Management Of Breakthrough Pain Research Articles

The safety and efficacy of diclofenac sodium suppository as adjunctive opioids in the treatment of cancer pain: A prospective, multi-center, real-world study.

12055 Background: Cancer pain is one of the most common and unbearable symptoms for cancer patients (pts), seriously affecting their quality of life. Diclofenac sodium is a potent third-generation non-steroidal anti-inflammatory drug known for its significant analgesic, anti-inflammatory, and antipyretic effects. It is commonly used to treat different types of cancer pain. The objective of this study was to assess the safety and effectiveness of diclofenac sodium suppository when used alongside opioids for managing cancer pain in pts with solid tumors. Methods: In this prospective, multi-center, real-world study, we enrolled pts diagnosed with malignancy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-3, numeric rating scale (NRS) score ≥ 3, and sustained cancer pain, who required additional analgesic medication were enrolled. Diclofenac sodium suppository is an anal administration suppository, prescribed once a day at a dosage of 50 mg. This study was conducted across 20 centers to observe the clinical characteristics of pain relief in pts with cancer pain . The primary endpoint of the study was to assess the safety of the medication. The secondary endpoints included evaluating the incidence of breakthrough pain (BP), NRS score, and Brief Pain Inventory (BPI) score on the second and sixth days of medication. Results: Of the 506 pts that were screened, 437 pts met the inclusion criteria. This included 10 pts who did not receive planned treatment and 2 pts who did not undergo post-baseline efficacy evaluation. Among the 425 pts in the full analysis set (FAS), 261 were man, and 169 (39.8%) had baseline BP. The mean age was 63.0±11.3 years old. Among 425 response-evaluable pts, compared to the baseline, the incidence of BP was reduced on the second (20.0% vs 39.8%), and sixth days (14.8% vs 39.8%) of medication and the difference was statistically significant ( P < 0.001, P < 0.001). For pts with baseline BP, 56.2% and 66.9% pts achieved BP relief on the second and sixth days of medication, respectively. From the baseline evaluation, the mean NRS scores for the three visits (baseline, second day, sixth day) were 5.28 ± 1.71, 3.73 ± 1.71, and 2.91 ± 1.88, respectively. The mean pain intensity at each visit was decreased compared to the baseline, and the difference was statistically significant ( P < 0.001, P < 0.001). 427 pts were included for safety analysis and 5 pts experienced any grade treatment emergent adverse events (TEAEs). All TEAEs were grade 1-2. TEAE leading to treatment discontinuation was occurred in one pt. Conclusions: This study demonstrated that diclofenac sodium suppository was an effective treatment option for managing breakthrough pain in patients with persistent cancer pain who required additional analgesic therapy. Moreover, diclofenac sodium suppository was found to be well tolerated when administered anally.

Definition and Assessment of Paediatric Breakthrough Pain: A Qualitative Interview Study.

Infants, children and young people with life-limiting or life-threatening conditions often experience acute, transient pain episodes known as breakthrough pain. There is currently no established way to assess breakthrough pain in paediatric palliative care. Anecdotal evidence suggests that it is frequently underdiagnosed and undertreated, resulting in reduced quality of life. The development of a standardised paediatric breakthrough pain assessment, based on healthcare professionals' insights, could improve patient outcomes. This study aimed to explore how healthcare professionals define and assess breakthrough pain in paediatric palliative care and their attitudes towards a validated paediatric breakthrough pain assessment. This was a descriptive qualitative interview study. Semi-structured interviews were conducted with 29 healthcare professionals working in paediatric palliative care across the UK. An inductive thematic analysis was conducted on the data. Five themes were generated: 'the elusive nature of breakthrough pain', 'breakthrough pain assessment', 'positive attitudes towards', 'reservations towards' and 'features to include in' a paediatric breakthrough pain assessment. The definition and assessment of breakthrough pain is inconsistent in paediatric palliative care. There is a clear need for a validated assessment questionnaire to improve assessment, diagnosis and management of breakthrough pain followed by increased healthcare professional education on the concept.

Efficacy and Safety of Epidural Chloroprocaine for Breakthrough Pain During Labor Analgesia: A Prospective, Double-Blind, Randomized Trial.

A significant number of women who undergo neuraxial labor analgesia experience breakthrough pain. Prompt mitigation of breakthrough pain is essential to improve maternal and fetal outcomes. We evaluated epidural chloroprocaine compared with ropivacaine in alleviating labor breakthrough pain. We performed a double-blind randomized controlled clinical trial between May and July 2023. Eligible parturients received epidural analgesia with ropivacaine and sufentanil. Those with breakthrough pain were randomized to receive either 0.125% epidural ropivacaine (groupR) or chloroprocaine at concentrations of 0.5% (groupC1), 1.0% (groupC2), or 1.5% (groupC3), all in a volume of 6mL. The primary outcome was the treatment success rate, indicated by a decrease of at least 4points on the numerical rating scale pain score 9min after analgesic injection. Secondary outcomes and adverse effects were also recorded. Out of 323 patients receiving epidural analgesia, 192 experienced breakthrough pain. After exclusion of three patients because of protocol deviation, there were 47, 48, 47, and 47 patients in groupR, C1, C2, and C3, respectively. GroupC3 demonstrated a higher treatment success rate (39/47, 83.0%) in managing breakthrough pain than groupR (26/47, 55.3%), groupC1 (12/48, 25.0%), and groupC2 (30/47, 63.8%) (p < 0.001). GroupC3had lower numerical rating scale scores at 6 and 9min after injection and required fewer patient-controlled epidural boluses than other groups. In addition, groupC3 reported greater satisfaction than the other groups (p < 0.001). No significant differences were observed in obstetric or neonatal outcomes across these groups. Parturients experiencing breakthrough pain could receive 1.5% epidural chloroprocaine, rather than lower chloroprocaine concentrations and ropivacaine, to achieve more rapid and better pain relief with higher patient satisfaction. Chinese Clinical Trial Registry, ChiCTR2300071069, http://www.chictr.org.cn/index.aspx .

A Novel Multimodal Postoperative Pain Protocol for 1- to 2-Level Open Lumbar Fusions: A Retrospective Cohort Study.

There has been increased interest in exploring methods to reduce postoperative pain without opioid medications. In 2015, a multimodal analgesia protocol was used involving the perioperative use of celecoxib, gabapentin, intravenous acetaminophen, lidocaine, and liposomal bupivacaine. Overall, the goal was to reduce the utilization of scheduled opioids in favor of nonopioid pain management. The results of a consecutive series of 1- to 2-level open primary lumbar fusions were compared to a cohort of patients after the implementation the perioperative multimodal pain management protocol. Primary endpoints included patient-reported pain scores and secondary endpoints included length of stay. There were 87 patients in the preprotocol cohort and 184 in the protocol cohort. Comparing protocol and preprotocol patients, there were no significant differences in patient demographics. There was significantly average lower pain in the protocol group on postoperative day (POD) 1 (4.50 vs 5.00, P < 0.02) and POD2 (4.42 vs 5.50, P < 0.03). There was a lower pain score on POD0 (4.80 vs 5.00), but it was only clinically significant. There was a correlation between pain and duration of surgery in the preprotocol patients (POD0 R = 0.23, POD1 R = 0.02, POD2 R = 0.38), but not in the protocol patients (POD0 R = -0.05, POD1 R = -0.08, POD2 R = -0.04). There was a shorter length of stay in the protocol cohort (2.0 vs 3.0, P < 0.01). Finally, there was an approximately 35% reduction in morphine milligram equivalents of opioids in the protocol vs preprotocol cohorts (36.2 vs 57.0, P < 0.05). Our novel multimodal pain management protocol significantly reduced postoperative pain, length of stay, and opioid consumption in this patient cohort. Opioid usage correlated to pain in the protocol patients, while the preprotocol patients had no correlation between opioid use and pain medication. In this study, we demonstrated that preoperative and intraoperative analgesia can reduce postoperative pain medication requirements. Furthermore, we introduced a novel concept of a correlation of pain with opioid consumption as a marker of effective pain management of breakthrough pain.

Design and Characterization of Microemulsion System for Fentanyl citrate

This research was aimed to formulate and characterize micro-emulsion systems as a sublingual delivery system of fentanyl citrate an opioid pain medicine used for treatment of breakthrough cancer pain that is not controlled by other medicines. The three phases i.e. oil, surfactant and co-surfactant were selected on the basis of their drug solubility and their efficiency to form ME. Pseudo-ternary phase diagrams were constructed and on the basis of ME existence ranges various formulations of FC were developed. The influence of Smix ratio on the ME formation and in vitro permeation of ME through cellophane membrane was studied respectively. The optimized ME formulation C2 consists of a globule size of 96.9 nm, polydispersity index of 0.263, pH 4.18, viscosity 20.4 cps, a zeta potential of -8.5and conductance of 131.7±0.42µS. The optimized ME formulation C2 exhibited a steady state flux of about 361.92±0.57 and thus exhibiting higher drug permeation through ME for mulations. Apart from this, the formulation was also evaluated for drug content, centrifugation and stability study. The results indicate that, the investigated MEmay be used as a promising alternative for FC therapy for breakthrough pain management.

Erector spinae plane block versus subcostal transversus abdominis plane block in patients undergoing open liver resection surgery: A randomized controlled trial

BackgroundThe aim of this study was to compare the analgesic efficacy of erector spinae plane block (ESPB) in relation to subcostal transversus abdominis plane block (TAPB) in patients undergoing open liver resection surgery. MethodsIn this randomized controlled trial, we included adult patients undergoing open liver resection surgery. After induction of general anaesthesia, the included patients were randomized to receive either ESPB (n = 30) or subcostal TAPB (n = 30). Postoperative pain was assessed using the numeric rating scale (NRS) at rest and during cough. Intravenous morphine boluses were used for management of breakthrough pain intra- and postoperatively. The study’s primary outcome was morphine consumption during the first 24 h postoperatively. Secondary outcomes included intraoperative morphine consumption, time to first postoperative morphine requirement, incidence of complications, and patient satisfaction. ResultsSixty patients were included and were available for the final analysis in this study. The intra-and postoperative morphine consumption were less in the ESPB group than the subcostal TAPB group (median [quartiles] morphine dose: 0 [0−0] vs 2 [0−5] mg, p = 0.007 and 20 [15–20] vs 25 [20−30] mg, p = 0.006, respectively). The time to first morphine requirement was longer in the ESPB group (median [quartiles]: 6.5 [5.5−6.5] h) than the subcostal TAPB group (median [quartiles]: 4.3 [1.0−6.5] h), P = 0.013. Patients in the ESPB group had lower incidence of sedation and higher level of satisfaction than the subcostal TAPB group. ConclusionIn patients undergoing open liver resection surgery, ESPB provided superior analgesic properties than subcostal TAPB.Clinical trial registration: NCT05253079, Principal investigator: Maha Mostafa, Date of registration: February 23, 2022.URL: https://clinicaltrials.gov/ct2/show/NCT05253079

Breakthrough Cancer Pain: The Current Pharmacological Management

Background: Breakthrough pain (BTP) is a transient increase in pain that occurs on a background of stable pain. It contributes substantially to the suffering experienced by most cancer patients. The pharmacologic options for management of BTP have been expanded considerably in the past decade. Opioids remain the most effective pharmaceuticals used for the BTP case. In this systematic review we attempted to provide the currently available clinical data about pharmacological treatment for breakthrough cancer pain.Objective: To evaluate the efficacy of pharmacological treatments for Breakthrough painMethods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed for the last ten years (from September 2010 to September 2020. Further potentially relevant studies were identified from reference lists of studies marked for inclusion and relevant reviews. Two review authors independently assessed trial quality and extracted data. We screened the search results and included studies if they met the selection criteria.Result: We screened 205 publications of which 14 met the inclusion criteria. In total, we analysed data from 2129 participants. Overall, participant with BTP were treated with short acting opioid. Literature searching did not find any published evidence of non opioid drug to treat the BTP. Most adverse effects of the investigated drugs seemed to be moderate.Conclusion: The findings of this review suggest that rapid onset opioids play significant role for BTP. Future studies may be conducted to explore the efficacy and safety profiles each regimen for patients with certain categories of cancer.

Analgesic efficacy of single-shot adductor canal block versus adductor canal block combined with intra-articular ropivacaine infusion after total knee arthroplasty.

AimsSingle-shot adductor canal block (ACB) after total knee arthroplasty (TKA) for postoperative analgesia is a common modality. Patients can experience breakthrough pain when the effect of ACB wears off. Local anaesthetic infusion through an intra-articular catheter (IAC) can help manage breakthrough pain after TKA. We hypothesized that combined ACB with ropivacaine infusion through IAC is associated with better pain relief compared to ACB used alone.MethodsThis study was a prospective double-blinded placebo-controlled randomized controlled trial to compare the efficacy of combined ACB+ IAC-ropivacaine infusion (study group, n = 68) versus single-shot ACB+ intra-articular normal saline placebo (control group, n = 66) after primary TKA. The primary outcome was assessment of pain, using the visual analogue scale (VAS) recorded at 6, 12, 24, and 48 hours after surgery. Secondary outcomes included active knee ROM 48 hours after surgery and additional requirement of analgesia for breakthrough pain.ResultsThe study group (mean visual analogue scale (VAS) pain score of 5.5 (SD 0.889)) experienced significant reduction in pain 12 hours after surgery compared to the control group (mean VAS 6.62 (SD 1.356); mean difference = 1.12, 95% confidence interval (CI) -1.46 to 0.67; p < 0.001), and pain scores on postoperative day (POD) 1 and POD-2 were lower in the study group compared to the control group (mean difference in VAS pain = 1.04 (-1.39 to -0.68, 95% CI, p < 0.001). Fewer patients in the study group (0 vs 3 in the control group) required additional analgesia for breakthrough pain, but this was not statistically significant. The study group had significantly increased active knee flexion (mean flexion 86.4° (SD 7.22°)), compared to the control group (mean 73.86° (SD 7.88°), mean difference = 12.54, 95% CI 9.97 to 15.1; p < 0.014).ConclusionCombined ACB+ ropivacaine infusion via IAC is a safe, reproducible analgesic modality after primary TKA, with superior analgesia compared to ACB alone. Further large volume trials are warranted to generate evidence on clinical significance on analgesia after TKA.Cite this article: Bone Jt Open 2021;2(12):1082–1088.

Second Signatory: Hindrance to Effective Breakthrough Pain Management?

Background: Breakthrough cancer pain is defined as a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. Fentanyl citrate sublingual Tablet (FST) is administered to control breakthrough pain (BTP) and a ‘top-up’ dose is administered in 15 minutes if the pain does not respond. However, Nursing &amp; Midwifery council (UK) recommends that for administration of controlled drugs (CD), a secondary signatory is required within secondary care. Aims: To establish that breakthrough analgesia is administered on an in-patient unit according to the guidance. Methods: Retrospective data was collected on patients at an adult Palliative care unit, requiring second dose of FST. Results and Analysis: Over a period of 3 months, 46 episodes of BTP requiring second dose of FST were recorded. Top-up dose was signed for at 15 minutes for only 13 (28.2%) episodes. Further 14 (30.4%) doses were signed for with 5 minutes delay (20 minutes in total from first dose). 19 (41.3%) doses were signed for after 20 minutes with a range of 25-50 minutes (10 – 35 minutes delay). Note that there will be a further delay in administering the dose. Conclusion: Majority of patients have BTP for less than 45 minutes. After reporting, it takes time to get the medication to patient. Second dose may get further delayed causing pain prolongation. This delay is due to finding second nurse to check medication. There are various solutions which could be employed to prevent this delay and to achieve effective BTP management.

FABRICATION OF MICROEMULSION LOADED SUBLINGUAL FILM FOR RAPID ABSORPTION OF FENTANYL CITRATE IN TRANSIENT BREAKTHROUGH PAIN

Objective: The present research work aims to develop a microemulsion loaded sublingual film for rapid absorption of fentanyl citrate in transient breakthrough pain.&#x0D; Methods: The Fentanyl citrate microemulsion loaded sublingual film was prepared using Capmul MCM C8 (oil), tween 20 (surfactant) and propylene glycol (co-surfactant) with different grades of film-forming polymer (HPMC) using a film casting machine. The films were evaluated for in vitro disintegration study, tensile strength, folding endurance, content uniformity, drug content, in vitro dissolution, pH, thickness and weight variation, scanning electron microscopy, ex vivo permeation study, droplet size, polydispersity index, zeta potential, % moisture content and stability study were evaluated.&#x0D; Results: The optimized film formulation showed desired mechanical properties (tensile strength of 0.291 kg/cm2) and a minimum disintegration time of 20 s. The optimized sublingual film formulation exhibited 43.16 % of FC microemulsion loading. Morphological study showed the absence of drug crystals on the polymeric surface. Permeation studies through goat sublingual mucosa indicated 89% fentanyl citrate release through fentanyl citrate microemulsion loaded sublingual film, whereas only 40% fentanyl citrate release was obtained when it was directly added to film without microemulsion strategy.&#x0D; Conclusion: The present study indicated that extend of permeation of fentanyl citrate when added to the sublingual film in microemulsion form was around 2.225 folds higher than when added directly to film without microemulsion. The present microemulsion embedded film technology could be a promising alternative to conventional drug delivery systems and traditional routes of administration for breakthrough pain management.

Healthcare professionals’ views of the use of oral morphine and transmucosal diamorphine in the management of paediatric breakthrough pain and the feasibility of a randomised controlled trial: A focus group study (DIPPER)

Background: Oral morphine is frequently used for breakthrough pain but the oral route is not always available and absorption is slow. Transmucosal diamorphine is administered by buccal, sublingual or intranasal routes, and rapidly absorbed. Aim: To explore the perspectives of healthcare professionals in the UK caring for children with life-limiting conditions concerning the assessment and management of breakthrough pain; prescribing and administration of transmucosal diamorphine compared with oral morphine; and the feasibility of a comparative clinical trial. Design/ participants: Three focus groups, analysed using a Framework approach. Doctors, nurses and pharmacists (n = 28), caring for children with life-limiting illnesses receiving palliative care, participated. Results: Oral morphine is frequently used for breakthrough pain across all settings; with transmucosal diamorphine largely limited to use in hospices or given by community nurses, predominantly buccally. Perceived advantages of oral morphine included confidence in its use with no requirement for specific training; disadvantages included tolerability issues, slow onset, unpredictable response and unsuitability for patients with gastrointestinal failure. Perceived advantages of transmucosal diamorphine were quick onset and easy administration; barriers included lack of licensed preparations and prescribing guidance with fears over accountability of prescribers, and potential issues with availability, preparation and palatability. Factors potentially affecting recruitment to a trial were patient suitability and onerousness for families, trial design and logistics, staff time and clinician engagement. Conclusions: There were perceived advantages to transmucosal diamorphine, but there is a need for access to a safe preparation. A clinical trial would be feasible provided barriers were overcome.

Intranasal Fentanyl for Intervention-Associated Breakthrough Pain After Cardiac Surgery.

BackgroundCardiac bypass surgery patients have early postoperative interventions that elicit breakthrough pain. We evaluated the use of intranasal fentanyl for breakthrough pain management in these patients.MethodsMultimodal analgesia (paracetamol 1 g three times a day, oxycodone 2–3 mg boluses with a patient-controlled intravenous pump) was used in 16 patients (age 49–70 years, weight 59–129 kg) after cardiac bypass surgery. Intranasal fentanyl 100 µg or 200 µg was used to manage breakthrough pain on the first and third postoperative mornings in a randomised order. Blood samples were collected for up to 3 h after fentanyl administration, pain was assessed with a numeric rating scale of 0–10. Plasma fentanyl concentration was assayed using liquid chromatography-mass spectrometry. Body composition was measured with a bioelectrical impedance device.ResultsBioavailability of intranasal fentanyl was high (77%), absorption half-time short (< 2 min) and an analgesic plasma concentration ≥ 0.5 ng/mL was achieved in 31 of 32 administrations. Fentanyl exposure correlated inversely with skeletal muscle mass and total body water. Fentanyl analgesia was effective both on the first postoperative morning with chest pleural tube removal and during physiotherapy on the third postoperative morning. The median time of subsequent oxycodone administration was 1.1 h after intranasal fentanyl 100 µg and 2.1 h after intranasal fentanyl 200 µg, despite similar oxycodone concentrations (median 13.8, range 5.2–35 ng/mL) in both fentanyl dose groups.ConclusionsIntranasal fentanyl 100 µg provided rapid-onset analgesia within 10 min and is an appropriate starting dose for incidental breakthrough pain in the first 3 postoperative days after cardiac bypass surgery.Clinical Trial RegistrationEudraCT Number: 2018-001280-22.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01002-4.

Six-year trends in postoperative prescribing and use of multimodal analgesics following total hip and knee arthroplasty: A single-site observational study of pain management.

Guidelines for acute postoperative pain management recommend administering analgesics in multimodal combination to facilitate synergistic benefit, reduce opioid requirements and decrease side-effects. However, limited observational research has examined the extent to which multimodal analgesics are prescribed and administered postoperatively following joint replacement. In this longitudinal study, we used three-point prevalence surveys to observe the 6-year trends in prescribing and use of multimodal analgesics on the orthopaedic wards of a single Australian private hospital. We collected baseline postoperative data from total hip and knee arthroplasty patients in May/June 2010 (Time 1, n=86), and follow-up data at 1year (Time 2, n=199) and 5years (Time 3, n=188). During the follow-up, data on prescribing practices were presented to anaesthetists. We found a statistically significant increase in the prescribing (p<0.001) and use (p<0.001) of multimodal analgesics over time. The use of multimodal analgesics was associated with lower rest pain (p=0.027) and clinically significant reduction in interference with activities (p<0.001) and sleep (p<0.001). However, dynamic pain was high and rescue opioids were likely under-administered at all time points. Furthermore, while patients reported high levels of side-effects, use of adjuvant medications was low. We observed significant practice change in inpatient analgesic prescribing in favour of multimodal analgesia, in keeping with contemporary recommendations. Surveys, however, appeared to identify a clinical gap in the bedside assessment and management of breakthrough pain and medication side-effects, requiring additional targeted interventions. Evaluation of 6-year trends in a large Australian metropolitan private hospital indicated substantial growth in postoperative multimodal analgesic prescribing. In the context of growing global awareness concerning multimodal analgesia, findings suggested diffusion of best-evidence prescribing into clinical practice. Findings indicated the effects of postoperative multimodal analgesia in real-world conditions outside of experimental trials. Postoperative multimodal analgesia in the clinical setting was only associated with a modest reduction in rest pain, but substantially reduced interference from pain on activities and sleep.

FABRICATION OF AN ABUSE DETERRENT AND MICROEMULSION-BASED SUBLINGUAL FILM OF BUPRENORPHINE HYDROCHLORIDE FOR BREAKTHROUGH PAIN MANAGEMENT

Objective: The present research work aims to develop an abuse deterrent rapidly dissolving buprenorphine microemulsion loaded sublingual film for the treatment of breakthrough pain.&#x0D; Methods: The Buprenorphine microemulsion loaded sublingual films were prepared using Capmul MCM C8 (oil), tween 20 (surfactant) and propylene glycol (co-surfactant) with different grades of film-forming polymer (HPMC) using film casting machine. The films were evaluated for in vitro disintegration and dissolution study, tensile strength, folding endurance, content uniformity, surface pH, thickness and weight variation, % loading of buprenorphine microemulsion in sublingual film, scanning electron microscope, ex vivo permeation study, droplet size and polydispersity index, Zeta potential, % moisture content, stability and abuse deterrent potential were evaluated.&#x0D; Results: The optimized film formulation showed desired mechanical properties with minimum disintegration time of 21s and exhibited 34.45 % loading of Buprenorphine microemulsion. Permeation studies through goat sublingual mucosa, indicated 87% Buprenorphine release, through Buprenorphine microemulsion loaded sublingual film, whereas only 30% Buprenorphine release when it was directly added to film without microemulsion strategy.&#x0D; Conclusion: The present study concludes that abuse deterrent and fast acting buprenorphine microemulsion-incorporated sublingual film of buprenorphine HCL and naloxone HCL is a promising alternative to mostly marketed buprenorphine injectable delivery systems and a non-invasive route of administration for breakthrough pain management.

Managing breakthrough pain for advanced malignancy in elderly patients: A real challenge

Pain management in advanced cancer patients using opioids like morphine is challenging due to presence of predisposing factors like renal insufficiency, hepatic insufficiency, hypoproteinemia, hypoalbuminemia, and anemia that can easily precipitate inadvertent toxic effects. We report a case morphine toxicity in an elderly patient of lung cancer with concomitant presence of chronic obstructive pulmonary disease (COPD) and recent onset renal impairment. Opioid analgesic overdose is a lethal but at the same time, a preventable and treatable condition. We managed the case using naloxone infusion. However, we emphasize early anticipation and recognition of predisposing factors followed by timely intervention to manage this life-threatening condition.

Prevalence and characterization of breakthrough pain in patients with cancer in Spain: the CARPE-DIO study

We aimed to evaluate the prevalence, characteristics and impact of breakthrough pain (BTP) in patients with cancer attending the main specialties involved in the diagnosis and management of BTP in Spain using a multicenter, observational, cross-sectional, multidisciplinary study. Investigators had to record all patients seen at the clinic during 1 month, determine whether the patients had cancer pain, and apply the Davies algorithm to ascertain whether the patients were suffering from BTP. Of the 3,765 patients with cancer, 1,117 (30%) had cancer-related pain, and of these patients, 539 had BTP (48%, 95%CI:45–51). The highest prevalence was found in patients from palliative care (61%, 95%CI:54–68), and the lowest was found in those from hematology (25%, 95%CI:20–31). Prevalence varied also according to sex and type of tumor. According to the Alberta Breakthrough Pain Assessment Tool duration, timing, frequency, location, severity, quality, causes, and predictability of the BTP varied greatly among these patients. BTP was moderate (Brief Pain Inventory [BPI]-severity median score = 5.3), and pain interference was moderate (BPI-interference median score = 6.1) with a greater interference with normal work, general activity, and enjoyment of life. Patients with BTP showed a mean ± standard deviation score of 28.5 ± 8.0 and 36.9 ± 9.5 in the physical and mental component, respectively, of the SF-12 questionnaire. In conclusion, prevalence of BTP among patients exhibiting cancer-related pain is high. Clinical presentation is heterogeneous, and therefore, BTP cannot be considered as a single entity. However, uniformly BTP has an important impact on a patient’s functionality, which supports the need for early detection and treatment.

Comparative efficacy of epidural clonidine versus epidural fentanyl for treating breakthrough pain during labor: a randomized double-blind clinical trial

BackgroundBreakthrough pain during neuraxial labor analgesia is typically alleviated with additional administration of epidural local anesthetics, with or without adjuvants. Sometimes avoiding neuraxial opioids may be warranted and clonidine is an alternative. In a randomized double-blind trial we compared the efficacy of clonidine versus fentanyl, added to bupivacaine, for the management of breakthrough pain. MethodsTerm parturients (n=98) receiving bupivacaine 0.0625% with fentanyl 2 μg/mL at 12 mL/h, a patient-administered bolus of 5 mL at lockout 6–10 min and a maximum of four boluses per hour, and experiencing breakthrough pain ≥5/10, were randomized to receive a 10 mL bolus containing 12.5 mg bupivacaine and either clonidine 100 μg or fentanyl 100 μg. The primary outcome was ‘success’ of study drug treatment, defined as a pain score reduction ≥4/10 within 15 min of administration. Maternal hemodynamics and fetal heart rate were documented for two hours after treatment. ResultsThere was no significant difference between groups in success rates (66.0% after clonidine (n=47) vs 74.5% after fentanyl (n=51), P=0.48) or in the incidence of hypotension (systolic blood pressure ≤80% of baseline or <90 mmHg) or sedation at 15 min, with 2/51 and 1/47 subjects in the fentanyl and clonidine groups, respectively, receiving phenylephrine. ConclusionEpidural clonidine 100 μg was not superior to fentanyl 100 μg for decreasing pain scores within 15 min of co-administration with bupivacaine 0.125% for intrapartum breakthrough pain. The analgesic efficacy and hemodynamic side effects did not significantly differ.

Buccal opioids for breakthrough pain in children with life-limiting conditions receiving end-of-life care.

Many palliative care health settings that care for children and young people (CYP) at the end of life use the buccal mucosa as a route of drug administration to manage the sudden onset of symptoms, such as seizures, agitation and dyspnoea, and for breakthrough pain management. The buccal route is a minimally invasive method that delivers fast symptom relief and is useful for those with swallowing impairment or reduced enteral absorption. This paper reports on a small retrospective study involving 26 CYP who received end-of-life care between January and December 2017 to review the advantages and disadvantages of using buccal opioids for breakthrough pain relief with a focus on diamorphine as the preferred opioid. A retrospective case note review. This paper shares the clinical practice experiences from one UK organisation of care for CYP at the end of their lives and contributes to the growing body of pharmacological evidence. Buccal opioids, specifically buccal diamorphine, are an effective strategy to treat breakthrough pain or dyspnoea in CYP.

Comparative study of the influence of adductor canal block plus multimodal periarticular infiltration versus combined adductor canal block, multimodal periarticular infiltration and intra-articular epidural catheter ropivacaine infiltration on pain relief after total knee arthroplasty: a prospective study

A combined regimen of adductor canal block (ACB) and multimodal periarticular infiltration (MPI) with local anesthetic (ropivacaine) is a known effective method of controlling pain in the first 6-8h after total knee arthroplasty (TKA); however, managing breakthrough pain after their combined effect wears off can be challenging. We hypothesized that, by additionally leaving an intra-articular epidural catheter (IAEC) inside the knee with intermittent infiltration of local anesthetic in conjunction with ACB and MPI, it would help manage the breakthrough pain when their combined effect wears off. We did a prospective study in our institution between December 2015 and August 2016 on a total of 206 patients undergoing primary unilateral TKA. The initial consecutive 106 patients received ACB + MPI (Group 1, n = 106), and the subsequent 100 patients received ACB + MPI + IAEC (Group 2, n = 100). The primary outcome measure was pain using visual analogue scale (VAS) recorded at 6, 12, 24 and 48h, and the secondary outcome measures were requirement for rescue analgesics and repeat adductor canal block and length of hospital stay. There was no statistically significant difference in VAS scores between the two groups at 6h but at 12, 24 and 48h; there was a statistically significant difference between the two groups in terms of VAS scores, rescue analgesic requirements, repeat adductor canal block and shorter hospital stay favoring the ACB + MPI + IAEC group. Intermittent knee infiltration with ropivacaine is a safe, reproducible and effective method to control pain in the first 48h postoperative period after TKA.

Effects of Age Among Elderly Cancer Patients on Breakthrough Pain Management with Sublingual Fentanyl Tablets.

IntroductionSublingual fentanyl tablets (SFTs) have been shown to be a safe and effective option in controlling breakthrough cancer pain (BTcP). However, further examination is required to investigate the use of SFTs among the elderly. The aim of this study was to examine the influence of age in BTcP management with SFTs in the elderly population.MethodsWe performed subgroup analyses of a recently completed trial in two subsets of individuals: patients aged 65–74 years (low age group) and patients ≥ 75 years (high age group). Pain intensity (PI), onset of pain relief, frequency and duration of BTcP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health status instruments used were the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) and the Short Form 12, version 2 (SF-12v2) questionnaire.ResultsLevels of PI at the end of the study improved significantly as compared with baseline in both the low and the high age groups (30.0% and 27.7% reduction, respectively). The onset of analgesia at the end of the study began in < 10 min in 85.0% of young–old subjects and in 62.5% of patients ≥ 75 years, but no significant differences were found. BTcP episodes lasted < 15 min in 75.0% of patients in the low age group and 58.3% in the high age group (p = 0.24). Most of patients in both groups experienced one to five BTcP daily episodes, at all assessment points. HADS-D decreased from 10.78 (± 4.33) to 8.21 (± 3.57) in the low age group, and from 10.96 (± 4.26) to 9.36 (± 3.35) in the high age group (p = 0.02). Significant differences in HADS-A scores from baseline to the end of the study were also observed in both subgroups (p < 0.05). Patients in the low age group had less favorable mental component summary (MCS) and physical component summary (PCS) scores than patients in the high age group. At the end of the study, 10.0% of young–old patients and 29.2% of patients aged ≥ 75 years reported AEs related to their treatment. The most commonly reported AEs included nausea, vomiting, constipation, somnolence, and skin disorders and they were generally mild to moderate in severity.ConclusionsThe results of this study showed that SFTs provided safe and clinically meaningful pain relief in both elderly subgroups. Clinical implications of these findings await validation in large, confirmatory studies to identify age subgroup divergences among elderly cancer patients treated with SFTs.