Science, Medicine, and the Anesthesiologist

Key Papers from the Most Recent Literature Relevant to AnesthesiologistsSafeguarding the Brains of our Smallest Children (SafeBoosC)–II trial previously reported a significant reduction in cerebral hypoxia and hyperoxia during the first 72 h after birth in a randomized study of use of cerebral oximetry in extremely preterm infants. However, it was not powered to evaluate clinical outcomes. This phase 3 trial (conducted at 70 sites in 17 countries in Asia, Europe, and North America) randomized 1,601 extremely preterm infants (gestational age less than 28 weeks), within 6 h after birth, to treatment guided by cerebral oximetry monitoring for the first 72 h after birth or to usual care. The primary outcome was a composite of death or severe brain injury (by cerebral ultrasonography) at 36 weeks postmenstrual age. Serious adverse events (death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis) were captured. Of the 1,579 subjects analyzed, no significant difference was noted in the primary outcome (35% oximetry vs. 34% usual care; relative risk, 1.03; 95% CI, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events was similar as well (85% vs. 87%; relative risk, 0.98; 95% CI, 0.94 to 1.01).Take home message: This multicenter, international, randomized phase 3 trial evaluating the utility of cerebral oximetry in extremely preterm infants over the first 72 h of birth did not find a lower incidence of death or severe brain injury at 36 weeks’ postmenstrual age relative to usual care.Three million Americans die every year, but very little is known regarding consciousness in the final minutes prior to death. Near-death experiences have been reported by 10 to 20% of cardiac arrest survivors, and experimental findings from animal studies suggest a paradoxical increase in brain activity compatible with transient correlates of consciousness. By analyzing electroencephalograms (EEGs) and electrocardiograms before and after withdrawal of ventilatory support in four intensive care unit patients with history of severe cardiac arrest–induced anoxic brain injury (n = 3) or extensive brain hemorrhage (n = 1), all of whom with Glasgow Coma Scores of 4 or lower, this study aimed at identifying neural correlates of the dying process. All four patients had their final heartbeat within 10 to 25 min after ventilator removal. In two of the four patients, the investigators found end-of-life EEG surges. The researchers argue that the alarming drop of oxygen triggered beta and gamma band hyperactivity in the frontal and central cortical regions as well as the temporal lobes. The amplitude of this high-frequency gamma activity was coupled to slower beta band activity between prefrontal cortex and somatosensory cortex, implying communication between the regions. Because the temporo-parietal-occipital junction is the gatekeeper of perceptual awareness, the scientist’s reason that these two patients may have experienced some level of consciousness before death.Take home message: In dying patients, global hypoxia increases gamma power and gamma coupling with slower oscillations, suggesting that the dying human brain can be briefly activated and experience “consciousness” shortly before death.The incidence and time course of cognitive decline and incident dementia after surgery in older adults has not been well defined. This prospective, observational cohort study analyzed 560 community-dwelling adults (58% female; mean age, 77 yr) participating in the ongoing Successful Aging after Elective Surgery study. The primary outcome was development of incident delirium following major elective surgery assessed daily during hospitalization using the Confusion Assessment Method supplemented with chart review. Cognitive performance was assessed with a battery of neuropsychological tests (preoperatively and multiple time points postoperatively to 72 months). Longitudinal cognitive change was assessed with a composite measure of neuropsychological performance termed general cognitive performance (GCP; 10 points is equivalent to 1 population SD). Retest effects were adjusted using a nonsurgical comparison group. A total of 2,637 person-years of follow-up were analyzed. Twenty-four percent of subjects developed postoperative delirium. Long-term cognitive change, adjusted for practice and recovery effects, occurred at −1.0 GCP units (95% CI, −1.1 to −0.9) per year (about 0.10 population SD units per year). Delirium was associated with a significantly faster long-term cognitive change with −1.4 units per year (about 0.14 population SD units per year).Take home message: This prospective longitudinal cohort study of older adults undergoing elective surgery reports a high incidence of perioperative delirium, suggesting that it is associated with a 40% acceleration in the slope of cognitive decline out to 72 months’ decline.Many brain regions have been implicated in acute and chronic pain in humans, but the role of the orbitofrontal cortex (OFC) in pain modulation is unclear. OFC is known to have reciprocal connections with the anterior cingulate cortex (ACC). Functional magnetic resonance imaging (fMRI) has been widely used to study brain activation, but fMRI does not directly measure individual neuronal activities. This study was conducted to directly assess neuronal activities using implanted intracranial electrodes in four human participants with chronic neuropathic pain, including poststroke pain. Although only 10% of stroke patients in the general population develop neuropathic pain, all three stroke patients in this study were preselected with neuropathic pain. For each patient, pain scores (numerical rating score and visual analog score) were reported multiple times daily over a range of 78 to 184 days, which was correlated with dynamic neural recordings in the ACC or OFC multiple times a day over the entire time course. The results of this study demonstrated that spontaneous and chronic pain states can be predicted from direct brain activities at the OFC and ACC. Given the small sample size (n = 4), caution must be taken to avoid overinterpretation.Take home message: This small pilot study of patients with primarily stroke-related chronic neuropathic pain undergoing prolonged neural recording from implanted intracranial electrodes in the orbitofrontal and anterior cingulate cortex provides new insights into the mechanisms of spontaneous and chronic neuropathic pain.The long-term efficacy after transcatheter edge-to-edge repair of severe mitral regurgitation has not been previously reported. This report presents 5-yr follow-up of 614 patients (78 sites, United States and Canada) with heart failure and moderate-to-severe or severe secondary mitral regurgitation (symptomatic despite the maximal doses of guideline-directed medical therapy) who were previously randomized to either transcatheter edge-to-edge repair with medical therapy (device group, n = 302) or medical therapy alone (control group, n = 312). The annualized rate of all hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, was assessed through 5 yr. Subjects in the device group had a significant reduction in the overall study outcome (33% vs. 57%; hazard ratio, 0.53; 95% CI, 0.41 to 0.68) along with all-cause mortality through 5 yr (57% vs. 67%; hazard ratio, 0.72; 95% CI, 0.58 to 0.89) and death or hospitalization (74% vs. 92%; hazard ratio, 0.53; 95% CI, 0.44 to 0.64). Device-specific safety events occurred in only 1% of subjects (all within 30 days of the procedure).Take home message: This industry-funded 5-yr follow-up of patients with heart failure receiving transcatheter edge-to-edge repair of severe mitral regurgitation versus medical therapy alone demonstrates a significant reduction in hospitalization for heart failure and all-cause mortality.This multicenter, noninferiority randomized controlled trial evaluated the safety, effectiveness, and costs of immediate sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS). Participants from 10 Dutch hospitals were randomly assigned (1:1) to either the ISBCS (intervention) group or the DSBCS (conventional procedure) group. The primary outcomes were the number of second eyes with a 4-week postoperative refractive outcome of less than 1.0 diopter, with a noninferiority margin of –5% for ISBCS versus DSBCS, and the incremental societal costs per quality-adjusted life-year. In the modified intention-to-treat analysis, the proportion of second eyes with a target refraction of 1.0 diopter or less was 97% (404 of 417 patients) in the ISBCS group versus 98% (407 of 417) in the DSBCS group. The percentage difference was –1% (90% CI, –3 to 1; P = 0.526), confirming noninferiority for ISBCS compared with DSBCS. Adverse events were comparable between groups. Societal costs were US$507 lower with ISBCS than with DSBCS. Annual cost savings were projected to be US$34.5 million.Take home message: This randomized, noninferiority trial demonstrated that ISBCS is noninferior in sight outcomes and safety with lower costs compared to DSBCS.It is widely accepted that observed patterns of brain activity are generated by the interactions between regional localized neuronal populations, that are connected anatomically by axonal tracts. An alternative view is that of “neural field theory,” which posits that the activity in billions of homogenously interconnected neurons is acting more like a wave propagating across the brain. Hence, any observed fundamental brain activity can be explained as arising from resonant “eigenmodes” of oscillation; this being the usual way of describing the dynamics of spatial wave patterns. These modes are primarily driven by overall shape of the brain, and not by the fine details of anatomical connections. When applied to more than 10,000 magnetic resonance imaging brain maps of experimentally observed task-evoked patterns of activation in space and time, geometric eigenmode models were superior to conventional anatomic connectivity-based eigenmode models. The activation patterns were dominated by long-wavelength modes across almost the whole brain. This challenges the conventional description of discrete localized spontaneous, or stimulus-evoked, activations.Take home message: The overall shape of the brain may be more important in shaping the EEG patterns than the details of its anatomic axonal connectivity.Opioid use disorder is a major concern with opioid prescribing and may increase the risk of opioid-related harms, including opioid-related deaths. The prevalence of opioid misuse is quite high in chronic pain patients such that there is a need to better understand the impact of opioid withdrawal in chronic pain conditions. This study assessed pain behavioral manifestations produced by nerve injury in mice during oxycodone exposure, after spontaneous withdrawal, and the associated molecular changes in the brain reward areas (medial prefrontal cortex [mPFC]), ventral tegmental area [VTA], and nucleus accumbens [NAc]). Oxycodone withdrawal produced thermal hyperalgesia and mechanical allodynia in noninjured and neuropathic mice. Gene expression using RNA-seq analysis revealed numerous gene dysregulation in the brain reward areas that are associated with neuropathic conditions compared to sham animals. Of note, oxycodone withdrawal induced specific transcriptional profiles in the mPFC, the VTA, and the NAc in pain-free versus neuropathic pain states. Bioinformatic predictions indicated that histone deacetylase (HDAC) 1 is critical in modulating gene expression associated with oxycodone withdrawal. HDAC1 was found to be expressed in cells of the mPFC and NAc. The inhibition of HDAC1/HDAC2 prevented oxycodone withdrawal-induced pain hypersensitivity and reduced affective symptoms in chronic pain animals.Take home message: Preclinical studies are fundamental to fully explore the molecular pathology of opioid use disorder in the hope of identifying highly relevant interventional targets, such as HDAC1/HDAC2, for the management of opioid withdrawal in chronic pain conditions.The updated European Society of Intensive Care Medicine clinical practice guidelines for acute respiratory distress syndrome (ARDS) were formulated by an expert panel using rigorous meta-analysis methods and address the definition, phenotypes, and respiratory support strategies for adult patients with ARDS. The panel determined a need to redefine ARDS to classify phenotypes, guide care in settings with limited access to mechanical ventilation, and discriminate among other causes of acute hypoxemic respiratory failure. Strong evidence was found to recommend continued use of low tidal volume ventilation and extend recommendations for prone positioning to include awake patients. New recommendations include use of high-flow nasal oxygen in nonintubated patients, avoidance of continuous neuromuscular blockade, and the use of extracorporeal membrane oxygenation for severe cases. Important changes include avoiding high-pressure recruitment maneuvers (35 cm H2O and above) and a withdrawal of a prior recommendation for increased positive end-expiratory pressure in more severe cases. There was insufficient evidence to make recommendations regarding other noninvasive ventilation methods, positive end-expiratory pressure titration strategies, or COVID-ARDS–specific therapies.Take home message: The updated guidelines identify a need for a broader definition of ARDS, reinforce the use of low tidal volume ventilation, and provide new evidence-based guidance for respiratory support in adults with ARDS.

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