Low-dose intranasal dexmedetomidine premedication improves epidural labor analgesia onset and reduces procedural pain on epidural puncture: a prospective randomized double-blind clinical study.

BACKGROUND: Epidural labor analgesia is a safe and effective method of pain management during labor with the drawbacks of delayed onset and maternal distress during epidural puncture. This study aimed to determine whether pretreatment with intranasal low-dose dexmedetomidine effectively shortens the onset of analgesia and reduces procedural pain. METHODS: In this prospective, randomized double-blind trial, nulliparous patients were randomly assigned to either the intranasal dexmedetomidine group or the control group. The intranasal dexmedetomidine group received 0.5 µg/kg dexmedetomidine intranasally, and the control group received an equal volume of normal saline intranasally. Both groups were maintained with a programmed intermittent epidural bolus. The primary outcome was the onset time of analgesia and scores of pain related to the epidural puncture. RESULTS: Seventy-nine patients were enrolled, and 60 completed the study and were included in the analysis. The time to achieve adequate analgesia was significantly shorter in the intranasal dexmedetomidine group than in the control group (hazard ratio = 2.069; 95% CI, 2.187 to 3.606; P = 0.010). The visual analogue scale pain scores during epidural puncture in the intranasal dexmedetomidine group were also significantly lower than those in the control group (2.0 (1.8-2.5) vs. 3.5 (3.3-4.5), P ≤ 0.001, Table 2). Pretreatment with intranasal dexmedetomidine before epidural labor analgesia was associated with improved visual analogue scale pain scores and Ramsay scores, less consumption of analgesics and higher maternal satisfaction (P < 0.05). No differences were observed for labor and neonatal outcomes or the incidence of adverse effects between the two groups. CONCLUSIONS: Pretreatment with intranasal dexmedetomidine before epidural labor analgesia yielded a faster onset of analgesia and decreased epidural puncture pain without increasing adverse effects. Pretreatment with intranasal dexmedetomidine may be a useful adjunct for the initiation of epidural analgesia, and further investigation should be encouraged to determine its utility more fully. TRIAL REGISTRATION: This trial was prospectively registered at Chictr.org.cn on 29/05/2020 with the registration number ChiCTR2000033356 ( http://www.chictr.org.cn/listbycreater.aspx ).

Postprocedural Pain Associated With 5 Versus 20 Intradetrusor Injections of onabotulinumtoxinA for Treatment of Overactive Bladder: A Multicenter Randomized Clinical Trial.

IMPORTANCE: Intradetrusor injection of onabotulinumtoxinA is performed via varying injection paradigms but no studies have studied the various effects of these paradigms on patient experience with the procedure. OBJECTIVES: This randomized clinical trial aims to compare pain and procedure time between patients receiving a 100-unit dose of onabotulinumtoxinA in 5 injections compared to 20 injections for the treatment of idiopathic overactive bladder or urgency urinary incontinence. STUDY DESIGN: Patients presenting with refractory overactive bladder or urgency urinary incontinence at 2 clinical sites were identified and randomized to undergo onabotulinumtoxinA treatment with 5 injections versus 20 injections. Patients rated their pain level on a 10-point visual analog scale at procedure completion. The procedure duration was recorded with a stopwatch. Patients were followed up 6 weeks postprocedure, at which time they completed a Global Response Assessment to determine subjective efficacy of treatment. Participants were additionally monitored for incidence of adverse events in the follow-up period. RESULTS: The average pain score was not statistically significant between groups (2; interquartile range, 1-4 for the 5 injection group vs 3; interquartile range, 2-4 for the 20 injection group; P = 0.27). Patients who received 5 injections experienced significantly shorter mean procedure time as compared with patients who received 20 injections (76 seconds vs 176 seconds; P < 0.001). There were no differences in subjective efficacy or adverse events between groups. CONCLUSIONS: Perceived pain, efficacy, and postprocedure complications did not significantly differ between patients receiving 5 injections and 20 injections, but procedure time was significantly shorter.

Tolerance of Fentanyl Pectin Nasal Spray for Procedural Pain in Geriatric Patients.

OBJECTIVES: We aimed to assess the tolerance of fentanyl pectin nasal spray (FPNS) when used to treat procedural pain caused by wound dressing or physiotherapy in patients older than 75 years with or without opioid background treatment. DESIGN: This is a prospective monocentric, noncontrolled, nonrandomized study conducted from December 2014 to October 2017 in 2 geriatric wards (rehabilitation and acute medicine). SETTING AND PARTICIPANTS: Fifty-seven patients were included and 314 procedures were monitored. METHODS: For each patient, 6 procedures were monitored: the first 2 without specific treatment, then fentanyl was started at 100 µg with a titration over a few procedures up to 800 µg in non-opioid-naïve patients and 400 µg in opioid-naïve. Sedation and respiratory scale were monitored during the procedures. All adverse drug events occurring from inclusion to 5 days after the intervention were collected and their imputability was assessed separately by 2 pharmacovigilance experts. RESULTS: Overall, 14.4% of the sessions with FPNS administration resulted in adverse drug events. Main adverse drug events were nausea and vomiting, somnolence, and confusion. Most of them were of mild to moderate severity. Four severe adverse events were due to accidental overdoses. No unexpected adverse event occurred. Tolerance was similar for opioid-naïve and non-opioid-naïve patients (P value = .93). CONCLUSION AND IMPLICATIONS: FPNS was overall well tolerated in geriatric patients. Given its interesting pharmacokinetics, fentanyl is a promising lead for procedural pain treatment in geriatric patients, even those who are opioid naïve.

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial.

PURPOSE: Hydrogen peroxide (H2O2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H2O2 + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action. METHODS AND MATERIALS: Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral H2O2 with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.5 Gy in 18 daily fractions (n = 6) to the whole breast ± locoregional lymph nodes in a single-center, nonrandomized study. H2O2 was mixed in 1% sodium hyaluronate gel (final H2O2 concentration 0.5%) before administration to slow drug release and minimize local discomfort. The mixture was injected intratumorally under ultrasound guidance twice weekly 1 hour before RT. The primary endpoint was patient-reported maximum intratumoral pain intensity before and 24 hours postinjection. Secondary endpoints included grade ≥3 skin toxicity and tumor response by ultrasound. Blood samples were collected before, during, and at the end of treatment for cell-death and immune marker analysis. RESULTS: Compliance with H2O2 and RT was 100%. Five of 12 patients reported moderate pain after injection (grade 2 Common Terminology Criteria for Adverse Events v4.02) with median duration 60 minutes (interquartile range, 20-120 minutes). Skin toxicity was comparable to RT alone, with maintained partial/complete tumor response relative to baseline in 11 of 12 patients at last follow-up (median 12 months). Blood marker analysis highlighted significant associations of TRAIL, IL-1ß, IL-4, and MIP-1α with tumor response. CONCLUSIONS: Intratumoral H2O2 with RT is well tolerated with no additional toxicity compared with RT alone. If efficacy is confirmed in a randomized phase 2 trial, the approach has potential as a cost-effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

Propofol versus midazolam for premedication: a placebo­controlled, randomized double­blinded study.

BACKGROUND: It has been previously reported that subhypnotic doses of propofol could offer an advantage over midazolam for premedication. This study was designed to test the hypothesis that a 20 mg IV dose of propofol would be more effective than a standard 2 mg IV dose of midazolam for reducing acute anxiety prior to induction of anesthesia. METHODS: One hundred twenty outpatients scheduled to undergo orthopedic surgery were randomly assigned to one of three study groups: control (saline); propofol (20 mg); or midazolam (2 mg). Immediately before administering the study medication, each patient evaluated their level of acute anxiety and sedation on 11­point verbal rating scales (VRSs) 0=none- 10=highest, and they were also shown a picture. Upon arrival in the OR ~5 min after administering the study medication, anxiety and sedation levels were reassessed and a second picture was shown. At discharge from the recovery area, anxiety and sedation levels and their ability to recall the two pictures were reassessed. RESULTS: Compared to the saline group, both propofol and midazolam produced significant increases in the patient's level of sedation upon entering the OR (+2.5±2.4 vs. +4.6±2.5 and +5.2±2.3, respectively [p<0.001]). Propofol was effective as midazolam compared to saline in reducing the patient's level of preinduction anxiety (from 3.2±2.2 to1.8±1.8 vs. 3.1±2.2 to 2.3±2.1 and 2.7±1.8 to 2.8±2.1, respectively). Propofol produced more pain on injection and midazolam significantly reduced recall of the second picture. CONCLUSIONS: When administered ~5 min prior to entering the OR, propofol, 20mg IV, was as effective as midazolam 2mg IV in reducing anxiety.