[A prospective comparative study on effectiveness of single versus continuous adductor canal block combined with local infiltration anesthesia in unicompartmental knee arthroplasty].

Objective: To compare the early analgesic effects and the impact on knee joint function recovery after unicompartmental knee arthroplasty (UKA) between single adductor canal block (SACB) and continuous adductor canal block (CACB) combined with local infiltration anesthesia (LIA) using a prospective study. Methods: The patients with knee osteoarthritis admitted between April 2022 and December 2023 were enrolled as a subject. Among them, 60 patients met the selection criteria and were enrolled in the study. They were randomly assigned to the SACB group or CACB group in a ratio of 1:1 using a random number table method. There was no significant difference between the two groups ( P>0.05) in terms of age, gender, height, body mass, body mass index, affected side, and preoperative resting visual analogue scale (VAS) score and active VAS score, Oxford knee score (OKS), and American Hospital of Special Surgery (HSS) score. All patients received multimodal analgesia management using LIA combined with SACB or CACB. The operation time, pain related indicators (resting and activity VAS scores, number and timing of breakthrough pain, opioid consumption), joint function related indicators (quadriceps muscle strength, knee range of motion, OKS score, and HSS score), as well as postoperative block complications and adverse events were recorded and compared between the two groups. Results: There was no significant difference in the operation time between the two groups ( P<0.05). All patients in the two groups were followed up with a follow-up time of (9.70±4.93) months in the SACB group and (12.23±5.05) months in the CACB group, and the difference was not significant ( P>0.05). The CACB group had a significant lower resting VAS score at 24 hours after operation compared to the SACB group ( P<0.05). There was no significant difference in resting and active VAS scores between the two groups at other time points ( P>0.05). The CACB group had a significantly lower incidence of breakthrough pain compared to the SACB group [9 cases (30.00%) vs. 17 cases (56.67%); P<0.05). However, there was no significant difference in the timing of breakthrough pain occurrence and opioid consumption between the two groups ( P>0.05). Four cases in the SACB group and 7 cases in the CACB group experienced adverse events, with no significant difference in the incidence of adverse events between the two groups ( P>0.05). The CACB group had significantly better knee joint mobility than the SACB group at 1 and 2 days after operation ( P<0.05). There was no significant difference between the two groups in knee joint mobility on 0 day after operation and quadriceps muscle strength and OKS and HSS scores at different time points ( P>0.05). Conclusion: In UKA, the analgesic effects and knee joint function recovery are similar when compared between LIA combined with SACB and LIA combined with CACB. However, SACB is simpler to perform and can avoid adverse events such as catheter displacement and dislocation. Therefore, SACB may be a better choice.

The influence of ambient environmental factors on breakthrough Cancer pain: insights from remote health home monitoring and a proposed data analytic approach.

BACKGROUND: Breakthrough cancer pain (BTCP) is primarily managed at home and can stem from physical exertion and emotional distress triggers. Beyond these triggers, the impact of ambient environment on pain occurrence and intensity has not been investigated. This study explores the impact of environmental factors on the frequency and severity of breakthrough cancer pain (BTCP) in the home context from the perspective of patients with advanced cancer and their primary family caregiver. METHODS: A health monitoring system was deployed in the homes of patient and family caregiver dyads to collect self-reported pain events and contextual environmental data (light, temperature, humidity, barometric pressure, ambient noise.) Correlation analysis examined the relationship between environmental factors with: 1) individually reported pain episodes and 2) overall pain trends in a 24-hour time window. Machine learning models were developed to explore how environmental factors may predict BTCP episodes. RESULTS: Variability in correlation strength between environmental variables and pain reports among dyads was found. Light and noise show moderate association (r = 0.50-0.70) in 66% of total deployments. The strongest correlation for individual pain events involved barometric pressure (r = 0.90); for pain trends over 24-hours the strongest correlations involved humidity (r = 0.84) and barometric pressure (r = 0.83). Machine learning achieved 70% BTCP prediction accuracy. CONCLUSION: Our study provides insights into the role of ambient environmental factors in BTCP and offers novel opportunities to inform personalized pain management strategies, remotely support patients and their caregivers in self-symptom management. This research provides preliminary evidence of the impact of ambient environmental factors on BTCP in the home setting. We utilized real-world data and correlation analysis to provide an understanding of the relationship between environmental factors and cancer pain which may be helpful to others engaged in similar work.

Programmed intermittent epidural bolus as an ideal method for labor analgesia: a randomized controlled trial.

BACKGROUND: Although programmed intermittent epidural bolus (PIEB) is effective for labor analgesia, an appropriate flow rate has not been established. Therefore, we investigated the analgesic effect based on different epidural injection flow rates. METHODS: Nulliparous women scheduled for spontaneous labor were enrolled in this randomized trial. After injection of intrathecal 0.2% ropivacaine 3 mg with fentanyl 20 µg, participants were randomized to three study groups. Epidural analgesics, 10 ml during one hour, were administered with patient controlled epidural analgesia as follows (0.2% ropivacaine 60 ml, fentanyl 180 µg, and 0.9% saline 40 ml): continuous (n = 28, 10 ml/h for continuous infusion), PIEB (n = 29, 240 ml/h for bolus infusion of 10 ml), or manual (n = 28, 1200 ml/h for bolus injection of 10 ml). The primary outcome was hourly consumption of the epidural solution. The time interval between labor analgesia and the first breakthrough pain was investigated. RESULTS: The median (Q1, Q3) hourly consumption of epidural anesthetics was significantly different among the groups (continuous: 14.3 [8.7, 16.9] ml, PIEB: 9.4 [6.2, 9.8] ml, manual: 8.6 [7.6, 9.9] ml; P < 0.001). The time to breakthrough pain for the PIEB group was longer than that for the other groups (continuous: 78.5 [35.8, 185.0] min, PIEB: 200.0 [88.5, 441.5] min, manual: 60.5 [37.3, 162.0] min, P = 0.027). CONCLUSIONS: PIEB, with a low-flow rate, provided more adequate labor analgesia than a continuous epidural infusion or manual injection with a high-flow rate.

A systematic review of qualitative research exploring patient and health professional perspectives of breakthrough cancer pain.

PURPOSE: Breakthrough cancer pain (BtCP) is a prevalent health issue which is difficult to manage. A plethora of quantitative research in this area exists. There is a paucity of research on the perspectives of health professionals and patients surrounding domains impacting effective treatment, including definitions of BtCP, treatment, and education opportunities. This review aims to identify and synthesize the extent of qualitative research exploring health professional and patient perspectives of BtCP. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach was undertaken. The approach was registered with Prospero. MEDLINE, EMBASE, and Web of Science were searched for peer-reviewed literature published any date prior to May 19, 2022. Eligible sources must have considered health professional and/or patient perspectives of BtCP. A narrative synthesis approach was utilized. RESULTS: Three sources met the review criteria. One source explored nurse perspectives, while two sources explored patient perspectives. Study quality was moderate to high. Overlapping themes across the three studies included communication, defining BtCP, impact of BtCP, management of BtCP, perceptions of BtCP, analgesia and pain relief, and training and professional development. CONCLUSION: Given limited research investigating clinician and patient perspectives of BtCP, a rich understanding informed by exploratory qualitative methods around identification, best management strategies, professional development, and factors promoting and inhibiting best practice remains unclear. Further qualitative inquiry is warranted, and it is expected such research will inform BtCP clinical guidelines.

[Prevalence and clinical characteristics of pain in patients with advanced chronic disease]. / Prevalencia y características clínicas del dolor en pacientes con enfermedad crónica avanzada.

OBJECTIVES: Determine pain prevalence and clinical characteristics in patients with advanced chronic disease and identify breakthrough pain frequency. DESIGN: Observational, descriptive, cross-sectional study. LOCATION: Three primary care teams and one intermediate care hospital. PARTICIPANTS: All patients with advanced chronic disease. MAIN MEASUREMENTS: A semi-structured interview was performed to collect demographic, clinical, and specific variables of pain using validated scales. Patient location (home, nursing home or hospital) and advanced chronicity trajectory (organ failure, oncological disease, dementia, or multimorbidity) were recorded. Pain was assessed based on the Brief Pain Inventory (BPI) and, in cases of disabling dementia, using the Pain Assessment in Advanced Dementia (PAINAD). A statistical descriptive, comparative analysis between variables was performed using the R software. RESULTS: Of all patients selected, 223 (60.4%) were included. Prevalence of pain: 83.9% (n=187), with no differences based on location or trajectory. Significant differences in pain intensity based on location (P=.0046) (moderate-severe in patients at home, moderate in hospital patients, and mild in nursing home patients) and on trajectory (P<.0001) (moderate-severe in patients with organ failure and multimorbidity, moderate in patients with cancer, and mild in patients with dementia). Global functional impact of pain was mild-moderate, emotional impact was severe in 41.5% of patients (n=51), and breakthrough pain was observed in 8.6% (n=13). CONCLUSIONS: Pain must always be explored and assessed in patients with advanced chronicity, since it was highly prevalent in all locations and trajectories, being particularly intense in patients at home with organ failure and multimorbidity. Breakthrough pain was found in non-oncological trajectories.

Knowledge and practice of the management of breakthrough cancer pain among general practitioners providing palliative care in Shanghai, China: a cross-sectional survey.

OBJECTIVE: This study examined knowledge and practice of breakthrough cancer pain (BTcP) management among general practitioners (GPs) providing palliative care in Shanghai. DESIGN: Cross-sectional study using a self-administered questionnaire. SETTING AND PARTICIPANTS: A total of 393 GPs providing palliative care in 32 community health service centres in Shanghai were recruited by stratified cluster random sampling between 1 May and 30 June 2022. OUTCOME MEASURES: Knowledge and practice concerning BTcP management. RESULTS: A total of 375 questionnaires were collected and declared valid. The median knowledge score was 11 out of 21 points. Only 36.3% (n=136) of the participating GPs scored 11 points or more, which was categorised as good knowledge. Only 24.8% (n=93) of the GPs used Davies' adapted diagnostic algorithm as the gold standard for diagnosis. All of the GPs assessed the intensity of BTcP; however, less than a quarter of the GPs evaluated the relationship between background pain and BTcP (22.1%, n=83), the impact of BTcP on activities of daily living (24.0%, n=90), the impact of BTcP on social relationships (14.4%, n=54) and the impact of BTcP on mood (10.1%, n=38). 56.5% (n=212) of the GPs reported that they used pain tools in the assessment of BTcP. All of the GPs prescribed immediate-release morphine as rescue medication for relieving BTcP; however, 60.5% (n=227) prescribed the dose based on their personal experiences, irrespective of the basal opioid dose, and 57.3% (n=215) did not conduct dose titration after providing the initial dose. No GPs reported that they ever administered interventional treatment to their patients. CONCLUSIONS: Insufficient knowledge and inappropriate behaviours in BTcP diagnosis, assessment and treatment were identified. There is an urgent need to improve BTcP management among GPs providing palliative care in Shanghai.

Intrathecal Analgesia via a Percutaneous Port With Patient-Controlled Intrathecal Analgesia for the Management of Movement-Evoked Breakthrough Cancer Pain of Refractory Lower Extremity Cancer Pain: A Retrospective Review.

BACKGROUND: Intrathecal analgesia (ITA) is a valuable treatment option for refractory cancer-related pain. However, there is still no general consensus on the analgesic effect of movement-evoked breakthrough pain (MEBTP) in the ITA setting. OBJECTIVES: This study aimed to conduct a retrospective observational study to examine the effect of ITA via percutaneous port (ITAPP) with patient-controlled ITA (PCIA) on analgesic efficacy, emphasizing MEBTP in patients with refractory lower extremity cancer pain. STUDY DESIGN: A retrospective chart review included all patients with refractory lower extremity cancer pain who received ITAPP at our hospital between January 2017 and December 2020. METHODS: Data on the Numeric Rating Scale scores of spontaneous resting pain intensity (SRPI) and MEBTP intensity (MEPI), opioid doses, and perceived time to onset were collected from medical records prior to ITAPP and at a one-month postimplant visit. RESULTS: A total of 16 patients were included in the study group. Mean SRPI decreased from 8.75 pre-ITAPP to 3.75 post-ITAPP (P < 0.05); mean MEPI fell from 8.83 pre-ITAPP to 4.25 post-ITAPP (P < 0.05); mean daily morphine equivalent dosing decreased from 360 mg/d to 48 mg/d (P < 0.05); and mean daily morphine equivalent dosing for MEBTP decreased from 87 mg/d to 6 mg/d (P < 0.05). Both total and breakthrough dosing of conventional opioid medications significantly decreased following the initiation of ITAPP with PCIA. The mean perceived time to onset with conventional MEBT medications was 38 minutes, and the mean perceived time to onset with PCIA was 8 minutes (P < 0.05). LIMITATIONS: An effective analysis of IT opioid efficacy was not possible because the power of such a small sample size was low. Second, it is a retrospective study without long-term follow-ups. CONCLUSIONS: In patients with refractory lower extremity cancer pain, ITAPP with PCIA was associated with improved pain control. Compared with conventional MEBTP regimens, appropriate ITAPP with PCIA provided superior analgesia and a much faster onset of action.

Validation of a French version of the Breakthrough Pain Assessment Tool in cancer patients: Factorial structure, reliability and responsiveness.

OBJECTIVE: Breakthrough cancer pain should be properly assessed for better-personalized treatment plan. The Breakthrough Pain Assessment Tool is a 14-item tool validated in English developed for this purpose; no French version is currently available and validated. This study aimed to translate it in French and assess the psychometric properties of a French version of the Breakthrough Pain Assessment Tool (BAT-FR). METHODS: First, translation and cross-cultural adaptation of the 14 items (9 ordinal and 5 nominal) of the original BAT tool in French language was made. Second, assessments of validity (convergent, divergent and discriminant validity), factorial structure (exploratory factor analysis) and test-retest reliability of the 9 ordinal items were done with data of 130 adult cancer patients suffering from breakthrough pain in a hospital-academic palliative care center. Test-retest reliability and responsiveness of total and dimension scores derived from these 9 items were also assessed. Acceptability of the 14 items was also assessed on the 130 patients. RESULTS: The 14 items had good content and face validity. Convergent and divergent validity, discriminant validity and test-retest reliability of the ordinal items were acceptable. Test-retest reliability and responsiveness of total and dimensions derived from ordinal items were also acceptable. The factorial structure of the ordinal items had two dimensions similar to the original version: "1-pain severity and impact" and "2-pain duration and medication". Items 2 and 8 had a low contribution to the dimension 1 they were assigned and item 14 clearly changed of dimension compared with the original tool. The acceptability of the 14 items was good. CONCLUSION: The BAT-FR has shown acceptable validity, reliability and responsiveness supporting its use for assessing breakthrough cancer pain in French-speaking populations. Its structure needs nevertheless further confirmation.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Epidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.  The superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.  Our prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates. OBJECTIVES: To assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term. SEARCH METHODS: We searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials. SELECTION CRITERIA: We included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined. DATA COLLECTION AND ANALYSIS: We used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.  The following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women. We used the GRADE system to assess the certainty of evidence associated with our outcome measures. MAIN RESULTS: We included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk. Our results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant. The incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores. WIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses. AUTHORS' CONCLUSIONS: Overall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.

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.

Association between breakthrough labor pain, patient-controlled epidural analgesia use, and numeracy: A pilot observational study.

OBJECTIVE: Labor analgesia can be maintained with a continuous epidural infusion, supplemented by patient-controlled epidural boluses. patient-controlled epidural boluses use and timing require numeric understanding, as patients need to understand when they can administer supplemental boluses, lockout intervals, and total doses. We hypothesized that women with lower numeric literacy have a higher rate of provider-administered supplemental boluses for breakthrough pain because they do not understand the concept behind patient-controlled epidural boluses. DESIGN: Pilot observational study SETTING: Labor and Delivery Suite PARTICIPANTS: Nulliparous, English-speaking patients with singleton, vertex pregnancies admitted for postdates (gestational age ≥ 41 weeks) induction of labor requesting neuraxial labor analgesia. INTERVENTIONS: Combined spinal-epidural labor analgesia was initiated with intrathecal fentanyl and epidural analgesia was maintained using continuous epidural infusion with patient-controlled epidural boluses. MEASUREMENTS AND FINDINGS: Numeric literacy was assessed using the Lipkus 7-item expanded numeracy test. Patients were stratified by whether or not they required supplemental provider-administered analgesia and patient-controlled epidural boluses use patterns were evaluated. A total of 89 patients completed the study. There were no demographic differences between patients who required supplemental analgesia compared with those who did not. Patients that required supplemental analgesia were more likely to request and receive patient-controlled epidural boluses (P<0.001). Hourly bupivacaine requirement was higher in women with breakthrough pain. There were no differences in numeric literacy between the two groups. KEY CONCLUSIONS: Patients who required treatment of breakthrough pain had higher patient-controlled epidural boluses demands-to-delivery ratio. Numeric literacy was not correlated with the need for provider-administered supplemental boluses. IMPLICATIONS FOR PRACTICE: Easy to understand scripts on how to use patient-controlled epidural boluses allows for understanding of patient-controlled epidural boluses use.

Efficacy of reconstituted intravenous fentanyl to sublingual solution versus oral morphine syrup for breakthrough pain among patients with chronic gynecologic cancer pain: A randomized, double-blind, placebo-controlled trial.

Rapid-acting fentanyl formulations are superior to oral morphine (OM) syrup in controlling breakthrough pain among patients with cancer, but they are expensive and unavailable in many countries. OBJECTIVE: To evaluate the efficacy of reconstituted intravenous fentanyl to sublingual solution (IFS) in relieving breakthrough pain as compared with OM. METHODS: In this randomized, double-blind, double-dummy, placebo-controlled trial, patients with gynecologic cancer aged ≥18 years experiencing chronic cancer pain with breakthrough pain were enrolled. Patients were randomly allocated (1:1) to receive either 50 µg IFS or 5 mg OM. Pain intensity level was assessed at 5, 15, 30, 45, 60, and 120 min after treatment. The primary outcome was the reduction in pain intensity at 15 min in the intention-to-treat population (ClinicalTrials.gov, NCT05037539). RESULTS: Between June 15, 2021 and December 30, 2021, 40 participants were equally and randomly assigned to receive IFS or OM. The primary outcome was significantly higher in the IFS group (4.25 vs. 1.05, p < 0.0001). The secondary outcomes also showed higher reduction in pain intensity at 5 min in the IFS group. Subsequent breakthrough pain did not differ between the two groups. However, the reduction in pain was lower in the IFS group at 45, 60, and 120 min, where pain was classified as mild. No severe adverse effects were observed in both groups. Burning sensation without noticeable lesion was found in 20% of the IFS group. CONCLUSION: IFS can reduce early breakthrough pain. IFS may be considered for breakthrough pain when rapid-acting fentanyl formulations are unavailable.

Efficacy of Patient-Controlled Intravenous Analgesia with Esketamine for Herpes Zoster Associated with Breakthrough Pain.

BACKGROUND: Some patients with herpes zoster (HZ) experience an intermittent spontaneous, short-lived and severe pain, which is called breakthrough pain (BTP). The effect of analgesic drugs and invasive procedures is not significant. Therefore, treatment of HZ associated with BTP is challenging. Esketamine is a new N-methyl-D-aspartate receptor antagonist, with enhanced analgesic effects. This study aimed to evaluate the efficacy and adverse reactions of patient-controlled intravenous analgesia (PCIA) with low-dose esketamine for HZ associated with BTP. OBJECTIVES: To evaluate the efficacy and adverse reactions of PCIA with low-dose esketamine for HZ associated with BTP. STUDY DESIGN: A retrospective, observational study. SETTING: The study was carried out in the Pain Department of the Affiliated Hospital of Jiaxing University in Jiaxing, China. METHODS: The clinical data of HZ associated with BTP treated by PCIA with low-dose esketamine at the Pain Department of the Affiliated Hospital of Jiaxing University, between October 2015 to October 2021, were collected retrospectively. The Numeric Rating Scale (NRS-11) scores of rest pain (RP) and BTP, frequency of BTP, Pittsburgh Sleep Quality Index (PSQI) score, and fasting blood glucose (FBG) were recorded and analyzed before treatment (T0) and on days one (T1) and 3 (T2), week one (T3), months one (T4), 3 (T5), and 6 (T6) after treatment. Adverse reactions during the treatment were recorded. RESULTS: Twenty-five patients treated by PCIA with low-dose esketamine were included finally. Compared with T0, the NRS-11 scores of RP at T2, T3, T4, T5, and T6 decreased significantly (P < 0.05). The NRS-11 score of RP at T4 was significantly lower than that of T3 (P < 0.001), but there was no statistical difference between T5 and T4 (P > 0.05), the efficacy of esketamine in the treatment of RP was stable at one month after treatment. Likewise, compared with T0, the NRS-11 scores of BTP, frequency of BTP, and PSQI score decreased significantly at each time point after treatment (P < 0.05). These at T5 were significantly lower than T4 (P < 0.05), but there was no statistical difference between T6 and T5 (P > 0.05), the efficacy of esketamine was stable at 3 months after treatment. FBG also decreased significantly at each time point after treatment (P < 0.05), it tended to be normal and stable one month after treatment. All patients had mild symptoms of dizziness during treatment, and though a slight increase in noninvasive blood pressure (BP) was noted in all, the elevated BP did not exceed 30% of the baseline value. Four patients (16%) developed nausea without vomiting. There were no serious adverse reactions, such as respiratory depression. LIMITATIONS: The nonrandomized, single-center, small sample size, retrospective design is a major limitation of this study. CONCLUSIONS: PCIA with low-dose esketamine has a significant and long-term effect in the treatment of HZ associated with BTP. The RP was controlled, and the degree and frequency of BTP were significantly reduced after treatment, leading to improved quality of life. There were no serious adverse reactions worthy of clinical promotion.

The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: a descriptive cohort study.

PURPOSE: We describe the prevalence of the Edmonton Classification System for Cancer Pain (ECS-CP) features in patients with bone metastasis and cancer-induced bone pain (CIBP) and the relationship between ECS-CP features, pain intensity, and opioid consumption. METHODS: We assessed ECS-CP features and recoded pain mechanisms and opioid use in adult patients with bone metastasis. Validated measures were used to assess pain intensity, incident pain, psychological distress, addictive behavior, and cognition. RESULTS: Among 147 eligible patients, 95.2% completed the assessment. Mean participant age was 73.2 years, the majority female (52.1%) with breast cancer occurring most commonly (25.7%). One or more ECS-CP features were present in 96.4% and CIBP in 75.7% of patients. The median average and worst pain scores were 3 and 6, respectively. Neuropathic pain was the most prevalent pain mechanism (45.0%) and was associated with breakthrough pain frequency (p=0.014). Three-quarters had incident pain, which was strongly associated with a higher average and worst pain scores (3.5 and 7, p<0.001 for both), background oral morphine equivalent daily dose (26.7mg, p=0.005), and frequency of daily breakthrough analgesia (1.7 doses/day, p=0.007). Psychological distress (n=90, 64.3%) was associated with a significantly higher average pain score (4, p=0.009) and a slightly higher worst pain score (7, p=0.054). Addictive behaviour and cognitive dysfunction were relatively uncommon (18.6% and 12.9%, respectively). CONCLUSION: There is a need to promote standardized assessment and classification of pain syndromes such as CIBP. The ECS-CP may allow us to consider CIBP in a systematic manner and develop personalized pain interventions appropriate to the pain profile. TRIAL REGISTRATION: Retrospectively registered in ANZCTR ACTRN12622000853741 (16/06/2022).

Methadone rotation versus other opioid rotation for refractory cancer induced bone pain: protocol of an exploratory randomised controlled open-label study.

BACKGROUND: A third of patients with advanced cancer and bone metastasis suffer from cancer induced bone pain (CIBP), impeding quality of life, psychological distress, depression and anxiety. This study will evaluate the impact of an opioid rotation, comparing methadone rotation with other opioid rotation in patients with refractory CIBP. METHODS: This open-label randomised controlled trial will recruit cancer patients with CIBP and inadequate pain control despite established baseline opioid and/or intolerable opioid side effects from cancer and palliative care services. Participants will be at least 18 years old, with a predicted prognosis of greater than 8 weeks, meet the core diagnostic criteria for CIBP, have a worst pain score of ≥ 4 of 10 from CIBP and/ or have opioid toxicity (graded ≥ 2 on Common Terminology Criteria for Adverse Events). Participants will have sufficiently proficient English to complete questionnaires and provide informed consent. Participants will be randomised 1:1 to be rotated to methadone to another opioid. The primary objective is to examine the impact of opioid rotation in improving CIBP by comparing analgesic efficacy, safety and tolerability in the two arms. Secondary objectives will assess changes in the intensity, duration and frequency of breakthrough pain, requirement of breakthrough analgesia, overall opioid escalation index, and time taken to observe improvement in pain reduction, pain interference and quality of life. DISCUSSION: Laboratory studies suggest the involvement of neuropathic involvement in the mechanism of CIBP, though there remains no clear evidence of the routine use of neuropathic agents. Methadone as an analgesic agent may have a role to play in this cohort of patients, thus warranting further exploratory studies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12621000141842. Registered 11 February 2021.

Breakthrough pain in patients with multiple myeloma: a secondary analysis of IOPS MS study.

OBJECTIVE: The aim of this study was to characterize breakthrough pain (BTcP) in patients with multiple myeloma (MM). PATIENTS AND METHODS: This was a secondary analysis of a large multicenter study of patients with BTcP. Background pain intensity and opioid doses were recorded. The BTcP characteristics, including the number of BTcP episodes, intensity, onset, duration, predictability, and interference with daily activities were recorded. Opioids prescribed for BTcP, time to achieve a meaningful pain relief after taking a medication, adverse effects, and patients' satisfaction were assessed. RESULTS: Fifty-four patients with MM were examined. In comparison with other tumors, in patients with MM BTcP was more predictable (p=0.04), with the predominant trigger being the physical activity (p<0.001). Other BTcP characteristics, pattern of opioids used for background pain and BTcP, satisfaction and adverse effects did not differ. CONCLUSIONS: Patients with MM have their own peculiarities. Given the peculiar involvement of the skeleton, BTcP was highly predictable and triggered by movement.

Breakthrough cancer pain in the radiotherapy setting: a systematic and critical review.

INTRODUCTION: Breakthrough pain (BP) is a complex phenomenon that has been reported to have a relevant role in the global management of cancer pain. Radiotherapy (RT) has a fundamental part in the treatment of many pain conditions, particularly oral mucositis and painful bone metastases. AREAS COVERED: The literature regarding the phenomenon of BP in the radiotherapy setting was reviewed. Three areas were assessed, including epidemiology, pharmacokinetics, and clinical data. EXPERT OPINION: Qualitative and quantitative data regarding BP in the RT setting are poor in terms of scientific evidence. Most papers assessed fentanyl products, particularly fentanyl pectin nasal spray, to resolve possible problems with transmucosal absorption of fentanyl due to mucositis of the oral cavity in patients with head and neck cancer or to prevent and treat procedural pain during RT sessions. According to the lack of clinical studies with large number of patients, BP should be included in the agenda of radiation oncologists.

Predicting tolerability of high-dose fentanyl buccal tablets in cancer patients.

BACKGROUND & AIMS: Fentanyl buccal tablets (FBTs) are a rapid-onset opioid indicated for breakthrough cancer pain (BTcP) and FBT titration is needed to optimize BTcP management. We aimed to predict which patients could tolerate a high dose of FBT (400 µg or more at a time). METHODS: A retrospective analysis was performed to assess the final FBT dose. The final FBT doses were compared according to the clinical features. The prediction accuracy of patients tolerant of 400 µg or higher FBT was compared using the area under the receiver operating characteristic (ROC) curves. A risk scoring model based on the odds ratio (OR) was developed from the final multivariable model, and patients were assigned into two groups: low tolerance (0-1 point) and high tolerance (2-3 points). RESULTS: Among 131 patients, the most frequently effective dose of FBT was 200 µg (54%), followed by 100 µg (30%). The median value of morphine equivalent daily doses (MEDD) was 60 mg/day, and the most common daily use was 3-4 times/day. In multivariable analysis, male sex, younger age, and use of FBTs three or more times per day were independently associated with high-dose FBT. According to the risk scoring model, the patients with a final FBT of 400 µg or higher were significantly more in the high tolerance group (17%) compared to the low tolerance group (3%; p = 0.023). CONCLUSIONS: According to the dose relationship between the final FBT dose and the clinical features, three factors (sex, age, daily use of FBT) were independently associated with the final dose of FBT. Our risk score model could help predict tolerance to high-dose FBT and guide the titration plan for BTcP.

Successful buprenorphine transition while overlapping with a full opioid agonist to treat chronic pain: a case report.

Buprenorphine is a partial mu opioid agonist that has been increasingly utilized to treat patients with chronic pain and opioid use disorder (OUD). The drug has proven to provide significant chronic pain relief at low doses ranging from 75 to 1800 mcg. The conventional buprenorphine transitional process delays its introduction until patients begin withdrawal. However, this process can pose a barrier to both patients and providers due to some patients' inability to tolerate traditional prerequisite withdrawal. To our knowledge, this is a rare reported case to describe a transitional process utilizing buccal buprenorphine in which a patient with chronic pain simultaneously tapered completely off an extended-release (ER) full opioid agonist and uptitrated buprenorphine. The patient was weaned from oxycodone ER 30 mg every 12 h and oxycodone/acetaminophen 10/325 mg 3x/day for breakthrough pain utilizing an unconventional approach. Tapering down to oxycodone ER 20 mg 2x/day for the first 2 weeks was successful. However, reducing to oxycodone ER 10 mg 2x/day for the following 2 weeks presented adherence difficulty and increased breakthrough pain. At this time, buccal buprenorphine was added at 300 mcg daily for 3 days. From days 4 to 6, buprenorphine was increased to 300 mcg 2x/day and oxycodone ER decreased to 10 mg daily. Six days later, oxycodone ER was discontinued and oxycodone/acetaminophen continued as needed. The patient exhibited no signs of withdrawal and adequate relief of symptoms through this tapering process. At the 1-month follow-up, the patient was doing well and was being treated solely with buprenorphine and oxycodone/acetaminophen to control her breakthrough pain. After 5 months, buprenorphine was increased to 600 mcg 2x/day and her oxycodone/acetaminophen decreased to 5/325 mg 3x/day as needed. From the start of the patient's taper to her current transition, the patient reduced her morphine milligram equivalent (MME) dosage from 135 MME to 22.5 MME. The Clinical Opioid Withdrawal Scale (COWS), which measures the severity of a patient's opioid withdrawal symptoms, was consistently less than 5. This buprenorphine schedule demonstrated a successful tapering approach for this patient because she had reported improved quality of life and function. A patient-centered osteopathic treatment approach was utilized when the patient presented with mid-taper adherence difficulty. Transitioning patients from full to partial opioid agonists could become an important practice standard for patient safety not only for formal pain management practices but also in primary care, family practice, and even geriatric offices.