Is breakthrough pain better managed by adding programmed intermittent epidural bolus to a background infusion during labor epidural analgesia? A randomized controlled trial.

BACKGROUND: Breakthrough pain (BTP) is a common problem during labor analgesia. Programmed intermittent epidural bolus (PIEB) has demonstrated superior to background epidural infusion (BEI) concerning BTP, but the effect of combining both modes remains unknown. We hypothesized that this combination could reduce BTP incidence. METHODS: Nulliparous parturients with early cervical dilation were randomized to receive 5 mL/h BEI of levobupivacaine 0.125% plus fentanyl 1.45 µg/mL (standard group) or 5 mL/h BEI + 10 mL/h PIEB (PIEB group). In case of BTP, patient-controlled epidural analgesia (PCEA) boluses of 10 mL (20-min lockout interval) were administered. If PCEA was insufficient, a 10-mL clinician bolus was delivered. The primary endpoint was the percentage of parturients who required supplementary epidural boluses. RESULTS: One hundred and twenty women were recruited. Eighty-nine percent of parturients required supplementary boluses in standard group versus 30% in PIEB group (RR=3.07; 95% CI: 1.99-4.76; P<0.001). Adding PIEB prevented BTP in 70% of cases. Duration of effective analgesia was longer in PIEB than in standard group (P=0.003). Supplementary boluses were decreased (P<0.001), while local anesthetic consumption increased (P<0.001) by PIEB addition. Sensory-motor block, mode of delivery, maternal satisfaction and neonatal outcomes were equally distributed in both groups. CONCLUSIONS: Adding PIEB to BEI+PCEA improved labor analgesia by significantly reducing the needs of rescue analgesia and prolonging the duration of effective analgesia. This combination provoked a higher consumption of local anesthetic with no detected clinical consequences.

Clinical observation of regular intermittent epidural injection combined with different puncture points in suppressing breakthrough pain in labour analgesia.

The aim of the current study was to evaluate the clinical effects of the regular intermittent epidural injection combined with different puncture points (RIEI-dPP) in suppressing breakthrough pain during a labour analgesia. A total of 90 primipara were randomly divided into three groups (n = 30): Group L2-3 (A), Group L3-4 (B) and Group L4-5 (C). The analgesic pump parameters were set as: impact dose 8 mL, locking time 15 minutes, background dose 0, and the additional impact dose 8 mL after each hour intermittence. The pain's visual analogue scale (VAS), breakthrough pain, maximum block segment, modified Bromage score, labour duration and the neonatal Apgar score were recorded and compared. Compared with the pre-analgesia time, the VAS scores were found to be significantly decreased in the three groups (p < .05), but there were significant differences among the three groups (p > .05). During analgesia, the maximum block segment in Group C was more significantly reduced than in the other two groups (p > .05), but there was no significant difference in the breakthrough pain among the three groups (p > .05). The comparison of other indexes among the three groups showed there was no significant difference (p > .05). RIEI-dPP at L2-3, L3-4 and L4-5 during labour analgesia can effectively inhibit breakthrough pain. Impact Statement What is already known on this subject? According to human anatomical features, the injection speed and capacity are the prerequisite for obtaining the ideal block range. Experiments confirm that a more uniform and wider drug distribution can be achieved by epidural intermittent rapid infusion with higher injection pressure than a continuous infusion with low injection pressure. Compared with the continuous epidural administration mode, the regular intermittent epidural injection mode can better inhibit breakthrough pain with a lower amount of anaesthetic. What the results of this study add? Similar labour analgesic effects can be achieved by regular intermittent epidural injection mode with different puncture points. What the implications are of these findings for clinical practice and/or further research? Compared with a continuous infusion, a regular intermittent epidural injection can achieve a more uniform drug distribution in the epidural space, so the block range can be more extensive, which can not only reduce the amount of anaesthetic but also effectively reduce the incidence of breakthrough pain. However, the selection of an intervertebral puncture site still lacks a uniform standard. The outcomes of this study can directly verify that regular intermittent epidural injection at L2-3, L3-4 and L4-5 can effectively inhibit breakthrough pain and achieve good analgesic effects, so selecting the intervertebral space with clear anatomical structure positioning and easier puncture pathway can benefit a labour analgesia.

Breakthrough Cancer Pain Influences General Activities and Pain Management: A Comparison of Patients with and without Breakthrough Cancer Pain.

BACKGROUND: Breakthrough cancer pain (BTcP) is a predictor of interference with general activities and poor pain management. The extent of this influence has not yet been determined. OBJECTIVE: This study aimed to investigate the influence of BTcP on general activities, and pain management in patients with controlled background pain. DESIGN: Single-center prospective observational study. SETTING/SUBJECTS: The study cohort comprised 258 consecutive patients (female, 40.0%; mean age, 64.5 years) who had received opioid medication for cancer pain for over 2 weeks. MEASUREMENTS: A recommended diagnostic algorithm was used to quantitate and compare interference with general activities, average background pain intensity over the previous 24 hours (24h-PI), and achievement of personalized pain goals (PPGs) (24h-PI≤PPG) of 119 patients with and 139 patients without BTcP. RESULTS: Interference with general activities, 24h-PI, and PPG scores [mean (standard deviation)] in patients with BTcP were 2.8 (2.2), 3.0 (1.7), and 1.8 (1.4), respectively, which are all significantly higher than for those without BTcP [1.3 (2.0), p < 0.01; 1.7 (1.6), p < 0.01; 1.5 (1.3), p = 0.03], respectively. A significantly smaller percentage of patients with BTcP than without BTcP achieved their PPGs (36.1% vs. 67.6%, p < 0.01). CONCLUSIONS: BTcP has a negative impact on general activities and pain management. Healthcare providers should recognize that management of BTcP is important in improving general activities and management of cancer pain.

Mediation of Movement-Induced Breakthrough Cancer Pain by IB4-Binding Nociceptors in Rats.

Cancer-induced bone pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Even when ongoing pain is well controlled, patients can suffer breakthrough pain (BTP), episodic severe pain that "breaks through" the medication. We developed a novel model of cancer-induced BTP using female rats with mammary adenocarcinoma cells sealed within the tibia. We demonstrated previously that rats with bone cancer learn to prefer a context paired with saphenous nerve block to elicit pain relief (i.e., conditioned place preference, CPP), revealing the presence of ongoing pain. Treatment with systemic morphine abolished CPP to saphenous nerve block, demonstrating control of ongoing pain. Here, we show that pairing BTP induced by experimenter-induced movement of the tumor-bearing hindlimb with a context produces conditioned place avoidance (CPA) in rats treated with morphine to control ongoing pain, consistent with clinical observation of BTP. Preventing movement-induced afferent input by saphenous nerve block before, but not after, hindlimb movement blocked movement-induced BTP. Ablation of isolectin B4 (IB4)-binding, but not TRPV1+, sensory afferents eliminated movement-induced BTP, suggesting that input from IB4-binding fibers mediates BTP. Identification of potential molecular targets specific to this population of fibers may allow for the development of peripherally restricted analgesics that control BTP and improve quality of life in patients with skeletal metastases.SIGNIFICANCE STATEMENT We present a novel preclinical measure of movement-induced breakthrough pain (BTP) that is observed in the presence of morphine controlling ongoing pain. Blockade of sensory input before movement prevented BTP, whereas nerve block after movement failed to reverse BTP. These observations indicate that blocking peripheral sensory input may prevent BTP and targeting central sites may be required for pain relief once BTP has been initiated. Preventing sensory input from TRPV1-expressing fibers failed to alter movement-induced BTP. In contrast, preventing sensory input from isolectin B4 (IB4)-binding fibers blocked movement-induced BTP. Therefore, examining molecular targets on this population of nociceptive fibers may prove useful for developing an improved strategy for preventing BTP in cancer patients with skeletal metastases.

Ultrasound-Guided Radiofrequency Treatment of Intercostal Nerves for the Prevention of Incidental Pain Arising Due to Rib Metastasis.

BACKGROUND: Breakthrough pain (BTP) arising due to rib metastasis is very distressing and often very difficult to manage by titration of traditional analgesics. This study is undertaken to determine the efficacy of radiofrequency (RF) treatment of intercostal nerves for the prevention of BTP. METHODS: The RF treatment of the intercostal nerves was carried out in 25 patients with uncontrolled BTP arising out of the rib metastasis. The intensity and episode of BTP, background pain, opioid dose, functional status (Karnofky score), and quality of life (Short-Form Health Survey [SF-36]) were noted at baseline visit and subsequently after the RF treatment. RESULTS: After the RF treatment, there was more than 50% decrease in both intensity and frequency of BTP in more than 50% of patients for 3 months, and there was more than 50% decrease in BTP opioid dose in more than 50% of patients throughout the study period. There was also significant improvement in background pain, functional status, and the quality of life after the RF. Interestingly, pain relief, lowering of opioid dose, and functional status improvement were found mostly in patients with mixed and neuropathic type of pain and in patients in whom the metastasis were confined to the ribs only. CONCLUSION: RF of the intercostal nerves is effective in preventing and deceasing the severity of BTP arising due to rib metastasis in selected group of patients with mixed and neuropathic type of pain and with the metastasis involving the ribs only.

Effect of hospice nonprofessional caregiver barriers to pain management on adherence to analgesic administration recommendations and patient outcomes.

Nonprofessional caregivers frequently experience barriers to using analgesics for pain in patients in home hospice settings, and patients in pain may suffer needlessly. For example, caregiver adherence to the administration of analgesics is lower for as-needed (PRN) regimens than for standard around-the-clock regimens. But little is known about the barriers caregivers experience and the effects of those barriers. Accordingly, we determined caregiver barriers to using analgesics to manage the pain of patients in the home hospice care setting, and how such barriers affected caregiver adherence and patient quality of life. To this end, we measured barriers, caregiver adherence to PRN analgesic regimens, and patient health outcomes (pain, depression, quality of life [QoL]). A 3-day longitudinal design was used. We recruited 46 hospice nonprofessional caregiver-patient dyads from a local community hospice agency. Barriers were measured with the Barrier Questionnaire II. Adherence to the PRN analgesic regimen was obtained with a 3-day pain and medication diary. Patient outcome measures included pain intensity, the Hospital Depression Scale, and the Brief Hospice Inventory for QoL. Barrier scores were moderate to low. Caregivers adhered to PRN analgesic regimens approximately 51% of the time. Higher caregiver adherence to PRN analgesic regimens was associated with lower patient pain intensity and higher patient QoL, but not, surprisingly, with barriers to pain management. Longitudinal studies are now needed to identify factors besides caregiver barriers that may unduly lower caregiver adherence to PRN analgesic regimens.

Epidural neostigmine and clonidine improves the quality of combined spinal epidural analgesia in labour: a randomised, double-blind controlled trial.

BACKGROUND: 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. OBJECTIVES: 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. DESIGN: Randomised double-blind controlled trial. SETTING: University Hospital of Leuven in Belgium. PARTICIPANTS: One hundred healthy, term (≥37 weeks) parturients. INTERVENTION: 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. MAIN OUTCOME MEASURES: The incidence of breakthrough pain, patient satisfaction and hourly ropivacaine use. RESULTS: Ropivacaine use decreased significantly by 32.6% in the neostigmine/clonidine (NC) group [11.6 ±â€Š4.2 vs. 17.2 ±â€Š5.3 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 ±â€Š5 vs. 88 ±â€Š11 mm after 1 h; 92 ±â€Š10 vs. 90 ±â€Š14 mm after 24 h). CONCLUSION: 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.

Do we need cephalic spread of spinal anaesthesia for caesarean section? A different approach to CSE-EVE for reducing hypotension.

Spinal anaesthesia is the most preferred anaesthetic technique for elective as well as for unplanned Caesarean sections. Spinal-induced hypotension remains the most important side effect with a reported incidence between 20% and 100%. It can cause -maternal discomfort (nausea and vomiting) and impaired utero-placental perfusion. The present study was designed to examine the influence of epidural volume effect on the spread and duration of low-dose hyperbaric levobupivacaine. The aim of this study was to evaluate the influence of epidural restriction (injection of saline) on the distribution of anaesthesia as well as the incidence of hypotension during the spinal anaesthesia.After the approval by the ethics committee, 60 full-term parturient women (ASA I or II) with uncomplicated pregnancies were prospectively randomized into 2 groups: the SA group (single shot spinal anaesthesia) included 37 patients and the CSE-EVR group (combined spinal-epidural anaesthesia) included 39 patients in whom we induced the restriction of the spinal space by epidural volume compression. The blocks were performed at the L2/3 or L3/4 level in a sitting position, in the CSE-EVR group using the needle-through-needle technique. The initial dose for CSE-EVR was exactly half of the SA dose (0.5 mg per 10 cm height of hyperbaric levobupivacaine and 20 microg fentanyl). After spinal injection, an epidural catheter was located in the CSE-EVR and a volume of 20 mL saline solution injected. After injection, the women were turned supine with a left uterine displacement. Surgery was allowed when a sensory block at or above the T8 dermatome was established. We evaluated the height of the block by the pinprick method and the motor block by the Bromage scale, 10 min after spinal injection, during the operation time and at the end of surgery. Haemodynamic monitoring (NIBP, HR) was assessed every 2 min until the childbirth, then every 5 min during operative time. Anaesthetic efficacy was evaluated for breakthrough pain by visual analogue pain score (VAPS), Apgar score at birth, umbilical artery pH, and epinephrine consumption.The level of anaesthesia 10 min after the induction was significantly higher in the spinal group (SA) than in the CSE-EVR T5 (T4-T7) vs. T7 (T6-T8) group.The SA group experienced complete motor block during the time of anaesthesia, while the CSE-EVR group demonstrated significantly faster motor recovery. The incidence of hypotension and ephedrine supplementation was significantly lower in the CSE-EVR group (19 vs. 35 patients) than in the SA group (p<0.05).The neonatal outcome and umbilical artery pH were higher in the CSE-EVR group. Both groups were comparable in demographic data, VAS scores, preloading and infusion volume, atropine or ephedrine use, and adverse effects such as nausea or skin pruritus.We demonstrated a possible restriction of the spread of spinal anaesthesia by using epidural volume restriction with 20 mL saline as part of a combined spinal epidural technique. The study shows that CSE with EVR using only 50% of the levobupivacaine dose provided adequate anaesthesia for elective Caesarean delivery, as well as better maternal haemodynamic stability.

Breakthrough cancer pain: an observational study of 1000 European oncology patients.

CONTEXT: Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients. OBJECTIVES: The aim of this study was to characterize breakthrough pain in a diverse population of cancer patients. METHODS: The study involved 1000 cancer patients from 13 European countries. Patients were screened for breakthrough pain using a recommended diagnostic algorithm and then questioned about the characteristics and management of their pain. RESULTS: Of the 1000 patients, 44% reported incident pain, 41.5% spontaneous pain, and 14.5% a combination. The median number of episodes was three a day. The median time to peak intensity was 10 minutes, with the median for patients with incident pain being five minutes (P < 0.001). The median duration of untreated episodes was 60 minutes, with the median for patients with incident pain being 45 minutes (P = 0.001). Eight hundred six patients stated that pain stopped them doing something, 66 that it sometimes stopped them doing something, and only 107 that it did not interfere with their activities. Patients with incident pain reported more interference with walking ability and normal work, whereas patients with spontaneous pain reported more interference with mood and sleep. As well, 65.5% of patients could identify an intervention that improved their pain (29.5%, pharmacological; 23%, nonpharmacological; 12%, combination). Regarding medications, 980 patients were receiving an opioid to treat their pain, although only 191 patients were receiving a transmucosal fentanyl product licensed for the treatment of breakthrough pain. CONCLUSION: Breakthrough cancer pain is an extremely heterogeneous condition.

Efficacy of rapid-onset oral fentanyl formulations vs. oral morphine for cancer-related breakthrough pain: a meta-analysis of comparative trials.

CONTEXT: Breakthrough cancer pain (BTcP) is widely recognized as a clinically significant complication of chronic cancer pain. With most BTcP episodes peaking in intensity within a few minutes and lasting for approximately 30 minutes, speed of onset is crucial for effective pain management. Although the last decade has seen the development of a number of rapid-onset fentanyl preparations, BTcP is still typically managed by supplemental or rescue doses of the patient's around-the-clock medication, such as oral morphine. Importantly, although the fentanyl preparations, such as fentanyl buccal tablet (FBT), sublingual fentanyl citrate orally disintegrating tablet (ODT), and oral transmucosal fentanyl citrate lozenge (OTFC), have all been proven to be efficacious in clinical studies, oral morphine has never been specifically tested in BTcP, other than as a comparator in studies of OTFC and fentanyl pectin nasal spray. OBJECTIVES: To determine the relative contributions to pain relief from oral morphine and the fentanyl preparations using placebo as a common comparator. METHODS: Relevant studies were identified by review of the literature and used in a mixed-treatment meta-analysis to indirectly compare fentanyl preparations, morphine, and placebo for the treatment of BTcP. RESULTS: Analysis incorporating the five relevant studies identified revealed that although the fentanyl preparations provide superior pain relief vs. placebo in the first 30 minutes after dosing (FBT provided an 83% probability of superior pain relief, ODT 66%, and OTFC 73% vs. placebo), oral morphine performed little better than placebo (56% probability). CONCLUSION: This mixed-treatment analysis suggests that FBT, ODT, and OTFC might provide more efficacious treatment options than oral morphine for BTcP.

Continuous saphenous nerve block as supplement to single-dose local infiltration analgesia for postoperative pain management after total knee arthroplasty.

BACKGROUND AND OBJECTIVES: Local infiltration analgesia (LIA) reduces pain after total knee arthroplasty without the motor blockade associated with epidural analgesia or femoral nerve block. However, the duration and efficacy of LIA are not sufficient. A saphenous nerve block, in addition to single-dose LIA, may improve analgesia without interfering with early mobilization. METHODS: Forty patients were included in this double-blind randomized controlled trial. All patients received spinal anesthesia for surgery and single-dose LIA during the operation. An ultrasound-guided saphenous nerve catheter was placed postoperatively in the adductor canal at midthigh level. Patients were randomized into 2 groups to receive 15-mL boluses of either ropivacaine 7.5 mg/mL or saline twice daily for 2 postoperative days. RESULTS: Worst pain scores during movement on the day of surgery were significantly lower in the ropivacaine group (median [range] visual analog scale, 3 [0-7] vs 5.5 [0-10]; P < 0.050), as well as pain at rest (visual analog scale, 2 [0-8] vs 4 [0-8]; P = 0.032). Breakthrough pain occurred later in the ropivacaine group (10.5 [range, 0.5-48] hours vs 3.4 [range, 0.5-24] hours; P = 0.011). All patients in the ropivacaine group were able to ambulate on the day of surgery versus 13 patients in the control group (P = 0.004). Fewer patients had sleep disturbance on the first postoperative night in the ropivacaine group (P = 0.038). We found no differences in morphine consumption. CONCLUSIONS: The combination of a saphenous nerve block with single-dose LIA offered better pain relief on the day of surgery than LIA alone.

Treatment strategies to overcome end-of-dose failure with oral and transdermal opioids.

Extended-release oral and transdermal opioids are increasingly being used for the management of chronic pain. Although the dosing intervals for these products were established through controlled clinical trials, expanded use of extended-release and transdermal dosage forms has resulted in awareness that a significant number of patients with chronic pain experience loss of baseline pain control prior to the next scheduled dose. End-of-dose failure (EDF) is the term used to describe this type of pain manifestation. By recognizing potential causes of EDF, strategies may be developed to overcome its occurrence to improve patients' pain control.

Dolor agudo o episodico por cáncer / Acute pain or episodical due to cancer

Introducción: A partir del concepto introducido por la Asociación Internacional para el Estudio y Tratamiento del Dolor, los conceptos de dolor agudo, subagudo, crónico e intermitente se consideran claves en la evolución del dolor en un paciente con cáncer, así como elementos relacionados con la fisiopatología del dolor. Objetivos: identificar la incidencia y prevalencia del dolor episódico, conocido como breakthrough pain, las definiciones dadas por varios autores, las características clínicas y su control con opioides. Desarrollo: se alude a las características fisiopatológicas del dolor por cáncer y las causas que lo pueden originar en su interrelación con el dolor agudo por cáncer. Se destaca el papel jugado por la actividad osteoclástica y osteoblástica y las sustancias algogénicas producidas a partir del estroma tumoral para ocasionar el dolor incidental. Se analiza las definiciones de breakthrough pain dadas por varios autores El empleo de opioides en el control basal del dolor por cáncer y la utilidad de los nuevos opioides de acción rápida son examinados como tratamiento ideal del dolor episódico por cáncer como definimos en castellano al término utilizado en inglés por años. Conclusiones: se alerta sobre el buen uso de estas formulaciones de fentanyl con una buena titulación de las dosis a emplear(AU)

Introduction: From the concept introduced by the International Association for the Study and Treatment of Pain, the terms acute, subacute, chronic and intermittent pain are considered and key in the course of pain in a cancer patient, as well as the elements related to pain pathophysiology. Objectives: To identify the incidence and prevalence of episodical pain know as breakthrough pain, the definitions of other authors, the clinical features and its control using opioids. Development: It is refer to the pathophysiological features of cancer pain and the causes that could originate it in its interrelation with acute pain due to cancer. It is emphasized the role played by the osteoclastic and osteoblastic activity and the allogenic substances produced from the tumor stroma causing the incidental pain. Authors analyzed the definitions of breakthrough pain mentioned by some authors. The use of opioids in the basal control of cancer pain and the usefulness of the new opioids of fast action are examined are the ideal treatment of episodical pain due to cancer how we define in Spanish language to the term used in English language during years. Conclusions: It is essential and important the appropriate use of the fentanyl formulas with a good titration of dose to be use(AU)

Dose equivalence of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone: a randomized, double-blind trial incorporating a measure of assay sensitivity.

UNLABELLED: Dose selection of a once-daily, osmotic-controlled extended-release (ER) hydromorphone assumes that this drug and immediate-release (IR) hydromorphone are dose equivalent. This trial evaluated dose equivalence using a measure of assay sensitivity. Patients were converted to open-label IR hydromorphone, underwent dose titration, and those on a satisfactory dose entered a randomized, double-blind phase receiving 7 days of: 1) hydromorphone IR 5 times/day at approximately this dose; 2) once-daily hydromorphone ER at this dose; or 3) once-daily hydromorphone ER at one-half this dose. Efficacy was measured using breakthrough medication use, pain, sleep, and global assessments. Of 148 patients, 113 (76%) were randomized. IR and full-dose ER groups produced comparable effects on all measures. Although the prespecified primary analysis of the difference in total daily dose of breakthrough medication between the full-dose ER and half-dose ER groups was not significant, more patients in the half-dose ER group required an increase in breakthrough medication (P = .026) and the half-dose ER group both increased the number of breakthrough doses (P = .026) and had greater percent change in the total daily dose of breakthrough medication (P = .037) than the full-dose group, suggesting that switching from IR to ER hydromorphone at the same daily dose provides equivalent analgesia. PERSPECTIVE: In a randomized, double-blind trial, the same total daily dose of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone had comparable effects. Detection of different effects between blinded dose levels was used as a measure of assay sensitivity. The measure of assay sensitivity can enhance the interpretation of dose equivalence or noninferiority trials.

Aberrant drug-related behavior observed during clinical studies involving patients taking chronic opioid therapy for persistent pain and fentanyl buccal tablet for breakthrough pain.

CONTEXT: Information on aberrant drug-related behaviors in the clinical study setting is limited. OBJECTIVES: This retrospective analysis was designed to identify the types and frequency of aberrant drug-related behaviors (including misuse and abuse) and associated patient characteristics in opioid-tolerant patients with chronic pain. METHODS: Data from opioid-tolerant patients participating in clinical studies of fentanyl buccal tablet (FBT) for breakthrough pain (up to 18 months of clinical study case-report forms) were retrospectively reviewed and coded for abuse, overdose, and aberrant behavior. Aberrant behaviors were categorized as those involving FBT (overuse, lost or stolen study drug) and those not involving FBT (patients seeking prescriptions from other sources, not returning for follow-up). RESULTS: Of the 1,160 patients evaluated, 10 (<1%) patients had an abuse-related event, 18 (<2%) had a positive urine drug screening (nonprescribed drug or illicit substance), and 12 (1%) had an event consistent with opioid overdose; 124 (11%) had aberrant behaviors related to FBT, and 68 (6%) had aberrant behaviors that were not. Aberrant behaviors were more frequent in men (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.1, 2.1; P<0.01), in patients 42 years or younger (OR: 2.5; 95% CI: 1.6, 4.0; P<0.01), and in patients 43 years to 49 years (OR: 1.9; 95% CI: 1.2, 3.1; P<0.01). CONCLUSION: The incidence of drug abuse events and aberrant drug-related behaviors was relatively low, probably because of the implementation of universal precautions and the controlled clinical study setting. Even in this setting, events occurred, highlighting the limits of screening and the need for ongoing monitoring of aberrant behavior.