Abstract Background: Data are lacking on the optimal scheduling of coronary artery bypass grafting (CABG) surgery after stroke. The authors investigated the preoperative predictors of adverse outcomes in patients undergoing CABG, with a focus on the importance of the time interval between prior stroke and CABG. Methods: The Hospital Episode Statistics database (April 2006–March 2010) was analyzed for elective admissions for CABG. Independent preoperative patient factors influencing length of stay, postoperative stroke, and mortality, were identified by logistic regression and presented as adjusted odds ratios (OR). Results: In all, 62,104 patients underwent CABG (1.8% mortality). Prior stroke influenced mortality (OR 2.20 [95% CI 1.47–3.29]), postoperative stroke (OR 1.99 [1.39–2.85]), and prolonged length of stay (OR 1.31 [1.11–1.56]). The time interval between stroke and CABG did not influence mortality or prolonged length of stay. However, a longer time interval between stroke and CABG surgery was associated with a small increase in risk of postoperative stroke (OR per month elapsed 1.02 [1.00–1.04]; P = 0.047). An interaction was evident between prior stroke and myocardial infarction for death (OR 5.50 [2.84–10.8], indicating the importance of the combination of comorbidities. Prominent effects on mortality were also exerted by liver disease (OR 20.8 [15.18–28.51]) and renal failure (OR 4.59 [3.85–5.46]). Conclusions: The authors found no evidence that more recent preoperative stroke predisposed patients undergoing CABG surgery to suffer postoperative stroke, death, or prolonged length of stay. The combination of prior stroke and myocardial infarction substantially increased perioperative risk.
Objective criteria can predict amputation after lower-extremity trauma. The authors examined the hypothesis that objective data, available early in the evaluation of patients with severe skeletal/soft-tissue injuries of the lower extremity with vascular compromise, might discriminate the salvageable from the unsalvageable limbs. The Mangled Extremity Severity Score (MESS) was developed by reviewing 25 trauma victims with 26 severe lower-extremity open fractures with vascular compromise. The four significant criteria (with increasing points for worsening prognosis) were skeletal/soft-tissue injury, limb ischemia, shock, and patient age. (There was a significant difference in the mean MESS scores; 4.88 in 17 limbs salvaged and 9.11 in nine limbs amputated; p less than 0.01). This scoring system was then prospectively evaluated in 26 lower-extremity open fractures with vascular injury over a 12-month period at two trauma centers. Again, there was a significant difference in the mean MESS scores; 4.00 for the 14 salvaged limbs and 8.83 for the 12 amputated limbs (p less than 0.01). In both the prospective and retrospective studies, a MESS score of greater than or equal to 7 had a 100% predictable value for amputation. This relatively simple, readily available scoring system of objective criteria was highly accurate in acutely discriminating between limbs that were salvageable and those that were unsalvageable and better managed by primary amputation.
Abstract Background Impaired consciousness has been associated with impaired cortical signal propagation following transcranial magnetic stimulation (TMS). Herein we hypothesized that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy. Methods Eight subjects underwent left occipital TMS coupled with high-density electroencephalograph (EEG) recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of evoked and induced source-space responses was used to investigate propofol’s effects on connectivity between regions. Results Propofol produced a wideband reduction in evoked power following TMS in five out of six electrodes. Bayesian Model Selection supported a DCM with hierarchical feedforward and feedback connections to best fit the data. DCM of induced responses revealed that the primary effect of propofol was impaired feedforward responses in cross frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, Family Wise Error corrected p<0.05). An exploratory analysis (thresholded at uncorrected p<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Posthoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left sided occipital and parietal cortex (T contrast p=0.004, Bonferroni corrected). Conclusions Our data suggest that propofol-induced loss of consciousness is associated with reduced evoked power and impaired hierarchical feedforward connectivity following occipital TMS.
Abstract Objective To quantify the association between major surgery and the age related cognitive trajectory. Design Prospective longitudinal cohort study. Setting United Kingdom. Participants 7532 adults with as many as five cognitive assessments between 1997 and 2016 in the Whitehall II study, with linkage to hospital episode statistics. Exposures of interest included any major hospital admission, defined as requiring more than one overnight stay during follow-up. Main outcomes measures The primary outcome was the global cognitive score established from a battery of cognitive tests encompassing reasoning, memory, and phonemic and semantic fluency. Bayesian linear mixed effects models were used to calculate the change in the age related cognitive trajectory after hospital admission. The odds of substantial cognitive decline induced by surgery defined as more than 1.96 standard deviations from a predicted trajectory (based on the first three cognitive waves of data) was also calculated. Results After accounting for the age related cognitive trajectory, major surgery was associated with a small additional cognitive decline, equivalent on average to less than five months of aging (95% credible interval 0.01 to 0.73 years). In comparison, admissions for medical conditions and stroke were associated with 1.4 (1.0 to 1.8) and 13 (9.6 to 16) years of aging, respectively. Substantial cognitive decline occurred in 2.5% of participants with no admissions, 5.5% of surgical admissions, and 12.7% of medical admissions. Compared with participants with no major hospital admissions, those with surgical or medical events were more likely to have substantial decline from their predicted trajectory (surgical admissions odds ratio 2.3, 95% credible interval 1.4 to 3.9; medical admissions 6.2, 3.4 to 11.0). Conclusions Major surgery is associated with a small, long term change in the average cognitive trajectory that is less profound than for major medical admissions. The odds of substantial cognitive decline after surgery was about doubled, though lower than for medical admissions. During informed consent, this information should be weighed against the potential health benefits of surgery.
Appraisal of printed and duplicated materials is an obvious primary responsibility of college and university archivists. Even after a sound appraisal of the long-term value of the publications has been made, however, the archivist faces another important decision. He must determine how best to obtain and accession those publications chosen for archival retention. Essentially two alternative methods are available. The first, based on traditional archival practice, is to establish schedules for periodic transfers of series of publications from the publishing office to the archives. The second is to collect current publications piecemeal through the use of a mailing list or by agreement with the publishing office. Most archivists would agree that the use of systematic records schedules offers a tested, practical method for acquiring many types of materials. On the other hand, college publishing offices often are unwilling or unable to preserve orderly series of publications. By the time the archivist discovers this problem, the publications may be scarce or unavailable. With this in mind, compelling arguments can be made for acquisition of current publications. Why should the archivist not preserve a valuable current record when it is abundant, rather than waiting until it becomes scarce? Will the archivist
For the greater part of the 20th century, research into the mechanisms of general anesthesia focused on biomolecular targets such as lipids and proteins. In the mid-1990s, this approach was complemented by emerging studies of anesthetic mechanisms based on systems neuroscience, which has thus far been a major focus in the 21st century. This line of investigation extends beyond the molecular and biophysical focus to the study of neural circuits and the properties of large-scale brain networks, as assessed, for example, by functional magnetic resonance imaging and electroencephalography. For the past 15 yr, neuroimaging and neurophysiologic data during anesthetic state transitions have been increasingly analyzed with measures of functional connectivity (how activities of different brain regions co-vary), directional or effective connectivity (how activities in one brain region influence that of another), and global network properties (how interconnected nodes behave in terms of overall efficiency and organization).1 Despite remarkable progress, questions remain, including how these various connectivity and network properties unfold during the induction of general anesthesia. Does the brain experience a smooth slide to the depths of oblivion? Or is there a kind of quantum leap into the void? In this issue of Anesthesiology, the study from Pullon, Warnaby, and Sleigh helps address this very quandary.2 The investigators reanalyzed data from a study of 16 healthy human volunteers who underwent a slow induction of propofol anesthesia while multichannel electroencephalography was recorded. Behavioral responsiveness was assessed by a command and button-pressing; after general anesthesia was established, passive emergence (rather than a symmetrical down-titration of propofol) was permitted. After the experiment, the investigators used the electroencephalographic data to assess functional connectivity, i.e., how the neurophysiologic activity around one electrode relates to—or coheres with—that of a more distant electrode. By way of analogy, imagine the three authors of this Editorial singing in harmony. Our activity (singing) would be functionally connected (harmony) even if we were not influencing one another directly because we were all reading from a single musical score.The investigators also measured a surrogate of shared information evident in the neurophysiologic signal and they analyzed network properties such as efficiency and clustering (i.e., how many of a node’s connections have connections with each other, like a close-knit group of friends). Finally, they analyzed complexity in the neurophysiologic signal, reflecting the diversity of activity across the brain. To complement these empirical studies, they also used a well-known computational model of oscillatory activity to link their empirical connectivity and complexity measures to an important dynamic feature of networks known as criticality. Criticality is when a system is poised on the boundary of order and disorder. In neurobiological terms, the advantage of dancing on this fine line is that the brain can flexibly respond to incoming stimuli without being entrenched in any one set of activities.Although these analytic techniques have all been employed before in the context of anesthetic state transitions, what is new in the article from Pullon et al.2 is the joint consideration of these network properties in the context of a slow, carefully controlled induction of propofol anesthesia. The gradual ramp-up of propofol infusion is important because a bolus dose would induce a rapid network change and thus mask the intrinsic nature of the state transition from consciousness to propofol-induced unresponsiveness. What the investigators found was evidence of a phase transition (i.e., a jump from one state of the network to another). This quantum leap is of relevance to the history of the aforementioned anesthetic mechanisms research because such a phase transition cannot be reduced trivially to the sum of micro-level events at molecular targets. Rather, it reflects the emergent and collective dynamics of the system as a whole. This is of interest to us as clinicians because it suggests that the brain is not sliding down to general anesthesia in a way that could be readily measured by a smooth and linear index. Furthermore, the investigators found that the transition could not be reduced to brain activity being hypercoherent or decoherent. Rather, the state of coherence depended on the frequency under consideration, where alpha oscillations (around 10 Hz) were hypersynchronized and slow oscillations were fragmented. This was associated with a rapid decline in network efficiency, which would be inhospitable to information exchange across the brain. This is relevant to general anesthesia because information integration appears to be an important prerequisite for normal conscious experience.1Consider that you and an attending surgeon get into a heated argument, speaking loudly to one another at the same time (we know this never happens, but just stretch your imagination). As a result, the rest of the staff in the operating room suddenly turn to their neighbors and break out into multiple local conversations. In this example, you and the surgeon would be abnormally synchronized (rather than healthily in sync), while the rest of the personnel would be desynchronized; at this point, the overall efficiency of the team would plummet, along with a disruption of information exchange among the team members. In other words, a dramatic shift in one set of events would have a host of attendant consequences at the same time. This is what Pullon, Warnaby, and Sleigh2 suggest is happening in brain networks during the induction of general anesthesia.Importantly, the investigators observed what is called “critical slowing down,” which refers to a change in the state of criticality already discussed. This was an interesting finding for two reasons. First, critical slowing signals that the network has undergone a phase transition, which confirms the interpretation of the data. Second, systems that undergo critical slowing take longer to recover than they did to be disrupted. In terms of general anesthesia, that asymmetry would be manifested as hysteresis, in which forward and reverse processes are not the same. Hysteresis has, indeed, been observed in both animals and humans undergoing state transitions and can be attributed to the underlying network dynamics rather than solely to pharmacokinetic factors.3–6As with all studies, this one had technical and analytical limitations, which the authors report clearly. Despite the limitations, the work of Pullon et al.2 prompts further scientific and clinical investigation. Scientifically, we still need to understand the link between micro-level events related to anesthetic mechanisms (i.e., molecular actions that might occur in a gradual manner) and macro-level events, which the authors argue happen in a sudden, discontinuous manner. Clinically, this work, along with that of others, makes us question the notion of a linear conceptualization of “depth of anesthesia,” in which, for example, a neurophysiologic index would smoothly slide down along with a gradual descent in level of consciousness. In fact, this study makes us reconsider the proposition that consciousness is a graded phenomenon at all. Furthermore, the investigators provide evidence that there is a sudden change in network dynamics when humans become unresponsive; however, we remain ignorant as to whether they remain conscious but disconnected from the environment (such as in a dream state) or whether they have abruptly transitioned to a state of unconsciousness.7 Is the electroencephalographic phase transition only a marker for loss of behavioral responsiveness, with the capacity for conscious experience continuing unperturbed? The next frontier is to understand whether unintended emergence from anesthesia is driven by a sudden reversal of these network dynamics, particularly when driven by nociceptive stimulation,8 and whether these analytic techniques can be used to rapidly identify or predict periods of vulnerability and anesthetic state instability.The authors are to be commended for highlighting how numerous network features that have been studied individually (hypersynchrony of alpha, decoherence of delta, and reduced efficiency, among others) appear to represent a constellation of properties that travel together as brain networks jump from the critical edge of consciousness into the void of anesthesia.Dr. Mashour is a consultant for TRYP Therapeutics (San Diego, California). The other authors are not supported by, nor maintain any financial interest in, any commercial activity that may be associated with the topic of this article.
Peri-operative stroke is a rare consequence of surgical intervention and anaesthesia that has profound effect on patient outcomes; incurring a cerebrovascular accident (CVA) in the setting of noncardiac, non-neurologic surgery is associated with an adjusted eightfold increase in mortality. Just as concerning as the high mortality is the degree of disability associated with a cerebrovascular event. Disability from stroke is broad in scope, ranging from mild deficits in cognition or mobility to complete dependence on others for activities of daily living. This chapter on cerebrovascular disease discusses peri-operative considerations (including timing of elective surgery, type of anaesthetic, blood pressure, anaemia, glycaemic control, and anticoagulation), and care of the patient with peri-operative CVA.
Abstract Delirium is associated with electroencephalogram (EEG) slowing and impairments in connectivity. We hypothesized that delirium would be accompanied by a reduction in the available cortical information (ie, there is less information processing occurring), as measured by a surrogate, Lempil-Ziv Complexity (LZC), a measure of time-domain complexity. Two ongoing perioperative cohort studies (NCT03124303, NCT02926417) contributed EEG data from 91 patients before and after surgery; 89 participants were used in the analyses. After cleaning and filtering (0.1–50Hz), the perioperative change in LZC and LZC normalized (LZCn) to a phase-shuffled distribution were calculated. The primary outcome was the correlation of within-patient paired changes in delirium severity (Delirium Rating Scale-98 [DRS]) and LZC. Scalp-wide threshold-free cluster enhancement was employed for multiple comparison correction. LZC negatively correlated with DRS in a scalp-wide manner (peak channel r2 = .199, p < .001). This whole brain effect remained for LZCn, though the correlations were weaker (peak channel r2 = .076, p = .010). Delirium diagnosis was similarly associated with decreases in LZC (peak channel p < .001). For LZCn, the topological significance was constrained to the midline posterior regions (peak channel p = .006). We found a negative correlation of LZC in the posterior and temporal regions with monocyte chemoattractant protein-1 (peak channel r2 = .264, p < .001, n = 47) but not for LZCn. Complexity of the EEG signal fades proportionately to delirium severity implying reduced cortical information. Peripheral inflammation, as assessed by monocyte chemoattractant protein-1, does not entirely account for this effect, suggesting that additional pathogenic mechanisms are involved.
The anesthetic properties of xenon have been known for more than 50 yr, and the safety and efficacy of xenon inhalational anesthesia has been demonstrated in several recent clinical studies. In addition, xenon demonstrates many favorable pharmacodynamic and pharmacokinetic properties, which could be used in certain niche clinical settings such as cardiopulmonary bypass. This inert gas is capable of interacting with a variety of molecular targets, and some of them are also modulated in anesthesia-relevant brain regions. Besides these anesthetic and analgesic effects, xenon has been shown to exert substantial organoprotective properties, especially in the brain and the heart. Several experimental studies have demonstrated a reduction in cerebral and myocardial infarction after xenon application. Whether this translates to a clinical benefit must be determined because preservation of myocardial and cerebral function may outweigh the significant cost of xenon administration. Clinical trials to assess the impact of xenon in settings with a high probability of injury such as cardiopulmonary bypass and neonatal asphyxia should be designed and underpinned with investigation of the molecular targets that transduce these effects.
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