[Breakthrough pain and short-acting opioids]. / Durchbruchschmerzen und kurz wirksame Opioide.

Conventional opioid therapy consists of the regular administration of extended-release opioids following fixed time intervals and, as needed, the supplemental use of an immediate-release formulation. For the patient needs of such rescue medication, recent studies distinguished different scenarios, such as an inadequate daily opioid dose or time interval (end-of-dose failure) from so-called breakthrough pain where the attacks can suddenly occur either spontaneously (idiopathic pain) or due to certain provocations (incident pain) despite optimal dose adjustment. In line with this time course, a fast and short-lasting elevation of the opioid plasma concentration seems to be reasonable. Although in a recent European survey breakthrough pain attacks in the majority of cancer pain patients were sufficiently treated with immediate-release opioids, currently running clinical trials examine whether the application of transmucosal or intranasal fentanyl with their known reduced time to maximum plasma concentrations show a possible advantage in comparison to immediate-release opioids. In these clinical trials the pain intensity and number of pain episodes were significantly reduced following transmucosal or intranasal fentanyl; however, the magnitude of these effects does not convincingly appear to be clinically relevant. Among other reasons this may be related to the fact that those patients who would perhaps benefit from such treatment have not yet been identified.

[Clinical significance of the placebo effect]. / Klinische Bedeutung des Placeboeffektes.

Placebo controlled studies examining clinical problems, e.g. in pain therapy, are considered the "gold standard" for evidence-based medicine. In these studies the placebo effect itself is not the main focus of interest, but serves more as a control for the specificity of the effect of a certain treatment. What physicians in this context often do not realize is that the placebo effect itself represents a true measurable correlate of an organism's psycho-neurobiological response and, thereby, influences the healing process, e.g. the pain relief. Placebo is, therefore, not equivalent to "no treatment". The number of placebo responders, the degree and the duration of the placebo effect is not fixed, but are subject to a much greater variability then hitherto believed. The myth that placebo responders have a certain personality has not been proven correct; instead, the relationships between physicians and patients as well as sociocultural factors have a considerable impact on the placebo effect. Psychological theories explain that classical conditioning, enhanced expectation and motivation of the patient determine the degree of the placebo effect. These directly influence neurobiological systems such as the endogenous opioids which according to modern brain imaging are predominantly activated in pain-relevant areas and contribute to the effect of placebo analgesia. Placebo effects that should be deliberately excluded in controlled clinical trials, can be desirable in clinical practice to optimize the total therapeutic effect. This should mean that the context effect of each therapeutic intervention is maximized towards an improved therapeutic effect, as outlined in the recent AWMF guidelines for postoperative pain therapy, but should not include the administration of an inert substance. The latter is controlled by rigorous ethical guidelines and is only permitted in the context of ethically approved controlled clinical trials. A possible alternative is suggested by Benedetti et al. in which the hidden administration of an active substance identifies the specific response in contrast to the open application of the same substance characterizing the specific plus the placebo effect, after which the pure placebo effect can be determined.

[Potential applications and significance of peripheral opioid analgesia]. / Anwendungsmöglichkeiten und Stellenwert der peripheren Opioidanalgesie.

Recently, the local application of analgesic substances has attracted much interest and has become increasingly relevant in daily clinical practice. The lack of the well-known therapy-limiting central side effects of systemically administered opioids is a clear advantage of "peripheral opioid analgesia". Important prerequisites for the occurrence of peripheral analgesic effects of opioids are good accessibility of the painful site, presence of clinically relevant pain, signs of a local inflammation, exclusion of a fast systemic absorption, and adequately potent analgesic substances. This review gives an outline of recent experience with various clinical applications of "peripheral opioid analgesia".

[Hydrofluoric acid burns. A rare chemical emergency situation]. / Verätzung mit Flusssäure. Ein seltener chemischer Notfall.

Burns caused by hydrofluoric acid can be life-threatening. Of special significance is the often underestimated local and sometimes delayed deep action of the highly diffusible free fluoride ions and the accompanying systemic toxicity. The specific antidote calcium gluconate can be topically applied, injected into tissue or infused intra-arterially. Because of the extreme danger of systemic toxicity even after seemingly trivial injuries, monitoring in the intensive care station, especially by measuring the calcium concentration in blood and electrocardiography, and therapy is recommended.