S(+)-ketamine, the pure dextrorotatory enantiomer of ketamine has been available for clinical use in analgesia and anesthesia for more than 25 years. The main effects are mediated by non-competitive inhibition of the N-methyl-D-aspartate (NMDA) receptor but S(+)-ketamine also interacts with opioid receptors, monoamine receptors, adenosine receptors and other purinergic receptors. Effects on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, metabotropic glutamate receptors (mGluR) and L‑type calcium chanels have also been described. S(+)-ketamine stimulates the sympathetic nerve system, making it an ideal drug for analgosedation or induction of anesthesia in instable patients. In addition, the neuroprotective properties, bronchodilatory, antihyperalgesic or antiepileptic effects provide interesting therapeutic options. In this article we discuss the numerous effects of S(+)-ketamine under pharmacological and clinical aspects especially for typical indications in emergency medicine as well as intensive care.

Introduction Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. Methods A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS—needle electrodes) and transcutaneous (tVNS—surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. Results A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges’ g/mean difference of − 1.95 (95% confidence interval [CI]: − 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (− 5.40 [− 8.94; − 1.85] vs. − 1.00 [− 1.55; − 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with − 0.70 [− 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12 months was shown. Overall, aVNS was very well tolerated. Conclusion This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes.

Additional benefits of passive exposures to intermittent hypoxia and hyperoxia on cognitive performance and functional exercise capacity have been demonstrated in geriatric patients who performed a multimodal training program. The main goal of the present study was to evaluate effects of adding intermittent hypoxic-hyperoxic training (IHHT) to a multimodal training intervention (MTI) on mobility and perceived health in old individuals at a Geriatric Day Hospital. Thirty-four patients between 64 and 92 years participated in the double blind, randomized and controlled clinical trial. The elderly patients attended in a 5–7 weeks lasting MTI (strength, endurance, balance, reaction, flexibility, coordination, and cognitive exercises) and performed IHHT (breathing 10–14% oxygen for 4–7 min followed by 2–4 min 30–40% oxygen) in the Hypoxic Group (HG) or placebo treatment with ambient air in the Normoxic Group (NG) in parallel. Before and after all treatments, mobility was assessed by the Tinetti Mobility Test (TMT), the Timed-Up-and-Go Test (TUG) and Barthel-Index, while perceived health was assessed by one part of the EQ-5D Test, the EQ visual analogue scale (EQ VAS). After the MTI plus IHHT or normoxia sessions, results of the TMT, TUG, Barthel Index and EQ-VAS revealed no significant difference between HG and NG (+ 14.9% vs + 15.4%, p = 0.25; − 21% vs − 26.3%, p = 0.51; + 4.2% vs + 3.6%, p = 0.56; + 37.9% vs + 33.9%, p = 0.24;). IHHT added to MTI did not elicit additional improvements in perceived health and mobility compared to MTI alone.

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC. Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive. Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.

Zusammenfassung Trotz aller positiven Entwicklungen wird postoperativen Schmerzen und ihrer Behandlung nach wie vor nicht immer die notwendige Aufmerksamkeit geschenkt. Starke Schmerzen nach chirurgischen Eingriffen betreffen einen erheblichen Anteil der Patienten. Diese Tatsache wirkt sich nicht nur auf den unmittelbaren Rekonvaleszenzprozess negativ aus, sondern kann auch die Grundlage für eine Schmerzchronifizierung bilden. Ein adäquates und effektives Management perioperativer Schmerzen erfordert geeignete organisatorische Strukturen. Das vorliegende multidisziplinäre Positionspapier, das die Österreichische Gesellschaft für Anästhesiologie, Reanimation und Intensivmedizin und die Österreichische Schmerzgesellschaft initiiert und gemeinsam mit zahlreichen mit der Thematik befassten Fachgesellschaften und Berufsverbänden entwickelt haben, soll dabei unterstützen, das perioperative Schmerzmanagement optimal zu gestalten und bewährte Konzepte zu nutzen. Ergänzende Empfehlungen beschreiben Besonderheiten der perioperativen Schmerztherapie bei ausgewählten Eingriffsarten.