[Cannabis-based medicines for chronic pain: indications, selection of drugs, effectiveness and safety : Experiences of pain physicians in Saarland]. / Cannabispräparate bei chronischen Schmerzen: Indikationen, Präparateauswahl, Wirksamkeit und Sicherheit : Erfahrungen der saarländischen Schmerztherapeuten.

BACKGROUND: There are uncertainties among physicians with respect to the indications, selection of drugs, effectiveness and safety of cannabis-based medicines for chronic pain. METHODS: All statutory health insurance pain physicians in Saarland were asked to complete a self-developed questionnaire assessing their experiences with cannabis-based medicines, which they prescribed between 10 March 2017 and 30 November 2018 for adult patients with chronic cancer and non-cancer pain. RESULTS: All statutory health insurance pain physicians participated in the survey and 13 out of 20 reported having prescribed cannabis-based medicines. The most frequent reasons for prescriptions in 136 patients (1.9% of the patients of the institutions) were failure of established treatment (73%) and desire of the patient (63%). In 35% of patients the type of pain was nociceptive, in 34% neuropathic, in 29% nociceptive and neuropathic and in 13% nociplastic. Dronabinol was prescribed for 95% of the patients and 71% were responders (clinically relevant reduction of pain or of other symptoms). In 29% of patients treatment was terminated due to either a lack of efficacy or adverse events. CONCLUSION: Statutory health insurance pain physicians in Saarland were reluctant to prescribe cannabis-based medicines. Dronabinol was effective and well-tolerated in the majority of the highly selected patients.

The attenuation of hepatic microcirculatory alterations by exogenous substitution of nitric oxide by s-nitroso-human albumin after hemorrhagic shock in the rat.

Hepatic microcirculatory disorders such as narrowing of sinusoids after hemorrhagic shock play a major role in the pathogenesis of organ failure. It is known that the balance of vasoactive mediators such as endothelin and nitric oxide (NO) regulate microvascular perfusion, including the diameter of hepatic sinusoids. The present study was designed to evaluate the role of exogenous substitution of NO by S-nitroso-albumin (S-NO-HSA) in the prevention of pathophysiological alterations of hepatic microcirculation. Anesthetized Sprague-Dawley rats were instrumented for invasive hemodynamic monitoring. Hemorrhagic shock was induced by bleeding to a mean arterial pressure (MAP) of 40 mmHg and was maintained for 60 min. Thereafter, the animals were resuscitated with shed blood and Ringer's solution. During the first hour of resuscitation, S-NO-HSA or pure HSA was infused continuously (10 micromol/kg/h) and hepatic microcirculation was detected by intravital epifluorescence microscopy either 5 or 24 h after the insult. Results were compared with a sham-treated group (n = 6-8 per group). Shock-induced microcirculatory narrowing of sinusoids was significantly reduced in the S-NO-HSA group compared with the HSA group both at 5 and 24 h (HSA: 9.3 +/- 0.2 microm; S-NO-HSA: 12.1 +/- 0.2 microm, P < 0.05). Sinusoidal perfusion was significantly higher in the S-NO-HSA group than in the HSA group (HSA: 50,934 +/- 1,382 microm3/s; S-NO-HSA: 78,120 +/- 2,348 microm3/s, P < 0.05). Reversible leukocyte adhesion to sinusoidal endothelium, an indicator of the inflammatory response, was significantly reduced in the S-NO-HAS-treated group. The findings of this study in a rat model of hemorrhagic shock suggest that NO substitution by S-NO-HSA during resuscitation attenuates both early and late hepatic microcirculatory disturbances as well as the increase in leukocyte adherence.