Alveolar hyperinflation in patients with focal ARDS ventilated with the ARDSnet protocol is attenuated by a physiologic approach to PEEP setting based on the stress index measurement.

1 Tramadol is a centrally acting analgesic with low opioid receptor affinity and therefore presumably other mechanisms of analgesic action. Tramadol inhibits noradrenaline uptake but since 5-hydroxytryptamine (5-HT) is also involved in the modulation of pain perception, we tested the effects of tramadol on 5-HT uptake and release in vitro. 2 Tramadol inhibited the uptake of [3H]-5-HT into purified rat frontal cortex synaptosomes with an IC50 of 3.1 pm. The (+)-enantiomer was about four times more potent than the (-)-enantiomer; the main metabolite of tramadol, O-desmethyltramadol, was about ten times less potent. 3 Rat frontal cortex slices were preincubated with [3H]-5-HT, then superfused anA stimulated electrically. Tramadol facilitated the basal outflow of [3H]-5-HT, at concentrations greater than 1 pm, while the uptake inhibitor 5-nitroquipazine enhanced both basal and stimulation-evoked overflow. Effects of the (+)-enantiomer were more potent than either the racemate, the (-)-enantiomer or the principal metabolite. 4 The effects of tramadol on the basal outflow of [3H]-5-HT were almost completely abolished when the superfusion medium contained a high concentration of the selective 5-HT uptake blocker, 6-nitroquipazine.5 The results provide evidence for an interaction of tramadol with the neuronal 5-HT transporter. An intact uptake system is necessary for the enhancement of extraneuronal 5-HT concentrations by tramadol indicating an intraneuronal site of action.

1 The centrally acting analgesic, tramadol, has low affinity for opioid receptors and therefore presumably other mechanisms of analgesic action. Neurotransmitter release and uptake experiments were used to characterize the effects of tramadol on the central noradrenergic and dopaminergic systems. 2 Tramadol inhibited the uptake of [3H]-noradrenaline into purified rat hypothalamic synaptosomes with an IC50 of 2.8 pM; the (-)-enantiomer was about ten times more potent than the (+)-enantiomer. Results with the principal metabolite 0-desmethyltramadol were very similar. Inhibition of dopamine uptake into purified rabbit caudate nucleus synaptosomes was very weak with 62% inhibition at 100 tiM. 3 Rat occipital cortex slices were preincubated with [3H]-noradrenaline and rabbit caudate nucleus slices with [3H]-dopamine, then superfused and stimulated electrically. Tramadol, 1 and 10 SAM, enhanced the stimulation-evoked [3H]-noradrenaline overflow by 25 and 69%, respectively; the (-)-enantiomer was more potent than the racemate or the (+ )-enantiomer. Tramadol, 10 1M, had no effect on dopamine release. 4 The effects of tramadol on the stimulation-evoked [3H]-noradrenaline release were abolished when uptake sites were already blocked by a high concentration of cocaine. 5 The metabolite 0-desmethyltramadol showed a slight facilitation of the stimulation-evoked noradrenaline release; the effect was more pronounced in the presence of a high concentration of naloxone. In the presence of cocaine, inhibition of the release was observed similar to the effect of morphine but less potent. 6 The results show that tramadol blocks noradrenaline uptake with selectivity as compared to dopamine uptake. The interaction with the noradrenaline transporter is stereoselective. The principal metabolite 0-desmethyltramadol shows in addition to noradrenaline uptake inhibition, opioid inhibition of noradrenaline release.

In isoflurane-anesthetized dogs, mechanical ventilation with 40% oxygen appeared to maintain significantly better lung aeration and gas exchange than ventilation with 100% oxygen.