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Dexmedetomidine-Mediated Prevention of Renal Ischemia-Reperfusion Injury Depends in Part on Cholinergic Anti-Inflammatory Mechanisms

期刊: ANESTHESIA AND ANALGESIA, 2020; 130 (4)

BACKGROUND: Organ ischemia-reperfusion injury often induces local and systemic inflammatory responses, which in turn worsen organ injury. These inflammatory responses can be regulated by the central nervous system, particularly by the vagal nerve and nicotinic acetylcholine receptors, which are the key components of cholinergic anti-inflammatory pathway. Activation of the cholinergic anti-inflammatory pathway can suppress excessive inflammatory responses and be a potential strategy for prevention of ischemia-reperfusion injury of organs including the kidney. METHODS: Vagal nerve activity, plasma acetylcholine, catecholamine and inflammatory mediators, renal tissue injury, and cell death were measured in mice with bilateral renal ischemia/reperfusion with or without treatment with dexmedetomidine (Dex), an alpha(2)-adrenergic receptor agonist. RESULTS: Dex significantly increased the discharge frequency of the cervical vagal nerve by up to 142 Hz (mean) (P < .001), and preserved kidney gross morphology and structure and attenuated cell apoptosis after ischemia-reperfusion. Furthermore, Dex also significantly increased acetylcholine release to 135.8 pmol/L (median) when compared to that (84.7 pmol/L) in the sham group (P < .001) and reduced the levels of several inflammatory mediators induced by renal ischemia/reperfusion. All the effects were abolished by vagotomy, splenectomy, or combinative administration of atipamezole, an alpha(2)-adrenergic receptor antagonist. CONCLUSIONS: Our findings suggest that Dex provides renoprotection, at least in part, through anti-inflammatory effects of the parasympathetic nervous system activation in addition to its direct actions on alpha(2)-adrenergic receptors.

Evaluating Propofol Concentration in Blood From Exhaled Gas Using a Breathing-Related Partition Coefficient

期刊: ANESTHESIA AND ANALGESIA, 2020; 130 (4)

BACKGROUND: The anesthetic side effects of propofol still occur in clinical practice because no reliable monitoring techniques are available. In this regard, continuous monitoring of propofol in breath is a promising method, yet it remains infeasible because there is large variation in the blood/exhaled gas partial pressure ratio (R-BE) in humans. Further evaluations of the influences of breathing-related factors on R-BE would mitigate this variation. METHODS: Correlations were analyzed between breathing-related factors (tidal volume [TV], breath frequency [BF], and minute ventilation [V-M]) and R-BE in 46 patients. Furthermore, a subset of 10 patients underwent pulmonary function tests (PFTs), and the parameters of the PFTs were then compared with the R-BE. We employed a 1-phase exponential decay model to characterize the influence of V-M on R-BE. We also proposed a modified R-BE (R-DCM) that was not affected by the different breathing patterns of the patients. The blood concentration of propofol was predicted from breath monitoring using R-BEM and R-BE. RESULTS: We found a significant negative correlation (R = -0.572; P < .001) between V-M and R-BE (N = 46). No significant correlation was shown between PFTs and R-BE in the subset (N = 10). R-BEM demonstrated a standard Gaussian distribution (mean, 1.000; standard deviation [SD], 0.308). Moreover, the predicted propofol concentrations based on breath monitoring matched well with the measured blood concentrations. The 90% prediction band was limited to within +/- 1 mu g.mL(-1). CONCLUSIONS: The prediction of propofol concentration in blood was more accurate using R-BEM than when using R-BE and could provide reference information for anesthesiologists. Moreover, the present study provided a general approach for assessing the influence of relevant physiological factors and will inform noninvasive and accurate breath assessment of volatile drugs or metabolites in blood.

Positive End-Expiratory Pressure During Anesthesia for Prevention of Postoperative Pulmonary Complications: A Meta-analysis With Trial Sequential Analysis of Randomized Controlled Trials

期刊: ANESTHESIA AND ANALGESIA, 2020; 130 (4)

BACKGROUND: Whether intraoperative positive end-expiratory pressure (PEEP) can reduce the risk of postoperative pulmonary complications remains controversial. We performed a systematic review of currently available literature to investigate whether intraoperative PEEP decreases pulmonary complications in anesthetized patients undergoing surgery. METHODS: We searched PubMed, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) that compared intraoperative PEEP versus zero PEEP (ZEEP) for postoperative pulmonary complications in adults. The prespecified primary outcome was postoperative pulmonary atelectasis. RESULTS: Fourteen RCTs enrolling 1238 patients met the inclusion criteria. Meta-analysis using a random-effects model showed a decrease in postoperative atelectasis (relative risk [RR], 0.51; 95% confidence interval [CI], 0.35-0.76; trial sequential analyses [TSA]-adjusted CI, 0.10-2.55) and postoperative pneumonia (RR, 0.48; 95% CI, 0.27-0.84; TSA-adjusted CI, 0.05-4.86) in patients receiving PEEP ventilation. However, TSA showed that the cumulative Z-curve of 2 outcomes crossed the conventional boundary but did not cross the trial sequential monitoring boundary, indicating a possible false-positive result. We observed no effect of PEEP versus ZEEP ventilation on postoperative mortality (RR, 1.78; 95% CI, 0.55-5.70). CONCLUSIONS: The evidence that intraoperative PEEP reduces postoperative pulmonary complications is suggestive but too unreliable to allow definitive conclusions to be drawn.

Low Tidal Volumes Are Associated With Slightly Improved Oxygenation in Patients Having Cardiac Surgery: A Cohort Analysis

期刊: ANESTHESIA AND ANALGESIA, 2020; 130 (5)

BACKGROUND: Mechanical ventilation with low tidal volumes appears to provide benefit in patients having noncardiac surgery; however, whether it is beneficial in patients having cardiac surgery is unclear. METHODS: We retrospectively examined patients having elective cardiac surgery requiring cardiopulmonary bypass through a median sternotomy approach who received mechanical ventilation with a single lumen endotracheal tube from January 2010 to mid-August 2016. Time-weighted average tidal volume (milliliter per kilogram predicted body weight [PBW]) during the duration of surgery excluding cardiopulmonary bypass was analyzed. The association between tidal volumes and postoperative oxygenation (measured by arterial partial pressure of oxygen (Pao(2))/fraction of inspired oxygen ratio [Pao(2)/Fio(2)]), impaired oxygenation (Pao(2)/Fio(2) <300), and clinical outcomes were examined. RESULTS: Of 9359 cardiac surgical patients, larger tidal volumes were associated with slightly worse postoperative oxygenation. Postoperative Pao(2)/Fio(2) decreased an estimated 1.05% per 1 mL/kg PBW increase in tidal volume (97.5% confidence interval [CI], -1.74 to -0.37; P-Bon = .0005). An increase in intraoperative tidal volumes was also associated with increased odds of impaired oxygenation (odds ratio [OR; 97.5% CI]: 1.08 [1.02-1.14] per 1 mL/kg PBW increase in tidal volume; P-Bon = .0029), slightly longer intubation time (5% per 1 mL/kg increase in tidal volume (hazard ratio [98.33% CI], 0.95 [0.93-0.98] per 1 mL/kg PBW; P-Bon < .0001), and increased mortality (OR [98.33% CI], 1.34 [1.06-1.70] per 1 mL/kg PBW increase in tidal volume; P-Holm = .0144). An increase in intraoperative tidal volumes was also associated with acute postoperative respiratory failure (OR [98.33% CI], 1.16 [1.03-1.32] per 1 mL/kg PBW increase in tidal volume; P-Holm = .0146), but not other pulmonary complications. CONCLUSIONS: Lower time-weighted average intraoperative tidal volumes were associated with a very modest improvement in postoperative oxygenation in patients having cardiac surgery.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on the Role of Neuromonitoring in Perioperative Outcomes: Electroencephalography

期刊: ANESTHESIA AND ANALGESIA, 2020; 130 (5)

Electroencephalographic (EEG) monitoring to indicate brain state during anesthesia has become widely available. It remains unclear whether EEG-guided anesthesia influences perioperative outcomes. The sixth Perioperative Quality Initiative (POQI-6) brought together an international team of multidisciplinary experts from anesthesiology, biomedical engineering, neurology, and surgery to review the current literature and to develop consensus recommendations on the utility of EEG monitoring during anesthesia. We retrieved a total of 1023 articles addressing the use of EEG monitoring during anesthesia and conducted meta-analyses from 15 trials to determine the effect of EEG-guided anesthesia on the rate of unintentional awareness, postoperative delirium, neurocognitive disorder, and long-term mortality after surgery. After considering current evidence, the working group recommends that EEG monitoring should be considered as part of the vital organ monitors to guide anesthetic management. In addition, we encourage anesthesiologists to be knowledgeable in basic EEG interpretation, such as raw waveform, spectrogram, and processed indices, when using these devices. Current evidence suggests that EEG-guided anesthesia reduces the rate of awareness during total intravenous anesthesia and has similar efficacy in preventing awareness as compared with end-tidal anesthetic gas monitoring. There is, however, insufficient evidence to recommend the use of EEG monitoring for preventing postoperative delirium, neurocognitive disorder, or postoperative mortality.

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