PubMed Health⌕ Search

Biomedical subjects

Daniel B Carr

Publications and source records attributed to Daniel B Carr.

At least 19 recordsLinked to original sources

Efficacy of mu-opioid agonists in the treatment of evoked neuropathic pain: Systematic review of randomized controlled trials.

UNLABELLED: Several reviews of randomized controlled trials (RCTs) have shown the efficacy of mu-opioids in reducing spontaneous neuropathic pain (NP). However, relatively little is known about their specific efficacy for evoked pain, which is a significant problem for many patients with NP. The present systematic review assesses the efficacy of opioid agonists for the treatment of evoked NP based upon published RCTs. We searched articles in any language using the MEDLINE database (1966 to December 2004), the Cochrane Central Register of Controlled Trials (4th quarter, 2004) and the reference lists of retrieved papers, employing search terms for RCTs, opioids and NP. Only RCTs in which opioid agonists were given to treat NP of any etiology, and evoked pain was assessed were included. Data were extracted by two independent investigators. Nine articles met inclusion criteria and were classified as short-term (less than 24h; n=7) or intermediate-term trials (4 weeks; n=2). Although the scarcity of retrieved data precluded formal meta-analysis of short-term trials, we found that the intensity of dynamic mechanical allodynia was significantly attenuated by opioids relative to placebo in all studies. In contrast, no consistent effects on the magnitude of static allodynia, the threshold for mechanical allodynia or the threshold or magnitude of heat allodynia were found. The threshold and magnitude of cold-induced allodynia generally responded positively to opioid treatments in patients with peripheral pain syndromes, but not central pain syndromes. Evoked pain was studied in only two intermediate-term trials, in both of which oxycodone was significantly superior to placebo. The results of the two trials were combinable for a meta-analysis that showed an overall 24 points difference in endpoint pain intensities between patients given opioids and those treated with placebo (95% CI -33 to -15; p<0.00001). IN CONCLUSION: short-term studies show that opioids can reduce the intensity of dynamic mechanical allodynia and perhaps of cold allodynia in peripheral NP. Insufficient evidence precludes drawing conclusions regarding the effect of opioids on other forms of evoked NP. A meta-analysis of intermediate-term studies demonstrates the efficacy of opioids over placebo for evoked NP. These findings are clinically relevant because dynamic mechanical allodynia and cold allodynia are the most prevalent types of evoked pain in NP.

Analgesics, Opioid↗

American pain society recommendations for improving the quality of acute and cancer pain management: American Pain Society Quality of Care Task Force.

BACKGROUND: The American Pain Society (APS) set out to revise and expand its 1995 Quality Improvement Guidelines for the Treatment of Acute Pain and Cancer Pain and to facilitate improvements in the quality of pain management in all care settings. METHODS: Eleven multidisciplinary members of the APS with expertise in quality improvement or measurement participated in the update. Five experts from organizations that focus on health care quality reviewed the final recommendations. MEDLINE and Cumulative Index to Nursing and Allied Health Literature databases were searched (1994-2004) to identify articles on pain quality measurement and quality improvement published after the development of the 1995 guidelines. The APS task force revised and expanded recommendations on the basis of the systematic review of published studies. The more than 3000 members of the APS were invited to provide input, and the 5 experts provided additional comments. The task force synthesized reviewers' comments into the final set of recommendations. RESULTS: The recommendations specify that all care settings formulate structured, multilevel systems approaches (sensitive to the type of pain, population served, and setting of care) that ensure prompt recognition and treatment of pain, involvement of patients and families in the pain management plan, improved treatment patterns, regular reassessment and adjustment of the pain management plan as needed, and measurement of processes and outcomes of pain management. CONCLUSION: Efforts to improve the quality of pain management must move beyond assessment and communication of pain to implementation and evaluation of improvements in pain treatment that are timely, safe, evidence based, and multimodal.

Acute Disease↗

Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: systematic review and meta-analysis of randomized controlled trials.

CONTEXT: In the United States, an estimated 2 million persons have neuropathic pain that is often resistant to therapy. The use of opioids for neuropathic pain remains controversial, in part because studies have been small, have yielded equivocal results, and have not established the long-term risk-benefit ratio of this treatment. OBJECTIVE: To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain based on published randomized controlled trials (RCTs). DATA SOURCES: We searched MEDLINE (1966 to December 2004) and the Cochrane Central Register of Controlled Trials (fourth quarter, 2004) for articles in any language, along with reference lists of reviews and retrieved articles, using a combination of 9 search terms for RCTs with 32 terms for opioids and 15 terms for neuropathic pain. STUDY SELECTION: Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded. DATA EXTRACTION: Data were extracted by 2 independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects. DATA SYNTHESIS: Twenty-two articles met inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = 8-56 days; n = 8) trials. The short-term trials had contradictory results. In contrast, all 8 intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. A fixed-effects model meta-analysis of 6 intermediate-term studies showed mean posttreatment visual analog scale scores of pain intensity after opioids to be 14 units lower on a scale from 0 to 100 than after placebo (95% confidence interval [CI], -18 to -10; P<.001). According to number needed to harm (NNH), the most common adverse event was nausea (NNH, 3.6; 95% CI, 2.9-4.8), followed by constipation (NNH, 4.6; 95% CI, 3.4-7.1), drowsiness (NNH, 5.3; 95% CI, 3.7-8.3), vomiting (NNH, 6.2; 95% CI, 4.6-11.1), and dizziness (NNH, 6.7; 95% CI, 4.8-10.0). CONCLUSIONS: Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain. Intermediate-term studies demonstrate significant efficacy of opioids over placebo for neuropathic pain, which is likely to be clinically important. Reported adverse events of opioids are common but not life-threatening. Further RCTs are needed to establish their long-term efficacy, safety (including addiction potential), and effects on quality of life.

Analgesics, Opioid↗

Endomorphins interact with tachykinin receptors.

Soon after the discovery of endomorphins several studies indicated differences between pharmacological effects of endomorphins and other MOR selective ligands, as well as differences between the effects of endomorphin I and endomorphin II. We now propose that these differences are the result of an additional non-opioid property of endomorphins, namely, their weak antagonist properties with respect to tachykinin NK1 and NK1 receptors.

Animals↗

Topical anesthetics for dermal instrumentation: a systematic review of randomized, controlled trials.

STUDY OBJECTIVE: We compare the analgesic efficacy of topical anesthetics for dermal instrumentation with conventional infiltrated local anesthesia and also compare topically available amide and ester agents with a eutectic mixture of local anesthetics (EMLA). METHODS: We conducted a systematic review of randomized, controlled trials. Relevant literature was identified through searches of MEDLINE, Cochrane Central Register of Controlled Trials, and the Excerpta Medica Database Drugs and Pharmacology. We limited the type of procedures to puncture of intact skin with a needle. The primary outcome was analgesic efficacy, reflected in the patient's self-report of pain intensity during dermal instrumentation. Where possible, quantitative methods were used to summarize the results. RESULTS: We identified 25 randomized controlled trials including 2,096 subjects. The results of the trials comparing the efficacy of EMLA with infiltrated local anesthetic were inconsistent. Qualitative analysis demonstrated comparable analgesic efficacy between liposome-encapsulated lidocaine and EMLA. The weighted mean difference in 100-mm visual analogue scale pain scores favored topical tetracaine over EMLA (-8.1 mm; 95% confidence interval -15.6 mm to -0.6 mm). Liposome-encapsulated tetracaine provided greater analgesia than EMLA according to the weighted mean difference in 100-mm visual analogue scale scores (-10.9 mm; 95% confidence interval -15.9 mm to -5.9 mm). CONCLUSION: EMLA may be an effective, noninvasive means of analgesia before dermal procedures. However, we identified 3 topical anesthetics that are at least as efficacious as EMLA: tetracaine, liposome-encapsulated tetracaine, and liposome-encapsulated lidocaine. Liposomal lidocaine is commercially available in the United States and offers a more rapid onset and less expensive alternative to EMLA.

Administration, Cutaneous↗

Best practice recommendations for anesthetic perioperative care and pain management in weight loss surgery.

OBJECTIVE: To develop evidence-based recommendations that optimize the safety and efficacy of perioperative anesthetic care and pain management in weight loss surgery (WLS) patients. RESEARCH METHODS AND PROCEDURES: This Task Group examined the scientific literature on anesthetic perioperative care and pain management published in MEDLINE from January 1994 to March 2004. We also reviewed additional data from other sources (e.g., book chapters). The search yielded 195 abstracts, of which 35 references were reviewed in detail. Task Group consensus was used to provide recommendations when evidence in the literature was insufficient. RESULTS: We developed anesthesia practice and patient safety advisory recommendations for preoperative evaluation, intraoperative management, and postoperative care and pain management of WLS patients. We also provided suggestions related to medical error reduction and systems improvements, credentialing, and future research. DISCUSSION: Obesity-related comorbidities including obstructive sleep apnea place WLS patients at increased risk for complications perioperatively. Regarding perioperative safety and outcomes, conclusive evidence beyond the accepted standard of care in the reviewed literature is limited. Few reports specifically address the perioperative needs of severely obese patients. In this advisory, we synthesize current knowledge and make best practice recommendations for perioperative care and pain management in WLS patients. These recommendations require periodic review as further medical knowledge and evidence evolve.

Analgesia↗

Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial.

BACKGROUND: Meta-analyses report similar numbers needed to treat for nonsteroidal antiinflammatory drugs (NSAIDs) and opioids. Differences in baseline pain intensity among the studies from which these numbers needed to treat were derived may have confounded the results. NSAIDs have an opioid-sparing effect, but the importance of this effect is unclear. Therefore, the authors sought to compare the proportions of subjects who obtain pain relief with ketorolac versus morphine after surgery and to determine whether the opioid-sparing effect of an NSAID reduces the magnitude of opioid side effects. METHODS: The study was a double-blind, randomized controlled trial. The authors randomly assigned 1,003 adult patients to receive 30 mg ketorolac or 0.1 mg/kg morphine intravenously. They calculated the proportion of subjects who achieved at least 50% reduction in pain intensity 30 min after analgesic administration. Further, so long as pain intensity 30 min after analgesic administration was 5 or more out of 10, patients received 2.5 mg morphine every 10 min until pain intensity was 4 or less out of 10. The authors assessed the presence of opioid-related side effects. RESULTS: Five hundred patients received morphine and 503 received ketorolac. Fifty percent of patients in the morphine group achieved pain relief, compared with 31% in the ketorolac group (difference, 19%; 95% confidence interval, 13-25%). The ketorolac-morphine group required less morphine (difference, 6.5 mg; 95% confidence interval, -5.8 to -7.2) and had a lower incidence of side effects (difference, 11%; 95% confidence interval, 5-16%) than the morphine group. CONCLUSIONS: Opioids are more efficacious analgesics than NSAIDs, although historic data for these two drugs yield similar numbers needed to treat. Adding NSAIDs to the opioid treatment reduces morphine requirements and opioid-related side effects in the early postoperative period.

Adult↗

Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and meta-analysis.

We reviewed randomized controlled trials to determine the efficacy and safety of systemically administered local anesthetics compared with placebo or active drugs. Of 41 retrieved studies, 27 trials of diverse quality were included in the systematic review. Ten lidocaine and nine mexiletine trials had data suitable for meta-analysis (n = 706 patients total). Lidocaine (most commonly 5 mg/kg IV over 30-60 min) and mexiletine (median dose, 600 mg daily) were superior to placebo (weighted mean difference on a 0-100 mm pain intensity visual analog scale = -10.60; 95% confidence interval: -14.52 to -6.68; P < 0.00001) and equal to morphine, gabapentin, amitriptyline, and amantadine (weighted mean difference = -0.60; 95% confidence interval: -6.96 to 5.75) for neuropathic pain. The therapeutic benefit was more consistent for peripheral pain (trauma, diabetes) and central pain. The most common adverse effects of lidocaine and mexiletine were drowsiness, fatigue, nausea, and dizziness. The adverse event rate for systemically administered local anesthetics was more than for placebo but equivalent to morphine, amitriptyline, or gabapentin (odds ratio: 1.23; 95% confidence interval: 0.22 to 6.90). Lidocaine and mexiletine produced no major adverse events in controlled clinical trials, were superior to placebo to relieve neuropathic pain, and were as effective as other analgesics used for this condition.

Anesthetics, Local↗

The epidemiology of cancer pain.

We identified 28 epidemiological surveys by applying a sensitive search in Medline and CancerLit databases, supplemented by hand searches. Only two surveys enrolled more than 10,000 patients with cancer. The remaining were hospital or clinic-based surveys of at most a few hundred patients. Fourteen surveys were conducted in the United States. The majority of the remaining studies were conducted in Europe (Finland, France, Germany, UK/Ireland). No single survey identified a prevalence of any type of pain below 14%. The prevalence of pain reported in these surveys varies with the specific type of pain (e.g., breakthrough pain) and/or population studied. Based on these surveys an aggregate statement could not be deduced regarding the correlation between the occurrence of pain and patient factors, disease characteristics, the setting in which care is provided (e.g., primary care or specialized oncology or pain treatment clinics), or specific treatments directed towards the underlying disease and its associated pain. However, these surveys suggest that a significant number of patients with cancer worldwide will, during the course of their disease, experience pain that requires medical and/or other treatment.

Epidemiologic Studies↗

Corticotropin-releasing hormone (CRH) produces analgesia in a thermal injury model independent of its effect on systemic beta-endorphin and corticosterone.

To determine separately the effect of corticotropin-releasing hormone (CRH) on analgesia and on inflammation, rats were assigned to receive CRH 60 microg/kg, CRH 300 microg/kg, morphine 4 mg/kg, or normal saline intravenously 15 min before a burn injury. Two mesh chambers that allowed collection of fluid had been previously implanted subdermally in each rat. The skin overlying the right chamber was subject to thermal injury. The left chamber served as a control. We assessed systemic analgesia, and levels of beta-endorphin and corticosterone in plasma and in chamber fluid before, 1, 4 and 24 h after drug administration. The CRH groups exhibited longer tail flick latencies than the control group (P=0.0001) although the increase in latency was of smaller magnitude than in the morphine group. We did not observe a CRH dose response for analgesia. Plasma corticosterone levels were higher in the CRH 300 microg/kg group than in the normal saline group at 4 h (P=0.03). Levels of beta-endorphin in plasma as well as the levels of corticosterone and beta-endorphin in chambers were similar in the CRH 300 microg/kg group and in the normal saline group (all P values>0.1). Thus, systemically administered CRH produces analgesia in thermal injury independent of its effect on these two markers of local or systemic inflammation.

Analgesia↗

Spinal antinociceptive effects of AA501, a novel chimeric peptide with opioid receptor agonist and tachykinin receptor antagonist moieties.

The use of "multimodal" combination analgesic therapies or novel single molecules possessing multiple analgesic targets is becoming increasingly attractive. In previous experiments we showed that a substance P antagonist injected intrathecally potentiated the antinociceptive effects of potent opioid receptor agonist, biphalin. Based on examination of the biphalin structure-activity relationship, we designed and synthesized a novel chimeric peptide, termed AA501 (N'(Tyr-D-Ala-Gly-Phe), N"(Z-Trp) hydrazide, Z=benzyloxycarbonyl). AA501 consists of an opioid receptor agonist pharmacophore related to biphalin and a substance P receptor antagonist pharmacophore, both linked by a hydrazide bridge. The present study evaluates the ability of a novel chimeric peptide, AA501, to bind to opioid and substance P receptors and to produce antinociception in tail-flick and formalin tests, and in a neuropathic pain model when administered intrathecally to rats.

Analgesics↗

Altered hematologic profiles following donor right hepatectomy and implications for perioperative analgesic management.

Living liver donors for adult liver transplant recipients undergo extensive liver resection. Partial donor hepatectomies may alter postoperative drug metabolism and hemostasis; thus, the risks and the benefits of pain management for this unique patient population may need to be reassessed. The safety and efficacy of combined epidural analgesia and field infiltration in our initial living liver donor group are presented. A thoracic epidural catheter was placed before general anesthesia in 2 female and 6 male donors (44.2 +/- 11.3 years old, mean +/- standard deviation [SD], range 26-56). At the end of surgery, incisions were infiltrated (bupivacaine 0.25%), and an epidural infusion was used (bupivacaine 0.1% + hydromorphone hydrochloride 0.02%). Clinical outcomes were followed for 5 days. The time sequence of pain intensity on a 0-10 visual analog scale clustered into 3 phases, the intensity of which differed significantly from each other (2.2 +/- 0.6, 0.69 +/- 0.2, and 2.37 +/- 0.3 respectively, P = 0.028). Right shoulder pain was observed in 75% of the donors. Sedation, pruritus, and nausea were minimal. Consistently maximal international normalized ratio elevation occurred at 17.6 +/- 7 hours postoperatively, then slowly declined. Platelet counts were lowest on day 3. No neurologic injury or local anesthetic toxicity was observed. This 2-site approach provided effective, safe, postoperative analgesia for our donors. Universally, coagulopathy ensued, indicating a potentially increased risk for epidural hemorrhage at epidural catheter removal and mandating close postoperative neurologic and laboratory monitoring. Research is needed to advance the understanding of postoperative coagulopathy and hepatic dysfunction in these donors to further optimize their perioperative management, including that of analgesia.

Adult↗