Prevalence of opioid-induced adverse events across opioids commonly used for analgesic treatment in Japan: a multicenter prospective longitudinal study.

PURPOSE: Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan. METHODS: This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE (constipation, nausea and vomiting, delirium, and drowsiness) with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site. RESULTS: In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (n = 25, 6.3%) was the most frequent, followed by drowsiness (n = 21, 5.3%), nausea and vomiting (n = 19, 4.8%), and constipation (n = 28, 4.6%). The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE. CONCLUSION: There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.

Prevalence and associated factors of orphan symptoms in advanced cancer patients: a multicenter observational study.

PURPOSE: The aims of this study were to examine the prevalence of myoclonus, sweating, pruritus, hiccup, and vesical and rectal tenesmus, and to explore associated factors in patients with advanced cancer. METHODS: This multicenter prospective cohort study was conducted in 23 inpatient hospices/palliative care units in Japan from January to December 2017. The prevalence and characteristics of each symptom were assessed on admission and in the 3 days before death. We selected factors that might influence the occurrence of each symptom and investigated the association. RESULTS: A total of 1896 patients were enrolled. The prevalence of orphan symptoms rose from admission to the 3 days before death: myoclonus 1.3 to 5.3% (95% CI 0.9-1.9%/4.3-6.5%), sweating 1.8 to 4.1% (95% CI 1.3-2.6%/3.1-5.1%), hiccup 1.1 to 1.8% (95% CI 0.7-1.7%/1.2-2.6%), and tenesmus 0.7 to 0.9% (0.4-1.2%/0.5-1.5%). Prevalence of pruritus fell from 3.5 to 2.5% (95% CI 2.7-4.4%/1.8-3.4%). Sweating, pruritus, and hiccups persisted throughout the day in nearly half of the patients. Myoclonus was significantly associated with brain tumors, sweating with opioids and antipsychotics, pruritus with liver and biliary tract cancer, cholestasis and severe diabetes, hiccup with male gender, digestive tract obstruction, severe diabetes, and renal failure. Vesical tenesmus was associated with urinary cancer, antipsychotics, and anticholinergics and rectal tenesmus with pelvic cavity cancer. CONCLUSION: We found that orphan symptoms occurred in 0.5-5.0% of patients, increased over time except for pruritus, and persisted in half of the patients.

Patient-perceived symptomatic benefits of olanzapine treatment for nausea and vomiting in patients with advanced cancer who received palliative care through consultation teams: a multicenter prospective observational study.

PURPOSE: To examine the safety, effectiveness, and patient-perceived benefit of treatment with olanzapine for nausea and vomiting (N/V) in patients with advanced cancer. METHODS: We conducted a multicenter prospective observational study in a tertiary care setting (Trial registration number: UMIN000020493, date of registration: 2016/1/12). We measured the following: average nausea in the last 24 h using a Numeric Rating Scale (NRS: range 0-10) at baseline and day 2, patient-perceived treatment benefit (based on a 5-point verbal scale), and adverse events (AEs; using the Common Terminology Criteria for Adverse Events version 4). RESULTS: The 85 participants (45% men) had a mean age of 58.7±15.8 years. Major causes of N/V were opioids (44%) and chemotherapy (34%). All patients received a daily dose of olanzapine of 5 mg or less as first-line treatment (N=35) or second- or later-line treatment (N=50). Nausea NRS decreased from 6.1±2.2 to 1.8±2.0 (differences: -4.3, 95% CI -3.7 to -4.9, p<0.001). The proportion of patients who did not experience vomiting episodes in the last 24 h increased from 40-89%. Mean decrease in nausea NRS by patient-perceived treatment benefit were as follows: -0.8 for "none" (n=4, 5%); -2.8 for "slight" (n=17, 20%); -3.3 for "moderate" (n=14, 16%); -4.7 for "lots" (n=25, 29%); and -6.1 for "complete" (n=25, 29%; p-for-trend<0.001). The most prevalent AE was somnolence (n=15, 18%). CONCLUSION: Short-term and relatively low-dose olanzapine treatment was effective for multifactorial N/V. Confirmatory studies with longer observation periods are needed to clarify the duration of the effect and adverse events.

Cancer Pain Management in Patients Receiving Inpatient Specialized Palliative Care Services.

CONTEXT: Cancer pain is a common complication that is frequently undertreated in patients with cancer. OBJECTIVES: This study is aimed at assessing the time needed to achieve cancer pain management goals through specialized palliative care (SPC). METHODS: This was a multicenter, prospective, longitudinal study of inpatients with cancer pain who received SPC. Patients were continuously followed up until they considered cancer pain management successful, and we estimated this duration using the Kaplan-Meier method. We investigated the effectiveness of pain management using multiple patient-reported outcomes (PROs) and quantitative measures, including pain intensity change in the Brief Pain Inventory. A paired-sample t-test was used to compare the pain intensity at the beginning and end of the observation period. RESULTS: Cancer pain management based on the PROs was achieved in 87.9% (385/438) of all cases. In 94.5% (364/385) of these cases, cancer pain management was achieved within 1 week, and the median time to pain management was 3 days (95% confidence interval [CI], 2-3). The mean worst pain intensity in the last 24 h at the start and end of observation were 6.9 ± 2.2 and 4.0 ± 2.3, respectively, with a difference of -2.9 (95% CI, -3.2 to -2.6; p < 0.01). Overall, 81.6% of the patients reported satisfaction with cancer pain management, and 62 adverse events occurred. CONCLUSION: SPC achieved cancer pain management over a short period with a high level of patient satisfaction resulting in significant pain reduction and few documented adverse events.

[Anesthetic management of a patient implanted with a CRT-P device undergoing laparoscopic nephrectomy].

A 76-year-old man implanted with a CRT-P device (cardiac resynchronization therapy pacemaker) was diagnosed with renal tumor by chance. Right laparoscopic nephrectomy was performed under general and epidural anesthesia. Urologists were going to use a monopolar electrocautery during the operation. Before beginning the operation, we converted his pacing mode from DDD to DOO with a precordial magnet because electrocautery has the potential for causing device reset. His blood pressure and heart rate were stable during DOO mode. When the former CRT-P, for example InSync8040 (Medtronic) which we reported in 2009, was converted from DDD mode to DOO mode, the optimal atrioventricular (AV) delay had become invalid in DOO mode. In this case, new device Syncra (Medtronic) which had been marketed in March 2011 was implanted. DOO mode could be used keeping the optimal AV delay and right ventricular-left ventricular delay and the effect of cardiac resynchronization was valid. New CRT-P could be managed as single chamber or double chamber pacemaker. Recently in Japan, CRT becomes more common and operations in the patients implanted with CRT-P or CRT-D (CRT with defibrillation) will become more frequent. CRT will require attention for anesthetic management.

Gestation-related reduction in lumbar cerebrospinal fluid volume and dural sac surface area.

BACKGROUND: Facilitation of the spread of neuraxial anesthesia in pregnant women may be attributable in part to compression of the dural sac by the engorged epidural venous plexus. In this study, we used magnetic resonance imaging to examine pregnancy-induced changes in the lumbosacral cerebrospinal fluid (CSF) volume and dural sac surface area. METHODS: Magnetic resonance images of 18 healthy women (mean age 29 yr, mean height 158 cm, and mean weight 58 kg) were obtained to measure lumbosacral CSF volume and dural sac surface area in the nonpregnant and pregnant states (median 36 wk gestation [31-39]) and the paired images were compared. RESULTS: The mean lumbosacral CSF volume and dural sac surface area in the nonpregnant state were 39.6 +/- 5.8 mL and 11.0 +/- 0.8 cm(2), respectively. Pregnancy was associated with compression of the dural sac, resulting in a significantly reduced mean CSF volume (33.2 +/- 6.2 mL) and dural sac surface area (9.9 +/- 1.0 cm(2)) in all subjects (P < 0.001). The mean change in CSF volume and dural sac surface area was 16.7% +/- 0.8% and 10.0% +/- 0.5%, respectively. Gestational week (between 31 and 39 wk) correlated significantly with the reduction in CSF volume (rho = 0.74, P < 0.001) and dural sac surface area (rho = 0.66, P < 0.01). CONCLUSIONS: These findings indicate an association between gestational week (Weeks 31-39) and a reduction in both CSF volume and dural sac surface area. These reductions may, at least in part, explain the facilitation of the spread of intrathecal anesthesia in pregnant women.

Serratus Plane Block for Persistent Pain after Partial Mastectomy and Axillary Node Dissection.

Persistent pain after breast cancer surgery (PPBCS) is defined as chronic neuropathic pain that persists for more than 3 months after surgery. The pain can be sufficiently severe to cause long-term disabilities and interfere with sleep and daily life. Serratus plane block (SPB) is a novel, ultrasound-guided regional anesthetic technique that is suggested to achieve complete anesthesia of the anterolateral chest wall. Here, we demonstrate the efficacy of SPB as one of the treatment modalities for patients with PPBCS. A 73-year-old woman underwent a left partial mastectomy and axillary node dissection for breast cancer. Four months after surgery, she experienced burning pain with nocturnal exacerbation rated 10/10 on a numerical rating scale (NRS), hot flashes, numbness, and hyperesthesia of the left axilla. Pharmacological therapy did not improve her symptoms, and 15 months after the surgery, she experienced depression. We treated her with SPB with 10 mL of 1% lidocaine; this treatment was repeated 10 times over 6 months at 2- to 4-week intervals and she was simultaneously treated with pharmacological, physical, and cognitive behavioral therapy. With her improved pain control, she was able to perform physical therapy and subsequently experienced marked improvement in her functional status and ability to perform daily activities. She has not required any interventional pain management since the last SPB performed 11 months ago. SPB represents one of the treatment modalities for PPBCS and is an advantageous technique because it can be performed more safely and easily than neuraxial approaches.