Daniel B. Carr

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations

AbstractObjective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of d

The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials.

We performed meta-analyses of randomized, control trials to assess the effects of seven analgesic therapies on postoperative pulmonary function after a variety of procedures: epidural opioid, epidural local anesthetic, epidural opioid with local anesthetic, thoracic versus lumbar epidural opioid, intercostal nerve block, wound infiltration with local anesthetic, and intrapleural local anesthetic. Measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), vital capacity (VC), peak expiratory flow rate (PEFR), PaO2, and incidence of atelectasis, pulmonary infection, and pulmonary complications overall were analyzed. Compared with systemic opioids, epidural opioids decreased the incidence of atelectasis (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.33-0.85) and had a weak tendency to reduce the incidence of pulmonary infections (RR 0.53, 95% CI 0.18-1.53) and pulmonary complications overall (RR 0.51, 95% CI 0.20-1.33). Epidural local anesthetics increased PaO2 (difference 4.56 mm Hg, 95% CI 0.058-9.075) and decreased the incidence of pulmonary infections (RR 0.36, 95% CI 0.21-0.65) and pulmonary complications overall (RR 0.58, 95% CI 0.42-0.80) compared with systemic opioids. Intercostal nerve blockade tends to improve pulmonary outcome measures (incidence of atelectasis: RR 0.65, 95% CI 0.27-1.57, incidence of pulmonary complications overall: RR 0.47, 95% CI 0.18-1.22), but these differences did not achieve statistical significance. There were no clinically or statistically significant differences in the surrogate measures of pulmonary function (FEV1, FVC, and PEFR). These analyses support the utility of epidural analgesia for reducing postoperative pulmonary morbidity but do not support the use of surrogate measures of pulmonary outcome as predictors or determinants of pulmonary morbidity in postoperative patients. Implications: When individual trials are unable to produce significant results, it is often because of insufficient patient numbers. It may be impossible for a single institution to study enough patients. Meta-analysis is a useful tool for combining the data from multiple trials to increase the patient numbers. These meta-analyses confirm that postoperative epidural pain control can significantly decrease the incidence of pulmonary morbidity. (Anesth Analg 1998;86:598-612)

Core outcome domains for chronic pain clinical trials

&NA; Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia, governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy.

Pain Management: A Fundamental Human Right

This article surveys worldwide medical, ethical, and legal trends and initiatives related to the concept of pain management as a human right. This concept recently gained momentum with the 2004 European Federation of International Association for the Study of Pain (IASP) Chapters-, International Association for the Study of Pain- and World Health Organization-sponsored “Global Day Against Pain,” where it was adopted as a central theme. We survey the scope of the problem of unrelieved pain in three areas, acute pain, chronic noncancer pain, and cancer pain, and outline the adverse physical and psychological effects and social and economic costs of untreated pain. Reasons for deficiencies in pain management include cultural, societal, religious, and political attitudes, including acceptance of torture. The biomedical model of disease, focused on pathophysiology rather than quality of life, reinforces entrenched attitudes that marginalize pain management as a priority. Strategies currently applied for improvement include framing pain management as an ethical issue; promoting pain management as a legal right, providing constitutional guarantees and statutory regulations that span negligence law, criminal law, and elder abuse; defining pain management as a fundamental human right, categorizing failure to provide pain management as professional misconduct, and issuing guidelines and standards of practice by professional bodies. The role of the World Health Organization is discussed, particularly with respect to opioid availability for pain management. We conclude that, because pain management is the subject of many initiatives within the disciplines of medicine, ethics and law, we are at an “inflection point” in which unreasonable failure to treat pain is viewed worldwide as poor medicine, unethical practice, and an abrogation of a fundamental human right.

Neurolytic celiac plexus block for treatment of cancer pain : a meta-analysis

We performed a meta-analysis of the efficacy and safety of neurolytic celiac plexus block (NCPB) for cancer pain. A literature search yielded 59 papers, but data on NCPB in two or more patients was available in only 24 papers. Twenty-one studies were retrospective, one was prospective, and two were randomized and controlled. Cancer type was stated in 1117 of 1145 patients reported (63% pancreatic, 37% nonpancreatic). A bilateral posterior approach with 150-50 mL of 50%-100% alcohol was the most common technique. Nonradiologically guided NCPB was performed in 246 patients (32%); guidance was by computed tomography (CT) in 214 (28%), radiograph in 271 (34%), fluoroscopy in 36 (5%), or ultrasound in 7 (<1%). Good to excellent pain relief was reported in 878/989 patients (89%) during the first 2 wk after NCPB. Long-term followup beyond 3 mo revealed persistent benefit. Partial to complete pain relief continued in approximately 90% of patients alive at 3 mo post-NCPB and in 70%-90% until death even if beyond 3 mo post-NCPB. Patients with pancreatic cancer responded similarly to those with other intraabdominal malignancies. Common adverse effects were transient, including local pain (96%), diarrhea (44%), and hypotension (38%); complications occurred in 2%. This analysis suggests that: 1) NCPB has long-lasting benefit for 70%-90% of patients with pancreatic and other intraabdominal cancers, regardless of the technique used; 2) adverse effects are common but transient and mild; and 3) severe adverse effects are uncommon. (Anesth Analg 1995;80:290-5)

Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials

STUDY OBJECTIVE To compare outcomes during conventional analgesia (as-needed intramuscular dosing) and patient-controlled analgesia (PCA) in postoperative patients by analyzing data from published comparative trials. DESIGN Meta-analyses of 15 randomized control trials. PATIENTS Seven hundred eighty-seven adult patients (aged 16 to 65) undergoing various operative procedures. INTERVENTIONS Either PCA or conventional analgesia for postoperative pain control. MEASUREMENTS AND MAIN RESULTS Data were extracted on analgesic efficacy, analgesic use, patient satisfaction, length of hospital stay, and side effects. Meta-analyses of the data showed the following: (1) greater analgesic efficacy when PCA was used, with a mean additional benefit of 5.6 on a scale of 0 to 100 (SED, 2.2; p = 0.006); (2) a nonsignificant trend toward reduced analgesic use in PCA patients, based on a count of trials finding in one direction or the other (p = 0.092); (3) a 42% difference in the proportion of patients expressing satisfaction over dissatisfaction (SED, 20%; p = 0.02), with PCA being preferred; (4) a nonsignificant trend toward shortening of length of hospital stay with PCA use (mean, 0.15 days, SED, 0.13; p = 0.24); (5) no significant differences in the occurrence of any side effect. CONCLUSIONS Patient preference strongly favors PCA over conventional analgesia. Patients using PCA also obtain better pain relief than those using conventional analgesia, without an increase in side effects. Favorable effect of PCA upon analgesic usage and length of hospital stay did not in the initial trials attain statistical significance. Nonetheless, the favorable trends in the mean effect sizes for both outcomes argue that further studies of both outcomes should be performed to determine whether the favorable impact of PCA upon either may become statistically significant if larger numbers of patients are enrolled.

Itching after epidural and spinal opiates

&NA; When opiates are administered by the epidural and spinal routes, itching occurs as a side effect. We reviewed 52 reports in the literature of the use of epidural and spinal opiates to assess the incidence of itching and found an overall incidence of 8.5% in patients receiving epidural opiates, and 46% in patients receiving spinal opiates. The symptom is a recognised, though rare, side effect of systemically administered opiates, and in the case of systemic administration the itching is generalised. In the case of epidural and spinal administration, the itching may be generalised. But often a segmental distribution is demonstrable, centred on the level of injection, or the itching is localised to a particular area such as the nose and face. It is likely therefore, in the latter case, that there is an effect upon the spinal cord itself. Although occasionally spinal opiate‐induced itching is extremely troublesome and lessens the value of spinal opiate pain relief, in the majority of cases, the itching is not severe and is treatable with naloxone. However, the frequent occurrence of the symptom and the likelihood of a spinal cord mechanism do provide valuable information about opioid actions, and benefit may be derived from better understanding the phenomenon. This paper states a hypothesis to explain spinal opiate‐induced itch and explores the possible mechanisms of the effect.

Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review ☆

Side effects can limit opioid dosage and reduce quality of life. The purpose of this systematic review was to assess the management of opioid side effects in the context of cancer pain management or, in the event that no evidence was available for cancer pain, for chronic noncancer pain. The side effects studied were constipation, pruritus, nausea and vomiting, myoclonus, sedation, respiratory depression, and delirium. Opioid rotation to manage side effects was also studied. For each side effect, we searched MEDLINE and the Cochrane Controlled Trials Register and identified 657 possible titles for inclusion. Of these, 67 studies met inclusion criteria for analysis. The lack of well-designed, randomized controlled trials and the heterogeneity of populations and study designs made the drawing of firm conclusions difficult and precluded performance of meta-analysis. The type, strength, and consistency of evidence for available interventions to manage opioid side effects vary from strong (eg, on the use of naloxone to reverse respiratory depression or constipation) to weak (eg, changing from the oral to epidural route of morphine administration to manage sedation). Well-designed trials in the specified populations are required to furnish clinicians with secure evidence on managing opioid side effects successfully.

Physical Conditioning Facilitates the Exercise-Induced Secretion of Beta-Endorphin and Beta-Lipotropin in Women

EXERCISE training is used increasingly to prevent and treat disease, and millions of healthy persons participate in strenuous sports; yet, the mechanisms by which exercise produces various clinical...

The Role of the Anesthesiologist in Fast-Track Surgery: From Multimodal Analgesia to Perioperative Medical Care

BACKGROUND:Improving perioperative efficiency and throughput has become increasingly important in the modern practice of anesthesiology. Fast-track surgery represents a multidisciplinary approach to improving perioperative efficiency by facilitating recovery after both minor (i.e., outpatient) and major (inpatient) surgery procedures. In this article we focus on the expanding role of the anesthesiologist in fast-track surgery. METHODS:A multidisciplinary group of clinical investigators met at McGill University in the Fall of 2005 to discuss current anesthetic and surgical practices directed at improving the postoperative recovery process. A subgroup of the attendees at this conference was assigned the task of reviewing the peer-reviewed literature on this topic as it related to the role of the anesthesiologist as a perioperative physician. RESULTS:Anesthesiologists as perioperative physicians play a key role in fast-track surgery through their choice of preoperative medication, anesthetics and techniques, use of prophylactic drugs to minimize side effects (e.g., pain, nausea and vomiting, dizziness), as well as the administration of adjunctive drugs to maintain major organ system function during and after surgery. CONCLUSION:The decisions of the anesthesiologist as a key perioperative physician are of critical importance to the surgical care team in developing a successful fast-track surgery program.