541 Balanced Opioid-free Anesthesia with Dexmedetomidine versus Balanced Anesthesia with Remifentanil for Major or Intermediate Noncardiac Surgery: The Postoperative and Opioid-free Anesthesia (POFA) Randomized Clinical Trial
It has been suggested that opioid-free anesthesia could provide adequate pain control while reducing postoperative opioid consumption. The Postoperative and Opioid-free Anesthesia (POFA) trial was a randomized, controlled trial in 312 patients undergoing major or intermediate noncardiac surgery that tested the hypothesis that an opioid-free balanced anesthetic with dexmedetomidine would decrease postoperative opioid-related adverse events compared to a balanced anesthetic with remifentanil and morphine. The primary outcome was a composite of the postoperative opioid-related adverse events hypoxemia, ileus, and cognitive dysfunction within the first 48 h after extubation. This primary outcome occurred in 122 of 156 (78%) patients in the dexmedetomidine group and 105 of 156 (67%) patients in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33). Hypoxemia occurred in 110 of 152 dexmedetomidine patients (72%) and in 94 of 155 remifentanil patients (61%). The incidences of postoperative ileus and cognitive dysfunction were similar in the two groups. The trial was stopped due to severe bradycardia in five patients in the dexmedetomidine group. See the accompanying Editorial on page 509.
577 Complications as a Mediator of the Perioperative Frailty–Mortality Association: Mediation Analysis of a Retrospective Cohort
Higher levels of preoperative frailty have been associated with higher postoperative mortality rates as have higher rates of postoperative complications. The hypothesis that the occurrence of postoperative complications would mediate a substantial proportion of the total effect of frailty on mortality after elective noncardiac surgery was tested in a retrospective cohort study using prospectively collected surgical registry data for 205,051 patients. Preoperative frailty was assessed using the Risk Analysis Index–Administrative, a multidimensional frailty score that is a continuous variable with a range from 0 to 81, with higher scores indicating greater frailty. The mean ± SD frailty score was 6 ± 5. Within 30 days of surgery, 1,474 (0.7%) people died and 20,211 (9.9%) experienced a serious complication. Of those who died, 1,028 (69.7%) suffered a complication before dying. The total effect of a 12-point greater frailty score was 3.79-fold greater odds of mortality, which resulted from a direct effect attributable to frailty (odds ratio, 1.76) and an indirect effect mediated by complications (odds ratio, 2.15).
562 A Lower Tidal Volume Regimen during One-lung Ventilation for Lung Resection Surgery Is Not Associated with Reduced Postoperative Pulmonary Complications
Postoperative pulmonary complications are common, especially in thoracic surgery patients. Protective ventilation may improve postoperative pulmonary function and reduce the incidence of complications. The hypothesis that a one-lung protective ventilation regimen would be independently associated with decreased odds of pulmonary complications after lung resection surgery was tested in a retrospective observational study. The primary outcome was a composite of 11 major postoperative pulmonary complications. Cases were considered to have been conducted with protective ventilation if both median tidal volume was less than or equal to 5 ml/kg predicted body weight and median positive end-expiratory pressure was greater than or equal to 5 cm H2O. Of the 388 cases that met the protective ventilation definition, 381 (98.2%) were propensity score–matched to nonprotective ventilation cases, resulting in a primary aim study population of 762 patients. In a conditional logistic regression model, protective ventilation was not found to be associated with differential risk of pulmonary complications (adjusted odds ratio, 0.86; 95% CI, 0.56 to 1.32).
552 Association between In-hospital Mortality and Low Cardiac Output Syndrome with Morning versus Afternoon Cardiac Surgery: A Retrospective Cohort Study
A recent retrospective study found an increased risk of cardiac-related complications when aortic valve replacement surgery occurred in the morning, with worse outcomes attributed to reduced myocardial ischemic tolerance. The hypothesis that the incidence of a composite outcome of mortality and low cardiac output syndrome is higher for morning (8 to 11 am) than for afternoon (2 to 5 pm) cardiac surgery when adjusted for previously identified risk factors was tested in a retrospective, observational, single-center cohort study. Low cardiac output syndrome was selected because it has been associated with a twelvefold increase in risk for postoperative mortality after cardiac surgery. Potential confounding factors were adjusted with stabilized propensity score weighting. The incidence of the composite outcome was 3.0% (292 of 9,734) overall, 2.8% (195 of 6,859) for morning surgery, and 3.4% (97 of 2,875) for afternoon surgery (unadjusted odds ratio, 0.84; 95% CI, 0.65 to 1.07). The incidence of the composite outcome did not differ between morning and afternoon surgery, with an adjusted odds ratio of 0.96 (95% CI, 0.75 to 1.24).
617 Median Effective Volume of 0.5% Ropivacaine for Ultrasound-guided Costoclavicular Block: A Dose-finding Study
The costoclavicular block is a recently described infraclavicular brachial plexus block approach. A dose-finding study was conducted in 38 patients scheduled to undergo forearm and hand surgeries to determine the dose of 0.5% ropivacaine required to produce a successful ultrasound-guided costoclavicular block for surgical anesthesia in half of the patients (the median effective dose, ED50). The extents of sensory and motor block were assessed in the median, radial, ulnar, and musculocutaneous nerve distributions and graded using 3-point scales by a blinded observer every 5 min, starting at 5 min after injection, until 30 min had passed. Maximal composite sensorimotor score was 16; the block was considered to be successful when a minimum score of 14 was achieved. The volume of local anesthetic administered through the block needle was determined using the small-sample up-and-down sequential allocation study design of binary response variables and ranged from 8 to 26 ml. The median effective dose was 13.5 ml (95% CI, 11.5 to 15.4 ml).
588 Forebrain Acetylcholine Modulates Isoflurane and Ketamine Anesthesia in Adult Mice
Acetylcholine is one of the main neurotransmitters responsible for arousal. Decreased signaling from basal forebrain cholinergic neurons has been shown to increase sensitivity to a general anesthetic. The hypothesis that mice with genetic deficiency of forebrain acetylcholine transporter have increased anesthetic sensitivity to isoflurane and ketamine was tested in heterozygous knockdown mice with an approximately 45% decreased vesicular acetylcholine transporter expression in the brain and in forebrain knockout mice with a homozygous vesicular acetylcholine transporter deletion restricted to the forebrain. Loss of the righting reflex was used as the behavioral endpoint to investigate the hypnotic properties of isoflurane and ketamine. The isoflurane concentrations (mean ± SD) that induced loss of the righting reflex in homozygous forebrain knockout, heterozygous knockdown, and wild-type groups were 0.76 ± 0.08%, 0.78 ± 0.07%, and 0.83 ± 0.07%, respectively. The cumulative doses of intraperitoneally administered ketamine that induced loss of the righting reflex for forebrain knockout, heterozygous knockdown, and wild-type groups were 144 ± 39, 162 ± 32, and 168 ± 24 mg/kg, respectively. See the accompanying Editorial on page 515.
629 Management of Patient–Ventilator Asynchrony (Clinical Focus Review)
Patient–ventilator asynchrony reflects a mismatch between a mechanically ventilated patient’s demand for flow, volume, or pressure as functions of time and what the ventilator is supplying to the patient. It can impede adequate oxygenation and ventilation and may reflect patient distress and discomfort. Because asynchrony is a mismatch between what the patient wants and what the ventilator is delivering, it can theoretically be corrected by altering either the patient’s characteristics or the ventilator mode and settings. Although patient–ventilator asynchrony is commonly addressed by increasing the depth of patient sedation or using a neuromuscular blocking drug, these strategies have consequences. If there are limited options for altering the patient’s characteristics, asynchrony can be corrected by understanding the nature of the patient demand–ventilator delivery mismatch and adjusting the ventilator mode and settings accordingly. This may facilitate management of the spontaneously ventilating patient not only in critical care but also in the operating room.
645 Perioperative Opioid Administration: A Critical Review of Opioid-free versus Opioid-sparing Approaches (Review Article)
Balanced general anesthesia is produced by administration of a combination of drugs to produce unconsciousness, amnesia, antinociception, and immobility. The use of opioids as the primary agents of antinociception both intraoperatively and postoperatively has been modified recently with the advent of multimodal analgesia, which aims to control perioperative pain while reducing opioid requirements and minimizing adverse effects of individual agents. The opioid epidemic has led to interest in opioid-free perioperative analgesia strategies despite the absence of evidence that perioperative use of opioids to provide analgesia affects the risk of persistent opioid use. Because effective perioperative analgesia is both a humane necessity and important for prevention of short- and long-term complications, this review article provides a timely critical assessment of perioperative opioid use, with a focus on opioid-sparing and opioid-free analgesia strategies. Opioid-free analgesic techniques neither allow analgesic titration based on patient needs nor decrease the risk of persistent opioid use, and there is no evidence that they have benefits beyond those of opioid-sparing strategies. See the accompanying Editorial on page 509.