Faster Onset Of Analgesia Research Articles

Effect of nalbuphine plus ropivacaine on vaginal labor in epidural analgesia

BackgroundVarious approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients.MethodsClinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2–3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded.ResultsCompared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups.ConclusionsNalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.

A Comparative Study of Epidural Butorphanol and Epidural Fentanyl for Postoperative pain relief in Lower Limb Orthopaedic Surgeries.

Background: Epidural narcotic agonists like fentanyl, and morphine has been studied as an adjunct to Bupivacaine for intraoperative and to provide epidural postoperative analgesia. Side effects like pruritus, nausea, vomiting, respiratory depression, and urinary retention occur with their use. The search for an effective analgesic with no or low incidence of side effects is continuing. Aims and objective: To evaluate the onset of anaesthesia, duration of analgesia with epidural administration of Butorphanol and fentanyl in 2 groups. Observe and compare side effects between these groups during post-operative period. Material and Methods: We had done this study on 60 patients with Orthopaedic fractures (lowerlimb), which are treated with IM IL nailing femur and tibia distributed to two groups of 30 each. Surgery was done under CSE technique, with Group A receiving butorphanol and Group B Fentanyl as adjuvant. The onset, duration of analgesia and side effects were recorded in each group. Results: The onset of analgesia was rapid in Fentanyl group (3.26+/- 0.95) than Butorphanol group (6.54 +/-1.10). Duration of analgesia was longer in Butorphanol group (330 +/- 62 minutes) in comparison to Fentanyl group (210 +/- 32 minutes). Quality of analgesia is better in Butorphanol group (80%) than Fentanyl group (43 %). Side effects were more in Group B than Group A. Conclusion: Epidural Fentanyl has faster onset of analgesia. Epidural Butorphanol has longer duration of analgesia with better quality of analgesia. Epidural butorphanol has fewer side effects when compared to Fentanyl.

Labor epidural analgesia: Comparison of intermittent boluses of ropivacaine with three different concentrations of fentanyl – A randomized controlled trial

Background and Aims: Labor epidural analgesia can be provided with local anesthetics alone or in combination with opioids. The aim of this study was to compare the duration of analgesia, onset time, and obstetric and fetal outcomes with three different concentrations of fentanyl. Methods: This double-blinded trial was conducted on 75 parturients who delivered with epidural analgesia. They were randomly assigned to three groups by the closed envelope technique. Groups A, B, and C received a bolus dose of 20 ml 0.1% ropivacaine with 1 μgml-1, 1.5 μgml-1, and 2 μgml-1 fentanyl, respectively, as an initial epidural dose. The duration, time to onset of analgesia, top-up doses required, hemodynamics, fetal-maternal outcomes, and complications were compared. Results: The mean duration of analgesia with the first epidural dose was 57.4 ± 14.207, 121.52 ± 33.951, and 165.08 ± 34.271 min in the A, B, and C groups, respectively, with a P of <.001. There was a higher duration of analgesia in the B group than in the A group (p-value <.001), in the C group than in the B group (p. 016), and in the C group than in the A group (p-value <.001). The onset of analgesia was faster in the C group than in the A and B groups (7.960 ± 1.695, 6.800 ± 1.607, and 5.960 ± 1.645 min in groups A, B, and C, respectively, with a P of. 001). The number of epidural boluses required was 3.480 ± 0.509, 2.640 ± 0.489, and 2.120 ± 0.331 in the A, B, and C groups, respectively. Conclusion: Labor epidural analgesia with a higher concentration of fentanyl produces a prolonged and faster onset of analgesia with fewer requirements for top-up boluses.

Місце епідуральної аналгезії з проколом твердої мозкової оболонки як сучасного методу знеболювання пологів

Пологи — фізіологічний процес, що супроводжується вираженим больовим синдромом. У патологічний процес можуть бути залучені фізіологічні та психологічні чинники. Підвищення концентрації катехоламінів може сприяти зниженню матково-плацентарної перфузії. Біль під час пологів може призвести до гіпервентиляції матері, що, зі свого боку, може вплинути на кислотно-основний стан плода та стан новонародженого. Тривалий больовий синдром може призвести до розвитку тяжких психологічних розладів із порушенням зв’язку між матір’ю і новонародженим. Гострий біль під час пологів може трансформуватися в хронічний у післяпологовому періоді. Найбільш ефективними є нейроаксіальні методи знеболювання пологів: епідуральна аналгезія (ЕА), комбінована спінально-епідуральна аналгезія (КСЕА) та їх модифікації. Класична ЕА справляє мінімальні небажані та побічні ефекти, але може бути пов’язана з високою частотою недостатнього рівня знеболювання. Частота неадекватних епідуральних блокад доходить до 23 %. КСЕА на відміну від ЕА має вищу якість сенсорної блокади, але вона пов’язана з більшою частотою побічних ефектів, таких як гіпотензія, виражений моторний блок, порушення частоти серцевих скорочень плода. З 2005 року в практику акушерських анестезіологів почала впроваджуватись епідуральна аналгезія з проколом твердої мозкової оболонки (Dural puncture epidural — DPE) як метод, що покликаний покращити якість класичної ЕА з мінімальними небажаними ефектами КСЕА. Дані наявних досліджень показують, що DPE потенційно покращує якість аналгезії (швидше настає знеболювання, краще покриття сакральних сегментів, нижча частота неадекватних блокад) порівняно з ЕА та менше викликає гіпотензію, порушення ритму частоти серцевих скорочень плода порівняно з КСЕА. Але в досягненні даних ефектів важливий діаметр спінальної голки. Подальші дослідження можуть бути націлені на визначення тривалості пологів, варіанта розродження та можливого впливу DPE на вегетативну регуляцію пологів та більш широке вивчення впливу данного методу на плід і новонародженого.

A randomized comparison of epidural, dural puncture epidural, and combined spinal-epidural without intrathecal opioids for labor analgesia.

Background and Aims:Dural puncture epidural (DPE) has been shown to improve labor analgesia over epidural (EPL), with fewer side effects than a combined spinal-epidural (CSE). However, there is some debate regarding the superiority of DPE over EPL and CSE. Therefore, we aimed to compare the effects of EPL, DPE, and CSE without intrathecal opioids on the epidural local anesthetic (LA) consumption and occurrence of side effects in early labor.Material and Methods:We randomly assigned parturient to one of the 3 groups; EPL, DPE, or CSE. EPL and DPE groups received a 10 mL loading dose of 0.1% bupivacaine with fentanyl 2 μg/mL. CSE group received intrathecal 2.5 mg bupivacaine (without opioids). Labor analgesia was maintained in all patients via patient-controlled epidural analgesia (PCEA). The primary outcome was the mean hourly consumption of epidural LA.Results:The mean hourly consumption of epidural LA anesthetic was significantly lower in CSE (9.55 mL), compared with the EPL (11 mL), and DPE (10.5 mL), P < 0.01; but no significant difference was seen between EPL and DPE. Compared with EPL and DPE, CSE achieved faster time to complete analgesia defined as a numeric rating pain scale (NRPS) ≤1 and sensory block, lower NRPS in the first hour and higher frequencies of complete analgesia. There were no differences between groups in terms of physician top-up boluses, the occurrence of side-effects, mode of delivery, Apgar scores, and maternal satisfaction.Conclusion:Compared with EPL and DPE, CSE without intrathecal opioids, had a less epidural LA consumption, faster onset of analgesia, with no difference in the incidence of side effects.Trial Registration:This study was registered at www.clinicaltrials.gov (NCT03980951).

Attitudes toward Complementary and Alternative Medicine, Beliefs in Afterlife and Religiosity among Psychiatrists, Psychologists and Theologists.

The aim of our study was to investigate the differences in beliefs, attitudes toward CAM, beliefs in afterlife and religiosity among the sample of psychiatrists, psychologists, and theologists. Relationship among these constructs could have impact on the concept of mental health. Research was conducted in the Split urban area, Croatia, during 2017 on a sample of psychiatrists (n=51), psychologists (n=55), and theologists (n=25). Participants were presented a figure of the human body, which contained numbers identifying eight different regions of the body. Participants were asked to select which region best represents the location of the self, soul, and mind in the body. We used CAIMAQ (The Complementary, Alternative and Integrative Medicine Attitudes Questionnaire) which contains five subscales. The Afterdeath Beliefs Scale was used to measure the varieties of afterlife beliefs. Analyses showed that applied questionnaires have appropriate reliability and expected factor structure. The most frequent locations of the Soul were 9 (37%, Not located in any centralized region in the body) and 5 (31% chest), whereas Self and Mind were mostly located in the head (43% and 73%). Psychiatrists and psychologists have average scores on positive pole of CAIMAQ but did not differ significantly (p>0.05). There were statistical differences between theologists and psychologists/psychiatrists on two subscales: "nutritional counseling and dietary/food supplements can be effective in the treatment of pathology" and "attitudes toward a holistic understanding of the disease" (p<0.05). There were significant correlations between religion and three CAIMAQ subscales. Although they were mostly religious, psychiatrists and psychologists had a higher average score on Annihilation than theologists. They also did not believe in body resurrection and connection between behavior during life and after death. The results of our study could have impact on the concept of mental health and in the future must be deeper evaluated within qualitative research methodology.

Effect of tramadol as a local anesthetic adjuvant in epidural labor analgesia: Randomized controlled study

ABSTRACT Background: Epidural analgesia has been established to be the best modality for painless labor. This study hypothesized to evaluate the effect of adding tramadol as an adjuvant to bupivacaine in epidural labor analgesia. Methods: Sixty parturients were allocated into two equal groups. Group B received a total volume of 10 ml bupivacaine 0.25% in normal saline. Group BT received a total volume of 10 ml bupivacaine 0.25% plus tramadol 5 mg/ml in normal saline as a loading dose, followed by continuous infusion of bupivacaine 0.125% at rate 10 ml/h 15 min after a loading dose for both groups. The onset of analgesia, degree of motor block, sedative effect, hemodynamic parameters, visual analogue scale (VAS), number of top-up doses, fetal outcomes, any related side effects, and maternal satisfaction were recorded. Results: Faster onset of analgesia was achieved in BT group compared to B group (7.9 ± 2.68 vs 15.3 ± 3.3, respectively: P < 0.001). BT group has a longer duration of analgesia (181.1 ± 44.3 min) than B group (89.6 ± 32.6 min) (P < 0.001). VAS was significantly decreased at 10, 15, 60, 120 and 180 min in BT group compared to B group (P < 0.001, < 0.001, 0.001, < 0.001, and 0.006, respectively). Motor block was comparable between both groups. Higher levels of sedation were reached in group BT. Conclusion: Tramadol in epidural labor analgesia as an adjuvant to bupivacaine can provide a better quality of analgesia with faster onset, and prolonged duration with no relevant adverse effects Pan African Clinical Trial registration: (PACTR201804003261749)

Effectiveness of low dose epidural magnesium sulphate in labour analgesia

Magnesium sulphate is common adjuvant in central neuraxial blocks because of its analgesic action due to antagonistic action on N-methyl-D-aspartate receptors. It has been earlier used as epidural adjuvant in labour analgesia in dose of 50 mg. In current study magnesium sulphate was used epidurally in 25 mg dose and its effectiveness was assessed. The current randomized control trial, double blind study was conducted in 100 parturients, divided in group M and C with 50 in each. All the parturient received 15 microgm of fentanyl intrathecally and bolus dose of 8ml 0.1% bupivacaine epidurally followed by epidural infusion of 0.1% bupivacaine at rate of 8ml/hr. In addition to above, group M received 50mg of magnesium sulphate epidurally and group C received volume adjusted sterile saline. The pilot study conducted on 5 parturients, all parturients in group M developed motor block, which was attributed to magnesium sulphate so the dose of it decreased to 25 mg. The synergistic action of magnesium sulphate was evaluated by pain assessment by Visual analogue scale and number of breakthrough pain. The faster onset of analgesia and better pain relief was found in group M. The breakthrough pain was less in group M in both stage 1 and stage 2 of labour. The duration of labour, incidence of instrumentation, need of caesarean section and neonatal outcome were comparable in both the groups.Magnesium sulphate is an effective epidural adjuvant in labour analgesia even in 25mg dose without any adverse effect.

Comparison of Intrathecal Injection of Fentanyl and Sufentanil on the Onset, Duration, and Quality of Analgesia in Labor: A Randomized, Double-Blind Clinical Trial.

BackgroundLabor pain is a severe pain, and intrathecal opioid injection is one of the analgesia methods to reduce it.ObjectivesWe assessed the effects of intrathecal Fentanyl and Sufentanil on the onset, duration, and quality of analgesia for labor analgesia.MethodsIn this double-blind, randomized clinical trial, 54 healthy nulliparous women 18 - 45 years in the active phase of labor who were requesting labor analgesia were enrolled in two groups fentanyl (F) and sufentanil (S). Patients received 75 µg fentanyl or 7.5 µg sufentanil intrathecally in the fentanyl group (n = 27) and the sufentanil group (n = 27), respectively. Pain relief, onset, duration of analgesia, hemodynamic parameters, patients' satisfaction, and neonatal Apgar score were assessed in this study. Data were analyzed by using SPSS16.ResultsThere were no significant differences between the groups in terms of demographic and hemodynamic parameters. The onset time of analgesia was 5.6 ± 4.3 and 3.6 ± 2.1 minutes, in the sufentanil and fentanyl groups, respectively (P = 0.037). The duration of analgesia was higher in patients who received sufentanil than those who received fentanyl (113 ± 45 vs. 103 ± 22 minutes (P = 0.629)). The pain score in the Fentanyl group was significantly lower at 5, 10, and 15 minutes after spinal analgesia (P < 0.05). The sedation score at 1 and 5 minutes was significantly higher in the fentanyl group than the sufentanil group (P < 0.05). The frequency and severity of pruritus and satisfaction rate in the fentanyl group were significantly higher than the sufentanil group.ConclusionsIntrathecal fentanyl and sufentanil have a similar analgesic effect on labor. Fentanyl is associated with a faster onset of analgesia and more satisfaction, while sufentanil has longer analgesia.

Comparative evaluation of oral flupirtine and oral diclofenac sodium for analgesia and adverse effects in elective abdominal surgeries.

Background:Flupirtine is a centrally-acting, nonopioid analgesic that interacts with N-methyl-D-aspartate receptors.Aim:The present study was designed to compare analgesic efficacy and adverse effects of orally administered flupirtine and diclofenac sodium for postoperative pain relief.Settings and Design:In a prospective, randomized double-blind study, 100 patients of American Society of Anesthesiologist grade I and II in the age group of 18–65 years of either sex undergoing elective abdominal surgeries were included after taking informed consent.Materials and Methods:The present study started after 12 h of surgery and patients were randomly divided into two groups of 50 each. For postoperative analgesia, group A received flupirtine 100 mg orally and group B received diclofenac sodium 50 mg orally and study drugs were repeated every 6 hourly for 5 days postoperatively. Vital parameters and visual analogue scale (VAS) scores for pain were recorded at 0, 1, 2, 4, 6, 8, 12, 16 and 24 h, and adverse effects were noted for 48 h of the study period.Statistical Analysis:Data were compiled and analyzed statistically using Chi-square test and two-tailed Student's t-test.Results:Visual analogue scores decreased more rapidly in diclofenac group during 1st h, hence there was rapid onset of analgesia in this group as compared to flupirtine group but later on VAS was comparable in both groups at all measured intervals (P > 0.05). Patients in diclofenac group experienced significantly more heartburn (P = 0.00), impaired taste sensation (P < 0.001) and dizziness (P = 0.004) as compared to flupirtine group.Conclusion:Oral flupirtine and diclofenac sodium were equally effective for postoperative analgesia. There was faster onset of analgesia with diclofenac sodium, but flupirtine was better tolerated by the patients because of its minimal adverse effects.

Can topical duloxetine be used for neuropathic pain?

Duloxetine is a serotonin and norepinephrine re-uptake inhibitor with both anti-depressant and pain-relieving properties. Its pain-relieving properties are due to its action on the descending inhibitory pain pathways. However, the fast onset of analgesia may be mediated by mechanisms other than the descending inhibitory pain pathways. This study posits the hypothesis that duloxetine may have pain-relieving property by peripheral analgesic effects. Ways of testing this hypothesis and its potential topical use are discussed.

Faster, higher, stronger? Evidence for formulation and efficacy for ibuprofen in acute pain

A Cochrane review of ibuprofen in acute pain suggested that rapidly absorbed formulations of salts, or features to speed absorption, provided better analgesia than standard ibuprofen as the free acid. We examined several lines of evidence to investigate what benefit derived from fast-acting formulations. A systematic review of the kinetics of oral ibuprofen (30 studies, 1015 subjects) showed that median maximum plasma concentrations of fast-acting formulations occurred before 50min (29–35min for arginine, lysine, and sodium salts) compared with 90min for standard formulations. An updated analysis of clinical trials (over 10,000 patients) showed that fast-acting formulations produced significantly better analgesia over 6h and fewer remedications than standard formulations in both indirect and direct comparisons. In dental studies, 200-mg fast-acting ibuprofen (number needed to treat 2.1; 95% confidence interval 1.9–2.4) was as effective as 400 mg standard ibuprofen (number needed to treat 2.4; 95% confidence interval 2.2–2.5), with faster onset of analgesia. Individual patient data analysis in dental pain demonstrated a strong correlation between more rapid reduction of pain intensity over 0–60min and better pain relief over 0–6h. Rapid initial reduction of pain intensity was also linked with reduced need for remedication. Fast-acting formulations of ibuprofen demonstrated more rapid absorption, faster initial pain reduction, good overall analgesia in more patients at the same dose, and probably longer-lasting analgesia, but with no higher rate of patients reporting adverse events. Achieving a better analgesic effect with fast-acting nonsteroidal anti-inflammatory drug formulations has important implications for safety. Formulation chemistry is of potential importance for analgesics.

Analgesic Efficacy and Safety of a Novel Injectable Formulation of Diclofenac Compared With Intravenous Ketorolac and Placebo After Orthopedic Surgery

A novel injectable formulation of diclofenac, Dyloject, utilizes hydroxypropyl-β-cyclodextrin (HPβCD) as a solubilizing agent, allowing dosing as a small-volume intravenous bolus for postoperative pain. In this test of the efficacy and safety of HPβCD diclofenac, we hypothesized that HPβCD diclofenac would relieve moderate and severe pain after orthopedic surgery. Adults 18 to 85 years old with moderate and severe pain within 6 hours after surgery were randomized to HPβCD diclofenac, ketorolac tromethamine, or placebo, and stratified by risk cohort. The HPβCD diclofenac non-high-risk cohort dose was 37.5 mg, the high-risk cohort received 18.75 mg, and patients ≥95 kg received 50 mg. The ketorolac dose was 30 mg in the non-high-risk and high-weight cohorts and 15 mg in the high-risk cohort. Rescue intravenous morphine was given for pain as needed. Efficacy was measured by the sum of pain intensity differences (SPID). Mean SPID scores of 277 patients were significantly better with HPβCD diclofenac and ketorolac than with placebo (P<0.0001), across all risk cohorts (P<0.05). HPβCD diclofenac was associated with better SPID scores, faster onset of analgesia, and significantly lower opioid requirement (P<0.008) than ketorolac. In patients more than or equal to 65 years, HPβCD diclofenac was associated with significantly better analgesic efficacy (P=0.05), and lower opioid requirement versus ketorolac. The incidence of treatment-related adverse events was similar across groups. HPβCD diclofenac is safe and efficacious for acute moderate and severe pain after orthopedic surgery and significantly spares morphine use.

A novel formulation of ibuprofen sodium has a faster onset of analgesia than standard ibuprofen tablets in the treatment of postoperative dental pain

A novel formulation of ibuprofen sodium has a faster onset of analgesia than standard ibuprofen tablets in the treatment of postoperative dental pain

Efficacy and safety of combined spinal: Epidural versus epidural technique for labor analgesia in parturients with rheumatic valvular heart disease

Background: Hemodynamic changes induced by labor pain and apprehension in addition to physiological changes may pose risk to parturients with rheumatic heart disease (RHD). Therefore, it is important to provide adequate pain relief during labor in these patients. We planned this study to compare the efficacy and safety of epidural (E) versus combined spinal - epidural (CSE) for labor analgesia in parturients with rheumatic valvular heart disease. Methods: Twenty-five parturients with RHD included in this study were randomized to one of the two groups - E group (n = 12), received 6 mL of 0.0625% bupivacaine with 25 μg fentanyl or CSE group (n = 13), received 25 μg of fentanyl with 1.25 mg bupivacaine diluted to 1 mL in subarachnoid space. Afterward, a continuous infusion of 0.1% bupivacaine with 2 μg/mL fentanyl was started at 6-8 mL/h. Primary outcome, analgesic efficacy, was assessed by visual analog scale (VAS) for pain. VAS ≤ 3 was considered as effective analgesia. Rescue analgesia in the form of epidural bolus was given if VAS > 3. Results: Demographic characteristics of the patients were comparable. Mitral stenosis was the predominant valvular lesion. The VAS at which the parturients received analgesia was comparable. The mean time to achieve effective analgesia was significantly faster in CSE group (4.46 ± 0.87 min) compared with group E (15.09 ± 5.7 min) (P < 0.001). Significantly lower median pain scores were recorded until the initial 15 min in CSE group. Afterward, median VAS for pain was comparable between the groups. VAS for pain was significantly low at all time intervals than baseline in both the groups. Maternal satisfaction and incidence of cesarean rate and complication were comparable between the groups. Conclusion: Both epidural and CSE are equally effective and safe for labor analgesia in parturients with rheumatic valvular heart disease. However, CSE technique provides a faster onset of analgesia.

Analgesic Properties of Dexketoprofen Trometamol

SUMMARYDexketoprofen trometamol is the dextrorotary enantiomer of the NSAID ketoprofen formulated as a tromethamine salt. The purpose of administering 50% of the racemic mixture is to keep the same analgesic and anti-inflammatory effect while reducing the adverse events due to both enantiomers. This article describes the pharmacological properties and evaluates the analgesic effects of dexketoprofen trometamol reported in acute and chronic pain conditions. The main conclusions are that dexketoprofen trometamol appears as effective as the double dose of the racemic drug. However, the reduction of adverse effects still has to be demonstrated. In addition, the formulation as tromethamine salt appears beneficial regarding fast onset of analgesia in acute pain conditions.

Fentanyl Sublingual

Fentanyl is a potent opioid with a short duration of action. Fentanyl sublingual has been formulated as a rapidly disintegrating tablet that is quickly absorbed, producing a fast onset of analgesia. In two randomized, double-blind clinical trials, fentanyl sublingual as single fixed or titrated doses reduced pain intensity during breakthrough pain episodes to a significantly greater extent than placebo in opioid-tolerant cancer patients. In a fixed-dose phase II trial and a titrated-dose phase III trial, fentanyl sublingual (as a single 400 μg dose and as titrated doses) reduced mean pain intensity difference (PID) to a significantly greater extent than placebo over the entire treatment period (up to 60 minutes), reaching statistical significance 15 minutes post-dose. In the titrated-dose study, the mean sum of PID (area under the PID vs time curve) at 30 minutes post-dose was significantly greater with fentanyl sublingual than placebo, with significant improvements in PID seen at 10 minutes maintained at 60 minutes post-dose. In the phase III study, patients receiving fentanyl sublingual were more satisfied with their treatment than patients receiving placebo (measured using the Patient Global Evaluation of Medication score), and almost half of all fentanyl sublingual recipients were satisfied or very satisfied with their treatment. Fentanyl sublingual was generally well tolerated in the two trials and most adverse events were mild to moderate in intensity.

An enhanced bunionectomy model as a potential tool for early decision-making in the development of new analgesics

bunionectomy has been used as a model of postoperative pain for opioids and nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors with a fast onset of analgesia. The present study was conducted to assess whether the utility of the model can be broadened in assessing the efficacy of analgesics with diverse mechanisms and pharmacokinetic profiles in drug development and to enhance the sensitivity of a bunionectomy model. this was a single center, randomized, double-blind, placebo-controlled, three-arm, parallel group methodology study to evaluate the effects of pregabalin and naproxen sodium on postoperative pain following bunionectomy. Patients (n=100) were randomized 1:1:1 to three treatments (administered 1 hour before and at defined intervals after surgery): pregabalin 300 mg before surgery and 150 mg every 8 hours; naproxen sodium 550 mg before surgery and 550 mg every 12 hours; or placebo in a double-dummy fashion. Primary endpoints were patient-controlled analgesic (PCA) hydromorphone consumption and the time to first PCA hydromorphone use postsurgery over 24 hours. of the 100 patients randomized, 96 completed the study. Relative to placebo, pregabalin and naproxen sodium, respectively, reduced PCA hydromorphone consumption by 51% (P=0.005) and 65% (P<0.001) and increased the median time to first use of PCA hydromorphone by 1.5 hours (P=0.004) and 3.7 hours (P<0.001). Both drugs significantly (P<0.050) decreased use of oral opioid rescue medication over 24-48 hours postsurgery relative to placebo. Although there were no statistically significant differences between naproxen sodium and pregabalin in opioid consumption and global evaluation of medication, overall naproxen sodium appeared to be more effective at reducing pain. the model provided a sensitive method for evaluating efficacy of compounds with diverse mechanisms and pharmacokinetic profiles. The robustness of the enhanced pain model renders bunionectomy pain a valuable tool to assess novel analgesic compounds in small numbers of subjects early in drug development.

Diclofenac Sodium Injection (Dyloject®)

*A new formulation of the nonselective NSAID diclofenac sodium suitable for intravenous bolus injection has been developed using hydroxypropyl beta-cyclodextrin as a solubility enhancer (HPbetaCD diclofenac). * HPbetaCD diclofenac intravenous bolus injection was shown to be bioequivalent to the existing parenteral formulation of diclofenac containing propylene glycol and benzyl alcohol as solubilizers (PG-BA diclofenac), which is relatively insoluble and requires slow intravenous infusion over 30 minutes. * Single-dose HPbetaCD diclofenac 3.75, 9.4, 18.75, 25, 37.5, 50 and 75 mg administered by intravenous bolus injection produced significantly greater responses than placebo for total pain relief (TOTPAR) over 6 hours or pain intensity at 4 hours in the treatment of moderate or severe postoperative dental pain in randomized, double-blind trials. HPbetaCD diclofenac 37.5 and 75 mg were similar in efficacy to intravenous bolus ketorolac 30 mg. * In a well controlled trial, single-dose HPbetaCD diclofenac 75 mg intravenous bolus injection was shown to be superior to PG-BA diclofenac 75 mg intravenous infusion with respect to TOTPAR over 4 hours, indicating faster onset of analgesia in the treatment of moderate or severe postoperative dental pain. Both HPbetaCD diclofenac and PG-BA diclofenac were superior to placebo. * HPbetaCD diclofenac was generally well tolerated during single-dose treatment of postoperative pain. The tolerability profile was similar to that of PG-BA diclofenac, but with a lower incidence of thrombophlebitis.

The role of combined spinal epidural analgesia for labour: is there still a question?

HEN combined spinal epidural (CSE) analgesia was introduced as a technique for labour analgesia, two distinct camps of opinion quickly emerged amongst anesthesiologists practicing obstetrical anesthesia: those who believe benefits of CSE are advantageous to every woman requesting a labour epidural; and those who believe the benefits over a standard epidural do not justify the intentional “invasion” of the dura nor the side effects. Efficacy has been well proven by a plethora of CSE studies, but safety remains a concern for many. In this issue of the Journal, Rofaeel et al. 1 report on a CSE study, examining hyperbaric bupivacaine vs isobaric bupivacaine. The study finds that when added to intrathecal (IT) sufentanil 2.5 µg, isobaric bupivacaine 2.5 mg, the standard dose which many anesthesiologists use, provides better analgesia within the first ten minutes post injection, compared to a 2.5-mg dose of hyperbaric bupivacaine. This difference disappears by 20 min post injection. The far more important finding of the study is that the incidence of sustained fetal bradycardia, defined as fetal heart rate 60 sec, was 33% in the isobaric group vs 10% in the hyperbaric group. This result is both statistically and clinically significant. While initial reports on CSE showed a high incidence of fetal bradycardia, more contemporary prospective studies, including those by Wong et al. 2 in 2005 and Van de Velde et al. 3 in 2004, report an incidence of prolonged decelerations varying between 3.9%–12%. None of the fetal bradycardias reported in Rofaeel’s study resulted in emergency obstetrical intervention, but perhaps this is a high cost to pay for a difference of ten minutes to attainment of excellent analgesia. One might conclude from this study that IT isobaric bupivacaine should no longer be used. But, it raises a more important issue: are the benefits of CSE over a standard epidural for labour analgesia enough to justify this risk of fetal harm? As a provider of CSE labour analgesia, I have established my own set of exclusion criteria based on interpretation of the literature. For instance, like the authors of this study, I do not use the technique when there is a poor fetal heart trace, nor when I wish to know the epidural catheter is functioning unequivocally at the time of insertion. I also use CSE for those who may gain the most benefit: women in advanced labour and those in extreme pain. However, given the incidence of fetal bradycardia observed in both groups of Rofaeel’s study, perhaps it is time to reassess whether CSE should continue to have a role in labour analgesia. Today, the purported benefits of CSE are: faster onset of analgesia, superior analgesia in late labour, better subsequent functioning of the epidural catheter, and higher patient satisfaction. It has been well-proven that when compared to dilute epidural solutions, CSE offers no advantage in terms of obstetrical intervention, nor any difference in the ability to be mobile. 4 The usually quoted disadvantages include: fetal bradycardia; unknown reliability of epidural catheter function; risk of central nervous system infection and respiratory depression; and significant pruritus. Risks of hypotension and post-dural puncture headache have been shown to be no different than with epidural analgesia. 4