Michel Y Dubois, M.D.

Pain, ethics, and public policy
Rich, Ben A; Dubois, Michel
2011 Sep;12(9):1295-1296, Pain medicine
— id: 137456, year: 2011, vol: 12, page: 1295, stat: Journal Article,

Medical practice perspective: identification and mitigation of risk factors for mortality associated with intrathecal opioids for non-cancer pain
Coffey, Robert J; Owens, Mary L; Broste, Steven K; Dubois, Michel Y; Ferrante, F Michael; Schultz, David M; Stearns, Lisa J; Turner, Michael S
2010 Jul;11(7):1001-1009, Pain medicine
OBJECTIVE: The authors recently determined that early and longer term mortality after initiation or reinitiation of intrathecal opioid therapy is higher than previously appreciated: 0.088% within 3 days, 0.39% at 1 month, and 3.89% at 1 year. These rates were 7.5 (confidence interval, 5.7-9.8), 3.4 (confidence interval, 2.9-3.8), and 2.7 (confidence interval, 2.6-2.8) times higher, respectively, at each interval than expected based on the age- and gender-matched general U.S. population. A substantial portion of this excess mortality is probably therapy related and cannot be entirely accounted for by underlying demographic or patient-related factors, or by device malfunctions. We also analyzed multiple complementary internal, governmental, and insurance databases to quantify mortality and to identify medical practice patterns that appear to be associated with patient mortality risks, and to suggest measures for physicians and health care facilities to consider in order to reduce those risks. Both of those objectives involve judgments, which may be controversial and are subject to practical limitations. RESULTS: Multiple clinical and patient- or therapy-related factors appear to increase the risk for early post-implant mortality. Specific risk mitigation measures associated with each factor include: close attention to the starting intrathecal opioid dose (or restarting dose after therapy interruption); avoidance of outpatient implant or other device procedures that involve less than 24-hour monitoring for respiratory depression; supervision of concomitant opioid, respiratory depressant, or other central nervous system active drug intake early post-implant and chronically in the outpatient setting; and careful programming or dosage calculations and decisions in order to avoid the unintentional administration of high intrathecal opioid drug doses. CONCLUSIONS: Mortality after initiation of or device interventions in intrathecal drug delivery patients appears to occur as a result of multiple factors that present possible mitigation opportunities for physicians and health care facilities
— id: 130399, year: 2010, vol: 11, page: 1001, stat: Journal Article,

American academy of pain medicine ethics council statement on conflicts of interest: interaction between physicians and industry in pain medicine
Dubois, Michel Y
2010 Feb;11(2):257-262, Pain medicine
New concerns have appeared recently in regard to the increasingly complex relationship between physicians and the pharmaceutical or devices industry. The American Academy of Pain Medicine (AAPM) Council on Ethics has discussed the issue, especially focusing on the implication of conflicts of interest for Pain Medicine, and published several recommendations for specific professional situations that the Pain Medicine physician may encounter
— id: 111631, year: 2010, vol: 11, page: 257, stat: Journal Article,

A new muscle pain detection device to diagnose muscles as a source of back and/or neck pain
Hunter, Corey; Dubois, Michel; Zou, Shengping; Oswald, William; Coakley, Kathleen; Shehebar, Mourad; Conlon, Ann Marie
2010 Jan;11(1):35-43, Pain medicine
BACKGROUND: Trigger point (TrPs) identification has become the mainstay of diagnosis for the treatment of Myofascial Pain Syndrome; however, manual pressure (MP) to identify TrPs by determining low-pressure pain threshold has low interrater reliability and may lack validity since it is done on inactive muscles. To elicit contractions and mimic an active muscle or movement that 'causes' pain, a Muscle Pain Detection Device (MPDD) has been developed. A selected muscle is stimulated and painful muscles are precisely detected, allowing distinctions between primary and referred muscle pain as well as distinguishing other functional muscle pain thought to cause MPS. METHODS: An IRB approved randomized controlled study is presented of MP (20 patients) control vs MPDD (20 patients) to identify which muscle(s) was the source of pain in subjects presenting to the NYU Pain Management Center with a minimum 3 months history of back pain. Patients were unaware of their diagnostic method. Subjects were injected in 1-3 sites identified via MP or MPDD by a separate, blinded physician. Prior to, and following treatment at one week and one month, the patients were administered Oswestry and visual analog scale pain questionnaires by a blinded evaluator, and their range of motion was measured by a blinded physical therapist. RESULTS: The MPDD group reported significantly larger improvements in pain, mood and Oswestry scores compared with the control (P < 0.05). Moreover, the MPDD group reported 82.5% pain relief at 1 month, compared with 53.2% in the control (P < 0.001). The range of motion measurements failed to reveal any significant difference between the groups. CONCLUSIONS: Using the MPDD appears to be more valid and potentially more reliable than palpation to identify muscles causing regional pain that could benefit from injections
— id: 109669, year: 2010, vol: 11, page: 35, stat: Journal Article,

Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) type I
Walton, K D; Dubois, M; Llinas, R R
2010 Jul;150(1):41-51, Pain
Complex Regional Pain Syndrome (CRPS) is a neuropathic disease that presents a continuing challenge in terms of pathophysiology, diagnosis, and treatment. Recent studies of neuropathic pain, in both animals and patients, have established a direct relationship between abnormal thalamic rhythmicity related to Thalamo-cortical Dysrhythmia (TCD) and the occurrence of central pain. Here, this relationship has been examined using magneto-encephalographic (MEG) imaging in CRPS Type I, characterized by the absence of nerve lesions. The study addresses spontaneous MEG activity from 13 awake, adult patients (2 men, 11 women; age 15-62), with CRPS Type I of one extremity (duration range: 3months to 10years) and from 13 control subjects. All CRPS I patients demonstrated peaks in power spectrum in the delta (<4Hz) and/or theta (4-9Hz) frequency ranges resulting in a characteristically increased spectral power in those ranges when compared to control subjects. The localization of such abnormal activity, implemented using independent component analysis (ICA) of the sensor data, showed delta and/or theta range activity localized to the somatosensory cortex corresponding to the pain localization, and to orbitofrontal-temporal cortices related to the affective pain perception. Indeed, CRPS Type I patients presented abnormal brain activity typical of TCD, which has both diagnostic value indicating a central origin for this ailment and a potential treatment interest involving pharmacological and electrical stimulation therapies
— id: 111814, year: 2010, vol: 150, page: 41, stat: Journal Article,

Mortality associated with implantation and management of intrathecal opioid drug infusion systems to treat noncancer pain
Coffey, Robert J; Owens, Mary L; Broste, Steven K; Dubois, Michel Y; Ferrante, F Michael; Schultz, David M; Stearns, Lisa J; Turner, Michael S
2009 Oct;111(4):881-891, Anesthesiology
BACKGROUND: In 2006, the authors observed a cluster of three deaths, which circumstances suggested were opioid-related, within 1 day after placement of intrathecal opioid pumps for noncancer pain. Further investigation suggested that mortality among such patients was higher than previously appreciated. The authors performed investigations to quantify that mortality and compare the results to control populations, including spinal cord stimulation and low back surgery. METHODS: After analyzing nine index cases--three sentinel cases and six identified by a prospective strategy--the authors used epidemiological methods to investigate whether mortality rates reflected patient- or therapy-related differences. Mortality rates after intrathecal opioid therapy and spinal cord stimulation were derived by correlating Medtronic device registration data with de-identified data from the Social Security Death Master File. Aggregate demographic and comorbidity data were obtained from Medicare and United Healthcare population databases to examine the influence of demographics and comorbidities on mortality. RESULTS: Device registration and Social Security analyses revealed an intrathecal opioid therapy mortality rate of 0.088% at 3 days after implantation, 0.39% at 1 month, and 3.89% at 1 yr-a higher mortality than after spinal cord stimulation implants or after lumbar diskectomy in community hospitals. Demographic, illness profile, and mortality analyses of large databases suggest, despite limitations, that excess mortality was related to intrathecal opioid therapy, and could not be fully explained by other factors. These findings were consistent with the nine index cases that revealed that respiratory arrest caused or contributed to death in all patients. No device malfunctions associated with overinfusion were identified among cases where data were available. CONCLUSIONS: Patients with noncancer pain treated with intrathecal opioid therapy experience increased mortality compared to similar patients treated by using other therapies. Respiratory depression as a consequence of intrathecal drug overdosage or mixed intrathecal and systemic drug interactions is one plausible, but hypothetical mechanism. The exact causes for patient deaths and the proportion of those deaths attributable to intrathecal opioid therapy remain to be determined. These findings, although based on incomplete information, suggest that it may be possible to reduce mortality in noncancer intrathecal opioid therapy patients
— id: 130400, year: 2009, vol: 111, page: 881, stat: Journal Article,

Pain medicine position paper
Dubois, Michel Y; Gallagher, Rollin M; Lippe, Philipp M
2009 Sep;10(6):972-1000, Pain medicine
— id: 130401, year: 2009, vol: 10, page: 972, stat: Journal Article,

A randomized controlled evaluation of a new muscle pain detection device (MPDD) to diagnose muscle pain as the source of back and/or neck pain in patients
Hunter C.W.; Dubois M.; Zou S.; Oswald W.; Coakley K.; Shehebar M.; Conlon A.M.
2009 ;10(1):233-233, Pain medicine
Introduction: Manual pressure (MP) to identify Trigger Points (TrPs) by determining low pressure pain threshold has low inter-rater reliability and may lack validity since it is done on inactive muscles. Muscle pain is generally experienced with activity. To elicit a muscle contraction and mimic movement that causes pain, a Muscle Pain Detection Device (MPDD) has been developed. A selected muscle is stimulated and painful muscles are precisely detected, allowing distinctions between primary and referred muscle pain [in our nomenclature, Muscle Pain Amenable to Injection vs. TrPs] as well as distinguishing other functional muscle pain thought to cause myofascial pain syndrome. MPDD could provide a valid, reliable assessment of muscle pain which is frequently ignored/mistreated. Methods: An IRB approved doubleblind, randomized controlled study of the MPDD (20 patients) vs. MP (20 patients) control to identify which muscle(s) was the source of pain in 40 subjects presenting to the NYU Pain Management Center with a minimum 3 month history of back pain. Patients were unaware of their diagnostic group. Subjects were injected in 1-3 sites identified via MP or MPDD by a separate physician blinded from the method of detection. Prior to, and following treatment at one week and one month, the patients are given a physical exam and administered Oswestry and VAS pain questionnaires by a blinded evaluator. Results: The MPDD group reported statistically significant improvement in pain, mood and Oswestry scores at 1 week and one month (P < 0.004 - 0.001). The control reported no statistical improvements except for the Oswestry scores at 1 week. Moreover, the MPDD group reported 82.5% pain relief at 1 month, compared to 53.2% in the control (P < 0.001). Conclusion: Using the MPDD appears to be more valid and reliable than palpation to identify muscles causing regional pain that could benefit from muscle injections
— id: 111414, year: 2009, vol: 10, page: 233, stat: Journal Article,

Psychiatry and pain: An irreversible symbiosis
Dubois, Michel Y
2007 ;14(9):46-47 Sep, Primary Psychiatry
Immense progress in pain research in the last 40 years has led to improved diagnosis and treatment of pain patients. Since Melzak and Wall's landmark gate theory published in 1965, overwhelming evidence, from both basic science research and clinical investigation, has replaced the simplistic 'wire concept' of pain transmission with new and more subtle pathophysiologic mechanisms. One of the main findings has been that, whereas acute pain can be related to tissue injury, and pain is usually a symptom of this injury, lasting chronic pain has been shown to represent a different condition which is not related to peripheral nociceptive input but represents a disease state of its own. This disease state is created by neural plastic changes of the nervous system usually referred to as 'sensitization.' Because it is a disease involving the nervous system, it is not surprising that chronic pain may be associated with significant psychological effects leading to psychopathology.
— id: 92731, year: 2007, vol: 14, page: 46, stat: Journal Article,

Open-label exploration of an intravenous nalbuphine and naloxone mixture as an analgesic agent following gynecologic surgery
Gordon, Assaf T; Levine, Jon D; Dubois, Michel Y; D'Angelo, Robert; Conlon, Ann M; Levacic, Danijela; Lebovits, Allen
2007 Sep;8(6):525-530, Pain medicine
OBJECTIVE: The purpose of this series was to explore a 12.5:1 fixed-dose ratio of an intravenous nalbuphine and naloxone mixture (NNM) for use in patients following gynecologic surgery. DESIGN AND PATIENTS: Open-label, nonrandomized case series. The first series was a dose-ranging investigation for 12 patients following elective total abdominal hysterectomy or myomectomy. In this series, fentanyl was used for intraoperative analgesia, and patients were assigned to a lower NNM (2.5 mg/0.2 mg) or to a higher NNM (5 mg/0.4 mg) dose group. The second series evaluated the fixed dose of 5 mg nalbuphine/0.4 mg naloxone for four patients undergoing ambulatory gynecologic procedures. In the second series, no opioid agents were administered intraoperatively to eliminate the possibility of mu-opioid reversal by naloxone postoperatively. OUTCOME MEASURES: Pain control was assessed using a Verbal Pain Scale (0-10). Vital signs, side effects, and adverse events were recorded to determine drug safety. RESULTS: In the first series, there were no adverse events; however, each patient required rescue medication (either morphine or fentanyl). In the second series, two of the four patients reported a reduction in pain following drug administration and did not require any further analgesic agents in the 3-hour postoperative period. One patient had an asymptomatic lowering of heart rate after receiving the drug. CONCLUSION: Additional research of the unique combination therapy of nalbuphine and naloxone is warranted to further determine its potential clinical efficacy and safety
— id: 74683, year: 2007, vol: 8, page: 525, stat: Journal Article,

Conflicts of interest with the health industry
Dubois, Michel Y
2006 Sep-Oct;7(5):463-465, Pain medicine
— id: 96431, year: 2006, vol: 7, page: 463, stat: Journal Article,

Ethical challenges for the pain physician: Recognizing conflicts of interest
Schofferman, J; Rich, BA; Dubois, MY
2006 SEP-OCT ;7(5):457-465, Pain medicine
— id: 68755, year: 2006, vol: 7, page: 457, stat: Journal Article,

Diagnostic and treatment issues in postamputation pain after landmine injury
Wiffen, Philip; Meynadier, Jacques; Dubois, Michel; Thurel, Calude; deSmet, Johan; Harden, R Norman
2006 Nov-Dec;7 Suppl 2:S209-S212, Pain medicine
— id: 145739, year: 2006, vol: 7 Suppl 2, page: S209, stat: Journal Article,

The birth of an ethics charter for pain medicine
Dubois, Michel Y
2005 May-Jun;6(3):201-202, Pain medicine
— id: 96432, year: 2005, vol: 6, page: 201, stat: Journal Article,

Pharmacologic treatment of complex regional pain syndrome [invited review]
Cohen SP; Dubois M
2003 ;24:35-42, Current reviews in clinical anesthesia
— id: 45595, year: 2003, vol: 24, page: 35, stat: Journal Article,

Chronic pain management
Dubois MY; Gharibo C; Lebovits AH
Wylie and Churchill-Davidson's a practice of anesthesia London : Arnold, 2003,
— id: 3486, year: 2003, vol: , page: 1235, stat: Chapter,

Pain management at the end of life: often a difficult call
Dubois, Michel Y; Fine, Perry G; Fischberg, Daniel; Ferrell, Betty; Taylor, Mary Lou
2003 Mar;4(1):81-84, Pain medicine
— id: 45554, year: 2003, vol: 4, page: 81, stat: Journal Article,

Chronic nonmalignat pain
Dubois MY; Fisher P; Heckber LA; Paice JA
2002 ;4(2):20, 23-24, Medical crossfire
— id: 32118, year: 2002, vol: 4, page: 20, 23, stat: Journal Article,

Is optimal pain relief at the end of life real relief?
Dubois, Michel Y; Cahana, Alex; Portenoy, Russell K; Zhukovsky, Donna S
2002 Sep;3(3):289-291, Pain medicine
— id: 96435, year: 2002, vol: 3, page: 289, stat: Journal Article,

Incompetence, drug diversion or pain management? Trying to draw the line
Dubois, Michel Y; Livovich, Jeffrey; Fletwood, Janet; Joranson, David E; Vaillancourt, Philippe D
2002 Mar;3(1):73-77, Pain medicine
— id: 96433, year: 2002, vol: 3, page: 73, stat: Journal Article,

Psychologists and pain physicians: can they share all the information about their patients?
Dubois, Michel Y; Okifuji, Akiko; Hamaty, Daniel; Taylor, Mary Lou
2002 Jun;3(2):169-171, Pain medicine
— id: 96434, year: 2002, vol: 3, page: 169, stat: Journal Article,

Pain medicine is now a reality. [Spanish]
Dubois MY
2001 ;8(1):1-2, Revista de la Sociedad Espanola del Dolor
The management of chronic pain is a total and important part of the clinical practise in many countries. The problem in suffering terms and economic resources make that the creation of organic structures to solve this problem was a priority.
— id: 26875, year: 2001, vol: 8, page: 1, stat: Journal Article,

When it's hard to please everybody: etiquette serving ethics when you disagree with a colleague
Dubois MY; Banja J; Hamaty D; Orr R
2001 Mar;2(1):83-86, Pain medicine
— id: 45550, year: 2001, vol: 2, page: 83, stat: Journal Article,

Ethics and standards of care
Dubois, M Y; Welz, M; Livovich, J; King, L A; Arnold, B; Gordin, V
2001 Dec;2(4):355-358, Pain medicine
— id: 130402, year: 2001, vol: 2, page: 355, stat: Journal Article,

Ethical dilemmas in pain management
Ferrell BR; Novy D; Sullivan MD; Banja J; Dubois MY; Gitlin MC; Hamaty D; Lebovits A; Lipman AG; Lippe PM; Livovich J
2001 Jun;2(3):171-180, Journal of pain
The purpose of this study was to survey the membership of the American Pain Society and the American Academy of Pain Medicine to determine their beliefs about ethical dilemmas in pain management practice. Respondents rated ethical dilemmas for their importance as well as their own competence in dealing with these ethical issues. The survey also included an open-ended question that asked respondents to describe clinical situations in which they had encountered ethical dilemmas. A total of 1,105 surveys were analyzed, with physicians (N = 612), nurses (N = 189), and psychologists (N = 166) representing the professions with the greatest response. Management of pain at the end of life, general undertreatment of pain, and undertreatment of pain in the elderly were the most frequently encountered dilemmas. Qualitative data were analyzed to identify ethical issues in the case examples provided by the respondents. Major themes included inappropriate pain management, barriers to care, interactions and conflicts with others, regulatory/legal issues, euthanasia, assisted suicide, and research issues. We conclude that ethical dilemmas are common in pain management practice and that resolution of these dilemmas requires commitment by individual professionals as well as health systems
— id: 45553, year: 2001, vol: 2, page: 171, stat: Journal Article,

Satisfaction with epidural and intravenous patient-controlled analgesia
Lebovits AH; Zenetos P; O'Neill DK; Cox D; Dubois MY; Jansen LA; Turndorf H
2001 Dec;2(4):280-286, Pain medicine
Objective. Postoperative intravenous (IV) versus epidural morphine patient-controlled analgesia (PCA) were compared regarding maintenance of initial PCA route, pain levels, side effects, and levels of satisfaction. Additionally, the role of preoperative attitudinal expectations in predicting postoperative levels of satisfaction with pain management as well as maintenance of initial PCA route was evaluated. Design. After either abdominal or thoracic surgery, 70 eligible patients were randomized to receive morphine either through an epidural route (n = 37) or an intravenous PCA pump (n = 33). Setting. A large tertiary university teaching hospital in a major northeastern city. Outcome measures. Patients completed visual analogue rating scales 1 week before surgery regarding attitudes such as expectations of satisfaction with pain management after surgery and expectations of medication efficacy postsurgically. Postoperatively, beginning the day after surgery, patients were asked to complete visual analogue rating scales every 12 hours until they were discharged, for a maximum of 3 postoperative days. The scales evaluated included pain, ability to think, and satisfaction with pain control. Results. There were no significant between-group differences on the postoperative visual analogue scales. Although the overall rate of changing the initial PCA route to which the patients were randomized was identical for both groups (30%), those patients who had thoracic surgery changed their route of PCA administration significantly less when their initial PCA route was epidural (20%) than when their initial PCA route was IV (46%) (P <.05). Patients who were satisfied with pain control postoperatively were more likely to have been started on IV PCA (P =.001), have lower preoperative expectations of postoperative satisfaction with pain (P <.001), and have higher preoperative expectations of medication effects on postoperative pain (P <.001). Additionally, older patients (P =.007) and patients with lower preoperative expectations of postoperative satisfaction with pain (P =.003) were more likely to adhere to their initial treatment protocol. Conclusions. Both techniques, IV and epidural PCA, result in high levels of satisfaction. Satisfaction with PCA can be accurately predicted in nearly three of four patients based on initial PCA route and preoperative attitudes. Additionally, maintaining the initial treatment plan can be accurately predicted based on age and preoperative attitudes. Patient expectations about pain relief should be addressed preoperatively, particularly with younger patients, for optimal results
— id: 45485, year: 2001, vol: 2, page: 280, stat: Journal Article,

The pain-procedure-insurance triad: bonds to help may hurt
Dubois MY
2000 Jun;1(2):183-185, Pain medicine
— id: 45551, year: 2000, vol: 1, page: 183, stat: Journal Article,

Why an "Ethics" forum in pain medicine?
Dubois MY
2000 Jun;1(2):105-106, Pain medicine
— id: 45552, year: 2000, vol: 1, page: 105, stat: Journal Article,

Cannabinoids in the treatment of pain. An overview
Dubois, Michel; Nahas, Gabriel; Sutin, Kenneth
Marihuana and medicine Totowa, NJ : Humana Press,
— id: 2563, year: 1999, vol: , page: 573, stat: Chapter,

The management of severe chronic pain with a focus on new treatment modalities
McGuire, D; Luther, RR; DuBois, M
1998 MAY ;34(5):481-486, Drugs of today (Barcelona, Spain : 1998)
Pain is the most common reason for consultation with a physician, but because pain is not objectively measurable, it is often neglected or underestimated. Chronic, severe pain is a major complication of cancer and HIV-1 infection. Current therapy typically employs stepwise treatment first with nonopioid analgesics, followed by weak and then strong opioids. Nevertheless, treatment can be limited both by side effects and by the development of tolerance, and patients with neuropathic pain are often resistant to all conventional therapies. Much has been learned about the neuroanatomy and physiology of both acute and chronic pain. Drugs now being developed, such as alpha(2)-receptor agonists, the N-type calcium channel blocker, SNX-111 and NMDA antagonists, take advantage of current knowledge of the neurochemistry of pain transduction and target neurotransmitter modulation as a means of achieving analgesia. These new drugs and alternative administration methods, such as intraspinal drug delivery and preemptive analgesia for postoperative pain, should add substantially to the current analgesic armamentarium. (C) 1998 Prous Science. Ail rights reserved
— id: 53413, year: 1998, vol: 34, page: 481, stat: Journal Article,

Pharmacodynamics of rocuronium with and without prior administration of succinylcholine
Dubois MY; Lea DE; Kataria B; Gadde PL; Tran DQ; Shearrow T
1995 Feb;7(1):44-48, Journal of clinical anesthesia
STUDY OBJECTIVES: To compare succinylcholine (S) and rocuronium (R) used for endotracheal intubation, and to assess the possible action of S on subsequently administered R. DESIGN: Double-blind, randomized, phase III study. SETTING: University Medical Center. PATIENTS: 24 ASA physical status I and II patients, ages 28 to 65, undergoing general anesthesia for abdominal procedures. INTERVENTION: Double-blind administration of R 600 mcg/kg (Group A) or S 1 mg/kg was achieved with open label R 150 mcg/kg. Standardized general anesthetic technique with sodium thiopental, fentanyl, and nitrous oxide in oxygen was administered. MEASUREMENTS AND MAIN RESULTS: Neuromuscular junction was tested by ulnar nerve stimulation and mechanomyograph. Intubation was attempted at 80% first twitch depression of train-of-four. Heart rate and blood pressure were recorded throughout. Onset times were 74 +/- 37 seconds for S and 130 +/- 46 seconds for R. Intubation times were 76 +/- 29 seconds for S and 85 +/- 23 seconds for R (no significant difference). Good to excellent intubation conditions were achieved in both groups. S given prior to R decreased onset time and increased duration of R, when compared with R given alone. No drug related cardiovascular events were noted. CONCLUSION: Rapid intubation conditions can be obtained after both S and R. Given its overall safety profile, R can be used when S is contraindicated, or in healthy patients with no apparent difficult airway, when procedures are expected to last more than 25 minutes
— id: 45555, year: 1995, vol: 7, page: 44, stat: Journal Article,

Inclusion of women in clinical research
Dubois MY; Burris JF
1994 Sep;69(9):693-694, Academic medicine
— id: 45556, year: 1994, vol: 69, page: 693, stat: Journal Article,

The pharmacokinetics of propofol in children using three different data analysis approaches
Kataria BK; Ved SA; Nicodemus HF; Hoy GR; Lea D; Dubois MY; Mandema JW; Shafer SL
1994 Jan;80(1):104-122, Anesthesiology
BACKGROUND: Accurate dosing of propofol in children requires accurate knowledge of propofol pharmacokinetics in this population. Improvement in pharmacokinetic accuracy may depend on the incorporation of individual patient factors into the pharmacokinetic model or the use of population approaches to estimating the pharmacokinetic parameters. We investigated whether incorporating individual subject covariates (e.g., age, weight, and gender) into the pharmacokinetic model improved the accuracy. We also investigated whether the use of a mixed-effects population model (e.g., the computer program NONMEM) improved the accuracy of the pharmacokinetic model beyond the accuracy obtained with models estimated using two simple approaches. METHODS: We studied 53 healthy, unpremedicated children (28 boys and 25 girls) ranging from 3 to 11 yr of age. Twenty children only received an initial loading dose of 3 mg/kg intravenous propofol. In the remaining 33 children, an initial intravenous propofol dose of 3.5 mg/kg was followed by a propofol maintenance infusion. Six hundred fifty-eight venous plasma samples were gathered and assayed for propofol concentrations. Three different regression techniques were used to analyze the pharmacokinetics: the 'standard two-stage' approach, the 'naive pooled-data' approach, and the nonlinear mixed-effects modeling approach (as implemented in NONMEM). In both the pooled-data and mixed-effects approaches, individual covariates (age, weight, height, body surface area, and gender) were added to the model to examine whether they improved the quality of the fit. Accuracy of the model was measured by the ability of the model to describe the observed concentrations. RESULTS: The pharmacokinetics of propofol in children were best described by a three-compartment pharmacokinetic model. There were no appreciable differences among the pharmacokinetics estimated using the two-stage, pooled-data, and mixed-effects approaches. Weight was a significant covariate, and the weight-proportional model was supported by all three regression approaches. The pharmacokinetic parameters of the weight-proportional pharmacokinetic model (pooled-data approach) were: central compartment (V1) = 0.52 1 x kg-1; rapid-distribution compartment (V2) = 1.01 x kg-1; slow-distribution compartment (V3) = 8.2 1 x kg-1; metabolic clearance (Cl1) = 34 ml.kg-1 x min-1; rapid-distribution clearance (Cl2) = 58 ml.kg-1 x min-1; and slow-distribution clearance (Cl3) = 26 ml.kg-1 x min-1. The inclusion of age as an additional covariate of V2 statistically improved the model, but the actual improvement in the fit was small. CONCLUSIONS: The pharmacokinetics of propofol in children are well described by a standard three-compartment pharmacokinetic model. Weight-adjusting the volumes and clearances significantly improved the accuracy of the pharmacokinetics. Adjusting the pharmacokinetics for inclusion of additional patient covariates or using a mixed-effects model did not further improve the ability of the pharmacokinetic parameters to describe the observations
— id: 45557, year: 1994, vol: 80, page: 104, stat: Journal Article,

Pharmacodynamic effects of three doses of ORG 9426 used for endotracheal intubation in humans
Dubois MY; Lapeyre G; Lea D; Tran DQ; Kataria BK
1992 Nov-Dec;4(6):472-475, Journal of clinical anesthesia
STUDY OBJECTIVE: To determine the pharmacodynamic characteristics of three incremental doses of ORG 9426 used for endotracheal intubation in patients. DESIGN: Double-blind, randomized administration of one of three doses of intravenous ORG 9426. SETTING: Inpatients requiring surgery at Georgetown University Medical Center. PATIENTS: Thirty-six patients, ages 18 to 65, ASA physical status I, II, and III, scheduled for general surgery. INTERVENTIONS: After Georgetown University Institutional Review Board approval and patient consent, patients were premedicated with midazolam or droperidol. Anesthesia was induced with thiopental sodium and fentanyl. Anesthesia was maintained with 60% nitrous oxide in oxygen. The ulnar nerve was stimulated supramaximally with a 2 Hz train-of-four (TOF) every 20 seconds. Thumb contractions were measured with a force transducer. When TOF and anesthesia were stable, 2, 2.5, or 3 times the ED95 of ORG 9426 (570 micrograms/kg, 710 micrograms/kg, or 850 micrograms/kg) was administered randomly. Tracheal intubation was attempted at maximal depression of the first TOF response (T1). MEASUREMENTS AND MAIN RESULTS: The following parameters were measured: time interval from the injection of ORG 9426 to 90% depression of T1 (T1 90% block), maximal T1 depression (onset time), intubating conditions, clinical duration (time for return of T1 to 25% of control), heart rate (HR), blood pressure (BP), and any adverse clinical experience. ORG 9426 provided adequate intubating conditions in all patients but two, independent of the dose used. Its onset time was rapid, but increasing the dose did not shorten the onset. T1 90% block was achieved rapidly (75 +/- 25 seconds to 78 +/- 18 seconds, means +/- SD). The clinical duration of ORG 9426 was relatively short and lengthened with increasing doses (from 36 +/- 18 minutes at 570 micrograms/kg to 42 +/- 10 minutes at 850 micrograms/kg. Spontaneous twitch recovery from 10% to 25% was similar in all dosage groups (5 +/- 1 minutes to 6 +/- 4 minutes). No clinically significant changes in HR and BP and no adverse clinical experiences were noted in any group. CONCLUSION: These findings warrant further clinical evaluation of ORG 9426 for induction and maintenance of muscle relaxation in humans
— id: 45558, year: 1992, vol: 4, page: 472, stat: Journal Article,

New techniques in postoperative analgesia. Including patient-controlled intravenous administration
Dubois MY
1991 Nov 1;90(6):143-6, 149, Postgraduate medicine
New and more efficient techniques of postoperative pain management have been recently introduced. Patient-controlled intravenous (and perhaps subcutaneous) administration of analgesics is an improvement over traditional intramuscular injection. Its efficacy, safety, and high acceptance by patients, surgeons, and nurses make this technique increasingly popular for routine management of postoperative pain. Epidural or intrathecal administration of narcotic agents, although more efficient in controlling pain than intravenous infusion, should probably be reserved for indications such as major thoracic and abdominal procedures. Spinal administration requires more routine surveillance and, when inadequately managed, has the potential for serious side effects and complications. Clinical investigations currently in progress are aimed at finding more successful and safer methods of postoperative pain control. The best methods will likely involve a multifaceted therapeutic approach rather than the simple effect of one 'magic bullet.'
— id: 45559, year: 1991, vol: 90, page: 143, stat: Journal Article,

Effects of succinylcholine on the pharmacodynamics of pipecuronium and pancuronium
Dubois MY; Fleming NW; Lea DE
1991 Mar;72(3):364-368, Anesthesia & analgesia
To study the effects of succinylcholine on subsequent pharmacodynamics of nondepolarizing muscle relaxants, a comparative pharmacodynamic study was carried out in patients having balanced anesthesia (thiopental, fentanyl, nitrous oxide/oxygen) in whom equipotent doses of pipecuronium (80 micrograms/kg) and pancuronium (100 micrograms/kg) were given with or without prior administration of succinylcholine (1 mg/kg). Fifty-two patients were randomly assigned to one of the following four groups: 1, pancuronium (100 micrograms/kg); 2, pipecuronium (80 micrograms/kg); 3, succinylcholine (1 mg/kg) plus pancuronium (100 micrograms/kg); and 4, succinylcholine (1 mg/kg) plus pipecuronium (80 micrograms/kg). In groups 3 and 4, the nondepolarizing relaxant was given after succinylcholine when the twitch height recovered to 75% of its control value. For maintenance of neuromuscular blockade, additional increments of pancuronium (20 micrograms/kg) or pipecuronium (15 micrograms/kg) were given. Neuromuscular function was monitored throughout induction, maintenance, spontaneous recovery, and pharmacologic reversal of the neuromuscular block. Mean onset times for pancuronium (group 1) and pipecuronium (group 2) given without succinylcholine were (mean +/- SEM) 2.5 +/- 0.3 and 2.8 +/- 0.2 min, respectively. Mean onset times (times to maximum twitch depression) of the two drugs given after succinylcholine (groups 3 and 4) were significantly shorter (1.4 +/- 0.4 and 1.6 +/- 0.1 min, respectively). Clinical durations (i.e., until 25% twitch recovery of pancuronium and pipecuronium) were not significantly different among the four groups, varying from 81.1 +/- 5.4 (group 4) to 107.0 +/- 17.0 (group 2) min.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 45560, year: 1991, vol: 72, page: 364, stat: Journal Article,

Pharmacodynamic effects of vecuronium: a dose response study
Kaufman JA; Dubois MY; Chen JC; Lea DE
1989 ;1(6):434-439, Journal of clinical anesthesia
Vecuronium was administered to patients in dosages of 0.1, 0.2, 0.3, and 0.4 mg/kg to determine the clinical efficacy of large doses of vecuronium. Onset times shortened with larger doses up to 0.3 mg/kg. With 0.4 mg/kg, however, there was no significant improvement in onset time and the duration of action became unpredictable and often prolonged. Mean onset times were 172, 138, 106, and 100 seconds for the four groups, respectively. Prolonged duration of action (43, 96, 111, and 174 minutes, respectively) was observed with increasing dosages. Recovery rates for the first twitch response of the train-of-four stimulus from 10% to 25% were similar in all groups. There were no adverse hemodynamic effects secondary to large doses of vecuronium
— id: 45561, year: 1989, vol: 1, page: 434, stat: Journal Article,

Effects of enflurane on brainstem auditory evoked responses in humans
Dubois MY; Sato S; Chassy J; Macnamara TE
1982 Nov;61(11):898-902, Anesthesia & analgesia
The effects of enflurane anesthesia on brainstem auditory evoked responses (BAERs) was determined in 10 patients with normal hearing undergoing various surgical procedures. Arterial blood pressure, body temperature, and arterial Pco2 were controlled during the 2- to 5-hour recording sessions. End-tidal enflurane concentrations were continuously recorded on a chemetron Medspect II mass spectrometer in three subjects. BAERs were obtained by, and recorded on a Nicolet CA 1000, from C2 with reference to A1 or !2, with a 2000 click-averaging for each measurement. Enflurane administered at clinical concentrations (0.5% to 3%) produced a consistent changes in BAER latencies. The waves significantly affected (p less than 0.01) were waves III, IV, and V and interpeak latency I-V. The magnitude of theses changes was related to the concentration of enflurane and was magnified by temporarily decreasing the Paco2. These findings confirm similar data obtained in animals which have shown the same effects at doses that can produce generalized seizure activity. BAER analysis shows that changes predominate at the pons and midbrain levels and affect the brain stem conduction time, which likely reflects the action of enflurane on the activity of the reticular activating system
— id: 45562, year: 1982, vol: 61, page: 898, stat: Journal Article,