William George Brose

All Publications

• Weekly opioid shared medical prescribing appointments to remediate issues of chronic pain patient adherence, aberrance, and noncompliance. Journal of opioid management Clark, H. Y., Kromelow, J., Josefsberg, J., Schultz, S. K., Brose, W. G. 2025; 21 (5): 389-399

  Abstract

  This study evaluated the efficacy of weekly shared medical appointments (SMAs) for opioid prescribing in addressing adherence, aberrance, and noncompliance in chronic pain patients receiving long-term opioid therapy (LTOT).A retrospective observational study.This study was conducted as a structured intervention within a community pain specialty clinic that introduced a monitoring system over 12 months.A total of 355 patients on LTOT were included, of whom 70 were identified as high-risk (Red status) due to noncompliance with opioid use policies.Patients attended monthly telemedicine shared medical opioid education appointments delivered by pain specialists that aimed to increase adherence to practice standards. A stratified risk management approach was used, with patients categorized as Green, Yellow, or Red based on adherence behavior.Primary outcome measures were changes in compliance status (Red to Yellow or Green), opioid prescription changes (morphine milligram equivalent, MME), and overall patient adherence improvement.Of the 70 patients in Red status, 54 percent transitioned to Green status after weekly SMA participation. The median MME was reduced from 200 to 32. The most significant changes occurred among Red status patients, with 54 percent tapering off opioids completely. Compliance improved from 80 to 90 percent across all LTOT patients.Weekly shared medical appointments significantly improved adherence and compliance among LTOT patients. The program highlights the utility of frequent touchpoints in managing high-risk patients and offers an adaptable model for other pain management clinics.

  View details for DOI 10.5055/jom.0944

  View details for PubMedID 41123261

• Intrathecal methods NEUROSURGERY CLINICS OF NORTH AMERICA Kaplan, K. M., Brose, W. G. 2004; 15 (3): 289-?

  Abstract

  Although the use of opioids for intrathecal anesthesia was first reported in 1901, it was not until 25 years ago that the first report of selective blockade of pain by spinal opioids was described. Since its beginning, the promise of selective analgesics derived from intraspinal administration has generated much development in the field of pain management. In fact, many anesthesiologists who had previously relegated themselves to the confines of the operating room discovered that their needles and catheters could reach even beyond the inpatient wards, affording patients outside the hospital the opportunity to receive neuraxial drugs. The goal of this article is to report on the current state of spinal analgesic chemotherapy as it is now known.

  View details for DOI 10.1016/j.nec.2004.02.011

  View details for Web of Science ID 000222809500004

  View details for PubMedID 15246337

• The relationship between the visual analog pain intensity and pain relief scale changes during analgesic drug studies in chronic pain patients ANESTHESIOLOGY Angst, M. S., Brose, W. G., Dyck, J. B. 1999; 91 (1): 34-41

  Abstract

  Most analgesic drug studies in humans quantify drug action based on verbal reports of pain intensity and pain relief. Although measures of pain intensity and pain relief show a good overall correlation, it is not known if they relate to each other consistently over time Such consistency is necessary if both measures are used to depict analgesic drug action versus time. This study examined in chronic pain patients if the relationship between visual analog pain intensity and pain relief scores was consistent during two analgesic drug studies.Data from two independently performed analgesic drug studies were analyzed using linear regression. Data were split into pain intensity and pain relief scores recorded before and after patients' experience of maximum analgesia (>90% of maximum pain relief). The slopes of the linear regression line depicting pain intensity versus pain relief scores before and after maximum analgesia were statistically compared.The slope of the linear regression line before and after maximum analgesia was significantly different in both drug studies (nonoverlapping 95% confidence intervals), -2.16+/-0.57 versus -1.05+/-0.10 and -1.47+/-0.26 versus -1.09+/-0.07, respectively. These results are compatible with the observation that patients indicating the same pain intensity before and after maximum analgesia reported a different magnitude of pain relief.The relationship between visual analog pain intensity and pain relief scores changed systematically during both analgesic drug studies. The authors hypothesize that patients' interpretation of the pain relief scale had changed during the studies and therefore suggest using the pain intensity scale to quantify analgesic drug action over time.

  View details for PubMedID 10422926

• Pharmacokinetics of intravenous dynorphin A(1-13) in opioid-naive and opioid-treated human volunteers CLINICAL PHARMACOLOGY & THERAPEUTICS Gambus, P. L., Schnider, T. W., Minto, C. F., Youngs, E. J., Billard, V., Brose, W. G., Hochhaus, G., Shafer, S. L. 1998; 64 (1): 27-38

  Abstract

  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).The study subjects comprised 20 volunteers divided into two groups of 10 each, stratified by dose (low dose, 250 micrograms/kg; high dose, 1000 micrograms/kg). There were four volunteers receiving long-term opioid therapy and six opioid-naive volunteers (nonopioid group) within each dosing group. Dynorphin A(1-13) was infused over 10 minutes, and arterial blood samples were drawn and assayed for dynorphin immunoreactivity. A population modeling approach was used to characterize the pharmacokinetics. Dynorphin effects on heart rate and arterial blood pressure were also studied.The pharmacokinetics of dynorphin immunoreactivity were linear over the dose range studied and were best described by a three-compartment mammillary model whose parameters were volume 1, 5.0 L; volume 2, 0.80 L; volume 3, 12 L; clearance 1, 6.0 L/min; clearance 2, 0.054 L/min; and clearance 3, 0.044 L/min. Concomitant opioid medication did not affect the disposition of dynorphin immunoreactivity. Tachycardia and flushing were commonly observed side effects. The incidence of side effects was dose dependent and was not influenced by long-term opioid use.Intravenously administered dynorphin A(1-13) is very rapidly metabolized, on the basis of the time course of immunoreactivity in the blood. Long-term opioid therapy did not influence either the pharmacokinetics or incidence of side effects.

  View details for Web of Science ID 000075103400004

  View details for PubMedID 9695716

• Chronic pain ANNUAL REVIEW OF MEDICINE Russo, C. M., Brose, W. G. 1998; 49: 123-133

  Abstract

  Chronic pain is an emotional experience and is defined as pain lasting greater than six months. It is important to understand the neurophysiology of pain in order to treat it. Nociceptors in the periphery travel to the substantia gelatinosa of the spinal cord while secondary and tertiary afferents transmit information from the dorsal horn to the brain. Modification of pain information may take place in these ascending pathways or in descending pathways. Treatment of chronic pain is most successful when it is approached in a multidisciplinary fashion with the focus not only on treatment of underlying etiology, but also on the secondary impacts of pain on the patient's life. The management of chronic pain requires special expertise. Most of the experts in chronic pain assessment and management organize themselves into pain treatment centers. These centers vary widely in their approach to the problem. The most sophisticated is a multidisciplinary center that is university-based and includes teaching and research. Treatment of chronic pain includes a variety of medications, psychological support, and rehabilitation. Multidisciplinary pain management is also an integral part of the palliative care and hospice concept used to treat cancer pain.

  View details for Web of Science ID 000073046600009

  View details for PubMedID 9509254

• Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium channel blocker, in the management of intractable brachial plexus avulsion pain CLINICAL JOURNAL OF PAIN Brose, W. G., GUTLOVE, D. P., Luther, R. R., Bowersox, S. S., McGuire, D. 1997; 13 (3): 256-259

  Abstract

  The objective was to assess the analgesic, antihyperesthesic, and anti-allodynic properties of SNX-111 in neuropathic pain.We describe a patient with refractory, severe deafferentation pain successfully treated with SNX-111 in an open-label, baseline-controlled Phase I/II trial.The patient was hospitalized for treatment and observation.The patient was a 43-year-old man with intractable deafferentation pain of 23 years' duration secondary to brachial plexus avulsion.SNX-111, the first neuron-specific, N-type, voltage-sensitive calcium channel blocker developed for clinical use, was administered by continuous, constant-rate, intrathecal infusion via an indwelling cervical catheter.The primary outcome measures were the Visual Analog Scales of Pain Intensity (VASPI) and Pain Relief (VASPR).The patient experienced complete pain relief (VASPI = 0.0 cm and VASPR = 10.0 cm) with elimination of hyperesthesia and allodynia.SNX-111, administered intrathecally by continuous, constant-rate infusion, produced dose-dependent pain relief in a 43-year-old male patient with a 23-year history of intractable deafferentation and phantom limb pain secondary to brachial plexus avulsion and subsequent amputation. Dizziness, blurred vision, and lateral-gaze nystagmus were dose-dependent side effects that resolved with decreasing dose levels. Complete pain relief was achieved in this patient without side effects after dose adjustment. We conclude that SNX-111 is a potent analgesic, antihyperesthesic, and antiallodynic agent. Controlled studies of SNX-111 in patients with malignant and nonmalignant pain syndromes are warranted and are under way.

  View details for Web of Science ID A1997YF45600012

  View details for PubMedID 9303259

• Novel analgesics CHEMISTRY & INDUSTRY LAW, N. C., BROSE, W. 1997: 306-309

  View details for Web of Science ID A1997WW06200008

• Derivation and cross-validation of pharmacokinetic parameters for computer-controlled infusion of lidocaine in pain therapy ANESTHESIOLOGY Schnider, T. W., Gaeta, R., BROSE, W., Minto, C. F., Gregg, K. M., Shafer, S. L. 1996; 84 (5): 1043-1050

  Abstract

  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 the drug effect. Pharmacokinetic parameters were derived for CCIP administration of lidocaine in patients with chronic pain.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 micrograms.ml-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.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 micrograms.ml-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.kg-1, V2 0.452 +/- 33% 1.kg-1, Cl1 0.0215 +/- 25% 1.kg-1.min-1, and Cl2 0.0589 +/- 35% 1.kg-1.min-1. The median error measured by internal cross-validation was +1.9%, and the median absolute error was 14%.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.

  View details for Web of Science ID A1996UJ07100006

  View details for PubMedID 8623997

• HEALTH OUTCOMES CLINICAL JOURNAL OF PAIN Brose, W. G. 1994; 10 (2): 89-94

  View details for Web of Science ID A1994NN83200001

  View details for PubMedID 8075471

• MORPHINE AND HYDROMORPHONE EPIDURAL ANALGESIA - A PROSPECTIVE, RANDOMIZED COMPARISON ANESTHESIOLOGY Chaplan, S. R., Duncan, S. R., Brodsky, J. B., Brose, W. G. 1992; 77 (6): 1090-1094

  Abstract

  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.

  View details for Web of Science ID A1992KC86500008

  View details for PubMedID 1281625

• ANALGESIA AFTER CESAREAN DELIVERY - PATIENT EVALUATIONS AND COSTS OF 5 OPIOID TECHNIQUES REGIONAL ANESTHESIA Cohen, S. E., Subak, L. L., Brose, W. G., Halpern, J. 1991; 16 (3): 141-149

  Abstract

  The study was designed to compare five opioid analgesic regimens administered after cesarean delivery in a routine hospital setting with respect to patients' perceptions of their pain relief and the impact of analgesic technique on recovery and hospital costs. After cesarean delivery, 684 patients received one of the following: epidural morphine, alone (EM,n = 128), or with fentanyl (EM + F,n = 245); subarachnoid morphine (n = 48); intramuscular meperidine (n = 165), or patient-controlled analgesia using meperidine (PCA, n = 98). On the first three postoperative days (Days 1-3; day of operation is Day 1) patients were surveyed regarding their impressions of their analgesia, the incidence of side effects, times to resume normal activities and satisfaction with their technique. Information regarding drug interventions and costs was obtained from anesthetic records and nursing charts. Patients receiving intramuscular and PCA opioids reported significantly more severe pain during the first 16 hours than those receiving intraspinal opioids (p less than 0.05); differences were minimal for the remainder of Day 1. Among the intraspinal groups, analgesia was best overall with EM; specifically, fentanyl did not decrease early postoperative pain. Analgesia with PCA and intramuscular opioids was similar during the first 16 hours; however, PCA patients felt they had less pain thereafter. Side effects were common in all intraspinal groups and were least frequent with PCA (p less than 0.05 versus all intraspinal groups). Times to sit, walk and drink were similar in all patients except those receiving intramuscular opioids after general anesthesia, who experienced a several-hour delay. Other aspects of recovery did not differ among the groups. Satisfaction parallelled pain relief and was better with intraspinal than with systemic opioids. Costs were greatest with PCA, although differences were small (less than 1%) relative to total hospital charges.

  View details for PubMedID 1883771

• CSF AND BLOOD PHARMACOKINETICS OF HYDROMORPHONE AND MORPHINE FOLLOWING LUMBAR EPIDURAL ADMINISTRATION PAIN Brose, W. G., Tanelian, D. L., Brodsky, J. B., Mark, J. B., Cousins, M. J. 1991; 45 (1): 11-15

  Abstract

  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 pharmacokinetic 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 (mean +/- S.D.). 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.

  View details for PubMedID 1713663

• CONTINUOUS EPIDURAL HYDROMORPHONE FOR POSTTHORACOTOMY PAIN RELIEF ANNALS OF THORACIC SURGERY Brodsky, J. B., Chaplan, S. R., Brose, W. G., Mark, J. B. 1990; 50 (6): 888-893

  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, pruritus, and nausea) was less than reported with other epidurally administered opioids. Continuous infusion of lumbar epidural hydromorphone produced safe, predictable analgesia after thoracotomy.

  View details for PubMedID 1700682

• Systemic tumor embolism following thoracotomy partially masked by postoperative epidural analgesia. Journal of cardiothoracic anesthesia Brodsky, J. B., Brose, W. G., Cannon, W. B., MCKLVEEN, R. E. 1990; 4 (1): 95-96

  View details for PubMedID 1720030

• CARDIORESPIRATORY ARREST FOLLOWING INITIATION OF CRANIAL IRRADIATION FOR TREATMENT OF A BRAIN-STEM TUMOR ANESTHESIOLOGY Brose, W. G., SAMUELS, S. I., Steinberg, G. K. 1989; 71 (3): 450-451

  View details for Web of Science ID A1989AM76600024

  View details for PubMedID 2774274

• OXYHEMOGLOBIN SATURATION FOLLOWING CESAREAN-SECTION IN PATIENTS RECEIVING EPIDURAL MORPHINE, PCA, OR IM MEPERIDINE ANALGESIA ANESTHESIOLOGY Brose, W. G., Cohen, S. E. 1989; 70 (6): 948-953

  Abstract

  The frequency and severity of oxyhemoglobin desaturation was compared in 49 patients receiving epidural morphine, 5 mg (n = 21); patient-controlled analgesia (PCA) using meperidine (n = 20); or intramuscular (im) meperidine (n = 8) for postoperative analgesia following elective cesarean section performed with epidural anesthesia. Oxygen saturation (SpO2) was monitored for 24 h using a pulse oximeter; data were continuously collected and stored every 30 s via an interface connected to a computer. For analysis purposes, SpO2 was divided into five categories: 96-100%, 91-95%, 86-90%, 81-85%, and less than or equal to 80%. Although SpO2 remained above 95% for the majority of the monitored period, patients in all groups experienced periods of desaturation. PCA patients spent the longest cumulative time with SpO2 between 91 and 95%, 231 +/- 49 min (mean +/- SEM), compared with only 112 +/- 30 min and 152 +/- 42 min for the epidural and im groups, respectively (P less than 0.05 vs. epidural group). PCA patients also spent longest with SpO2 at 86-90% (19 +/- 10 min, vs. 6 +/- 3 and 0.5 +/- 0.3 min for the epidural and im groups, respectively), although this difference was not statistically significant. Severe desaturation episodes, defined as SpO2 less than or equal to 85% for more than 30 s, occurred in 71% of patients in the epidural group, 30% in the PCA group, and 63% in the im group (P less than 0.05 PCA vs. epidural and im).(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1989U898800011

  View details for PubMedID 2729636

• EPIDURAL LIDOCAINE FOR CESAREAN-SECTION - EFFECT OF VARYING EPINEPHRINE CONCENTRATION ANESTHESIOLOGY Brose, W. G., Cohen, S. E. 1988; 69 (6): 936-940

  View details for Web of Science ID A1988R353400021

  View details for PubMedID 3195763