with CR (109) than with IR (186) oxycodone (P=.006). CONCLUSION CR oxycodone every 12 hours was as effective as IR oxycodone four times daily in managing moderate to severe cancer-related pain and was associated with fewer reports of adverse events.

Long-Term Administration of Controlled-Release Oxycodone Tablets for the Treatment of Cancer Pain

We conducted a study of the safety of controlled-release (CR) oxycodone tablets (OxyContin Tablets) administered chronically to patients with cancer-related pain in a usual clinical setting. These patients had participated in 1 of 2 double-blind, active-control studies. Our study was an open, 3-month treatment study that included 87 patients. Patients received CR oxycodone tablets every 12 hr in a manner that reflected typical clinical practice. Supplemental immediate-release (IR) oxycodone was available PRN for breakthrough pain. Patients recorded medication use, adverse events, and evaluations of pain intensity and acceptability of therapy in a daily diary. Forty-four patients (51%) completed all 12 weeks of study; 43 patients (49%) discontinued participation. At baseline and throughout the study period, the overall mean pain-intensity score was slight to moderate. A comparison of initial and final doses showed a significant but modest increase in total daily CR oxycodone dose. An increase or decrease in titration of the oxycodone dose occurred for 66 patients (84%) at least once during the 12-week study period, primarily for increased pain. Forty-four patients (56%) did not undergo dose titration when the latter was indicated. Half of the patients used IR oxycodone rescue almost daily; the mean number of rescue doses per day was 1.5. Despite stable pain control and an increasing total daily CR oxycodone dose, the percentage of patients reporting common opioid-related adverse events decreased over the course of the study. CR oxycodone tablets administered every 12 hr were successfully used to manage cancer pain over a 12-week period. Importantly, side effects diminished over time without a concomitant change in efficacy.

The relationship between cigarette smoking and chronic low back pain

This study investigated the extent to which habitual cigarette smoking relates to physical and psychological indices of chronic pain. From a review of patient records, 54% of back pain patients referred for treatment of their pain admitted to smoking cigarettes. Response from a smoking questionnaire showed that 57% of the patients who smoked reported having a need to smoke when they were in pain. Most patients (91%), however, believed that smoking had no effect on their pain intensity. When smoking and nonsmoking back pain patients were compared, the smokers showed significantly higher levels of emotional distress, they tended to remain inactive, and they relied on medication more often than the nonsmoking patients. The results further suggest that pain patients are at risk for increasing smoking behavior when they are experiencing periods of heightened pain intensity.

Preferential cerebrospinal fluid acetylcholinesterase inhibition by rivastigmine in humans

This study sought to examine the feasibility of prolonged assessment of acetylcholinesterase (AChE) activity in the cerebrospinal fluid (CSF) of volunteers and to test the hypothesis that rivastigmine (ENA-713; Exelon, Novartis Pharma AG, Basel, Switzerland) selectively inhibits AChE in CSF in humans at a dose producing minimal inhibition of the peripheral enzyme. Lumbar CSF samples were collected continuously (0.1 mL x min(-1)) for 49 hours from eight healthy volunteers who took either placebo or a single oral dose of rivastigmine (3 mg). CSF specimens and samples of blood cells and blood plasma were analyzed at intervals for rivastigmine and its metabolite NAP 226-90 ([-] [3-([1-dimethylaminolethyl)-phenol]), erythrocyte AChE activity, CSF AChE activity, and plasma and CSF butyrylcholinesterase (BuChE) activity. Safety evaluations were performed 23 hours after drug dosing and at the end of the study. Evaluable data were obtained from six subjects. The mean time to maximal rivastigmine plasma concentration (tmax) was 0.83 +/- 0.26 hours, the mean maximal plasma concentration (Cmax) was 4.88 +/- 3.82 ng x mL(-1), the mean plasma area under the concentration versus time curve (AUC0-infinity) was 7.43 +/- 4.74 ng x hr x mL(-1), and the mean plasma t1/2 was 0.85 +/- 0.115 hours. The concentration of rivastigmine in CSF was lower than the quantification limit for assay (0.65 ng x mL(-1)), but NAP 226-90 reached a mean Cmax of 3.14 +/- 0.57 ng x mL(-1). Only minimal inhibition of erythrocyte AChE activity (approximately 3%) was observed. Inhibition of AChE in the CSF after rivastigmine administration was significantly greater than after placebo for up to 8.4 hours after the dose and was maximal (40%) at 2.4 hours. Plasma BuChE activity was significantly lower after rivastigmine than after placebo, but this was not clinically relevant. BuChE activity in CSF was significantly lower after rivastigmine than after placebo for up to 3.6 hours after dosing, but this difference was not sustained. This study confirms the feasibility of using continuous measurement of AChE activity in CSF over prolonged periods, that rivastigmine markedly inhibits CSF AChE after a single oral dose of 3 mg, and that the inhibition of central AChE is substantially greater than that of peripheral AChE or BuChE.

Intrathecal ketorolac tromethamine produces analgesia after chronic constriction injury of sciatic nerve in rat

PurposeThe study compared analgesic efficacy of intrathecally administered ketorolac tromethamine (K) and morphine hydrochlorïde (M) (in equimolar doses) in the chronic neuropathic pain model, induced by chronic constriction injury (CCI) of the sciatic nerve in rat.MethodsMale Sprague-Dawley rats (n = 30) were anaesthetized with halothane and an intrathecal catheter was inserted to the mid-lumbar level of the spinal cord. On the 5th postoperative day, rats were anaesthetized with halothane and four ligatures were loosely applied around the right sciatic nerve. Seven days later, those animals were randomly divided into three groups and were injected with either saline, M (20 nmoles) or K (20 nmoles). Two pain responses (foot-withdrawal delay and hind paw elevation time) were measured on both sides using the radiant heat method. Further, thermal (“cold”) allodynia was assessed by measuring of the total time of hind paw elevation in animals placed on the cold metal plate.ResultsTwenty nmoles of M and K injected intrathecally produced decrease of differential pain score calculated for both measured responses (hind paw withdrawal and hind paw elevation), compared with saline injected animals (P < 0.05). The reduction in pain response produced by K was less (P < 0.05) than the reduction in pain response observed in the animals receiving intrathecal M. Measurement of cold allodynia revealed that the animals in M and K injected groups demonstrated decreases in the total hind paw elevation lime, when compared with saline-injected animals (P < 0.05).ConclusionM and K produced hypoalgesia after intrathecal administration in rats with CCI, with M being more potent than K at an equimolar dose range. The analgesic effect of K was equal to equimolar doses of M for alleviation of cold allodynia.RésuméObjectifComparer l’efficacité analgésique sous-archnoïdienne de la trométhamine de kétorolac (K) à celle de l’hydrochlorure de morphine (M) (à doses équimolaires) sur un modèle de douleur neuropathique chronique induite par une lésion constrictive chronique (LCC) du nerf sciatique chez le rat.MéthodesTrente rats Sprague-Dawley ont été anesthésiés à l’halothane et un cathéter sous-arachnoïdien inséré au niveau lombaire rachidien moyen. Cinq jours plus tard, quatre ligatures ont été nouées lâchement autour du nerf sciatique droit. Sept jours plus tard, ces animaux ont été répartis aléatoirement entre trois groupes et ont reçu soit du sol. physiologique, soit M (20 nmoles), soit K (20 nmoles). Deux réponses à la douleur (l’intervalle jusqu’au retrait de la patte, et la durée de l’élévation de la patte de derrière) ont été mesurées bilatéralement avec la méthode de la chaleur radiante. En outre, l’allodynie thermique («froide») a été évaluée en mesurant la durée totale de l’élévation de la patte de derrière chez les animaux placés sur la plaque de métal froide.RésultatsL’injection sous-arachnoïdienne de 20 nmoles de M et de K a provoqué une baisse des scores de douleurs différentiels calculés pour les deux réactions mesurées (retrait et élévation de la patte de derrière) comparativement aux animaux qui avaient reçu le sol. physiologique (P < 0,05). La réduction de la réponse douloureuse produite par K était moindre (P < 0,05) que celle produite par M. La mesure de l’allodynie au froid a révélé que les animaux des groupes M et K présentaient des diminutions de la durée totale d’élévatoin de la patte de derrière comparativement aux groupe qui avait reçu du sol. physiologique (P < 0,05).ConclusionChez le rat porteur de LCC, l’administration sous-arachnoïdienne de M et de K a produit de l’hypoalgésie, mais M était plus puissant pour une gamme de doses équimolaires. Pour l’atténuation de l’allodynie au froid, à des doses équimolaires, l’effet analgésique de K était égal à celui de M.

Empirically derived Symptom Checklist 90 subgroups of chronic pain patients: A cluster analysis

Four hundred fifty-three chronic pain patients completed a Symptom Checklist 90 (SCL-90) and a comprehensive pain evaluation questionnaire. All patients were evaluated by a physician and rated on degree of pain pathology and pain behavior. The SCL-90 data were analyzed using two clustering procedures and replicated over two similar samples. Three distinct profiles emerged and represented high, medium, and low scores on the SCL-90. No differences were found between subgroups on demographic characteristics, compensation status, pain duration, or pain ratings. Patients in the high-profile subgroup showed the most emotional distress, reported that their pain interfered the most with all activities, and were most often judged to have high pain behavior. Little evidence was found to support a “denial” profile, as previously predicted. Further support was found for using the SCL-90 in assessing chronic pain patients.

Hazards in Operative Management of Patients with Systemic Mastocytosis

During the past two years, six patients with systemic mastocytosis have required general or regional anesthesia for operative correction of various surgical problems. Mastocytosis constitutes an extremely difficult problem in diagnosis and management. A large experience with patients with mastocytosis in the Vanderbilt Medical Center in the last decade has enhanced awareness of this disorder and increased its early recognition. The hazardous problems of systemic mastocytosis and the difficulties of its diagnosis and management are summarized and focussed on the increased hazard of those patients with this disease who require various surgical operations. Close collaboration between anesthesiologists, surgeons, and internists in this medical center in the past two years has made it possible to carry six of these patients through anesthesia, operation, and the postoperative period safely and without fatality.

The Use of Controlled-Release Oxycodone for the Treatment of Chronic Cancer Pain: A Randomized, Double-Blind Study

To compare the effectiveness and safety of controlled-release (CR) oxycodone tablets with immediate-release (IR) oxycodone in patients with chronic cancer pain, a multicenter, randomized, double-blind, parallel-group study was performed in 111 patients with cancer pain. Patients were treated with 6 to 12 tablets or capsules of fixed-combination opioid/nonopioid analgesics per day at study entry. Patients received 30 mg of CR oxycodone tablets every 12 hr or 15 mg of IR oxycodone four times daily for 5 days. No titration or supplemental analgesic medications were permitted. The mean (+/- SE) baseline pain intensity (0 = none, 1 = slight, 2 = moderate, 3 = severe) was 1.5 +/- 0.1 for the CR oxycodone-treated group and 1.3 +/- 0.1 for the group given IR oxycodone (P > 0.05). The 5-day mean pain intensity was 1.4 +/- 0.1 and 1.1 +/- 0.1 for the CR and IR groups, respectively (P > 0.05). Discontinuation rates were equivalent (33%). There was no significant difference between treatment groups in the incidence of adverse events. This study demonstrates that cancer pain patients given 6 to 12 tablets or capsules of fixed-dose combination analgesics can be equally well treated with CR oxycodone administered every 12 hr or IR oxycodone four times daily at the same total daily dose. CR oxycodone offers the benefits of twice daily dosing.

Chronic pain assessment using heat beam dolorimetry

&NA; The heat beam dolorimeter (HBD) was developed to evaluate cutaneous pain thresholds in humans. In the present study, the hypothesis that a patients underlying pain status affects his pain tolerance to an incident HBD stimulus was tested. Twenty‐seven chronic pain patients with a variety of clinical problems unresponsive to conventional algological therapy were scheduled for neurosurgical procedures. These patients were evaluated pre‐ and postoperatively by the HBD procedure. On initial testing, drug‐free pain patients showed significantly higher pain tolerance thresholds than normal volunteers (P < 0.02, Mann‐Whitney U test). Postoperatively, incident pain tolerance thresholds in the HBD test were reducedfrom pre‐surgical levels in these patients and were indistinguishable from the second evaluation latencies of volunteers (P > 0.05). Twenty‐four of the 27 patients reported significant pain relief following surgery. Our results show that, in chronic pain patients, endogenous pain significantly affected incident pain perception in the HBD test when compared with the responses of normal pain‐free volunteers. Consequently, HBD may be useful in objectively assessing chronic pain and its relief by neurosurgical procedures.