Intraoperative mechanical ventilation is a major component of general anesthesia. Two key ventilator settings are tidal volume and positive end-expiratory pressure (PEEP). The hypothesis that ventilation using different tidal volumes and PEEP levels affects oxygenation within the first hour in the postanesthesia care unit was tested in a robust 2-by-2 factorial crossover cluster trial of 2,860 adults having major orthopedic surgery with general anesthesia. Patients were assigned to factorial clusters with tidal volumes of 6 or 10 ml/kg of predicted body weight and to PEEP of 5 or 8 cm H2O in 1-week clusters. Oxygenation was defined by the peripheral oxygen saturation divided by the fraction of inspired oxygen (Spo2/Fio2 ratio), a surrogate measure of oxygenation. Because the interaction between tidal volumes and PEEP was not significant, the effects of tidal volumes and PEEP on time weighted average Spo2/Fio2 ratios were assessed independently. The time-weighted average Spo2/Fio2 ratios were not different in patients assigned to high and low tidal volumes or in those assigned to high and low PEEP. See the accompanying Editorial on page 381.

The incidence of difficult tracheal intubation in the general pediatric population is nearly 1.5%. The hypothesis that in children with difficult airways tracheal intubation under sedation would be associated with lower first-attempt success and more complications than tracheal intubation under general anesthesia was tested using data from difficult airway encounters in 34 hospitals between 2017 and 2020. Propensity score matching to minimize selection bias and the effect of baseline characteristics on the outcome resulted in 58 sedated patients being matched to at least 1 general anesthesia patient, with 522 general anesthesia patients being matched. First-attempt tracheal intubation was successful in 48% (28 of 58) of sedated patients and 47.9% (250 of 522) of anesthetized patients (odds ratio, 1.02; 95% CI, 0.59 to 1.76). To complete tracheal intubation, 28% (16 of 58) of sedation cases were converted to general anesthesia. Complications were observed in 26% (15 of 58) of sedated patients and 17.3% (90 of 521) of anesthetized patients (odds ratio, 1.63; 95% CI, 0.87 to 3.08). See the accompanying Editorial on page 384.

The combination of reduced cerebral perfusion, e.g., due to hypotension and compromised autoregulation, and impaired vasodilatory reserve, mediated by hypo- and hypercapnia, may create conditions for cerebral ischemia. The hypothesis that the combination of intraoperative hypo- or hypercarbia and intraoperative hypotension would be associated with postoperative stroke was tested in a multicenter, retrospective, observational case-control study. The primary outcome was perioperative ischemic stroke, defined as any new-onset cerebrovascular infarction that occurred within 30 days of surgery. One hundred twenty-two confirmed stroke cases were identified from the 1,244,881 noncardiac, nonintracranial neurologic, and nonmajor vascular surgical cases analyzed and matched 1:4 to controls for the primary analysis. The primary analysis included total area under the curve with mean arterial pressure less than 55 mmHg and Etco2 less than or equal to 30 mmHg followed by Etco2 less than or equal to 35 mmHg and Etco2 greater than or equal to 45 mmHg as a separate, secondary analysis. Intraoperative hypotension and both hypo- and hypercarbia were independently associated with postoperative ischemic stroke in an additive, nonsynergistic manner.

Tianeptine is an atypical antidepressant and cognitive enhancer that can be administered orally or intravenously. It may cause respiratory stimulation during opioid-induced respiratory depression by enhancing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated transmission and reducing glutamatergic transmission at N-methyl-d-aspartate (NMDA) receptors. However, tianeptine also acts as a µ-opioid receptor agonist, which may reduce its respiratory stimulatory capabilities. The hypothesis that tianeptine can effectively reverse opioid-induced respiratory depression was tested in 15 male and female subjects in a double-blind, randomized, placebo-controlled crossover study by determining the effect of four increasing target plasma tianeptine concentrations on remifentanil-induced respiratory depression at isohypercapnia. Over the plasma tianeptine concentration range tested (500 to 2,000 ng/ml), it did not produce respiratory stimulation during remifentanil-induced respiratory depression, but instead worsened respiratory depression with a further decline in ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg (V̇E55) by 5 l/min.

The hypothesis that adding five novel analgesic interventions to a standard multimodal analgesic regimen would decrease postoperative opioid requirements was tested in a randomized, double-blind, controlled trial of 78 patients undergoing total knee arthroplasty. All patients received a single-injection adductor canal block, spinal anesthesia with low-dose intrathecal morphine, intraoperative IV dexamethasone, periarticular local anesthetic infiltration, and round-the-clock oral acetaminophen and celecoxib, with immediate-release oxycodone or hydromorphone as needed. The treatment group also received a preoperative local anesthetic infiltration between the popliteal artery and posterior compartment of the knee, intraoperative IV infusions of low-dose dexmedetomidine and ketamine, a second dose of IV dexamethasone on postoperative day 1, and additional adductor canal block bolus injections on postoperative days 0 and 1. The additional interventions resulted in neither less opioid consumption or lower pain scores in the first 24 to 48 h after the operation nor better postoperative functional outcomes, quality of recovery, patient satisfaction, or longer-term pain and analgesic outcomes up to 6 weeks after surgery.

Positive-pressure ventilation has been reported to contribute to lung inflammation and might predispose general surgery and intensive care unit patients to a higher risk of ventilator-associated lung injury at high tidal volume (VT) ventilation. This review highlights recent evidence from prospective studies of the use of low VT ventilation and varying levels of positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS), intensive care unit patients without ARDS, and patients receiving one-lung ventilation during lung resection. A randomized controlled trial that compared traditional ventilation with ventilation with a lower VT in patients with ARDS reported decreased mortality, more ventilator-free days, and fewer organ failure days in the low VT group. In contrast, in randomized controlled trials clinically important outcomes did not differ between intensive care unit patients without ARDS ventilated with a low or higher VT or with low or higher PEEP. There is limited evidence to support use of protective lung ventilation, including manipulation of VT, PEEP, and driving pressure, during one-lung ventilation to reduce postoperative pulmonary complications.

Tobacco use is the leading cause of preventable death in many countries. Because receiving surgery is a teachable moment event for smoking cessation, anesthesiologists can play a unique role in the fight against this pandemic, providing not only immediate benefits to their tobacco-using patients’ health through reduction of perioperative risk but also long-term benefits through reduction in diseases related to tobacco use. This review begins with an overview of the origins and evolution of the tobacco use pandemic, the pathophysiology of tobacco use and the natural history of quitting, and effective options for treatment of the underlying disease. It then presents the rationale for addressing tobacco use in perianesthesia practices and concludes by reviewing practical strategies by which anesthesiologists can take advantage of their unique opportunities to help their patients, including what is referred to as multimodal perianesthesia tobacco treatment. This incorporates four core components of successful treatment programs: consistent ascertainment and documentation of tobacco use, advice to quit, access to nicotine replacement therapy or other pharmacotherapy, and referral to counseling resources.