Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP])-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A receptor blockade and [cAMP] elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP] and adenosine receptor blockade play a role in this response. Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia.

Background: Thoracic paravertebral blockade is an accepted anesthetic and analgesic technique for breast surgery. However, real-time ultrasound visualization of landmarks in the paravertebral space remains challenging. We aimed to compare ultrasound-image quality, performance times, and clinical outcomes between the traditional parasagittal ultrasound-guided paravertebral block and a modified approach, the ultrasound-guided proximal intercostal block. Methods: Women with breast cancer undergoing mastectomy (n = 20) were randomized to receive either paravertebral (n = 26) or proximal intercostal blocks (n = 32) under ultrasound-guidance with 2.5 mg/kg ropivacaine prior to surgery. Block ultrasound images before and after needle placement, and anesthetic injection videoclips were saved, and these images and vidoes independently rated by separate novice and expert reviewers for quality of visualization of bony elements, pleura, relevant ligament/membrane, needle, and injectate spread. Block performance times, postoperative pain scores, and opioid consumption were also recorded. Results: Composite visualization scores were superior for proximal intercostal compared to paravertebral nerve block, as rated by both expert (p = 0.008) and novice (p = 0.01) reviewers. Notably, both expert and novice rated pleural visualization superior for proximal intercostal nerve block, and expert additionally rated bony landmark and injectate spread visualization as superior for proximal intercostal block. Block performance times, needle depth, opioid consumption and postoperative pain scores were similar between groups. Conclusions: Proximal intercostal block yielded superior visualization of key anatomical landmarks, possibly offering technical advantages over traditional paravertebral nerve block. Trial registration: ClinicalTrials.gov, NCT02911168. Registred on the 22nd of September 2016.