Pharmacokinetic Analysis, Analgesic Effects, and Adverse Effects of Tapentadol in Cancer Patients with Pain.

In this study, we conducted a pharmacokinetic analysis of tapentadol (TP) in Japanese patients with cancer pain and identified covariates influencing pharmacokinetic parameters. In addition, the analgesic effects and adverse effects of TP were investigated. Data were collected from in-patients with cancer pain who had been administered TP as an extended-release formula. The median (range) estimated clearance (CL/F) and distribution volume (Vd/F) of TP were 86.7 (31.3-213.7) L/h and 1288 (189-6736) L, respectively. There was a strong negative correlation between CL/F and age, Child-Pugh score, and albumin-bilirubin (ALBI) score. The subjects were further divided into two groups according to the factors highly correlated with CL/F. The CL/F of patients in the Child-Pugh B group was 0.46-times that of patients in the Child-Pugh A group. In addition, the CL/F of patients with an ALBI score > -2.40 was 0.56-times that of patients with ALBI scores ≤-2.40, and both differences were statistically significant (p < 0.05). The mean intensity of pain over 24 h was investigated daily from before starting TP for the first 7 d of the treatment. TP reduced pain in six of nine patients; the mean pain visual analogue scale score decreased significantly from 59.2 mm before administration to 42.5 mm at days 5-7. Overall, the Child-Pugh and ALBI scores significantly affected the clearance of TP, which was reduced in patients with impaired liver function. These results suggest that TP is an opioid with a sufficient analgesic effect for cancer patients.

The Initial Subjective Sensory Change in the Dermatome During Intrathecal Injection of Plain Bupivacaine Predicts the Spread of Sensory Blockade: A Prospective Multi-Level Modeling Study.

BACKGROUND: Predicting the spread of anesthesia after intrathecal injection of plain local anesthetics is challenging owing to both patient and anesthesiologist-related factors. OBJECTIVES: This study aimed to examine the initial patient-reported sensory changes during intrathecal injections and used multi-level analyses to examine the relationships between these changes and other major factors affecting the spread of anesthesia. METHODS: The participants were 120 consecutive patients with the American Society of Anesthesiologists status I and II, who were scheduled for open repair of inguinal hernias under spinal anesthesia. Lumbar puncture was performed at the midline of the L3 - L4 vertebrae and 3 mL of 0.5% isobaric bupivacaine was administered at 0.25 mL/s. The onset, dermatome, and side of the initial subjective sensory changes (ISSCs) were assessed by patient report. The extent of sensory loss to ice and pinprick stimuli, the degree of motor block in lower extremities, blood pressure, and heart rate were examined at 5-minutes intervals for 20 minutes after intrathecal injection. RESULTS: All patients reported ISSCs after 9 (4, 18) seconds [median (minimum, maximum)] of the intrathecal injection onset. In 66.7% of the patients, ISSCs occurred in the L1 - L5 dermatomes. Three patients experienced pain during the early intraoperative period, and described ISSCs in the sacral dermatome. Height, mean blood pressure, and ISSCs were significantly correlated with sensory loss. Faster onset, lower dermatome, and floor-side of ISSCs predicted a narrower area of sensory loss, with dermatome as the most important indicator. CONCLUSIONS: Our findings demonstrate that ISSC, primarily based on dermatome, is a significant predictor for spinal anesthesia spread.

Short-term results of intrathecal injection of low-dose bupivacaine in outpatients with chronic low back and lower extremity pain.

PURPOSE: To investigate the safety and efficacy of intrathecal injection as an alternative to epidural injection for analgesia. METHODS: Seventy consecutive outpatients with chronic low back and lower extremity pain received lumbar intrathecal injection of low-dose isobaric bupivacaine using a 25-gauge pencil-point needle. The patients received 0.5, 1.0, and 1.5 mg of bupivacaine at 1-week intervals to determine the optimal dose. Thereafter, they received two more weekly injections with the optimal dose. The safety and efficacy of the treatment were assessed over a 1-year period. RESULTS: No serious adverse events were encountered. The optimal dose of bupivacaine (1.0 mg in 60% of patients) alleviated pain and disability (both, p < 0.0001) and provided anesthesia below L1 (L5-T6). Motor block was negligible, and balance impairment improved relative to baseline (p < 0.0001). CONCLUSION: Intrathecal injection of low-dose bupivacaine offers a safe and effective treatment for chronic low back and lower extremity pain. TRIAL REGISTRATION: The study was approved by the Kitasato University Hospital Ethics Committee, and written informed consent was obtained from all individual participants included in the study. This trial was registered with the University Hospital Medical Information Network (UMIN000008670). These slides can be retrieved under electronic supplementary material.

[Clinical Effects of Opioid Switching to Tapentadol - Retrospective Analysis of Efficacy and Adverse Effects].

The objective of our study was to evaluate the efficacy and adverse effects of opioid switching to tapentadol(TP). It was a retrospective survey carried out at the Kitasato University Hospital outpatient clinic between September 2014 and May 2016. We evaluated pain intensity using the visual analogue scale and the occurrence of adverse effects before switching, at the first evaluation after switching, and during the steady state of TP administration. We included 10 patients; of these, 3 patients discontinued TP owing to uncontrolled pain. The conversion ratio of the previously administered opioids to TP was 1.17 at the time of the first evaluation after switching and 1.42 during the steady state. The mean(±SD)pain intensity was 4.2±2.2 before opioid switching and 4.6±2.2 at the time of the first evaluation after switching. The mean(±SD)pain intensity in the 7 patients excluding the 3 patients who discontinued TP was 4.3±2.0 before opioid switching and 2.7±1.9 during the steady state. Somnolence improved in 5 patients and constipation improved in 2 patients when a stable dose was achieved. Opioid switching to TP was appropriately accomplished using the conversion ratio. Furthermore, pain, sleepiness, and constipation improved following successful titration. These data suggest that TP can be useful in the treatment of cancer pain, in addition to the currently used opioid preparations.

Visual/emotional stimuli and treatment with antidepressants alter Numerical Rating Scale score in patients with chronic pain.

STUDY OBJECTIVE: To examine the impact of visual stimulation (exciting red and tranquilizing green) on the score of the Numerical Rating Scale (NRS) questionnaire in patients with chronic pain. DESIGN: Prospective randomized study. SETTING: Outpatient pain clinic of a university hospital. PATIENTS: Two hundred outpatients with chronic pain. INTERVENTIONS: Patients were randomly assigned to receive the NRS questionnaire printed on either red paper (red group) or green paper (green group). MEASUREMENTS: The questionnaire included 5 questions consisting of the NRS in the worst, in the least, and in the average pain during last week and the NRS at rest and on movement at present. Calculation of the sample size was based on power of 0.8 and α=.01. MAIN RESULTS: The NRS scores were not different between the 2 groups. In patients on antidepressants (n=76) and with depression (n=49), the NRS scores, except the NRS in the worst pain during last week score in patients on antidepressants, were significantly higher in the red group than in the green group (all P≤.040). In the red group, the NRS scores were significantly higher in patients with than without depression (all P≤.003), whereas there was no difference in the scores between patients of the green group with and without depression. CONCLUSION: Our findings suggest that visual/emotional stimuli and treatment with antidepressants alter the NRS score in patients with chronic pain.

Response to intravenous fentanyl infusion predicts subsequent response to transdermal fentanyl.

PURPOSE: Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. METHODS: The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. RESULTS: The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p < 0.001), and to 4 (1-8) after FENtd (p < 0.001). The effects of FENiv, as evaluated by ΔNRS, CGI-I, and SS, were significantly greater than those of FENtd (p < 0.001, each), but not by the frequency and the severity of adverse effects, with the exception of dizziness. ΔNRS, and severity of adverse effects (drowsiness, dizziness, nausea, dry mouth, and pruritus) of FENiv correlated significantly with those of FENtd (rs > 0.04, each). CONCLUSIONS: The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.

[Three patients with cervical disc herniation whose severe pain was relieved with oral mini-pulse therapy of betamethasone].

Three patients with severe neck and radicular pain due to cervical disc herniation was not relieved of pain by common drug medication such as NSAIDs and anticonvulsants. Patients underwent oral mini-pulse therapy of betamethasone as the initial dose of 8 mg x day(-1) in the form of 8 tablets of 0.5 mg in a single dose twice a day (after breakfast and after lunch). The daily dose was reduced by half every 4 days, and the therapy was continued for 16 days. In all patients, the pain disappeared completely within the opening 10 days of the therapy, and the pain did not relapse after the therapy. All adverse events of betamethasone including irritation, insomnia and overeating disappeared without medication within several days.