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Background: Several retrospective studies suggest that perioperative care and anesthetic management for cancer resection may influence cancer recurrence or patient survival. Various intraoperative techniques such as paravertebral blocks, decreased opioid use, immunomodulation, and perioperative antiinflammatory administration, have previously been assessed for improved patient survival. The aim of this study was to assess associations between perioperative management and survival in patients undergoing resection of pancreatic adenocarcinoma. Methods: Survival data and anesthetic records for 144 patients who had surgical resection of pancreatic adenocarcinoma from 2001 to 2012 were obtained and associations were sought between survival and 19 predefined variables. The authors performed a propensity weighted multivariable statistical analysis using Cox proportional hazards. Results: Median length of survival was 562 days with 95% confidence interval (471, 680). In a multivariable Cox proportional hazard model of survival, the authors found increased survival in patients who received perioperative epidural analgesia and/or intraoperative dexamethasone. There was a 44% hazard ratio reduction, hazard ratio = 0.56, 95% confidence interval (0.38, 0.87), with dexamethasone. Adjuvant postoperative chemotherapy was associated with longer survival. A decrease in survival was noted in patients who received intraoperative blood transfusions, had poorer histologic grade, and advanced tumor stage. Conclusions: The authors report an association between perioperative dexamethasone administration and improved survival in human pancreatic adenocarcinoma patients. An association between use of epidural anesthesia during primary pancreatic cancer surgery and prolonged survival was also observed. Previously identified associations between perioperative blood transfusions and poor tumor histologic grade and decreased survival were confirmed. Further investigations regarding the use of perioperative dexamethasone and neuraxial anesthesia in this patient population are warranted.

Background A greater MAC fraction of nitrous oxide than isoflurane is required to prevent response to verbal commands and suppress the capacity to learn. Speculating that this difference between these agents may be caused by nitrous oxide's capacity to increase sympathetic activity, we tested the hypothesis that nitrous oxide may antagonize the suppression of learning found with isoflurane. Methods We administered a combination of isoflurane and nitrous oxide at three subanesthetic test concentrations (0.43, 0.56, and 0.68 MAC) to 24 healthy male volunteers. Assuming additivity of the anesthetics, the first test concentration was selected to suppress learning of new Information by 50% (ED50 for suppression of learning); the second concentration, to suppress the ability to respond appropriately to verbal command by 50% (MAC-awake); and the third, to provide 1.4 times MAC-awake. Three tests of learning were applied. At each test concentration, we provided 7 answers to “trivial pursuit”-type questions, resulting in a set of 21 answered questions for each volunteer; an additional 7 unanswered questions served as controls. At the highest test concentration, each volunteer also heard two examples from each of two categories (4 words) repeated 30 times (the category-example task), and a message instructing them to touch either their nose or their ear during a specified interval in the postanesthetic interview (the behavior task). Results The MAC-awake value for the combination of isoflurane and nitrous oxide was 118 ± 4% of the expected value (i.e., the two anesthetics were antagonistic for this effect). Consistent with antagonism, the anesthetic concentration predicted to suppress learning by 30% permitted significantly more learning, and the ED50 was 105 ± 2% of that predicted. Neither the category task nor the behavior task demonstrated evidence of learning at 1.4 times MAC-awake. Conclusions Our results are consistent with an antagonism between nitrous oxide and isoflurane; however, the degree of antagonism is small.

Previously, we found unconscious (implicit) learning in subjects given subanesthetic, but not anesthetic, concentrations of isoflurane. Other investigators, using different learning tasks, have reported implicit learning at anesthetic concentrations. We investigated whether one of these tasks might provide a more sensitive test of implicit learning. In addition, to determine whether suppression of explicit or implicit learning is dose-dependent, we studied one of the tasks at three subanesthetic concentrations.We applied a category-example task at 0.15, 0.28, and 0.4 minimum alveolar concentration (MAC) of isoflurane, and a behavior task only at 0.4 MAC. After anesthesia, we determined whether volunteers more frequently listed an example of a category (e.g., flute as an example of musical instrument) presented during anesthesia and/or demonstrated a behavior (touching ear, chin, or knee) suggested to them at 0.4 MAC.Results from the category task indicated implicit learning only at 0.15 MAC, a concentration that also permitted significant explicit learning. Explicit learning was demonstrated at 0.28 but not at 0.4 MAC (ED50 of 0.20 MAC and ED95 of 0.4 MAC). Results from the behavior task revealed neither implicit nor explicit learning.The ED50 that suppressed explicit learning in our volunteers equaled that previously reported (0.2 MAC) for implicit learning in volunteers measured using a different task. Combined, these results suggest that less than 0.45 MAC isoflurane suppresses learning in volunteers.

Background Suppression of response to command commonly indicates unconsciousness and generally occurs at anesthetic concentrations that suppress or eliminate memory formation. The authors sought midlatency auditory evoked potential indices that successfully differentiated wakeful responsiveness and unconsciousness. Methods The authors correlated midlatency auditory evoked potential indices with anesthetic concentrations permitting and suppressing response in 22 volunteers anesthetized twice (5 days apart), with desflurane or propofol. They applied stepwise increases of 0.5 vol% end-tidal desflurane or 0.5 microg/ml target plasma concentration of propofol to achieve sedation levels just bracketing wakeful response. Midlatency auditory evoked potentials were recorded, and wakeful response was tested by asking volunteers to squeeze the investigator's hand. The authors measured latencies and amplitudes from raw waveforms and calculated indices from the frequency spectrum and the joint time-frequency spectrogram. They used prediction probability (PK) to rate midlatency auditory evoked potential indices and concentrations of end-tidal desflurane and arterial propofol for prediction of responsiveness. A PK value of 1.00 means perfect prediction and a PK of 0.50 means a correct prediction 50% of the time (e.g., by chance). Results The approximately 40-Hz power of the frequency spectrum predicted wakefulness better than all latency or amplitude indices, although not all differences were statistically significant. The PK values for approximately 40-Hz power were 0.96 during both desflurane and propofol anesthesia, whereas the PK values for the best-performing latency and amplitude index, latency of the Nb wave, were 0.86 and 0.88 during desflurane and propofol (P = 0.10 for -40-Hz power compared with Nb latency), and for the next highest, latency of the Pb wave, were 0.82 and 0.84 (P < 0.05). The performance of the best combination of amplitude and latency variables was nearly equal to that of approximately 40-Hz power. The approximately 40-Hz power did not provide a significantly better prediction than anesthetic concentration; the PK values for concentrations of desflurane and propofol were 0.91 and 0.94. Changes of 40-Hz power values of 20% (during desflurane) and 16% (during propofol) were associated with a change in probability of nonresponsiveness from 50% to 95%. Conclusions The approximately 40-Hz power index and the best combination of amplitude and latency variables perform as well as predictors of response to command during desflurane and propofol anesthesia as the steady-state concentrations of these anesthetic agents. Because clinical conditions may limit measurement of steady-state anesthetic concentrations, or comparable estimates of cerebral concentration, the approximately 40-Hz power could offer advantages for predicting wakeful responsiveness.