Haemodynamic effects of methoxyflurane versus fentanyl and placebo in hypovolaemia: a randomised, double-blind crossover study in healthy volunteers.

Background: Methoxyflurane is approved for relief of moderate to severe pain in conscious adult trauma patients: it may be self-administrated and is well suited for use in austere environments. Trauma patients may sustain injuries causing occult haemorrhage compromising haemodynamic stability, and it is therefore important to elucidate whether methoxyflurane may adversely affect the haemodynamic response to hypovolaemia. Methods: In this randomised, double-blinded, placebo-controlled, three-period crossover study, inhaled methoxyflurane 3 ml, i.v. fentanyl 25 µg, and placebo were administered to 15 healthy volunteers exposed to experimental hypovolaemia in the lower body negative pressure model. The primary endpoint was the effect of treatment on changes in cardiac output, while secondary endpoints were changes in stroke volume and mean arterial pressure and time to haemodynamic decompensation during lower body negative pressure. Results: There were no statistically significant effects of treatment on the changes in cardiac output, stroke volume, or mean arterial pressure during lower body negative pressure. The time to decompensation was longer for methoxyflurane compared with fentanyl (hazard ratio 1.9; 95% confidence interval 0.4-3.4; P=0.010), whereas there was no significant difference to placebo (hazard ratio -1.3; 95% confidence interval -2.8 to 0.23; P=0.117). Conclusions: The present study does not indicate that methoxyflurane has significant adverse haemodynamic effects in conscious adults experiencing hypovolaemia. Clinical trial registration: ClinicalTrials.gov (NCT04641949) and EudraCT (2019-004144-29) https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004144-29/NO.

Tailored surgery in chronic pancreatitis after implementation of a multidisciplinary team assessment; a prospective observational study.

INTRODUCTION: Optimal management of chronic pancreatitis involves several specialties. Selection of patients for surgery may benefit from evaluation by a multidisciplinary team (MDT), similar to cancer care. The aim of this study was to evaluate outcomes in patients selected for surgery after MDT decision. METHODS: A prospective, observational study of consecutive patients operated for pain due to chronic pancreatitis after implementation of a MDT. The main outcome was Quality of life (QoL) assessed by EORTC-QLQ C30 and pain relief in patients followed >3 months. Complications were registered and predictive factors for pain relief analyzed. RESULTS: Of 269 patients evaluated by the MDT, 60 (22%) underwent surgery. Postoperative surgical complications occurred in five patients (8.3%) and reoperation within 30 days in two. There was no 90-days mortality. Complete or partial pain relief was achieved in 44 of 50 patients followed >3 months (88%). Preoperative duration of pain predicted lower probability of success. Postoperative improvement in QoL was most prominent for pain, appetite and nausea. CONCLUSIONS: After MDT evaluation, one in five patients was selected for surgery. Pain relief was obtained in a majority of patients with improved QoL. A tailored approach through a MDT seems warranted and efficient.

Determination of equi-analgesic doses of inhaled methoxyflurane versus intravenous fentanyl using the cold pressor test in volunteers: a randomised, double-blinded, placebo-controlled crossover study.

BACKGROUND: Inhaled methoxyflurane for acute pain relief has demonstrated an analgesic effect superior to placebo. Data comparing methoxyflurane to an opioid are needed. The aim of this study was to determine the equi-analgesic doses of inhaled methoxyflurane vs i.v. fentanyl. Both drugs have an onset within minutes and an analgesic effect of 20-30 min. METHODS: Twelve subjects were included in a randomised, double-blinded, placebo-controlled crossover study with four treatments: placebo (NaCl 0.9%), fentanyl 25 µg i.v., fentanyl 50 µg i.v., or inhaled methoxyflurane 3 ml. The subjects reported pain intensity using the verbal numeric rating scale (VNRS) from 0 to 10 during the cold pressor test (CPT). The CPT was performed before (CPT 1), 5 min (CPT 2), and 20 min (CPT 3) after drug administration. RESULTS: Inhaled methoxyflurane and fentanyl 25 µg reduced VNRS scores significantly compared with placebo at CPT 2 (-1.14 [estimated difference in VNRS between treatment groups with 95% confidence interval {CI}: -1.50 to -0.78]; -1.15 [95% CI: -1.51 to -0.79]; both P<0.001) and CPT 3 (-0.60 [95% CI: -0.96 to -0.24]; -0.84 [95% CI: -1.20 to -0.47]; both P<0.001). There were no significant differences between the two drugs. Methoxyflurane had significantly higher VNRS scores than fentanyl 50 µg at CPT 2 (0.90 [95% CI: 0.54-1.26]; P<0.001) and CPT 3 (0.57 [95% CI: 0.21-0.94]; P<0.001). CONCLUSIONS: Inhaled methoxyflurane 3 ml was equi-analgesic to fentanyl 25 µg i.v. at CPT 2. Both resulted in significantly less pain than placebo. Fentanyl 50 µg i.v. demonstrated analgesia superior to methoxyflurane. CLINICAL TRIAL REGISTRATION: NCT03894800.

Tapentadol versus oxycodone analgesia and side effects after laparoscopic hysterectomy: A randomised controlled trial.

BACKGROUND: Tapentadol is an opioid, which acts as a µ-opioid receptor agonist and inhibits noradrenaline reuptake in the central nervous system. This dual mechanism of action results in synergistic analgesic effects and potentially less side effects. This has been shown in treatment of chronic pain but postoperative studies are sparse. OBJECTIVES: The main aim was to compare the analgesic effect of tapentadol with oxycodone after laparoscopic hysterectomy. Opioid side effects were recorded as secondary outcomes. DESIGN: Randomised, blinded trial. SETTING: Single-centre, Oslo University Hospital, Norway, December 2017 to February 2019. PATIENTS: Eighty-six opioid-naïve American Society of Anesthesiologists physical status 1 to 3 women undergoing laparoscopic hysterectomy for nonmalignant conditions. INTERVENTION: The patients received either oral tapentadol (group T) or oxycodone (group O) as part of multimodal pain treatment. Extended-release study medicine was administered 1 h preoperatively and after 12 h. Immediate-release study medicine was used as rescue analgesia. MAIN OUTCOME MEASURES: Pain scores, opioid consumption and opioid-induced side effects were evaluated during the first 24 h after surgery. RESULTS: The groups scored similarly for pain at rest using a numerical rating scale (NRS) 1 h postoperatively (group T 4.4, 95% CI, 3.8 to 5.0, group O 4.6, 95% CI, 3.8 to 5.3). No statistically significant differences were found between the groups for NRS at rest or while coughing during the 24-h follow-up period (P = 0.857 and P = 0.973). Mean dose of oral rescue medicine was similar for the groups (P = 0.914). Group T had significantly lower odds for nausea at 2 and 3 h postoperatively (P = 0.040, P = 0.020) and less need for antiemetics than group O. No differences were found for respiratory depression, vomiting, dizziness, pruritus, headache or sedation. CONCLUSION: We found tapentadol to be similar in analgesic efficacy to oxycodone during the first 24 h after hysterectomy, but with significantly less nausea. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03314792.

A Five-Year Data Report of Long-Term Central Venous Catheters Focusing on Early Complications.

BACKGROUND: Long-term venous access has become the standard practice for the administration of chemotherapy, fluid therapy, antibiotics, and parenteral nutrition. The most commonly used methods are percutaneous puncture of the subclavian and internal jugular veins using the Seldinger technique or surgical cutdown of the cephalic vein. METHODS: This study is based on a quality registry including all long-term central venous catheter insertion procedures performed in patients >18 years at our department during a five-year period. The following data were registered: demographic data, main diagnosis and indications for the procedure, preoperative blood samples, type of catheter, the venous access used, and the procedure time. In addition, procedural and early postoperative complications were registered: unsuccessful procedures, malpositioned catheters, pneumothorax, hematoma complications, infections, nerve injuries, and wound ruptures. The Seldinger technique using anatomical landmarks at the left subclavian vein was the preferred access. Fluoroscopy was not used. RESULTS: One thousand one hundred and one procedures were performed. In eight (0.7%) cases, the insertion of a catheter was not possible, 23 (2.1%) catheters were incorrectly positioned, twelve (1.1%) patients developed pneumothorax, nine (0.8%) developed hematoma, and three (0.27%) developed infection postoperatively. One (0.1%) patient suffered nerve injury, which totally recovered. No wound ruptures were observed. CONCLUSIONS: We have a high success rate of first-attempt insertions compared with other published data, as well as an acceptable and low rate of pneumothorax, hematoma, and infections. However, the number of malpositioned catheters was relatively high. This could probably have been avoided with routine use of fluoroscopy during the procedure.

Out-of-Hospital Perimortem Cesarean Delivery Performed in a Woman at 32 Weeks of Gestation: A Case Report.

A 34-year-old pregnant woman experienced cardiac arrest at home. Out-of-hospital perimortem cesarean delivery was performed 27 minutes after the collapse. Both mother and child were resuscitated and had return of spontaneous circulation before they were transported to a university hospital. The mother underwent hysterectomy and developed disseminated intravascular coagulation. Despite intensive treatment, she died 8.5 hours after arrival. The infant was extubated the next day, and her subsequent hospital course was uneventful. She was later diagnosed with cerebral palsy and severe gastroesophageal reflux. At 2 years of age, she communicated by sounds, eye contact, and smiling.

Effects of COX inhibition on experimental pain and hyperalgesia during and after remifentanil infusion in humans.

Opioids may enhance pain sensitivity resulting in opioid-induced hyperalgesia (OIH). Activation of spinal cyclooxygenase may play a role in the development of OIH. The aim of this study was to demonstrate remifentanil-induced postinfusion hyperalgesia in an electrical pain and a cold pain model, and to investigate whether COX-2 (parecoxib) or COX-1 (ketorolac) inhibition could prevent hyperalgesia after remifentanil infusion. Sixteen healthy males were enrolled in this randomized, double-blind, placebo-controlled crossover study. Each subject went through 4 sessions: control, remifentanil, parecoxib+remifentanil, and ketorolac+remifentanil. Transcutaneous electrical stimulation induced acute pain and areas of pinprick hyperalgesia. The areas of pinprick hyperalgesia were assessed before, during, and after a 30-minute infusion of either remifentanil or saline. The cold-pressor test (CPT) was performed before, at the end of, and 1 hour after the infusions. The subjects received a bolus of either saline, 40 mg parecoxib, or 30 mg ketorolac intravenously after the first CPT. The areas of pinprick hyperalgesia and CPT pain after the end of remifentanil infusion increased significantly compared to control (P < 0.001 and P = 0.005, respectively). Pretreatment with parecoxib or ketorolac reduced the postinfusion area of pinprick hyperalgesia (P < 0.001 and P = 0.001, respectively), compared to the remifentanil group. Parecoxib reduced the area significantly more than ketorolac (P = 0.009). In the CPT, pretreatment with parecoxib or ketorolac did not prevent postinfusion hyperalgesia. These results demonstrated OIH in both models, and may suggest that COX-2 inhibition is more important than COX-1 inhibition in reducing hyperalgesia. Remifentanil-induced hyperalgesia was demonstrated for both electrically induced pain and cold-pressor pain. Both parecoxib and ketorolac prevented hyperalgesia in the electrical model, parecoxib to a larger extent.

A comparison of intravenous oxycodone and intravenous morphine in patient-controlled postoperative analgesia after laparoscopic hysterectomy.

INTRODUCTION: In this study, we investigated the dose requirements, pain relief, and side effects of oxycodone versus morphine after surgery with visceral pain. METHODS: Ninety-one women received IV oxycodone or morphine before the end of laparoscopic hysterectomy and then continued with patient-controlled analgesia for 24 h postoperatively. RESULTS: The accumulated oxycodone consumption was less (13.3 +/- 10.4 mg vs 22.0 +/- 13.1 mg, P = 0.001) than morphine. With oxycodone, the visual analog scale scores were significantly lower in the first hour postoperatively and sedation was less during the 24-h postoperative period, P = 0.006. CONCLUSIONS: Oxycodone was more potent than morphine for visceral pain relief but not for sedation.