Stability evaluation of morphine, hydromorphone, metamizole and esketamine containing analgesic mixtures applied for patient-controlled analgesia in hospice and palliative care.

In this study, different injection solutions containing opioid and nonopioid compounds used for patient-controlled analgesia in hospice and palliative care were evaluated in terms of analyte stability. Investigated injection solutions contained different combinations of morphine, hydromorphone, metamizole and esketamine. For the practical implementation, samples from infusion pumps were daily drawn over a period of 7 days at 22 and 37°C. Quantitative measurements were performed on a high-performance liquid chromatography system with ultraviolet detection applying a validated analytical method. All compounds apart from morphine showed no evident changes in concentration. However, a significant loss of morphine was observed for injection mixtures containing both morphine and metamizole at 37°C. After 7 days, only 72% of the initially measured morphine concentration was measured in the binary and 77% in the ternary mixture. Furthermore, an additional compound was detected that could represent the morphine-metamizole-adduct, "metamorphine". Based on these results, a significantly reduced morphine concentration must be expected after only 3 days if an injection solution mixture containing both morphine and metamizole is administered to a patient at 37°C. Since the analgesic effects of morphine-metamizole adducts have not yet been thoroughly investigated, further clinical studies are necessary before accurate conclusions can be drawn in this regard.

The impact of cannabinoids on methemoglobin formation and hemoglobin oxygen affinity: An ex-vivo study.

The affinity of hemoglobin (Hb) to oxygen (O2) influences processes of oxygen delivery and extraction at the tissue level. Despite cannabinoids being utilized or ingested in various ways, their possible impact on Hb-O2 affinity has barely been studied. This is an experimental ex-vivo trial. Venous blood samples were drawn from 5 male and 6 female healthy volunteers and subsequently exposed to different cannabinoid types: (delta-9-tetrahydrocannabinol [Δ9-THC], delta-8-tetrahydrocannabinol [Δ8-THC], cannabidiol [CBD]) at different concentrations. Oxygen dissociation curves (ODC) were measured and blood gas analyses were performed for methemoglobin (MetHb) determination. The results revealed no MetHb formation. Besides two statistically significant changes (+1.4 mmHg and -0.9 mmHg) in the female cohort, following Δ9-THC and Δ8-THC exposure, no further P50 changes could be observed. The study demonstrated an in-vitro effect of selected cannabinoids and dosages on P50 values in female participants, with variations not observed at other dosages, leaving the underlying mechanisms open for debate. MetHb formation, as potential mechanism, was not detected in this study. The precise reasons why changes only occurred at specific dosages remain unclear, indicating a need for further in-vivo research to understand the interaction between cannabinoids and Hb-O2 affinity completely.

Pain in Multiple System Atrophy a Systematic Review and Meta-Analysis.

Background: Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA. Objectives: Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: "pain," "multiple system atrophy," "MSA," "olivopontocerebellar atrophy," "OPCA," "striatonigral degeneration," "SND," "Shy Drager," and "atypical parkinsonism." Results: The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%-75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%-87%] vs. 45% [95% CI = 33%-57%], P = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment. Conclusions: We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA.

The impact of dexamethasone as a perineural additive to ropivacaine for PECS II blockade in patients undergoing unilateral radical mastectomy - A prospective, randomized, controlled and double-blinded trial.

STUDY OBJECTIVE: Dexamethasone is commonly used as an adjuvant to local anesthetics to prolong duration of peripheral nerve blocks with minimal side-effects. The present study investigates the efficacy of dexamethasone added to ropivacaine 0.2% as compared to ropivacaine 0.2% alone for pectoral nerves block II (PECS II) in unilateral radical mastectomy. DESIGN: A prospective, randomized, controlled and double-blinded trial. SETTING: The study was performed at Innsbruck Medical University Hospital, Austria, between January 2019 and October 2020. PATIENTS: Sixty female patients with an American Society of Anesthesiologists Score I-II (18-90 years, BMI 18-35) scheduled for unilateral radical mastectomy without one-stage immediate autologous breast reconstruction were randomly assigned to receive PECS II block with ropivacaine 0.2% with or without dexamethasone 8 mg. INTERVENTIONS: Patients were randomly assigned to receive PECS II block with ropivacaine 0.2% with or without dexamethasone 8 mg. MEASUREMENTS: Primary outcome parameter was the cumulative opioid consumption during the first 72 postoperative hours. Secondary outcome parameters were the duration of analgesia and the course of the visual analogue scale (VAS) and the area under the curve VAS (AUC-VAS). MAIN RESULTS: There was no difference in cumulative opioid consumption after 72 h between the ropivacaine 0.2% plus dexamethasone group and the ropivacaine 0.2% plus placebo group (11.89 vs 11.90 morphine milligram equivalent, respectively; p 0.831). Duration of analgesia also did not differ significantly between the ropivacaine 0.2% plus dexamethasone group and the ropivacaine 0.2% plus placebo group (12.75 versus 8.75 h, respectively; p 0.680). There also was no difference in the course of VAS and AUC-VAS. CONCLUSIONS: Dexamethasone 8 mg when added to ropivacaine 0.2% for PECS II block in unilateral radical mastectomy was not found to reduce total opioid consumption over 72 postoperative hours or to prolong duration of analgesia as compared to pure ropivacaine 0.2%.

Intercostal Catheters for Postoperative Pain Management in VATS Reduce Opioid Consumption.

BACKGROUND: Postoperative pain after video-assisted thoracoscopic surgery (VATS) affects patients' recovery, postoperative complications, and length of stay (LOS). Despite its relevance, there are no guidelines on optimal perioperative pain management. This study aims to analyse the effects of an additional intercostal catheter (ICC) in comparison to a single shot intraoperative intercostal nerve block (SSINB). METHODS: All patients receiving an anatomic VATS resection between June 2019 and May 2020 were analysed retrospectively. The ICC cohort included 51 patients, the SSINB cohort included 44 patients. RESULTS: There was no difference in age, gender, comorbidities, or duration of surgery between cohorts. Pain scores on the first postoperative day, after chest drain removal, and highest pain score measured did not differ between groups. The overall amount of opioids (morphine equivalent: 3.034 mg vs. 7.727 mg; p = 0.002) as well as the duration of opioid usage (0.59 days vs. 1.25 days; p = 0.005) was significantly less in the ICC cohort. There was no difference in chest drain duration, postoperative complications, and postoperative LOS. CONCLUSIONS: Pain management with ICC reduces the amount of opioids and number of days with opioids patients require to achieve sufficient analgesia. In conclusion, ICC is an effective regional anaesthesia tool in postoperative pain management in minimally invasive thoracic surgery.

Continuous Wound Infiltration After Hallux Valgus Surgery.

BACKGROUND: Hallux valgus surgery is associated with significant early postoperative pain. The aim of this study was to investigate the use of continuous wound infiltration (CWI) with ropivacaine for pain management after hallux valgus surgery. METHODS: In this prospective, randomized, double-blind, and placebo-controlled single-center trial, 50 patients undergoing distal metatarsal osteotomy for idiopathic hallux valgus were allocated to CWI with ropivacaine 2 mg/mL at a rate of 2 mL/h or placebo for 24 hours postoperatively. Average and peak pain levels on the verbal numeric rating scale (NRS; 1-10) during the first 48 hours after surgery were recorded as primary outcome parameters. Secondary outcome parameters included consumption of narcotics, clinical outcome, incidence of postoperative complications, and patient satisfaction. RESULTS: No significant difference in mean ( P = .596) and peak ( P = .353) postoperative pain level was found for CWI with either ropivacaine (mean NRS 1.9 ± 0.8; peak NRS 3.5 ± 2.0) or placebo (mean NRS 2.0 ± 0.7; peak NRS 3.9 ± 1.7) during the early postoperative course. Furthermore, no significant difference between both groups was detected regarding narcotic consumption ( P = .354) and all other secondary outcome parameters. Two severe complications (local dysesthesia with CWI, catheter accidentally fixed by a suture) and 5 catheter dislocations were observed. CONCLUSION: CWI with ropivacaine 2 mg/mL at a rate of 2 mL/h for 24 hours after hallux valgus surgery did not reduce postoperative pain level in an inpatient setting. LEVEL OF EVIDENCE: Level I, prospective randomized trial.

Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects.

Transmeatal cochlear laser (TCL) treatment has recently been proposed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. The aim of this study was to investigate whether TLC has any influence on the central nervous system using functional MRI with healthy young adults. The laser stimulation device was placed on the tympanic membrane of both ears. A laser stimulation run and a placebo run were performed in random order. The participants were unable to differentiate between verum and placebo stimulation. In the comparison of verum to placebo runs, we observed significant activations within the left superior frontal gyrus, the right middle and medial frontal gyrus, the right superior parietal lobule, the left superior occipital gyrus, the precuneus and cuneus bilaterally, the right anterior and the left and right middle and posterior cingulate gyrus and the left thalamus. This network of brain areas corresponds well to results from previous PET studies of patients with tinnitus. Though TCL seems to have a clinically measurable effect on the central nervous system the neurophysiological mechanism leading to the observed activated neuronal network remains unknown.

Mechanism of neopterin-induced myocardial dysfunction in the isolated perfused rat heart.

Neopterin is a sensitive marker for diseases involving increased activity of the cellular immune system in humans. Many studies, however, provide evidence for neopterin not only as a marker, but also for its characteristic effects. Recently, we were able to demonstrate a considerable influence of exogenous neopterin at a concentration of 100 mumol/l on cardiac performance in the Langendorff model of isolated perfused rat hearts. The present study was designed to investigate its possible mechanism. During co-infusion of neopterin at a concentration of 100 mumol/l with the unspecific nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine monoacetate, the nitric oxide donor PAPA NONOate, the free radical scavenger N-acetylcysteine, or the pro-inflammatory cytokine tumor necrosis factor-alpha the effects on cardiac contractility parameters and coronary vascular resistance were studied in 67 male Sprague-Dawley rats. The temperature-controlled and pressure-constant Langendorff apparatus was used with retrograde perfusion of the aorta and a Krebs-Henseleit buffer. Neither the unspecific nitric oxide synthase inhibitor nor the nitric oxide donor excludes nitric oxide from playing a mechanistic role in our perfusion studies. Tumor necrosis factor-alpha was without any synergistic or antagonistic effects when co-treated with neopterin. N-acetylcysteine was most effective in abolishing neopterin-dependent effects on cardiac function. The negative effects of neopterin on cardiac performance might be due to an enhancement of oxidative stress by neopterin that can be attenuated by the antioxidant N-acetylcysteine. Neopterin has to be considered a pathogenic factor in the development of cardiac dysfunction in chronic disease states with high neopterin levels secondary to activation of the immune system.

Functional magnetic resonance imaging detects activation of the visual association cortex during laser acupuncture of the foot in humans.

The aim of this study was to investigate the effect of laser acupuncture on cerebral activation. Using functional magnetic imaging (fMRI) cortical activations during laser acupuncture at the left foot (Bladder 67) and dummy acupuncture, were compared employing a block design in ten healthy male volunteers. All experiments were done on a 1.5 Tesla magnetic resonance scanner equipped with a circular polarized head coil. During laser acupuncture, we found activation in the cuneus corresponding to Brodmann Area (BA) 18 and the medial occipital gyrus (BA 19) of the ipsilateral visual cortex. Placebo stimulation did not show any activation. We could demonstrate that laser acupuncture of a specific acupoint, empirically related to ophthalmic disorders, leads to activation of visual brain areas, whereas placebo acupuncture does not. These results indicate that fMRI has the potential to elucidate effects of acupuncture on brain activity.

Frameless stereotactic cannulation of the foramen ovale for ablative treatment of trigeminal neuralgia.

OBJECTIVE: Ablative neurosurgical treatment of trigeminal neuralgia, including percutaneous radiofrequency thermocoagulation, requires cannulation of the foramen ovale. To maximize patient security and cannulation success, a frameless stereotactic system was evaluated in a phantom study, a cadaveric study, and a preliminary clinical trial. METHODS: Frameless stereotaxy using an optical navigation system, an aiming device, and a noninvasive vacuum mouthpiece-based registration and patient fixation technique was used for the targeting of a test body based on 1-, 3-, and 5-mm axial computed tomographic slices and of the foramen ovale in three cadavers and 15 patients based on 3-mm axial computed tomographic slices. RESULTS: The mean normal (x/y) localization accuracy/standard deviation (n = 360) was 1.31/0.67 mm (1-mm slices), 1.38/0.65 mm (3-mm slices), and 1.84/0.96 mm (5-mm slices). Significantly better results were achieved with 1- and 3-mm slices when compared with 5-mm slices (P < 0.001). The foramen ovale (3 x 6 mm) was successfully cannulated at the first attempt in all cadavers and patients, which indicates clinical localization accuracies better than 1.5 mm in the anteroposterior and 3 mm in the medial-lateral directions. CONCLUSION: Based on the noninvasive Vogele-Bale-Hohner vacuum mouthpiece, there is no need for invasive head clamp fixation. Imaging, real laboratory simulation, and the actual surgical intervention can be separated in time and location. The presented data suggest that frameless stereotaxy is a predictable and reproducible procedure, which may enhance patient security and cannulation success independent of the surgeon's experience.

Laser acupuncture induced specific cerebral cortical and subcortical activations in humans.

As recent studies demonstrated, acupuncture can elicit activity in specific brain areas. This study aims to explore further the central effect using laser acupuncture. We investigated the cerebral effects of laser acupuncture at both acupoints GB43 with functional magnetic resonance imaging (fMRI). As a control condition the laser was mounted at the same acupoints but without application of laser stimulation. The group results showed significant brain activations within the thalamus, nucleus subthalamicus, nucleus ruber, the brainstem, and the Brodmann areas 40 and 22 for the acupuncture condition. No significant brain activations were observed within the placebo condition. The activations we observed were laser acupuncture-specific and predominantly ipsilateral. This supports the assumption that acupuncture is mediated by meridians, since meridians do not cross to the other side. Furthermore, we could show that laser acupuncture allows one to design a pure placebo condition.

Korean hand acupressure reduces postoperative nausea and vomiting after gynecological laparoscopic surgery.

UNLABELLED: To investigate the effectiveness of prophylactic Korean hand acupressure in the prevention of postoperative vomiting in women scheduled for minor gynecological laparoscopic surgery, we conducted a double-blinded, randomized, placebo-controlled study. In one group (n = 40), acupressure was performed 30 min before the induction of anesthesia by using special acupressure seeds, which were fixed onto the Korean hand acupuncture point K-K9 and remained there for at least 24 h. The second group (n = 40) functioned as the Placebo group. The treatment groups did not differ with regard to demographics, surgical procedure, or anesthetic administered. In the Acupressure group, the incidence of nausea and vomiting was significantly less (40% and 22.5%) than in the Placebo group (70% and 50%). We conclude that Korean hand acupressure of the acupuncture point K-K9 is an effective method for reducing postoperative nausea and vomiting in women after minor gynecological laparoscopic surgery. IMPLICATIONS: This randomized study was performed to investigate the antiemetic effect of the Korean hand acupuncture point K-K9. Acupressure of K-K9 reduces the incidence of postoperative nausea and vomiting in female patients after minor gynecological laparoscopic surgery.