Incidence Of Breakthrough Pain Research Articles

High-volume patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia: a randomised controlled study.

The aim of neuraxial analgesia is to achieve excellent pain relief with the fewest adverse effects. The most recently introduced technique for epidural analgesia maintenance is the programmed intermittent epidural bolus. In a recent study, we compared this with patient-controlled epidural analgesia without a background infusion and found that a programmed intermittent epidural bolus was associated with less breakthrough pain, lower pain scores, higher local anaesthetic consumption and comparable motor block. However, we had compared 10 ml programmed intermittent epidural boluses with 5 ml patient-controlled epidural analgesia boluses. To overcome this potential limitation, we designed a randomised, multicentre non-inferiority trial using 10 ml boluses in each group. The primary outcome was the incidence of breakthrough pain and total analgesic intake. Secondary outcomes included motor block; pain scores; patient satisfaction; and obstetric and neonatal outcomes. The trial was considered positive if two endpoints were met: non-inferiority of patient-controlled epidural analgesia with respect to breakthrough pain; and superiority of patient-controlled epidural analgesia with respect to local anaesthetic consumption. A total of 360 nulliparous women were allocated randomly to patient-controlled epidural analgesia-only or programmed intermittent epidural bolus groups. The patient-controlled group received 10 ml boluses of ropivacaine 0.12% with sufentanil 0.75 μg.ml-1 ; the programmed intermittent group received 10 ml boluses supplemented by 5 ml patient-controlled boluses. The lockout period was 30 min in each group and the maximum allowed hourly local anaesthetic/opioid consumption was identical between the groups.Breakthrough pain was similar between groups (11.2% patient controlled vs. 10.8% programmed intermittent, p = 0.003 for non-inferiority). Total ropivacaine consumption was lower in the PCEA-group (mean difference 15.3 mg, p < 0.001). Motor block, patient satisfaction scores and maternal and neonatal outcomes were similar across both groups. In conclusion, patient-controlled epidural analgesia is non-inferior to programmed intermittent epidural bolus if equal volumes of patient-controlled epidural analgesia are used to maintain labour analgesia and superior with respect to local anaesthetic consumption.

The incidence of breakthrough pain associated with programmed intermittent bolus volumes for labor epidural analgesia: a randomized controlled trial

BackgroundIn this randomized, blinded study, we evaluated the effects of different programmed intermittent epidural bolus (PIEB) volumes for labor analgesia on the incidence of breakthrough pain and other analgesic outcomes. MethodsNulliparous women with term cephalic singleton pregnancies who requested labor analgesia had epidural analgesia initiated with 10 mL 0.1% ropivacaine with sufentanil 0.3 μg/mL. The pump was programmed to deliver a 4, 6 or 8 mL bolus every 45 min (groups 4, 6 or 8, respectively). The primary outcome was the incidence of breakthrough pain, defined as inadequate analgesia after two patient-controlled epidural analgesia administrations in a 20-min period. Secondary outcomes included ropivacaine consumption, time of the first patient-controlled epidural analgesia request, duration of the second stage of labor, and incidence of motor block. ResultsAmong 210 women randomly allocated the incidence of breakthrough pain was 34.9%, 19.7%, and 13.1%, for groups 4, 6 and 8, respectively (P=0.011). The incidence of breakthrough pain in group 8 was lower than in group 4 (P=0.006). The median (interquartile range) hourly ropivacaine consumption was 8.2 mg/h (7.1–11.3), 10.4 mg/h (9.2–13.0), and 12.0 mg/h (11.2–13.8) in groups 4, 6 and 8, respectively (P <0.001). Group 8 had a longer duration of effective analgesia and longer second stage of labor than group 4. There was no significant difference between groups in the incidence of motor block. ConclusionThe larger PIEB volumes were preferred for epidural labor analgesia compared with a smaller volume because of improved analgesia without clinically significant increases in adverse effects.

Prediction of breakthrough pain during labour neuraxial analgesia: comparison of machine learning and multivariable regression approaches

IntroductionRisk-prediction models for breakthrough pain facilitate interventions to forestall inadequate labour analgesia, but limited work has used machine learning to identify predictive factors. We compared the performance of machine learning and regression techniques in identifying parturients at increased risk of breakthrough pain during labour epidural analgesia. MethodsA single-centre retrospective study involved parturients receiving patient-controlled epidural analgesia. The primary outcome was breakthrough pain. We randomly selected 80% of the cohort (training cohort) to develop three prediction models using random forest, XGBoost, and logistic regression, followed by validation against the remaining 20% of the cohort (validation cohort). Area-under-the-receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were used to assess model performance. ResultsData from 20 716 parturients were analysed. The incidence of breakthrough pain was 14.2%. Of 31 candidate variables, random forest, XGBoost and logistic regression models included 30, 23, and 15 variables, respectively. Unintended venous puncture, post-neuraxial analgesia highest pain score, number of dinoprostone suppositories, neuraxial technique, number of neuraxial attempts, depth to epidural space, body mass index, pre-neuraxial analgesia oxytocin infusion rate, maternal age, pre-neuraxial analgesia cervical dilation, anaesthesiologist rank, and multiparity, were identified in all three models. All three models performed similarly, with AUC 0.763–0.772, sensitivity 67.0–69.4%, specificity 70.9–76.2%, PPV 28.3–31.8%, and NPV 93.3–93.5%. ConclusionsMachine learning did not improve the prediction of breakthrough pain compared with multivariable regression. Larger population-wide studies are needed to improve predictive ability.

Intrathecal delivery of hydromorphone vs morphine for refractory cancer pain: a multicenter, randomized, single-blind, controlled noninferiority trial.

Hydromorphone is an alternative to morphine for intrathecal drug delivery system to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (ITHM) and intrathecal morphine (ITMO) groups, respectively. The primary outcome was the clinical success rate, which was defined as ratio of patients achieving ≥50% pain relief. The noninferiority margin was defined as -0.15. Other outcomes included daily visual analogue scale score, breakthrough pain (BTP) incidence, intrathecal dose change, and patient-controlled analgesia bolus count change, GAD-7/PHQ-9. Clinical success was achieved in 85 and 79 of the 121 ITHM patients (70.2%) and 112 ITMO patients (70.5%), respectively. Compared to the corresponding baseline findings, significantly decreased visual analogue scale scores and BTP incidence were noted in both groups. The dose change rate decreased and increased with time in the ITHM and ITMO groups, respectively (ITHM -3.33% vs ITMO 35.4%, P < 0.01, t test) from the third week. The patient-controlled analgesia bolus change rate was lower in the ITHM group than in the ITMO group (ITHM -19.88% vs ITMO 7.79%, P < 0.01, t test) from first week. Our result shows that ITHM is noninferior to ITMO on pain relief to treat refractory cancer pain, however, at different doses and that the doses of morphine tended to increase, whereas those of hydromorphone decreased over time. Hydromorphone offers advantage over morphine in controlling BTP.

Reducing breakthrough pain during labour epidural analgesia: an update.

Neuraxial techniques are the current gold standard for labour analgesia, but are associated with up to 25% incidence of breakthrough pain. In this review, we aim to update clinicians on the latest research pertaining to the optimization of neuraxial labour analgesia. Attempts to improve the efficacy and reliability of epidural analgesia while minimizing adverse effects have resulted in the rising popularity of combined spinal epidural and the dural puncture epidural (DPE). Recent studies have focused on determining the safety, efficacy, and optimization of the DPE technique.Another research focus is on the development of individualized therapy in which patients may titrate their own labour analgesia according to their varying requirements, possibly augmented with computer-aided feedback systems and automated mandatory bolus techniques that automatically adjust drug delivery to the patients' analgesic requirements. The addition of a risk-stratification model based on maternal, anaesthetic, and obstetric factors will facilitate early institution of individualized therapy to forestall breakthrough pain in higher risk patients. Recent advances in combined spinal epidural, DPE, automated mandatory bolus, and individualized therapies have advanced our goal of providing effective labour analgesia that is titrated to changing analgesic requirements during labour and delivery and reducing breakthrough pain.

A Systematic Review and Meta-Analysis Comparing Programmed Intermittent Bolus and Continuous Infusion as the Background Infusion for Parturient-Controlled Epidural Analgesia

The programmed intermittent epidural bolus (PIEB) technique offers multiple benefits over continuous epidural infusion (CEI), but controversy still exists when it is used in conjunction with a parturient-controlled epidural analgesia (PCEA) regimen. A systematic review and meta-analysis was thus conducted using the Medline, EMBASE, CENTRAL and Web of Science databases with the aim of identifying those randomized controlled trials (RCTs) that performed a comparison between PIEB and CEI in healthy parturients using a PCEA regimen with regard to the duration of labor, labor pain, anesthesia interventions, maternal satisfaction and main side effects. The data were analyzed using a random-effects model. Eleven eligible trials were included, in which 717 participants were allocated to the PIEB + PCEA group and 650 patients were allocated to the CEI + PCEA group. The rate of instrumental delivery, incidence of breakthrough pain, PCEA usage rates and local anesthetic usage were significantly reduced, the labor duration was statistically shorter, and the maternal satisfaction score was significantly improved in the PIEB + PCEA group compared with that in the CEI + PCEA group. There were no differences in the side effects between the two groups. The results of the present study suggest that the PIEB technique in conjunction with the PCEA regimen was more advantageous than CEI + PCEA, but additional studies should be conducted to consistently demonstrate an improvement in the maternal and fetal obstetric outcomes.

Development and validation of a predictive risk factor model for epidural re-siting in women undergoing labour epidural analgesia: a retrospective cohort study

BackgroundEpidural catheter re-siting in parturients receiving labour epidural analgesia is distressing to the parturient and places them at increased complications from a repeat procedure. The aim of this study was to develop and validate a clinical risk factor model to predict the incidence of epidural catheter re-siting in labour analgesia.MethodsThe data from parturients that received labour epidural analgesia in our centre during 2014–2015 was used to develop a predictive model for epidural catheter re-siting during labour analgesia. Multivariate logistic regression analysis was used to identify factors that were predictive of epidural catheter re-siting. The forward, backward and stepwise variable selection methods were applied to build a predictive model, which was internally validated. The final multivariate model was externally validated with the data collected from 10,170 parturients during 2012–2013 in our centre.ResultsNinety-three (0.88%) parturients in 2014–2015 required re-siting of their epidural catheter. The training data set included 7439 paturients in 2014–2015. A higher incidence of breakthrough pain (OR = 4.42), increasing age (OR = 1.07), an increased pain score post-epidural catheter insertion (OR = 1.35) and problems such as inability to obtain cerebrospinal fluid in combined spinal epidural technique (OR = 2.06) and venous puncture (OR = 1.70) were found to be significantly predictive of epidural catheter re-siting, while spontaneous onset of labour (OR = 0.31) was found to be protective. The predictive model was validated internally on a further 3189 paturients from the data of 2014–2015 and externally on 10,170 paturients from the data of 2012–2013. Predictive accuracy of the model based on C-statistic were 0.89 (0.86, 0.93) and 0.92 (0.88, 0.97) for training and internal validation data respectively. Similarly, predictive accuracy in terms of C-statistic was 0.89 (0.86, 0.92) based on 2012–2013 data.ConclusionOur predictive model of epidural re-siting in parturients receiving labour epidural analgesia could provide timely identification of high-risk paturients required epidural re-siting.

Clinical application of intelligent patient-controlled pump for labor analgesia

Objective To evaluate the efficiency of intelligent patient-controlled pump for labor analgesia, and its influence on mothers and neonates. Methods One hundred and twenty primiparas were randomly divided into two groups(n=60), respectively utilizing intelligent(group I) and traditional(group T) patient-controlled pumps to deliver 0.1% ropivacaine plus 0.5 mg/L sufentanil for constant epidural analgesia. Both groups received an initial bolus of 12 ml analgesic solution, and the basic pump settings were 5 ml/h, 5 ml, 15 min for basal infusion rate, bolus dose, and lock time, respectively. In group T, the basic pump settings were used. In group I, the doses of analgesics were adjusted once every hour to meet patients demands for adequate analgesia. The pumps were stopped by the end of the second stage of labor. The follow outcome measures, including the VAS scores before maternal analgesia(T0), 15 min(T1), 30 min (T2), 2 h (T3) after analgesia, the full cervical dilatation(T4), and forced delivery at the second stage of labor(T5), delivery mode, the time of the second stage of labor, total duration of labor, total analgesia time, the usage of analgesics, hourly dosage, local anesthetic background infusion rate at delivery, the number of breakthrough pain, 1 min, 5 min Apgar score of the neonatal, the neonatal weight, side-effects as well as the maternal satisfaction, were recorded. Results We analyzed valid data from 113 parturient women(57 in group I and 56 in group T). Compared with group T, the VAS score at full cervical dilatation and the incidence of breakthrough pain in group I were significantly decreased(P<0.05), the infusion rate of analgesics during forced labor in group I was increased with better analgesia(P<0.05), there was no significant difference between two groups in, the usage of analgesics, the duration of labor, the mode of delivery, the condition of neonates, and the incidence of side-effects as well. Conclusions The intelligent patient-controlled analgesia pump is effective for labor analgesia. It lowers incidence of breakthrough pain and improves maternal satisfaction without increasing the dosage of analgesics and the risk of side-effects. Key words: Analgesia, obstetrical; The intelligent patient controlled analgesia pump; Patient controlled analgesia

The effect of pain self-management based on pain control diary on breakthrough pain.

10107 Background: Most patients suffer from cancer pain, especially breakthrough pain. The overall incidence of breakthrough pain is estimated to be 65%. Self-management makes patients actively participating in the use of drugs, transforming their roles and adjusting their moods in order to better cure their own diseases. Therefore, the aim of the study is to discuss the effect of reducing cancer pain patients' breakthrough pain through self-management based on pain control diary. Methods: From October, 2015 to October, 2016, a total of 200 patients treated with opioids for cancer pain were randomly divided into groups. Patients in the control group were given general management including the Standard "the three steps analgesic ladder treatment for cancer pain", the traditional form of health education and psychological care; While the intervention group in addition to conventional cancer pain management, self-management based on pain control diary was applied. Through repeated intensive training, patients learned how to do self-assessment, to master the feature of their own pain, problem-solving skills and formal report to their oncologists in charge. Results: After six weeks of intervention , 10% patients in the intervention group had suffer breakthrough pain compared with 54% patients in the control group (P &lt; 0.05). The whole processing management model is a whole process, specialization and humanization Care model for patients with advanced cancer pain management, can effectively improve patient medication compliance, reduce the cancer breakthrough pain's incidence, improve the patients,s life quality with cancer pain. The medication compliance of the intervention group was significantly higher than that of the control group(X2= 46.606, P&lt;0.001), and in intervention group the incidence of breakthrough pain was significantly lower than that of the control group (X2= 44.148, P&lt;0.001) Conclusions: The self management based on pain control diary is a whole process, specialization and humanization Care model for patients with advanced cancer pain management, can effectively improve patient medication compliance, reduce the cancer breakthrough pain's incidence, improve the patients's life quality with cancer pain.

Once-Daily OROS Hydromorphone for Management of Cancer Pain: an Open-Label, Multi-Center, Non-Interventional Study.

Extended-release osmotic extended-release oral delivery system (OROS) hydromorphone is a strong synthetic opioid designed to maintain a constant blood concentration by once daily dosing. The objective of this observational study was to investigate the clinical usefulness of OROS hydromorphone in patients with cancer pain of moderate to severe intensity. Patients with cancer pain who required strong opioids were administered with OROS hydromorphone for 4 weeks. We assessed changes in pain intensity using a numerical rating scale (NRS) as well as levels of sleep disturbance, breakthrough pain, end-of-dose failure, patient satisfaction, and overall assessment of drug effectiveness based on investigator evaluation. Of the 648 enrolled patients, 553 patients were included in the full analysis set. The mean pain intensity was significantly decreased from the NRS value of 5.07 ± 1.99 to 2.75 ± 1.94 (mean % change of 42.13 ± 46.53, P < 0.001). The degree of sleep disturbance significantly improved (mean NRS change of 1.61 ± 2.57, P < 0.001), and the incidence of breakthrough pain was significantly decreased (mean NRS change of 1.22 ± 2.30, P < 0.001). The experience of end-of-dose failure also significantly decreased from 4.60 ± 1.75 to 3.93 ± 1.70, P = 0.007). The patient satisfaction rate was 72.7%, and 72.9% of investigators evaluated the study drug as effective. OROS hydromorphone was an effective and tolerable agent for cancer pain management. It effectively lowered pain intensity as well as improved sleep disturbance, breakthrough pain, and end-of-dose failure (Identifier: NCT 01273454).

Clinical Usefulness of Hydromorphone-OROS in Improving Sleep Disturbances in Korean Cancer Patients: A Multicenter, Prospective, Open-Label Study.

PurposeTo evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain.Materials and MethodsOne hundred twenty cancer patients with pain (numeric rating scale [NRS] ≥ 4) and sleep disturbance (NRS ≥ 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator’s discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated.ResultsA total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea.ConclusionHM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.

Epidural neostigmine and clonidine improves the quality of combined spinal epidural analgesia in labour

In labour analgesia, the combination of epidural clonidine and neostigmine as adjuvants to local anaesthetics and opioids is under investigation to provide a longer duration of initial spinal analgesia with local anaesthetics and/or opioids. To evaluate the quality of analgesia with epidural neostigmine and clonidine, added to initial spinal analgesia, and to test the hypothesis that the incidence of breakthrough pain could be reduced and patient satisfaction improved. Randomised double-blind controlled trial. University Hospital of Leuven in Belgium. One hundred healthy, term (≥37 weeks) parturients. All patients received initial spinal analgesia with ropivacaine and sufentanil. Fifteen minutes after spinal injection, 10 ml of a solution containing neostigmine 500 μg and clonidine 75 μg, or 10 ml physiological saline alone was injected epidurally. Patient-controlled analgesia with ropivacaine and sufentanil was then made available. The incidence of breakthrough pain, patient satisfaction and hourly ropivacaine use. Ropivacaine use decreased significantly by 32.6% in the neostigmine/clonidine (NC) group [11.6 ± 4.2 vs. 17.2 ± 5.3 mg h in the NC group and placebo (P) group, respectively] and a significant difference in breakthrough pain was noted; only 3% in group NC had breakthrough pain compared with 36% in group P. Patient satisfaction was better after 1 h in group NC compared with group P (P <0.05) but not different after 24 h (visual analogue scale score 97 ± 5 vs. 88 ± 11 mm after 1 h; 92 ± 10 vs. 90 ± 14 mm after 24 h). The administration of epidural clonidine and neostigmine as adjuvants, following spinal injection of local anaesthetic, improves the quality of analgesia with less ropivacaine consumption, higher patient satisfaction 1 h after administration and a decrease in breakthrough pain compared to standard combined spinal and epidural analgesia and patient-controlled epidural analgesia with ropivacaine and sufentanil.

Low-dose ketamine with multimodal postcesarean delivery analgesia: a randomized controlled trial

Background Ketamine at subanesthetic doses has analgesic properties that have been shown to reduce postoperative pain and morphine consumption. We hypothesized that intravenous ketamine 10 mg administered during spinal anesthesia for cesarean delivery, in addition to intrathecal morphine and intravenous ketorolac, would decrease the incidence of breakthrough pain and need for supplemental postoperative analgesia. Methods Using a randomized double-blind placebo-controlled design, healthy women scheduled for cesarean delivery receiving hyperbaric spinal bupivacaine, fentanyl and morphine were randomized to intravenous ketamine 10 mg or saline following delivery. Postoperative analgesia included scheduled ketorolac and acetaminophen/hydrocodone tablets as needed for breakthrough pain. The primary outcome was the incidence of breakthrough pain in the first 24 h. Secondary outcomes included the number of acetaminophen/hydrocodone tablets administered and numeric rating scale for pain (0–10). Results Group characteristics did not differ. There was no difference in the incidence of breakthrough pain (ketamine 75% VS. saline 74%, P = 0.86). There was no difference in 24-h or 72-h use of supplemental acetaminophen/hydrocodone tablets between groups. Pain scores in the first 24 h were similar, but lower in the ketamine compared to the saline group 2 weeks postpartum (difference −0.6, 95% CI −1.1 to −0.9). Conclusions We found no additional postoperative analgesic benefit of low-dose ketamine during cesarean delivery in patients who received intrathecal morphine and intravenous ketorolac. Subjects who received ketamine reported lower pain scores 2 weeks postpartum.

Cancer pain management with hydromorphone OROS in Korean cancer patients: Evaluation of its clinical usefulness in reduction of breakthrough pain medication frequency: Multicenter, prospective, open-label study.

e19566 Background: A majority of patients with cancer experience cancer pain of higher than moderate severity during the progression of cancer. Of these, 2/3 of patients with cancer have been reported to be inflicted with breakthrough pain. Methods: The primary objective is to evaluate the clinical usefulness of hydromorphone OROS in reduction of breakthrough pain medication frequency in Korean patients. Subjects include patients who are given strong oral narcotic analgesics for the treatment of cancer pain. This study enrolled only patients who took immediate-release analgesics more than twice a day on average for the treatment of breakthrough pain during a 3-day period prior to Visit 2. When patients selected, patients were switched to test drug using a 2.5: 1 conversion ratio of controlled release oxycodone equivalent to hydromorphone hydrochloride, with no washout or overlap of previous opioid therapy and study medication. Results: Total 117 patients received the investigational drug and only 98 patients completed the last fourth assessment. The frequency of the use of immediate- release analgesics for the management of breakthrough pain was decreased from 2.93 times to 2.00 times (p<0.000). The incidence of breakthrough pain was also decreased from 3.67 times to 2.44 times (p<0.0001). K-BPI score was also decreased from 3.6 to 3.2. In 61.2% of patients had a satisfaction with the pain treatment. In regard to the preference to test drug in 83.7% of patients who completed the treatment, 82.95% of patients preferred test drug because ‘the cancer pain could be controlled with a one-time treatment'. 25.5% of patients showed improvement of CGI-I. In EORTC QLQ-C30 analysis, only pain and diarrhea among the symptom scales improved. In 91.2% of patients who used analgesics, the side effects occurred in such an order as constipation, drowsiness and dizziness. But there were no cases of uncontrolled specific side effects. Conclusions: A 24-hr sustained-release type of hydromorphone OROS tablet significantly diminished the use of immediate-release analgesics and the incidence of breakthrough pain. No significant financial relationships to disclose.

A Randomized Controlled Trial of Three Patient-Controlled Epidural Analgesia Regimens for Labor

Patient-controlled epidural analgesia (PCEA) is a safe and effective mode of maintaining labor analgesia; however, the ideal PCEA regimen is controversial. In this prospective, randomized, double-blind study, we examined the analgesic efficacy of demand-only PCEA and PCEA with background infusion. We recruited 300 nulliparous parturients. Analgesia was initiated with intrathecal ropivacaine 2 mg and fentanyl 15 microg and maintained with epidural ropivacaine 0.1% with fentanyl 2 microg/mL. Parturients were randomized to one of three groups. Group 0: demand-only PCEA, bolus of 5 mL, lockout interval of 15 min. Group 5: background infusion of 5 mL/h, bolus of 5 mL, lockout interval of 12 min. Group 10: background infusion of 10 mL/h, bolus of 5 mL, lockout interval of 10 min. The maximum dose of all groups was 20 mL/h. The primary outcome was incidence of breakthrough pain. Secondary outcomes included intrapartum pain scores, neuraxial blockade characteristics, side effects, the total and hourly volume of ropivacaine, neonatal outcomes, and obstetric outcomes. The incidence of breakthrough pain and the maximum visual analog scale (0-100 mm scale) pain scores were higher in Group 0 versus Groups 5 and 10 (43% vs 17% and 11%, P < 0.001 and 37 +/- 28 vs 22 +/- 26 and 16 +/- 25 [mean +/- SD], P < 0.001), respectively. Group 10 had a longer duration of effective analgesia compared with Group 0 (mean 895 min, 95% CI 823-966 vs 565 min, 95% CI 454-677, P < 0.001) and increased ropivacaine consumption, and was associated with a longer duration of the second stage of labor. Demand-only PCEA (5-mL bolus, 15-min lockout interval) resulted in less local anesthetic consumption but an increased incidence of breakthrough pain, higher pain scores, shorter duration of effective analgesia, and lower maternal satisfaction, when compared with PCEA with background infusion (5-mL bolus, 10-12-min lockout interval, and 5-10 mL/h infusion).

Chronobiology of parturients receiving neuraxial labour analgesia with ropivacaine and fentanyl: a prospective cohort study

Background The circadian variation in biologic rhythm has been known to affect labour pain. The duration of action of ropivacaine or fentanyl used in treatment of labour pain has been demonstrated to vary with different times of the day. The aim of this study is to find whether the need for epidural supplementation for breakthrough pain is significantly affected by the time of day, in patients who are on a continuous epidural infusion of these drugs. Methods In this prospective cohort study, parturients with spontaneous onset of labour were given a combined spinal-epidural technique with spinal ropivacaine 2 mg + fentanyl 15 μg followed by an epidural infusion of ropivacaine 0.1–0.125% with fentanyl 2 μg/mL at 10 mL/hour. A total of 1657 patients were divided into four groups: (1) morning: analgesia request: 7:01 to 13:00, delivery before 19:00; (2) afternoon: analgesia request: 13:01 to 19:00, delivery before 1:00; (3) evening: analgesia request: 19:01 to 1:00, delivery before 7:00 and (4) night: analgesia request: 1:00 to 7:00, delivery before 13:00. Pain scores before epidural analgesia, need for additional epidural supplementation, side effects and patient satisfaction scores were compared between the groups. Results The pain scores before epidural analgesia were significantly higher in evening and night groups than in morning and afternoon groups (6.95 ± 2.4, 7.38 ± 2.2 compared to 6.67 ± 2.5, 6.49 ± 2.7 respectively, P < 0.001). Incidence of breakthrough pain, side effects and parturient satisfaction scores were not significantly different between groups. Conclusion Parturients with labour onset and neuraxial analgesia request in the evening and night experienced higher pain scores. However, no significant differences in the incidence of breakthrough pain or the quality of analgesia were observed with the provision of commonly used concentrations of ropivacaine with fentanyl via continuous epidural infusion.

Fentanyl buccal tablet

Studies of populations with chronic cancer pain have shown a high prevalence of breakthrough pain (BTP), defined as transitory, severe flares of pain that occur on a background of otherwise controlled, persistent pain. High BTP prevalence rates have also been reported in patients with chronic noncancer pain, although data in these patient populations are more limited. The incidence of BTP appears to be associated with progression of chronic disease, with more than 80% of patients reporting BTP with far-advanced, end-stage cancer and noncancer terminal conditions (1). The most widely accepted therapeutic approach for the management of BTP involves use of short-acting opioids taken as needed in addition to the around-the-clock opioid regimen being used for the continuous component of the persistent pain syndrome. For some patients, an optimal treatment outcome for BTP may be unattainable because of a mismatch between the time course of the BTP episode and the onset of analgesia of short-acting opioids. Breakthrough pain typically reaches peak intensity within a few minutes, whereas the onset of analgesia with traditional, orally administered short-acting opioids is between 30 and 60 minutes (2-7). Consequently, treatment outcomes for BTP are likely to be improved with agents that have a more rapid onset of analgesia. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl indicated for the management of BTP in patients with cancer who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. The FBT formulation uses OraVescent (Cephalon, Inc., Frazer, PA, USA) drug delivery technology to provide rapid absorption of fentanyl through the buccal mucosa. In pharmacokinetic studies in healthy volunteers, FBT demonstrated high, early systemic absorption. In addition, FBT delivered a larger proportion of the fentanyl dose transmucosally and produced a greater early systemic exposure than oral transmucosal fentanyl citrate (OTFC), which is also indicated for the management of BTP in opioid-tolerant cancer patients. A number of short-term studies have evaluated the efficacy, safety and tolerability of FBT in the management of BTP in opioid-tolerant patients with chronic pain. All these studies included an open-label dose-titration phase prior to randomized, placebo-controlled, double-blind treatment. Pain Intensity of a BTP episode was measured using an 11-point scale (0 = no pain, 10 = worst pain), and the primary outcome measure was the Summed Pain Intensity Difference (SPID) at a specified time point. Secondary efficacy measures included Pain Relief, Pain Intensity Differences, and the proportion of BTP episodes demonstrating >or=33% and >or=50% improvement in Pain Intensity scores at each time point postdose, and the proportion of BTP episodes requiring supplemental medication. In a pivotal study of opioid-tolerant patients with cancer-related chronic pain and BTP, the primary outcome measure, SPID at 30 minutes (SPID(30)), significantly favored FBT compared with placebo (mean +/- SE: 3.0 +/- 0.12 vs. 1.8 +/- 0.18, p<0.0001). Better efficacy was also observed with FBT compared with placebo for pain relief, Pain Intensity Differences, and the proportion of episodes showing >or=33% and >or=50% improvement in Pain Intensity Scores. Treatment with FBT was generally well tolerated. Most adverse events were mild to moderate in severity and typical of those associated with opioid use (e.g., nausea, dizziness) (8). Similar results have been observed in studies of opioid-tolerant patients with BTP in association with noncancer-related chronic pain. In a study of patients with chronic low back pain, the primary outcome measure, SPID(60), significantly favored FBT over placebo (mean +/- SE: 8.3 +/- 0.66 vs. 3.6 +/- 0.57, p <0.0001). All secondary efficacy measures were similarly improved, with Pain Intensity Differences and Pain Relief scores showing significant differences versus placebo as early as 10 and 15 minutes, respectively. As in the study of cancer patients, treatment with FBT was well tolerated (9). Across all studies, there was no simple linear relationship between the effective dose of FBT and the dose of the around-the-clock opioid regimen or the previous supplemental opioid, indicating that doses of FBT should be individually titrated to effectiveness rather than calculated as a percentage of existing opioid regimens. This monograph summarizes current data on the clinical pharmacology, efficacy, safety and tolerability of FBT relating to the management of opioid-tolerant patients with BTP in association with chronic pain.

Introduction: The Scope of Breakthrough Pain in Clinical Practice

Breakthrough pain (BTP) is a common condition for patients with cancer and a variety of nonmalignant chronic diseases. The reported incidence of BTP varies widely from as low as 16% to as high as 95% of those with persistent pain syndromes. A large international study from the Working Group of the International Association for the Study of Pain Task Force on Cancer Pain estimated the overall prevalence of BTP in patients with cancer to be 65%[1]. Worldwide, the number of patients with low back pain is very likely much higher, as the prevalence of persistent low back pain is 17–50%[2]. The wide variability of the reported prevalence of …

Interscalene perineural ropivacaine infusion:a comparison of two dosing regimens for postoperative analgesia

Background and Objectives A continuous interscalene nerve block with a perineural infusion of ropivacaine 0.2% at 8 mL/h has been shown to provide potent analgesia following moderately painful shoulder surgery. However, this high basal rate limits infusion duration for ambulatory patients who must carry the local anesthetic reservoir. We undertook this investigation to determine if the basal rate of an interscalene perineural ropivacaine infusion could be decreased by 50% with a concurrent 200% increase in patient-controlled bolus dose without compromising infusion benefits in ambulatory patients undergoing moderately painful orthopedic shoulder surgery. Methods Preoperatively, patients (n = 24) received an interscalene perineural catheter and nerve block. Intraoperatively, patients received a standardized general anesthetic. Postoperatively, patients were discharged home with a portable infusion pump delivering ropivacaine 0.2% (500 mL reservoir) with a basal rate of 8 mL/h and a 2 mL patient-controlled bolus available each hour (“8/2” group, n = 12) or a 4 mL/h basal rate and 6 mL bolus dose (“4/6” group, n = 12), delivered in a randomized, double-blinded manner. Results Patients in the 4/6 group had higher baseline pain scores only on postoperative day (POD) 2 ( P = .011). However, these patients also experienced an increase in breakthrough pain incidence (5.8 boluses/d v 3.2, P = .035) and intensity (“worst” pain = 8/10 v 4/10, P < .05), sleep disturbances (2.0 v 0.0, P < .001), and a decrease in analgesia satisfaction (8 v 10, P = .003). Patients in the 8/2 group exhausted their local anesthetic reservoirs after a median of 61 hours, while the 4/6 group had a median of 131 mL remaining at infusion discontinuation after a median of 75 hours ( P < .001). Conclusions Following moderately painful ambulatory shoulder surgery, decreasing an interscalene perineural ropivacaine 0.2% basal rate from 8 to 4 mL/h provides similar baseline analgesia and lengthens infusion duration, but compromises other infusion benefits.