BACKGROUND: Patients suffering from obstructive sleep apnea (OSA) experience chronic sleep disturbances and desaturation, factors that have been associated with postoperative delirium and that can be aggravated after anesthesia for complex procedures. We investigated whether OSA is associated with delirium after anesthesia, and whether this association is modified by procedural complexity. METHODS: Hospitalized patients ≥60 years who underwent general anesthesia or procedural sedation for procedures of moderate-to-high complexity between 2009 and 2020 at a tertiary health care network in Massachusetts were included. The primary exposure was OSA, defined based on International Classification of Diseases (Ninth/Tenth Revision, Clinical Modification) (ICD-9/10-CM) diagnostic codes, structured nursing interviews, anesthesia alert notes, and a validated risk score (BOSTN [body mass index, observed apnea, snoring, tiredness, and neck circumference]). The primary end point was delirium within 7 days after the procedure. Multivariable logistic regression and effect modification analyses adjusted for patient demographics, comorbidities, and procedural factors were applied. RESULTS: A total of 46,352 patients were included, of which 1694 patients (3.7%) developed delirium, 537 (3.2%) with OSA, and 1,157 (4.0%) without OSA. In adjusted analyses, OSA was not associated with postprocedural delirium in the overall cohort (adjusted odds ratio [OR_adj], 1.06; 95% confidence interval [CI], 0.94–1.20; P = .35). However, a high procedural complexity modified the primary association (P value for interaction = .002). OSA patients had a higher risk of delirium after high-complexity procedures (≥40 work relative value units) such as cardiac (OR_adj, 1.33; 95% CI, 1.08–1.64; P = .007, P value for interaction = .005) or thoracic surgery (OR_adj, 1.89; 95% CI, 1.19–3.00; P = .007, P value for interaction = .009), but no increased risk after moderate complexity procedures, including general surgery (OR_adj, 0.86; 95% CI, 0.55–1.35; P = .52). CONCLUSIONS: Compared to non-OSA patients, a history of OSA is associated with a higher risk after high-complexity procedures such as cardiac or thoracic surgery but not after procedures of moderate complexity.

BACKGROUND: Buprenorphine is a partial agonist at the µ-opioid receptor and an antagonist at the delta and kappa opioid receptors. It has high affinity and low intrinsic activity at the µ-opioid receptor. Buprenorphine demonstrates no ceiling effect for clinical analgesia, but demonstrates this for respiratory depression and euphoria. It may provide effective analgesia while producing less adverse effects, making it a promising opioid analgesic. A systematic review and meta-analysis were performed to examine the analgesic efficacy of buprenorphine for patients with chronic noncancer pain. METHODS: PubMed, MEDLNE, Embase, and the Cochrane Library were searched up to January 2022. Randomized controlled trials were included if they compared buprenorphine versus placebo or active analgesic in patients with chronic noncancer pain, where pain score was an outcome. Nonrandomized controlled trials, observational studies, qualitative studies, case reports, and commentaries were excluded. Two investigators independently performed the literature search, study selection, and data collection. A random-effects model was used. The primary outcome was the effect of buprenorphine on pain intensity in patients with chronic noncancer pain based on standardized mean difference (SMD) in pain score. Quality of evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Two separate literature searches were conducted for patients with and without opioid use disorder (OUD). Only one study met the search criteria for those with OUD. Fourteen randomized controlled trials were included for those without OUD. Buprenorphine was associated with reduced pain score (SMD = –0.368, P < .001, I² = 89.37%) compared to placebo or active analgesic. Subgroup meta-analyses showed statistically significant differences in favor of buprenorphine versus placebo (SMD = –0.404, P < .001), for chronic low back pain (SMD = –0.383, P < .001), when administered via the transdermal route (SMD = –0.572, P = .001), via the buccal route (SMD = –0.453, P < .001), with length of follow-up lasting <12 weeks (SMD = –0.848, P < .05), and length of follow-up lasting 12 weeks or more (SMD = –0.415, P < .001). There was no significant difference when compared to active analgesic (SMD = 0.045, P > .05). Quality of evidence was low to moderate. CONCLUSIONS: Buprenorphine was associated with a statistically significant and small reduction in pain intensity compared to placebo. Both the transdermal and buccal routes provided pain relief. There was more evidence supporting its use for chronic low back pain.

BACKGROUND: Other than clinical observation of a patient’s vegetative response to nociception, monitoring the hypnotic component of general anesthesia (GA) and unconsciousness relies on electroencephalography (EEG)-based indices. These indices exclusively based on frontal EEG activity neglect an important observation. One of the main hallmarks of transitions from wakefulness to GA is a shift in alpha oscillations (7.5–12.5 Hz activity) from occipital brain regions toward anterior brain regions (“alpha anteriorization”). Monitoring the degree of this alpha anteriorization may help to guide induction and maintenance of hypnotic depth and prevent intraoperative awareness. However, the occipital region of the brain is completely disregarded and occipital alpha as characteristic of wakefulness and its posterior-to-anterior shift during induction are missed. Here, we propose an application of Narcotrend’s reduced power alpha beta (RPAB) index, originally developed to monitor differences in hemispheric perfusion, for determining the ratio of alpha and beta activity in the anterior-posterior axis. METHODS: Perioperative EEG data of 32 patients undergoing GA in the ophthalmic surgery department of Bern University Hospital were retrospectively analyzed. EEG was recorded with the Narcotrend® monitor using a frontal (Fp1-Fp2) and a posterior (T9-Oz) bipolar derivation with reference electrode over A2. The RPAB index was computed between both bipolar signals, defining the fronto-occipital RPAB (FO-RPAB). FO-RPAB was analyzed during wakefulness, GA maintenance, and emergence, as well as before and after the intraoperative administration of a ketamine bolus. FO-RPAB was compared with a classical quantitative EEG measure—the spectral edge frequency 95% (SEF-95). RESULTS: A significant shift of the FO-RPAB was observed during both induction of and emergence from GA (P < .001). Interestingly, the additional administration of ketamine during GA did not lead to a significant change in FO-RPAB (P = 0.81). In contrast, a significant increase in the SEF-95 in the frontal channel was observed during the 10-minute period after ketamine administration (P < .001). CONCLUSIONS: FO-RPAB appears to qualify as a marker of unconsciousness, reflecting physiological fronto-occipital activity differences during GA. In contrast to frontal SEF-95, it is not disturbed by additional administration of ketamine for analgesia.

BACKGROUND: Optimizing analgesia after cesarean delivery is essential to quality of patient recovery. The American Society of Anesthesiologists and the Society for Obstetric Anesthesia and Perinatology recommend multimodal analgesia (MMA). However, little is known about clinical implementation of these guidelines after cesarean delivery under general anesthesia (GA). We performed this study to describe the use of MMA after cesarean delivery under GA in the United States and determine factors associated with use of MMA, variation in analgesia practice across hospitals, and trends in MMA use over time. METHODS: A retrospective cohort study of women over 18 years who had a cesarean delivery under GA between 2008 and 2018 was conducted using the Premier Healthcare database (Premier Inc). The primary outcome was utilization of opioid-sparing MMA (osMMA), defined as receipt of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen with or without opioids and without the use of an opioid-combination drug. Any use of either agent within a combination preparation was not considered osMMA. The secondary outcome was use of optimal opioid-sparing MMA (OosMMA), defined as use of a local anesthetic technique such as truncal block or local anesthetic infiltration in addition to osMMA. Mixed-effects logistic regression models were used to examine factors associated with use of osMMA, as well as variation across hospitals. RESULTS: A total of 130,946 patients were included in analysis. osMMA regimens were used in 11,133 patients (8.5%). Use of osMMA increased from 2.0% in 2008 to 18.8% in 2018. Black race (7.9% vs 9.3%; odds ratio [OR] [95% confidence interval {CI}] 0.87 [0.81–0.94]) and Hispanic ethnicity (8.6% vs 10.0%; OR, 0.86 [0.79–0.950]) were associated with less receipt of osMMA compared to White and non-Hispanic counterparts. Medical comorbidities were generally not associated with receipt of osMMA, although patients with preeclampsia were less likely to receive osMMA (9.0%; OR, 0.91 [0.85–0.98]), while those with a history of drug abuse (12.5%; OR, 1.42 [1.27–1.58]) were more likely to receive osMMA. There was moderate interhospital variability in the use of osMMA (intraclass correlation coefficient = 38%). OosMMA was used in 2122 (1.6%) patients, and utilization increased from 0.8% in 2008 to 4.1% in 2018. CONCLUSIONS: Variation in osMMA utilization was observed after cesarean delivery under GA in this cohort of US hospitals. While increasing trends in utilization of osMMA and OosMMA are encouraging, there is need for increased attention to postoperative analgesia practices after GA for cesarean delivery given low percentage of patients receiving osMMA and OosMMA.

BACKGROUND: The anesthetic isoflurane can cause neurotoxicity in fetuses and offspring of rats, affecting their neurodevelopment. However, the underlying mechanisms and therapeutic targets of isoflurane-induced neurotoxicity remain to be identified. Alfaxalone (ALF) is a steroid anesthetic. Steroids have been reported to have neuroprotective effects. This study aimed to investigate whether ALF could alleviate the isoflurane-induced neurotoxicity in fetuses and offspring of rats. METHODS: On gestation day 15 (G15), the pregnant SD rats were randomly assigned to 4 groups: control 1 (CTL1) + control 2 (CTL2), isoflurane (ISO) + CTL2, CTL1 + ALF, and ISO + ALF. To analyze the changes in the expression levels of inflammatory cytokines, apoptotic factors, and synaptophysin, the brain tissues from the G15 fetuses and offspring at postnatal day 7 (P7), postnatal day 14 (P14), and postnatal day 31 (P31) were collected. The newborn neurons in the rats’ offspring at P7, P14, and P31 were counted using immunofluorescence techniques. The Morris water maze (MWM) test was performed to assess the learning and memory abilities of P31 offspring rats. RESULTS: ALF significantly alleviated the isoflurane-induced increase in the expression levels of inflammatory cytokines and apoptotic factors, such as interleukin (IL)-6 (ISO + CTL2 versus ISO + ALF: 5.133 ± 0.739 versus 1.093 ± 0.213, P < .001) and Caspase-3 (6.457 ± 0.6 versus 1.062 ± 0.1, P < .001) in the G15 fetuses. In P31 offspring rats, the expression levels of synaptophysin (0.719 ± 0.04 versus 1.068 ± 0.072, P < .001) and the number of newborn neurons in the dentate gyrus of the hippocampus were significantly lower in the ISO + CTL2 group as compared to those in the ISO + ALF group (118 ± 6 versus 140 ± 7, P < .001). These changes also occurred in the rat offspring at P7 and P14. In the MWM test, the escape latency of CTL1 + ALF group rats was significantly lower than that of ISO + ALF group rats (41 ± 6 versus 31 ± 7, P < .001) at P31. CONCLUSIONS: Based on these findings, this study suggested that isoflurane exposure during pregnancy in rats could cause neuroinflammation and death of embryos as well as impairment of cognitive function in the offspring rats. ALF can be used to counteract the negative effects of isoflurane.

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BACKGROUND: Emerging evidence has uncovered a vital role of nucleus accumbens (NAc) neurons that express the dopamine D1 receptor (D1R) and its upstream neural circuit in general anesthesia (GA) regulation. However, the underlying downstream neural basis of the modulation of GA emergence by NAc^D1R neurons remains unknown. In the present study, we explored the downstream neural mechanism of NAc^D1R neurons in the modulation of emergence from sevoflurane GA. METHODS: We traced the axonal projections of NAc^D1R neurons using a cell type-specific anterograde tracing method and immunohistochemical techniques in D1R-Cre mice. Optogenetic stimulations combined with electroencephalogram/electromyogram recordings and behavioral tests were used to determine the effects of optogenetic activation of the axonal terminals of NAc^D1R neurons on sevoflurane emergence during sevoflurane-induced continuous, steady-state general anesthesia (CSSGA) or burst-suppression oscillations. RESULTS: Labeled efferent fibers of NAc^D1R neurons were highly distributed in the ventral pallidum (VP), lateral hypothalamus (LH), and substantia nigra pars compacta. Optogenetic activation of the NAc^D1R–VP circuit during CSSGA with sevoflurane induced cortical activation (mean ± standard deviation [SD]; delta power: prestimulation versus during stimulation, 48.7% ± 5.7% vs 35.1% ± 3.3%, P < .0001; beta power: 7.1% ± 2.7% vs 14.2% ± 3.3%, P = .0264) and behavioral emergence, and restored the righting reflex in 66.7% of ChR2 mice. Optogenetic stimulation of the NAc^D1R–LH circuit also produced cortical activation (delta power: prestimulation versus during stimulation, 45.0% ± 6.5% vs 36.1% ± 4.6%, P = .0016) and behavioral emergence, and restored the righting reflex in 100% of the ChR2 mice during CSSGA with sevoflurane. Under a sevoflurane-induced burst-suppression state, NAc^D1R–VP/LH circuit activation produced evidence of cortical activation (burst-suppression ratio [BSR]: NAc^D1R–VP circuit, prestimulation versus during stimulation, 42.4% ± 4.0% vs 26.3% ± 6.0%, P = .0120; prestimulation versus poststimulation, 42.4% ± 4.0% vs 5.9% ± 5.6%, P = .0002; BSR: NAc^D1R–LH circuit, prestimulation versus during stimulation, 33.3% ± 13.4% vs 5.1% ± 4.9%, P = .0177; prestimulation vs poststimulation, 33.3% ± 13.4% vs 3.2% ± 4.0%, P = .0105) and behavioral emergence. CONCLUSIONS: Both NAc^D1R–VP and NAc^D1R–LH circuits are sufficient to promote reanimation from sevoflurane GA by simultaneously inducing cortical and behavioral emergence.

BACKGROUND: Surgical patients with preexisting neurological diseases create greater challenges to perioperative management, and choice of anesthetic is often complicated. We investigated neuraxial anesthesia use in total knee and hip arthroplasty (TKA/THA) recipients with multiple sclerosis or myasthenia gravis compared to the general population. METHODS: We retrospectively analyzed patients undergoing a TKA/THA with a diagnosis of multiple sclerosis or myasthenia gravis (Premier Health Database, 2006–2019). The primary outcome was neuraxial anesthesia use in multiple sclerosis or myasthenia gravis patients compared to the general population. Secondary outcomes were length of stay, intensive care unit admission, and mechanical ventilation. We measured the association between the aforementioned subgroups and neuraxial anesthesia use. Subsequently, subgroup-specific associations between neuraxial anesthesia and secondary outcomes were measured. We report odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 2,184,193 TKA/THAs, 7559 and 3176 had a multiple sclerosis or myasthenia gravis diagnosis, respectively. Compared to the general population, neuraxial anesthesia use was lower in multiple sclerosis patients (OR, 0.61; CI, 0.57–0.65; P < .0001) and no different in myasthenia gravis patients (OR, 1.05; CI, 0.96–1.14; P = .304). Multiple sclerosis patients administered neuraxial anesthesia (compared to those without neuraxial anesthesia) had lower odds of prolonged length of stay (OR, 0.63; CI, 0.53–0.76; P < .0001) mirroring neuraxial anesthesia benefits seen in the general population. CONCLUSIONS: Neuraxial anesthesia use was lower in surgical patients with multiple sclerosis compared to the general population but no different in those with myasthenia gravis. Neuraxial use was associated with lower odds of prolonged length of stay.

Perioperative medicine remains an evolving, interdisciplinary subspecialty, which encompasses the unique perspectives and incorporates the respective vital expertise of numerous stakeholders. This integrated model of perioperative medicine and care has a wide-ranging set of clinical, strategic, and operational goals. Among these various programmatic goals, a subset of 4, specific, interdependent goals include (1) enhancing patient-centered care, (2) embracing shared decision-making, (3) optimizing health literacy, and (4) avoiding futile surgery. Achieving and sustaining this subset of 4 goals requires continued innovative approaches to perioperative care. The burgeoning field of narrative medicine represents 1 such innovative approach to perioperative care. Narrative medicine is considered the most prominent recent development in the medical humanities. Its central tenet is that attention to narrative—in the form of the patient’s story, the clinician’s story, or a story constructed together by the patient and clinician—is essential for optimal patient care. If we can view the health care experience through the patient’s eyes, we will become more responsive to patients’ needs and, thereby, better clinicians. There is a potential clinical nexus between the perioperative medicine practice and narrative medicine skills, which, if capitalized, can maximize perioperative patient care. There are a number of untapped educational and research opportunities in this fruitful nexus between perioperative medicine and narrative medicine.