This Month in Anesthesiology

The cyclodextrin sugammadex encapsulates rocuronium and vecuronium to provide rapid effective reversal of neuromuscular blockade. The encapsulation dynamics might involve the eight negatively charged carboxyl thioether side chains at the edge of the hydrophobic cavity of the cyclodextrin molecule (the primary face) attracting the positively charged aminosteroidal neuromuscular blocking drugs, followed by encapsulation of the muscle relaxant into the central core of sugammadex. A molecular dynamics computer simulation of the molecular interaction between rocuronium and sugammadex was conducted to test the hypothesis that it would follow this sequence of rocuronium attraction by the sugammadex carboxyl thioether side chains, followed by encapsulation. In the process of encapsulation, the rocuronium molecule entered from the direction opposite to the sugammadex carboxyl thioether side chains where it optimally aligned with the 16 hydroxyl groups (the secondary face) and occupied a series of metastable states before finally occupying the hydrophobic cavity of the sugammadex molecule. Vecuronium was less avidly bound to sugammadex than rocuronium because it formed fewer hydrogen bonds with sugammadex. See the accompanying Editorial on page 129.Physicians are turning to alternative analgesic strategies to manage pain after surgical procedures with moderate or high postoperative pain, including use of adjunctive acetaminophen or NSAIDs, to limit excess opioid prescribing and related adverse effects in older patients in the postoperative period. The hypothesis that the number of patients at least 66 yr old dispensed a nonopioid analgesic in the immediate postdischarge period increased between fiscal years 2013 and 2019 was tested in a population-based cohort study using linked health administrative data of 278,366 admissions in Ontario, Canada. The percentage of patients filling an outpatient prescription for a nonopioid analgesic within 7 days postoperatively increased from 9% in 2013 to 28% in 2019, largely due to a shift from filling prescriptions for combination opioid/nonopioids to separate opioid and nonopioid prescriptions. After adjustment for measured confounders, patients who filled separate opioid and nonopioid prescriptions received a lower average morphine equivalent dose compared to those who filled a prescription for an opioid alone, a combination opioid/nonopioid, or a combination opioid/nonopioid and separate nonopioid analgesic.Acute kidney injury (AKI) is a common postoperative complication that worsens patient outcomes significantly. Many of the studies that identified female sex as a risk factor for AKI did not examine the influence of age on sex-related AKI. The hypothesis that the incidence of postoperative AKI after noncardiac surgery is lower in younger females than in males of similar age and the difference is lost in older females was tested in a retrospective cohort study of 390,382 adult patients undergoing surgery at 46 institutions between 2013 and 2019. To study the association of age and sex groups with postoperative AKI development, males and females were separated into age groupings of up to 50 yr old and more than 50 yr old. Development of postoperative AKI was a binary variable based on serum creatinine concentration criteria. Among the 390,382 patients, 25,809 (6.6%) developed postoperative AKI. When adjusted for AKI risk factors, compared to younger females, the odds of AKI were higher in older females (odds ratio 1.51), younger males (1.90), and older males (2.06).Neuroinflammation resulting from activation of cerebral microglia may contribute to postoperative cognitive dysfunction. Minocycline can inhibit microglial activity. The hypothesis that minocycline can prevent postoperative cognitive dysfunction was tested in a randomized placebo-controlled trial of 185 60- to 90-yr-old patients undergoing total knee arthroplasty under general anesthesia. Patients took minocycline (100 mg) or placebo capsules the evening before and the morning of surgery and in the mornings and evenings of postoperative days 1 to 7. Cognitive function was evaluated using a battery of four cognitive function tests before and 1 week and 3 months after surgery. The incidence of postoperative cognitive dysfunction 1 week after surgery was 9% (8 of 90 patients) in the minocycline group and 4% (4 of 95 patients) in the placebo group (odds ratio, 2.22 [95% CI, 0.64 to 7.65]). The incidence of postoperative cognitive dysfunction 3 months after surgery calculated using the multiple imputation method to correct for missing data was 17% in the minocycline group (15 of 90 patients) and 16% (15 of 95 patients) in the placebo group (odds ratio, 1.07 [95% CI, 0.49 to 2.32]).Older adults are at risk for experiencing postoperative delirium. Dexmedetomidine sedation of elderly patients in the intensive care unit after cardiac surgery was associated with reduced incidence, delayed onset, and shortened duration of postoperative delirium compared to propofol sedation. In a retrospective study, elderly patients undergoing orthopedic surgery with regional anesthesia and dexmedetomidine sedation had a lower incidence of postoperative agitated behavior than those sedated with propofol. The hypothesis that the incidence of postoperative delirium would be less in healthy older patients undergoing lower extremity orthopedic surgeries under spinal anesthesia with dexmedetomidine sedation than in those sedated with propofol was tested in a randomized controlled trial of 732 patients aged 65 yr and older. The occurrence of postoperative delirium on the first 3 postoperative days was determined using the confusion assessment method. The incidence of postoperative delirium was 3.0% (11 of 366 patients) in the dexmedetomidine sedation group and 6.6% (24 of 366 patients) in the propofol sedation group (odds ratio, 0.42 [95% CI, 0.20 to 0.86]).Practice guidelines are systematically developed recommendations that aim to improve patient care and outcomes by providing up-to-date information for patient care. The 2023 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting: Carbohydrate-containing Clear Liquids with or without Protein, Chewing Gum, and Pediatric Fasting Duration—A Modular Update of the 2017 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting provide evidence-based recommendations aimed at minimizing adverse consequences of fasting while keeping the risk of regurgitation and subsequent pulmonary aspiration low. The task force found that for patients with low risk of aspiration, carbohydrate-containing clear liquids until 2 h preoperatively was superior to absolute fasting with respect to beneficial outcomes without evidence of increased risks, but there is insufficient evidence to recommend protein-containing over other carbohydrate-containing or noncaloric clear liquids. They recommend not delaying a scheduled elective procedure if a patient chews gum for personal comfort or preference due to inconclusive evidence of harm. The task force was unable to recommend reducing the clear liquid fasting duration to 1 h in the pediatric population due to low-quality evidence.In his Classic Papers Revisited article, William L. Lanier, M.D., provides an account of how with hard work and carefully designed experiments his talented research team was able to discredit decades worth of untested conventional wisdom and replaced it with an empirically supported theory. At the time of the studies described, it was thought that succinylcholine-induced fasciculations might increase intracranial pressure by increasing intrathoracic pressure, which would increase central venous pressure, causing passive venous congestion and increased intracranial blood volume, resulting in increased intracranial pressure. Dr. Lanier’s observation of movement-associated brain stimulation and the identification by others that muscle afferents, predominantly muscle spindles, may be responsible for this stimulation led him to hypothesize that succinylcholine might stimulate the brain via muscle spindles, thereby affecting cerebral blood flow, cerebral blood volume, and intracranial pressure. Studies testing this and related hypotheses led to “the afferentation theory of cerebral arousal,” which predicts that the brain will be stimulated by drugs or maneuvers that produce muscle stretch or contraction of extrafusal striated muscles or stimulate muscle stretch receptors directly.

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