The spread of injectate with the TQL and TOP TQL approaches is cephalad from the lumbar point of administration between the quadratus lumborum and psoas major muscles, predominantly via a pathway posterior to the arcuate ligaments and into the thoracic paravertebral space to reach the somatic nerves and the thoracic sympathetic trunk in the intercostal and paravertebral spaces. The lumbar plexus and lumbar sympathetic trunk are not affected.

BackgroundElective cesarean section (ECS) can cause moderate to severe pain that often requires opioid administration. To enhance maternal recovery, and promote mother and baby interaction, it is important to reduce postoperative pain and opioid consumption. Various regional anesthesia techniques have been implemented to improve postoperative pain management following ECS. This study aimed to investigate the efficacy of bilateral ultrasound-guided transmuscular quadratus lumborum (TQL) block on reducing postoperative opioid consumption following ECS.MethodsA randomized double-blind trial with concealed allocation was conducted in 72 parturients who received bilateral TQL block with either 30 mL ropivacaine 0.375% or saline. TQL block injectate was deposited in the interfascial plane between the quadratus lumborum and psoas major muscles, posterior to the transversalis fascia. Primary outcome was opioid consumption, which was recorded electronically. Pain scores and time to first opioid request were also evaluated.ResultsOpioid consumption (oral morphine equivalents, OME) was significantly reduced in group ropivacaine (GRO) in the first 24 hours compared with group saline (65 mg OME vs 94 mg OME) with a mean difference of 29 mg OME; 95% CI 3 to 55, p<0.03. Time to first opioid request was significantly prolonged in GRO, p<0.003. Numerical rating scale pain scores were significantly lower in GRO in the first 6 hours after surgery, p<0.03.ConclusionsBilateral TQL block significantly reduced 24 hours’ opioid consumption. Further, we observed significant prolongation in time to first opioid, and significant reduction of pain during the first 6 postoperative hours.

Whether sympathetic activity influences cerebral blood flow (CBF) and oxygenation remains controversial. The influence of sympathetic activity on CBF and oxygenation was evaluated by the effect of phenylephrine on middle cerebral artery (MCA) mean flow velocity (Vmean) and the near-infrared spectroscopy-derived frontal lobe oxygenation (ScO2) at rest and during exercise. At rest, nine healthy male subjects received bolus injections of phenylephrine (0.1, 0.25, and 0.4 mg), and changes in mean arterial pressure (MAP), MCA Vmean, internal jugular venous O2 saturation (SjvO2), ScO2), and arterial PCO2 (PaCO2) were measured and the cerebral metabolic rate for O2 (CMRO2) was calculated. In randomized order, a bolus of saline or 0.3 mg of phenylephrine was then injected during semisupine cycling, eliciting a low (approximately 110 beats/min) or a high (approximately 150 beats/min) heart rate. At rest, MAP and MCA Vmean increased approximately 20% (P<0.001) and approximately 10% (P<0.001 for 0.25 mg of phenylephrine and P<0.05 for 0.4 mg of phenylephrine), respectively. ScO2 then decreased approximately 7% (P<0.001). Phenylephrine had no effect on SjvO2, PaCO2, or CMRO2. MAP increased after the administration of phenylephrine during low-intensity exercise (approximately 15%), but this was attenuated (approximately 10%) during high-intensity exercise (P<0.001). The reduction in ScO2 after administration of phenylephrine was attenuated during low-intensity exercise (-5%, P<0.001) and abolished during high-intensity exercise (-3%, P=not significant), where PaCO2 decreased 7% (P<0.05) and CMRO2 increased 17% (P<0.05). These results suggest that the administration of phenylephrine reduced ScO2 but that the increased cerebral metabolism needed for moderately intense exercise eliminated that effect.

Semaglutide is a human glucagon‐like peptide‐1 analog that has been co‐formulated with the absorption enhancer, sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate, for oral administration. This trial (NCT02016911) investigated whether hepatic impairment affects the pharmacokinetics, safety, and tolerability of oral semaglutide. Subjects were classified into groups: normal hepatic function (n = 24), and mild (n = 12), moderate (n = 12), or severe (n = 8) hepatic impairment according to Child‐Pugh criteria, and received once‐daily oral semaglutide (5 mg for 5 days followed by 10 mg for 5 days). Semaglutide plasma concentrations were measured during dosing and for up to 21 days post‐last dose. Area under the semaglutide plasma concentration–time curve from 0–24 hours after the 10th dose (primary end point) and maximum semaglutide concentration after the 10th dose appeared similar across hepatic function groups. Similarly, there was no apparent effect of hepatic impairment on time to maximum semaglutide concentration (median range 1.0–1.5 hours) or half‐life (geometric mean range 142–156 hours). No safety concerns were identified in subjects with hepatic impairment receiving semaglutide. Reported adverse events were in line with those observed for other glucagon‐like peptide‐1 receptor agonists. There was no apparent effect of hepatic impairment on the pharmacokinetics, safety, and tolerability of oral semaglutide. The results of this trial suggest that dose adjustment of oral semaglutide is not warranted in subjects with hepatic impairment.

Background: Percutaneous nephrolithotomy (PNL) is associated with severe postoperative pain. The current study aimed to investigate the analgesic efficacy of transmuscular quadratus lumborum (TQL) block for patients undergoing PNL surgery. Methods: Sixty patients were enrolled in this single centre study. The multimodal analgesic regime consisted of oral paracetamol 1 g and i.v. dexamethasone 4 mg before surgery and i.v. sufentanil 0.25 mg kg À1 30 min before emergence. After operation, patients received paracetamol 1 g regularly at 6 h intervals. Subjects were allocated to receive a preoperative TQL block with either ropivacaine 0.75%, 30 ml (intervention) or saline 30 ml (control). Primary outcome was oral morphine equivalent (OME) consumption 0e6 h after surgery. Secondary outcomes were OME consumption up to 24 h, pain scores, time to first opioid, time to first ambulation, and hospital length of stay. Results were reported as mean (standard deviation) or median (inter-quartile range). Results: Morphine consumption was lower in the intervention group at 6 h after surgery (7.2 [8.7] vs 90.6 [69.9] mg OME, P<0.001) and at 24 h (54.0 [36.7] vs 126.2 [85.5] mg OME, P<0.001). Time to first opioid use was prolonged in the intervention group (678 [285e1020] vs 36 [19e55] min, P<0.0001). Both the time to ambulation (302 [238e475] vs 595 [345e925] min, P<0.004) and length of stay (2.0 [0.8] vs 3.0 [1.2] days, P 0.001) were shorter in the intervention group. Conclusions: This is the first blinded, RCT that confirms that unilateral TQL block reduces postoperative opioid consumption and hospital length of stay. Further study is required for confirmation and dose optimisation. Clinical trial registration: NCT02818140.

Objective-Vitamin E, the most potent naturally occurring lipid soluble antioxidant has been suggested to possess both anti-inflammatory and analgesic activity in humans. This double blind and randomised study used a broad spectrum of clinical and laboratory parameters to investigate whether there was any additional anti-inflammatory or analgesic effects, or both, of orally administered -tocopherol in rheumatoid arthritis patients who were already receiving antirheumatic drugs. Methods-Forty two patients were enrolled and treated with -tocopherol (n=20) at a dose of 600 mg twice a day (2 × 2 capsules) or with placebo (n=22) for 12 weeks. The following parameters were measured: (1) Three clinical indices of inflammation-the Ritchie articular index, the duration of morning stiVness, and the number of swollen joints; (2) three measures of pain-pain in the morning, pain in the evening, and pain after chosen activity; (3) haematological and biochemical measures of inflammatory activity; (4) assays for the oxidative modification of proteins and lipids. Results-All laboratory measures of inflammatory activity and oxidative modification were unchanged. Furthermore, the clinical indices of inflammation were not influenced by the treatment. However, the pain parameters were significantly decreased after vitamin E treatment when compared with placebo. Conclusion-The results provide preliminary evidence that vitamin E may exert a small but significant analgesic activity independent of a peripheral antiinflammatory eVect, but which complements standard anti-inflammatory treatment.

BackgroundRobotic and hand-assisted laparoscopic nephrectomies are often associated with moderate to severe postoperative pain. The aim of the current study was to investigate the analgesic efficacy of the transmuscular quadratus lumborum (TQL) block for patients undergoing robotic or hand-assisted laparoscopic nephrectomy.MethodsFifty patients were included in this single-center study. All patients were scheduled for elective hand-assisted or robotic laparoscopic nephrectomy under general anesthesia. Preoperatively, patients were randomly allocated to TQL block bilaterally with ropivacaine 60 mL 0.375% or 60 mL saline and all patients received standard multimodal analgesia and intravenous patient-controlled analgesia. Primary outcome was postoperative oral morphine equivalent (OME) consumption 0–12 hours. Secondary outcomes were postoperative OME consumption up to 24 hours, pain scores, time to first opioid, nausea/vomiting, time to first ambulation and hospital length of stay (LOS).ResultsMean (95% CI) OME consumption was significantly lower in the intervention group at 12 hours after surgery 50 (28.5 to 71.5) mg versus control 87.5 (62.7 to 112.3) mg, p=0.02. At 24 hours, 69.4 (43.2 to 95.5) mg versus 127 (96.7 to 158.6) mg, p<0.01. Time to first opioid was significantly prolonged in the intervention group median (IQR) 4.4 (2.8–17.6) hours compared with 0.3 (0.1–1.0) hours in the control group, p<0.001. No significant intergroup differences were recorded for time to first ambulation, pain scores, nausea/vomiting nor for LOS.ConclusionPreoperative bilateral TQL block significantly reduced postoperative opioid consumption by 43% and significantly prolonged time to first opioid.Trial registration numberNCT03571490.

There was a slight non-statistically significant increase in semaglutide exposure when oral semaglutide was administered with omeprazole, but this is not considered clinically relevant and no dose adjustment is likely to be required.