Opioid Rescue Research Articles

Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting

Objective:Assess comparative efficacy of liposome bupivacaine administered at doses ≤266 mg and bupivacaine HCl administered at doses ≤200 mg for postsurgical analgesia.Research design and methods:Analysis of pooled efficacy and safety data from nine double-blind, placebo or active (bupivacaine HCl) controlled multimodal analgesia studies using a single dose of liposome bupivacaine or comparator, given via administration into the surgical site before end of surgery (i.e., inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy). Data from study arms that received liposome bupivacaine doses ≤266 mg were included.Clinical trial registration:Pooled data analysis includes nine studies: Study 1 – NCT01203644; Study 2 – NCT00485433; Study 3 – NCT00485693; Study 4 – NCT00529126; Study 5 – NCT00745290; Study 6 – NCT00744848; Study 7 – NCT00813111; Study 8 – NCT00890721; Study 9 – NCT00890682.Main outcome measures:Outcome measures included area under the curve (AUC) of pain intensity scores assessed by numeric rating scale (NRS) through 72 h postsurgery, time to first use of rescue opioid medications, total amount (mg) of opioid medications used, and occurrence of opioid-related adverse events (ORAEs). Incidence of overall AEs was also assessed.Results:Mean cumulative pain score (AUC of NRS through 72 h) was significantly lower with liposome bupivacaine (283) compared with bupivacaine HCl (329, p = 0.039). Median time from administration of study drug to first use of opioid rescue medication was significantly longer for liposome bupivacaine (10 h vs 3 h, p < 0.0001). Liposome bupivacaine was associated with a significant reduction in opioid use (12 mg vs 19 mg; p < 0.0001) and incidence of ORAEs (20% vs 36%; p < 0.0001), compared with bupivacaine HCl.Conclusions:In this pooled analysis from nine studies representing five different surgical procedures, liposome bupivacaine administered at doses ≤266 mg in a multimodal setting was associated with statistically significant and clinically meaningful lower cumulative pain score at 72 h, delayed and less consumption of opioids, and fewer ORAEs than bupivacaine HCl.

Liposomal Bupivacaine: An Innovative Nonopioid Local Analgesic for the Management of Postsurgical Pain

Local anesthetics are a cornerstone of multimodal pain control strategies in the surgical setting as they have a long history of use and an established safety profile. Although effective, their duration of action is relatively short, which usually leads to the use of other agents, such as opioids, for effective postsurgical pain control in most patients. A medical need exists to extend the duration of analgesia with local anesthetics to help reduce the reliance on opioids in the postsurgical setting. Liposomal bupivacaine uses a product delivery platform to release bupivacaine slowly over 96 hours after infiltration at the surgical site. Liposomal bupivacaine was compared with placebo in two pivotal, multicenter, randomized, double-blind, parallel-group trials in 189 adults undergoing soft-tissue surgery (hemorrhoidectomy) and 193 adults undergoing orthopedic surgery (bunionectomy). Among patients undergoing hemorrhoidectomy, liposomal bupivacaine significantly reduced cumulative pain scores for up to 72 hours (primary end point) as measured by the area under the curve of pain scores on the numeric rating scale (p<0.0001), reduced overall opioid consumption (p ≤ 0.0006), increased the proportion of patients who did not receive opioids (p<0.0008), delayed time to first opioid by more than 13 hours (p<0.0001), and was associated with significantly higher rates of patient satisfaction (p=0.0007) compared with placebo. Similarly, in patients undergoing bunionectomy, liposomal bupivacaine significantly reduced total consumption of rescue opioids (p=0.0077) and cumulative pain scores as measured by the area under the curve of pain scores on the numeric rating scale (p=0.0005) during the first 24 postsurgical hours (primary end point) relative to placebo. Furthermore, liposomal bupivacaine also significantly delayed the time to first use of opioid rescue (p<0.0001) and increased the proportion of patients requiring no rescue opioid treatment (p ≤ 0.0404) compared with placebo. The most common adverse events with liposomal bupivacaine were nausea, vomiting, and constipation. No adverse effects on the QTc interval or cardiac safety signal have been detected in the clinical trial development program (823 patients) when liposomal bupivacaine was infiltrated into the surgical site. The beneficial effects of liposomal bupivacaine on postsurgical pain management and opioid use, significantly reducing both, are likely to translate into improved clinical and economic outcomes.

Dexmedetomidine: a guide to its use for sedation in the intensive care unit in the EU

Intravenous dexmedetomidine (Dexdor®) provides an effective and generally well tolerated option for short- or longer-term primary sedation for patients in the intensive care unit (ICU) setting. It reduces the need for rescue sedation and opioids, and patients sedated with dexmedetomidine are calm and easy to arouse and manage. Moreover, dexmedetomidine is similar to propofol and midazolam in maintaining target sedation levels in ventilated ICU patients requiring longer-term sedation.

Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postsurgical analgesia

BackgroundLiposome bupivacaine is a novel formulation of the local anesthetic bupivacaine, designed to provide prolonged postsurgical analgesia. This analysis examined pooled efficacy data as reflected in cumulative pain scores from 10 randomized, double-blind liposome bupivacaine clinical studies in which the study drug was administered via local wound infiltration.MethodsA total of 823 patients were exposed to liposome bupivacaine in 10 local wound infiltration studies at doses ranging from 66 mg to 532 mg in five surgical settings; 446 patients received bupivacaine HCl (dose: 75–200 mg) and 190 received placebo. Efficacy measures were assessed through 72 hours after surgery.ResultsOverall, 45% of patients were male and 19% were ≥65 years of age. In the analysis of cumulative pain intensity scores through 72 hours, liposome bupivacaine was associated with lower pain scores than the comparator in 16 of 19 treatment arms assessed, achieving statistically significant differences compared with bupivacaine HCl (P < 0.05) in five of 17 treatment arms. These results were supported by results of other efficacy measures, including time to first use of opioid rescue medication, proportion of patients avoiding opioid rescue medication, total postsurgical consumption of opioid rescue medication, and patient/care provider satisfaction with postoperative analgesia. Local infiltration of liposome bupivacaine resulted in significant systemic plasma levels of bupivacaine, which could persist for 96 hours; systemic plasma levels of bupivacaine following administration of liposome bupivacaine were not correlated with local efficacy. Liposome bupivacaine and bupivacaine HCl were generally well tolerated.ConclusionBased on this integrated analysis of multiple efficacy measures, liposome bupivacaine appears to be a potentially useful therapeutic option for prolonged reduction of postsurgical pain in soft tissue and orthopedic surgeries.

Evaluating Therapeutic Benefit in Postsurgical Analgesia Requires Global Assessment: An Example From Liposome Bupivacaine in Hemorrhoidectomy

Background and Objective: Interpreting analgesic efficacy based solely on measures of pain intensity can be misleading. Here, we use data from an adult hemorrhoidectomy study to demonstrate the importance of evaluating pain intensity scores with other outcome measures in interpreting analgesic study results. Methodology: We looked for coordinated outcome measures including pain intensity at rest using a numeric rating scale (NRS), postsurgical consumption of rescue medication, subject-reported results from the Brief Pain Inventory, subject satisfaction with postsurgical analgesia, and adverse events. Results: The analgesic efficacy of liposome bupivacaine was reflected in a significant reduction in pain intensity scores at each timed assessment during the first 12 to 24 hours after surgery (meanNRS at 12 hours: liposome bupivacaine, 2.2; placebo, 2.9; P = 0.04), and less consumption of opioid rescue medications thereafter through 72 hours postsurgery (mean total amount of opioids consumed: liposome bupivacaine, 10 mg; placebo, 18 mg; P = 0.0006). These observations are supported by results of other outcome measures, including time to first use of opioid rescue medication, pain-related interference of subject functionality, and subject satisfaction with postsurgical analgesia. Conclusion: Liposome bupivacaine produced superior analgesia when compared with placebo at early postoperative time points, but appropriate use of rescue medication diminished this effect after 12 hours. However, based on our assessment of multiple outcome measures used in the study, it appears that the therapeutic benefit associated with the tested analgesic lasted throughout the 72-hour study period.

The Efficacy and Safety of DepoFoam Bupivacaine in Patients Undergoing Bilateral, Cosmetic, Submuscular Augmentation Mammaplasty: A Randomized, Double-Blind, Active-Control Study

Breast augmentation can result in significant postsurgical pain. The authors evaluate the extent and duration of analgesia achieved with extended-release DepoFoam bupivacaine (Pacira Pharmaceuticals, Inc., Parsippany, New Jersey) in patients undergoing bilateral, cosmetic, submuscular augmentation mammaplasty under general anesthesia. In this randomized, multicenter, double-blind study, patients received a single dose of DepoFoam bupivacaine 600 mg or bupivacaine HCl 200 mg divided into the implant pockets at the conclusion of surgery. The primary efficacy measure was cumulative pain score with activity through 72 hours postoperatively. Secondary efficacy measures included pain intensity with activity and at rest, postsurgical consumption of rescue opioids, and integrated rank analysis combining pain scores at rest with the amount of opioid used. One hundred thirty-six patients were randomized and treated (DepoFoam bupivacaine, n = 66; bupivacaine HCl, n = 70). Reflecting the underpowered nature of the study, the mean cumulative pain score (numeric rating scale with activity through 72 hours) was 441.5 with DepoFoam bupivacaine versus 468.2 with bupivacaine HCl (P = .3999). Total amounts of opioid consumed were significantly lower in the DepoFoam bupivacaine group through 24 hours (P = .0211) and through 48 hours (P = .0459). The prespecified integrated rank analysis showed statistically-significant differences at multiple time points up to and including 60 hours; results on most other efficacy measures trended in favor of DepoFoam bupivacaine. No serious adverse events were reported, and no patients discontinued the study due to adverse events. DepoFoam bupivacaine trended toward benefit versus bupivacaine HCl on most efficacy measures. Due to early termination, the study was underpowered to achieve statistical significance.

Short stay and less pain after ambulatory anterior cruciate ligament (ACL) repair: COX‐2 inhibitor versus glucocorticoid versus both combined

Many studies have demonstrated that either COX-2 antagonists or glucocorticoids are efficient analgesics after orthopaedic surgery. We wanted to evaluate if the combination of these two drugs was better than one drug alone when added to paracetamol, local anaesthesia, and cryo-cuff for outpatient anterior crucial ligament (ACL) surgery. In a double-blind design, 89 adult patients scheduled for day-case ACL repair in general anaesthesia were randomly assigned into three groups: The COXIB group (n = 30) received either 40 mg parecoxib iv or 120 mg etoricoxib orally 1 h before surgery. The STEROID group (n = 30) received 8 mg dexamethasone iv, and the combination group (Group COMBI, n = 29) received both. At 24 h, Group COMBI had significantly lower visual analogue scale (0-10 cm) scores during rest (2.1 ± 1.3) (mean ± standard deviation) and movement (4.2 ± 2.5) when compared to both the COXIB group (P = 0.04) and the STEROID group (P = 0.035). The accumulated consumption of rescue opioids (5.2 ± 4,5 mg morphine) was also significantly lower at 24 h compared to the other groups (P = 0.02). Mean time to discharge from hospital was about 3 h in all groups. The pain scores in the post-anaesthetic care unit, mobilization at 24 h and 7 days, and general level of satisfaction were similar between the groups. The combination of a COX-2 inhibitor and dexamethasone results in better pain relief 24 h after surgery in patients undergoing outpatient ACL surgery, compared to COX-2 inhibitor alone or dexamethasone alone. With a dedicated multimodal pain regime, most ACL patients may be discharged within 3 h.

Evaluation of DepoFoam ® Bupivacaine for the Treatment of Postsurgical Pain

SUMMARYAn extended-release, multivesicular liposome-encapsulated form of the local anesthetic bupivacaine, DepoFoam(®) bupivacaine (proposed proprietary name EXPAREL™), is in development for use as part of a multimodal regimen for the treatment of postsurgical pain. Placebo- and active-controlled clinical trials in patients who have undergone either orthopedic or soft-tissue procedures indicate that a single local administration into the surgical site results in analgesic activity for up to 3-4 days and decreases the use of opioid rescue medication. The safety profile of DepoFoam bupivacaine appears to be similar to that of bupivacaine HCl, and adverse events are dose-related.

A phase 3, randomized, placebo-controlled trial of DepoFoam® bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy

DepoFoam® bupivacaine (Pacira Pharmaceuticals, Inc., San Diego, CA, USA), an extended-release liposomal bupivacaine-based analgesic, was compared with placebo for the prevention of pain after bunionectomy in a randomized, multicenter, double-blind phase 3 clinical study. Patients received placebo (n = 96) or DepoFoam bupivacaine 120 mg (n = 97) via wound infiltration prior to closure. Pain intensity was assessed using a numeric rating scale (NRS) from time 0 through to 72 hours postsurgically. The primary efficacy measure was area under the curve (AUC) of NRS scores through 24 hours. Other efficacy measures included AUC of NRS at other time points, proportion of patients who were pain-free, time to first opioid use, and total postsurgical consumption of supplemental opioid medication. Adverse events were also assessed. The AUC for NRS scores was significantly less in patients treated with DepoFoam bupivacaine versus patients receiving placebo at 24 hours (P = 0.0005) and 36 hours (P < 0.0229). More patients treated with DepoFoam bupivacaine avoided use of opioid rescue medication during the first 24 hours (7.2% vs. 1%; P < 0.0404) and were pain-free (NRS ≤ 1) at 2, 4, 8, and 48 hours. Median time-to-first-opioid use was delayed in favor of DepoFoam bupivacaine (4.3 vs. 7.2 hours; P < 0.0001). Fewer adverse events were reported by patients treated with DepoFoam bupivacaine (59.8%) versus placebo (67.7%). DepoFoam bupivacaine, a long-acting local analgesic, provided extended pain relief and decreased opioid use after bunionectomy, compared with placebo.

Dexmedetomidine versus remifentanil in combination with sevoflurane for gynecological laparoscopy

Objective To compare the efficacy of dexmedetomidine versus remifentanil in combination with sevoflurane for gynecological laparoscopy. Methods Forty ASA Ⅰ or Ⅱ patients aged 18-64 yr with body mass index of 18-30 kg/m2 undergoing gynecological laparoscopy were randomly assigned to one of two groups ( n =20 each): dexmedetomidine group (group D) and remifentanil group (group R). Starting from 5 min before induction of anesthesia, dexmedetomidine was infused at 0.05 μg · kg - 1 · min- 1 in group D and remifentanil at 0.1 μg· kg- 1· min-1 in group R for 10 min, then dexmedetomidine infusion rate was increased to 0. 3 μg· kg-1 · h-1 and remifentanil infusion rate was increased to 0.15 μg· kg-1 · min-1 . Anesthesia was induced with propofol 1.5-2.0 mg/kg and fentanyl 2 μg/kg. Tracheal intubation was facilitated with cis-atracurium 0.15 mg/kg. Anesthesia was maintained with sevoflurane and fentanyl 1 μg/kg and intermittent iv boluses of cis-atracurium. Narcotrend index was maintained at 40-50. Blood sample was taken from external jugular vein for blood gas analysis and determination of serum concentrations of corticosteroid, norepinephrine and epinephrine before administration, at 5 min after intubation, at 10 min of aeroperitoneum and at 5 min after extubation. The pH value and concentrations of lactic acid and glucose were recorded. The time for recovery of spontaneous breathing, eye-opening time, extubation time, orientation time and perioperative side-effects were recorded. Numeric rating scale was used to assess the intensity of pain during 2 h after operation. The analgesics used were also recorded. Results The serum concentrations of norepinephrine and epinephrine were significanfly lower at 10 min of aeroperitoneum, the time for recovery of spontaneous breathing was shorter, eye-opening time longer and the incidence of shivering and nausea and vomiting lower, the percentage of patients requiring rescue opioids lower in group D than in group R ( P ＜ 0.05). Conclusion The efficacy of dexmedetomidine combined with sevoflurane anesthesia is better than remifentanil combined with sevoflurane anesthesia for gynecological laparoscopy. Key words: Dexmedetomidine; Piperidines; Anesthetics, inhalation; Laparoscopy

Preemptive multimodal analgesia facilitates same-day discharge following robot-assisted hysterectomy.

We aimed to determine whether early hospital discharge following minimally invasive surgery can be achieved through the use of preemptive multimodal analgesia without compromising patient safety or comfort. Data were retrospectively collected for 150 patients who underwent robotic-assisted laparoscopic hysterectomy for benign indications from 9 December 2009 to 6 October 2010 at Cox Health Systems (Springfield, MO, USA). One surgeon performed 100 consecutive cases with all patients receiving preemptive multimodal treatment with celecoxib and ropivacaine. These cases were compared with 50 patients treated with an opioid-based postoperative analgesia regimen by one of four other surgeons at the same center. Patient characteristics, perioperative outcomes, opioid requirement, and time to discharge were compared between groups. The patients in the multimodal group had significantly reduced opioid requirements intraoperatively (25.0mg vs. 29.9mg, P=0.0077), postoperatively on the day of surgery (10.9mg vs. 17.9mg, P=0.0030), and on the first postoperative day (3.1mg vs. 15.3mg, P=0.0001). There were no differences in procedure time, transfusions, or readmission rates between groups. Time in the Post-Anesthesia Care Unit (PACU) was decreased in the multimodal group (72.0min vs. 88.4min, P<0.0001), as was time to discharge from the hospital (8.5h vs. 30.2h, P<0.0001). Age and body mass index were both significantly lower in the multimodal group; however, regression analyses demonstrated that analgesia regimen was the only parameter that predicted opioid requirement and time to discharge. Preemptive multimodal analgesia reduced the total dose of rescue opioids, facilitating same-day discharge without compromising patient comfort or safety.

Epidural Steroid and Clonidine for Chronic Intractable Post‐thoracotomy Pain: A Pilot Study

Chronic post-thoracotomy pain is relatively common after major thoracic surgery. The primary results of a pilot study using thoracic epidural steroid and clonidine injection to treat chronic intractable post-thoracotomy pain are presented. Twenty-one patients with intractable post-thoracotomy pain participated in the study. Thirteen patients received thoracic epidural injection of a mixture of 150 μg clonidine and 80 mg of methylprednisolone acetate diluted in 8 mL 0.5% lidocaine. Eight patients continued with comprehensive medical management and served as a control group. A visual analog scale (VAS) for pain was recorded before treatment, 30 minutes after the epidural injection and before discharge, at 3 weeks and 6 months. Pain, sleep disturbances, appetite changes and daily activity, as well as the incidence of complications were recorded. The need for opioid rescue medications was recorded. Twelve of 13 patients in the injection group reported improvement (> 50% reduction of pain) at 3 weeks and 6 months following the injection. Allodynia improved in all injection group patients compared to four of eight in the control group. Sleep disturbance, appetite changes and daily activity were improved in the injection group. The number of patients requiring opioid rescue medications was reduced from 61.5% to 15.3% during the 6-month duration of study. Injection caused transient hypotension in 46.2% of patients. Mild sedation was noted in 30.7% of patients receiving injection; 15.3% of the patients had localized back pain at the site of injection. Our preliminary data suggest possible efficacy of thoracic epidural steroid and clonidine mixture in the treatment of chronic post-thoracotomy pain. No serious adverse effects were noted in this pilot study.

Postoperative Analgesia: Comparing Continuous Epidural Catheter Infusion of Local Anesthetic and Opioid and Continuous Wound Catheter Infusion of Local Anesthetic

Continuous wound infusion has been investigated as a method of postoperative pain control and its efficacy has been demonstrated when compared to saline infusion. The objective of this study was to compare the quality of postoperative analgesia, the use of opioids as rescue analgesia, patient satisfaction, and the incidence of complications between epidural catheter infusion of local anesthetic and opioids and continuous wound infusion of local anesthetic. Thirty-eight patients undergoing elective laparotomy under general anesthesia, randomly divided into two groups, participated in this study. Group I (GI) received postoperative patient-controlled epidural analgesia (PCEA) with continuous infusion of ropivacaine and fentanyl, while Group II (GII) receive postoperative patient-controlled continuous wound catheter infusion of ropivacaine. In the postoperative period, the following parameters were assessed: quality of analgesia through the Visual Analogue Scale; use of rescue opioids; and adverse effects driving patient satisfaction. Decreased pain at rest and with movements (p < 0.05) and lower consumption of rescue opioids (p < 0.05) were observed in GI in all intervals evaluated, as well as greater patient satisfaction in the post anesthesia care unit (PACU). The incidence of complications was similar in both groups except for pruritus which prevailed in GI between 6 (p < 0.05) and 24 (p < 0.001) postoperative hours. Postoperative analgesia with opioids and local anesthetics via PCEA was superior to the patient-controlled local anesthetic infusion into surgical wound. The incidence of side effects was similar in both groups.

Local Anaesthetic Wound Infiltration after Internal Fixation of Femoral Neck Fractures: A Randomized, Double-Blind Clinical Trial in 33 Patients

Pain control may assist early mobilisation after internal fixation of femoral neck fractures. Systemic opioids have significant side effects in elderly patients. We present an evaluation of the effect of local anaesthetic infiltration in such cases , the objective being to decrease the need for postoperative opioids and to improve pain control for patients after surgery. 33 patients undergoing internal fixation with 2 parallel hook pins were randomized into 2 groups in a double blind study (ClinicalTrials.gov: NCT00529425). 33 patients received intraoperative infiltration followed by 6 postoperative injections through an intraarticular catheter in eight-hour intervals. 19 patients received ropivacaine and 14 received saline. The intervention period was 48 hours and the observation period was 5 days. In both groups there were no restrictions on the total daily dose of rescue analgesics. Pain was assessed at specific postoperative time-points and the daily consumption of opioid drugs needed for analgesia was registered. There was no significantly reduced consumption of standardized opioid rescue analgesics or pain in the study group receiving ropivacaine injections. Apart from a reduction in nausea in the study group on the second postoperative day, there were no significant differences in the occurrence of side effects between the groups. On day 2 the placebo group had less pain than the study group. Local anaesthetic infiltration after fixation of femoral neck fractures does not reduce opioid consumption or pain'.

Local Anesthetic Irrigation and Postoperative Pain in Patients Undergoing Breast Augmentation

Objective: To determine if the irrigation of the breast cavity with local anesthetics in patients who undergo breast augmentation surgery reduces rescue analgesic requirements and postoperative pain intensity level, measured with the visual analogue scale (VAS). Methods: This study is a Placebo controlled non randomized clinical trial. In the intervention group (group 1) the breast cavity was irrigated with 1% lidocaine with epinephrine (7 mg/kg), 0.5% bupivacaine (3 mg/kg) and normal saline solution. In the second control group (group 0) the breast cavity was irrigated with saline solution. Anesthetic and analgesic techniques were standardized. The type (morphine, hydromorphone and meperidine) and total required dose of opioid rescue analgesic medication in the Post Anesthetic Care Unit (PACU) were also registered. Postoperative pain intensity level was also registered at the moment of consciousness recovery, thirty minutes, the first hour, two, six and twenty four hours of postoperative period. Results: There was a difference in the number of patients requiring opioid rescue analgesia with morphine at PACU (p<0.01), 10% in the intervention group versus 50% in the control group. Likewise, there was difference in pain intensity level (p<0.01). Conclusions: Local anesthetic irrigation in patients who underwent breast augmentation surgery reduces opioid rescue analgesia requirements and postoperative pain intensity level.

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.

W3.2 Magnesium sulphate and pre-eclampsia

Droperidol is a dopamine receptor antagonist that functions as an analgesic, sedative, and antiemetic. In 2001, the U.S. Food and Drug Administration required a black box warning in response to case reports of QT prolongation and potential fatal arrhythmias. The aim of this study was to evaluate the effectiveness and safety of droperidol in patients presenting to a United States Emergency Department (ED).Observational cohort study of all droperidol administrations from 1/1/2012 through 4/19/2018 at an academic ED. The primary endpoint was mortality within 24 h of droperidol administration. Secondary endpoint included use of rescue analgesics.A total of 6,881 visits by 5,784 patients received droperidol of whom 6,353 visits authorized use of their records for research, including 5.4% administrations in children and 8.2% in older adults (≥65). Droperidol was used as an analgesic for pain (N = 1,387, 21.8%) and headache (N = 3,622, 57.0%), as a sedative (N = 550, 8.7%), and as an antiemetic (N = 794, 12.5%). No deaths secondary to droperidol administration were recorded within 24 h. Need for rescue analgesia occurred in 5.2% of patients with headache (N = 188) and 7.4% of patients with pain (N = 102); 1.1% of patients with headache received rescue opioids (N = 38) after droperidol, as did 5.4% of patients with pain other than headache (N = 75). No patients had fatal arrhythmias. Akathisia occurred in 2.9%.No fatalities were seen among this large cohort of patients who received droperidol in the ED. Our findings suggest droperidol's effectiveness and safety when used as an analgesic, antiemetic and/or sedative.

Caesarean section wound infiltration with local anaesthesia for postoperative pain relief: any benefit?th lo

Delivery by caesarean section (CS) is becoming more frequent. Childbirth is an emotion-filled event, and the mother needs to bond with her baby as early as possible. Any intervention that leads to improvement in pain relief is worthy of investigation. Local anaesthetics have been employed as an adjunct to other methods of postoperative pain relief, but reports on the effectiveness of this strategy are conflicting. This review attempted to assess the effects of local anaesthetic agent wound infiltration and/or abdominal nerve blocks on pain after CS and the mother's well-being and interaction with her baby. Methods. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2009).The selection criteria were randomised controlled trials of local analgesia during CS to reduce pain afterwards. Twenty studies (1 150 women) were included. Results. Women who had wound infiltration after CS performed under regional analgesia had a decrease in morphine consumption at 24 hours compared with placebo (morphine dose -1.70 mg; 95% confidence interval (CI) -2.75 to -0.94). Women who had wound infiltration and peritoneal spraying with local anaesthetic after CS under general anaesthesia (1 study, 100 participants) had a reduced need for opioid rescue (risk ratio (RR) 0.51; 95% CI 0.38 to 0.69). The numerical pain score (0 -10) within the first hour was also reduced (mean difference (MD) -1.46; 95% CI -2.60 to -0.32). Women with regional analgesia who had local anaesthetic and non-steroidal anti-inflammatory cocktail wound infiltration consumed less morphine (1 study, 60 participants; MD -7.40 mg; 95% CI -9.58 to -5.22) compared with those who had local anaesthetic control. Women who had regional analgesia with abdominal nerve blocks had decreased opioid consumption (4 studies, 175 participants; MD -25.80 mg; 95% CI -50.39 to -5.37). For outcome in terms of the visual analogue pain score (0 - 10) over 24 hours, no advantage was demonstrated in the single study of 50 participants who had wound infiltration with a mixture of local analgesia and narcotics versus local analgesia. Conclusions. Local anaesthetic infiltration and abdominal nerve blocks as adjuncts to regional analgesia and general anaesthesia are of benefit in CS by reducing opioid consumption. Non-steroidal anti-inflammatory drugs may provide additional pain relief.

Recent development in therapeutics for breakthrough pain

Breakthrough pain is defined as transitory flares of pain. Breakthrough pain is caused by cancer, cancer complications, treatment or comorbidities. The usual onset to maximum breakthrough pain intensity time is 3 min and duration is 30 min; therefore, the assessment for response needs to be at short intervals. The rapid onset and offset of pain results in inadequate responses when oral opioids are used to manage pain flares. Several strategies have been used to manage breakthrough pain: titration of the chronic opioid, independent titration of rescue opioids and alternative routes. Buccal fentanyl has a rapid onset to analgesia and appears to be superior to oral morphine. Newer fentanyl preparations have been released to manage breakthrough pain in the opioid-tolerant individual. Other routes of administration that have a rapid onset to analgesia include intranasal hydrophilic and lipophilic opioids, inhaled opioids delivered by special delivery devices and parenteral morphine. In a small series of patients experiencing severe flares of pain with spinal opioids unrelieved by parenteral opioids, sublingual ketamine and bolus doses of intrathecal local anesthetics have been effective. Nonpharmacological approaches to managing activity-related pain include radiation therapy, surgical correction of impending fractures, kyphoplasty and radioisotopes.

Diclofenac potassium liquid-filled soft gelatin capsules in the management of patients with postbunionectomy pain: A phase III, multicenter, randomized, double-blind, placebo-controlled study conducted over 5 days

Background: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is a rapidly absorbed formulation of diclofenac potassium developed for the treatment of mild to moderate acute pain.Objective: The present study was conducted to assess the efficacy and safety profile of DPSGC 25 mg in patients with pain after first-metatarsal bunionectomy.Methods: This was a Phase III, multicenter, randomized, double-blind, parallel-group, placebo-controlled study conducted over 5 days. Patients experiencing the requisite level of pain (score ≥4 on an 11-point numeric pain rating scale [NPRS] from 0 = no pain to 10 = worst possible pain) on the day after bunionectomy were randomized to receive DPSGC 25 mg or matching placebo. A second dose was given when patients requested additional medication for pain. Subsequent doses were given every 6 hours over a 48-hour inpatient multiple-dose period and continued over an additional 48-hour outpatient multiple-dose period. Opioid rescue medication was available as needed after the second dose of study medication. The primary efficacy end point was the mean NPRS score over the 48-hour inpatient multiple-dose period. Additional measures included NPRS scores at predefined times over 48 hours, the summed pain intensity difference over 48 hours (SPID48), the time-weighted sum of pain relief scores over the first 8 hours, the mean dosing interval (the time from dosing to the time rescue medication or the next dose of study medication was administered, whichever was less), the proportion of patients requiring rescue medication, and the onset of perceptible and meaningful pain relief (2-stopwatch method). Tolerability was assessed based on physician monitoring and patient reporting of adverse events (AEs) and the results of standard laboratory tests.Results: Of 201 randomized patients (102 DPSGC 25 mg, 99 placebo; 86.6% female; 58.2% white; mean [SD] age, 45.2 [11.5] years; weight range, 49.4–108.0 kg), 198 completed the study. Mean baseline NPRS scores did not differ significantly between the DPSGC and placebo groups (6.9 and 7.3, respectively). DPSGC was associated with significant improvements compared with placebo in mean NPRS score over 48 hours (2.5 vs 5.6, respectively; P < 0.001), mean SPID48 (210.0 vs 90.3; P < 0.001), and overall mean dosing interval (331.5 vs 263.9 min; P < 0.001). Significant differences in NPRS scores between DPSGC 25 mg and placebo were noted at all time points from baseline through 48 hours (P < 0.001). The proportion of patients requiring rescue medication was significantly lower in the DPSGC group compared with the placebo group (39.2% vs 87.9% on day 1; 21.6% vs 64.6% on day 2; both, P < 0.001). Patients receiving DPSGC had a significantly faster onset of meaningful pain relief compared with those receiving placebo (P = 0.008). The most commonly reported AEs were nausea (7.8% vs 18.2%), headache (5.9% vs 9.1%), vomiting (3.9% vs 9.1%), and constipation (3.9% vs 2.0%). The overall incidence of AEs occurring in ≥2% of patients was significantly lower in the DPSGC group than in the placebo group (20.6% vs 44.4%; P < 0.05); no patient receiving DPSGC had a serious AE.Conclusions: DPSGC 25 mg taken every 6 hours was effective in reducing postbunionectomy pain in the patients studied. DPSGC was well tolerated, suggesting that it may be a practicable option for the treatment of mild to moderate acute pain. ClinicalTrials. gov identifier: NCT00366444