No debate on the minimal decline in pain intensity that patients can discern.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M Soledad Cepeda
Publications and source records attributed to M Soledad Cepeda.
Economic evaluation of oral treatments for neuropathic pain.
UNLABELLED: The effectiveness of amitriptyline, carbamazepine, gabapentin, and tramadol for the treatment of neuropathic pain has been demonstrated, but it is unknown which one is the most cost-effective. We designed a cost-utility analysis of a hypothetical cohort with neuropathic pain of postherpetic or diabetic origin. The perspective of the economic evaluation was that of a third-party payor. For effectiveness and safety estimates, we performed a systematic review of the literature. For direct cost estimates, we used average wholesale prices, and the American Medicare and Clinical Laboratory Fee Schedules. For utilities of health states, we used the Health Utilities Index. We modeled 1 month of therapy. For comparisons among treatments, we estimated incremental cost per utility gained. To allow for uncertainty from variations in drug effectiveness, safety, and amount of medication needed, we conducted a probabilistic Monte Carlo simulation. Amitriptyline was the cheapest strategy, followed by carbamazepine, and both were equally beneficial. Gabapentin was the most expensive as well as the least beneficial. A multivariable probabilistic simulation produced similar results to the base-case scenario. In summary, amitriptyline and carbamazepine are more cost-effective than tramadol and gabapentin and should be considered as first-line treatment for neuropathic pain in patients free of renal or cardiovascular disease. PERSPECTIVE: Prescription practices should be based on the best available evidence, which includes the evaluation of the medication's cost-effectiveness. This does not mean that the cheapest or the most expensive, but rather the most cost-effective medication should be chosen-the one whose benefits are worth the harms and costs. We report a cost-effectiveness evaluation of treatments for neuropathic pain.
Administration, Oral↗
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↗
Addition of ultralow dose naloxone to postoperative morphine PCA: unchanged analgesia and opioid requirement but decreased incidence of opioid side effects.
Ultralow doses of naloxone (0.001-0.1 microg/kg) produce analgesia in animal models. However, no clinical study has evaluated the combination of ultralow dose naloxone and morphine using patient-controlled analgesia (PCA). This randomized, double blind controlled study sought to determine if the combination of ultralow dose naloxone and morphine in PCA solutions affects opioid requirements, analgesia, and side effects. Two-hundred and sixty-five patients (18-65 years old) undergoing operations were randomized to receive PCA morphine 1 mg/ml (n=129) or PCA morphine 1 mg/ml plus naloxone 0.6 microg/ml (n=136). We evaluated the numbers of supplemental rescue doses, the cumulative dose of each PCA solution, pain intensity, pain relief, and opioid side effects during the first 24 h after surgery. We found that opioid requirements did not differ significantly between groups. The morphine+naloxone group on average required 0.07 mg more morphine (95% CI -1.1 to 1.3) during the 24 h than the morphine group. Pain intensity levels were also similar in both groups. The morphine+naloxone group had 0.06 units lower (95% CI -0.5 to 0.4) pain intensity levels than the morphine group. The morphine+naloxone group had a lower incidence of nausea and pruritus than the morphine group (P=0.01 for both symptoms). However, the incidence of vomiting, time to tolerate fluids, sedation, and urinary retention were similar between groups (all P values >0.1). The combination of ultralow dose naloxone and morphine in PCA does not affect analgesia or opioid requirements, but it decreases the incidence of nausea and pruritus.
Adolescent↗
Comparison of logistic regression versus propensity score when the number of events is low and there are multiple confounders.
The aim of this study was to use Monte Carlo simulations to compare logistic regression with propensity scores in terms of bias, precision, empirical coverage probability, empirical power, and robustness when the number of events is low relative to the number of confounders. The authors simulated a cohort study and performed 252,480 trials. In the logistic regression, the bias decreased as the number of events per confounder increased. In the propensity score, the bias decreased as the strength of the association of the exposure with the outcome increased. Propensity scores produced estimates that were less biased, more robust, and more precise than the logistic regression estimates when there were seven or fewer events per confounder. The logistic regression empirical coverage probability increased as the number of events per confounder increased. The propensity score empirical coverage probability decreased after eight or more events per confounder. Overall, the propensity score exhibited more empirical power than logistic regression. Propensity scores are a good alternative to control for imbalances when there are seven or fewer events per confounder; however, empirical power could range from 35% to 60%. Logistic regression is the technique of choice when there are at least eight events per confounder.
Bias↗
Side effects of opioids during short-term administration: effect of age, gender, and race.
OBJECTIVE: Little is known about risk factors that increase the risk of development of opioid side effects. Our objective was to evaluate the effect of the type of opioid, age, gender, and race on the incidence of side effects from short-term opioid use. METHODS: A secondary analysis of a retrospective cohort study in 35 community-based and tertiary hospitals was done. There were 8855 black or white subjects aged 16 years and older. Patients received meperidine (INN, pethidine), morphine, or fentanyl as part of their treatment. Measurements were made to assess the presence of nausea and vomiting and respiratory depression. RESULTS: Of the patients, 26% had nausea and vomiting and 1.5% had respiratory depression after opioid administration. After adjustment for opioid dose, route of administration, age, gender, and race, meperidine produced less nausea and vomiting (odds ratio [OR] = 0.7; 95% confidence interval [CI], 0.5-0.8) and less respiratory depression (OR = 0.6; 95% CI, 0.2-0.9) than morphine. The risk of respiratory depression increased with age. Compared with patients aged between 16 and 45 years, those aged between 61 and 70 years had 2.8 times the risk of development of respiratory depression (95% CI, 1.2-6.6); those aged between 71 and 80 years had 5.4 times the risk (95% CI, 2.4-11.8); and those aged older than 80 years had 8.7 times the risk (95% CI, 3.8-20.0). Men had less nausea and vomiting than women (OR = 0.5; 95% CI, 0.4-0.6). White subjects had more nausea and vomiting than black subjects (OR = 1.4; 95% CI, 1.1-1.7). CONCLUSIONS: Meperidine produced fewer side effects than morphine during short-term use. The risk of respiratory depression increases substantially after 60 years of age. Women have nausea and vomiting more often than men. The effect of race deserves further investigation.
Adolescent↗
What decline in pain intensity is meaningful to patients with acute pain?
Despite widespread use of the 0-10 numeric rating scale (NRS) of pain intensity, relatively little is known about the meaning of decreases in pain intensity assessed by means of this scale to patients. We aimed to establish the meaning to patients of declines in pain intensity and percent pain reduction. Upon arrival to the postanesthesia care unit, postsurgical patients rated their baseline pain intensity on both a 0-10 NRS and on a 4-point verbal scale. Patients whose NRS was higher than 4/10 received intravenous opioids until their pain intensity declined to 4/10 or lower. During opioid titration, patients were asked every 10 min to rate pain intensity on a NRS and to indicate the degree of pain improvement on a 5-point Likert scale from 'no improvement' to 'complete pain relief'. Seven hundred adult patients were enrolled. For patients with moderate pain, a decrease of 1.3 units (20% reduction) corresponded to 'minimal' improvement, a decrease of 2.4 (35% reduction) to 'much' improvement, a decrease of 3.5 units (45% reduction) corresponded to 'very much' improvement. For patients with severe pain, the decrease in NRS pain score and the percentage of pain relief had to be larger to obtain similar degrees of pain relief. The change in pain intensity that is meaningful to patients increases as the severity of their baseline pain increases. The present findings are applicable in the clinical setting and research arena to assess treatment efficacy.
Acute Disease↗
Optimal matching with a variable number of controls vs. a fixed number of controls for a cohort study. trade-offs.
Matching is used to control for imbalances between groups, but the preferable strategy for matching is not always clear. We sought to compare two algorithms-optimal matching with a fixed number of controls (OMFC), and optimal matching with a variable number of controls (OMVC). We compared the degree of bias reduction and relative precision using Monte Carlo simulations. We systematically changed the magnitude of the matching variable difference, the variance ratios of the matching variable in the exposed and unexposed groups, the sample size, and the number of unexposed subjects available for matching. OMVC always produced larger removal of bias than the OMFC. The mean percentage reduction of bias was 38.3 with the OMFC and 52.6 with OMVC. OMVC increased the variance 6%. OMVC should be employed when researchers have access to a pool of unexposed subjects because it removes more bias with little loss in precision.
Algorithms↗
Women experience more pain and require more morphine than men to achieve a similar degree of analgesia.
UNLABELLED: Sex differences in pain perception and in response to opioids have been described, but the findings are inconsistent. We sought to determine the effect of sex on pain perception, morphine consumption, and morphine analgesia after surgery. We designed a prospective cohort study and included 423 women and 277 men who emerged from general anesthesia after surgical procedures and who reported pain intensity of >or=5 on the 0-10 numeric rating scale (NRS). We administered 2.5 mg of morphine IV every 10 min until the pain intensity was <or=4 of 10. Every 10 min, patients rated their pain on the NRS and indicated the degree of pain relief on a 5-point Likert scale. After adjustment for type of operation and age, we found that women had more intense pain and had larger morphine consumption than men. The difference in NRS pain intensity was 0.4 U (95% confidence interval, 0.1-0.6 U). Women required 0.03 mg/kg more morphine than men (95% confidence interval, 0.02-0.04 mg/kg). We conclude that women have more intense pain and require 30% more morphine to achieve a similar degree of analgesia compared with men. Clinicians should anticipate the differences in opioid requirement to avoid undertreatment of pain in women. IMPLICATIONS: The effect of sex on opioid response is not clear. To determine the effect of sex on morphine consumption and morphine analgesia, we designed a cohort study. We found that women had more intense pain and required 30% more morphine to achieve a similar degree of analgesia compared with men.
Abdomen↗
The combination of low dose of naloxone and morphine in PCA does not decrease opioid requirements in the postoperative period.
The continuous infusion of low doses of naloxone has been reported to decrease postoperative opioid requirements and opioid side effects. However, there is no study that evaluates the effectiveness of the combination of a low dose of naloxone and morphine using patient-controlled analgesia (PCA). This prospective, randomized double-blind controlled study sought to determine if the combination of a low dose of naloxone and morphine in a PCA solution decreases postoperative opioid requirements and pain intensity. One hundred sixty-six patients (18-65 years old) undergoing operations of less than 3 h duration with an American Society of Anesthesiologist physical status I or II were randomized to receive PCA morphine 1 mg/cc plus normal saline or PCA morphine 1 mg/cc plus naloxone 6 microg/cc. Initial PCA settings were 0.5 cc per demand with a lockout time of 10 min. The numbers of 2.5 cc supplemental rescue doses and the cumulative dose of each solution were recorded in the first 24 h after the surgical procedure. Pain intensity and opioid side effects were evaluated every 10 min in the post-anesthesia care unit and every 4 h afterwards. Patient satisfaction was assessed at the end of the 24 h of observation. The morphine+naloxone group had more treatment failures (P=0.0001), higher opioid requirements (P=0.0097), greater pain intensity (P=0.04), less pain relief (P=0.004), and less satisfaction (P=0.01) than the morphine group. The incidence of side effects was similar in both groups (P=0.3). Contrary to previous reports, adding low doses of naloxone to a morphine PCA solution increases opioid requirements and pain.
Adult↗
Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: a narrative and systematic review.
OBJECTIVE: There is growing controversy on the value of blocking the sympathetic nervous system for the treatment of complex regional pain syndromes (CRPS). The authors sought to evaluate the efficacy of sympathetic blockade with local anesthetic in these syndromes. In addition, they performed a comprehensive review of the pathophysiology and other treatments for CRPS. DESIGN: Systematic review of the literature was performed. MEDLINE was searched from 1966 through 1999. The authors identified only three randomized controlled trials (RCTs) that evaluated sympathetic blockade with local anesthetic, but because of differences in study design they were unable to pool the study data. The authors therefore included nonrandomized studies and case series. INTERVENTIONS: Studies were included if local anesthetic sympathetic blockade was used in at least 10 patients. Studies were excluded if continuous infusion techniques, somatic nerve blocks, or combined sympatholytic therapies were evaluated. OUTCOME MEASURES: Pain relief was classified as full, partial, or absent. The lack of a comparison group in the studies allowed only the calculation of distribution of the response categories, and the sum of the pooled rates does not equal 100%. RESULTS: Twenty-nine studies were included that evaluated 1,144 patients. Nineteen studies were retrospective, 5 prospective case series, 3 RCTs, and 2 nonrandomized controlled studies. The quality of the publications was generally poor. Twenty-nine percent of patients had full response, 41% had partial response, and 32% had absent response. It was not possible to estimate the duration of pain relief. CONCLUSIONS: This review raises questions as to the efficacy of local anesthetic sympathetic blockade as treatment of CRPS. Its efficacy is based mainly on case series. Less than one third of patients obtained full pain relief. The absence of control groups in case series leads to an overestimation of the treatment response that can explain the findings.
Complex Regional Pain Syndromes↗