This Month in Anesthesiology

Nonsurgical risk factors are reported to play an important role in developing chronic opioid dependence for patients not using opioids before surgery. Most postoperative opioid use literature focuses on opioid-naive patients. The hypothesis that patient characteristics, including preoperative opioid use, and intraoperative factors predict opioid consumption 3 months after surgery was tested in a multicenter, prospective observational study. Of 545 patients who did not take opioids preoperatively, 23 (4%) reported taking opioids 3 months after their surgery and 73 (54%) of 135 patients who took opioids preoperatively were taking opioids at 3 months. Although other factors were associated with opioid use at 3 months, preoperative opioid use was the only predictor of opioid use at 3 months in the multivariable statistical model (adjusted odds ratio, 18.6; 95% credible interval, 10.3 to 34.5). There was no correlation between opioid taking at 3 months and surgical site pain at 3 months. Only three strong predictors of surgical site pain at 3 months were found in the multivariate model: preoperative surgical site pain, knee replacement surgery, and spine surgery. See the accompanying Editorial on page 457.

The Revised Cardiac Risk Index is a commonly used cardiac risk stratification measure. Biomarkers such as N-terminal-prohormone brain natriuretic peptide (NT-proBNP) can add incremental information to clinical risk scores. Growth differentiation factor 15 (GDF-15) concentration was independently associated with postoperative morbidity and mortality in cardiac surgery and improved risk stratification when added to preoperative risk score and NT-proBNP concentration. The hypothesis that GDF-15 would have incremental predictive value when added to a preoperative risk score and NT-proBNP in patients undergoing major noncardiac surgery was tested in a prospective nested biobank cohort study that included 5,238 patients. A preoperative serum GDF-15 concentration greater than or equal to 1,500 pg/ml was associated with a 24.9% risk of myocardial injury or vascular death 30 days after noncardiac surgery, compared to 8.6% in patients with a GDF-15 concentration of less than 1,500 pg/ml. GDF-15 concentration improved risk prediction in one of six patients when used in combination with preoperative NT-proBNP concentration and Revised Cardiac Risk Index compared to the combination of NT-proBNP concentration and Revised Cardiac Risk Index alone.

Radial artery cannulation in young children can be challenging even for anesthesiologists proficient in ultrasound guidance. The hypothesis that a single-operator, laser-assisted 3-dimensional ultrasound-guided system would improve the first-attempt success rate of radial arterial cannulation in young pediatric patients compared to a traditional ultrasound-guided, short-axis, out-of-plane, dynamic needle-tip positioning technique was tested in a randomized controlled trial of 80 children younger than 2 yr old undergoing major elective or emergency surgery under general anesthesia. The first-attempt success rate in the single-operator, laser-assisted ultrasound-guidance group was 90% (36 out of 40) and that in the traditional ultrasound-guidance group was 70% (28 out of 40) for an absolute difference (95% CI) of 20% (2.3% to 36.6%). The authors report that the results may be attributed to the more precise direction of insertion under laser guidance.

Multiple exposures to anesthetics are reported to affect brain development in rodents and nonhuman primates. The hypothesis that neonatal sevoflurane exposures would alter the atlas of hippocampal cell clusters and have neuronal and nonneuronal cell type–specific effects in mice of both sexes was tested in mice randomly allocated to receive 60% oxygen balanced with nitrogen or 3% sevoflurane in 60% oxygen balanced with nitrogen for 2 h on postnatal days 6, 8, and 10. The Morris water maze test on postnatal day 36 confirmed the successful establishment of cognitive impairment model in mice of both sexes. Animals were euthanized on postnatal day 37 and hippocampi were harvested for single-cell nucleus RNA sequencing analysis. A sex-specific distribution of hippocampal cell types was observed in control mice as were cell type– and sex-specific effects of sevoflurane exposure on distinct hippocampal cell populations. Sevoflurane-induced hippocampal cell–type effects included sex-specific perturbations in cellular cross-talk, dentate gyrus granule cell neurogenesis, microglia differentiation, CA1 pyramidal cell diversity, and oligodendrocyte myelination. See the accompanying Editorial on page 460.

Heparin is used to provide anticoagulation during cardiopulmonary bypass, but it has disadvantages including potential development of antiplatelet factor 4/heparin antibodies. A recommended alternative to heparin, bivalirudin, has its own disadvantages including the lack of a reversal agent. Dabigatran may be a better alternative in patients with contraindications to the use of heparin because it has an approved reversal agent. The hypothesis that dabigatran would provide sufficient anticoagulation for cardiopulmonary bypass was tested in a first-use, proof-of-concept study using a rabbit model of cardiopulmonary bypass that included a comparison group receiving heparin. The dabigatran loading dose and maintenance infusions were designed after first determining its pharmacokinetics in rabbits and the target concentration in an in vitro simulation of cardiopulmonary bypass. Dabigatran provided acceptable anticoagulation to prevent thrombosis during 2 h of cardiopulmonary bypass in rabbits that was similar to that provided by heparin and was well tolerated despite accumulating well above the target concentration during the period of anesthesia and cardiopulmonary bypass.

Oxylipins, which are derived from the metabolism of arachidonic acid and other precursor polyunsaturated fatty acids, play important roles in the modulation of inflammation. The hypothesis that plasma thromboxane B₂, prostaglandin E₂, 15-hydroxyeicosatetraenoate, and 11-hydroxyeicosatetraenoate concentrations would increase in response to mechanical ventilation was tested by characterizing oxylipin profiles in the plasma of blood samples collected at intubation and the following morning from 25 patients undergoing mechanical ventilation in the intensive care unit. Twenty-three of the 58 oxylipins detected were above the limit of quantitation in at least 80% of samples and included in the formal analysis; these did not include thromboxane B₂ or prostaglandin E₂. No oxylipin, including 15-hydroxyeicosatetraenoate and 11-hydroxyeicosatetraenoate, concentration increased during the first day of mechanical ventilation but plasma concentrations of 12-hydroxyeicosatetraenoate decreased in that time.

Granger causality analysis of multichannel electroencephalogram recordings describes the amount of information flow between two electrodes by using autoregressive models to assess whether past information in one electrode helps predict current information in another electrode. In an earlier study, the authors reported that cortical information flow assessed by bivariate Granger causality decreased abruptly in all parts of the brain at propofol-induced loss of responsiveness. The authors subsequently noted that there is no accepted convention for the sign of the autoregressive coefficients. The present Research Letter reports that the transfer function used in the original analysis was derived from sign-reversed coefficients and compares the results of the original analysis with those of the orthodox Granger analysis. The propofol-induced state of unresponsiveness was marked by a profound decrease in information flow over most of the brain when using sign-reversed Granger analysis but the propofol-induced changes in global information flow were much more heterogenous and subtle when using the orthodox Granger analysis, with consistent decreases confined to a few brain regions.

Nonsurgical bleeding is generalized, often diffuse bleeding at sites remote from the surgical field that is often due to coagulopathy and platelet dysfunction. This Review Article begins with a discussion of the definition of severe bleeding and how to identify procedures and patients with a high bleeding risk. The pathophysiology of coagulation disorders in trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage are then reviewed, and evolving therapeutic approaches to manage bleeding conditions that occur commonly in these clinical settings are described. The article notes that recent guidelines for perioperative bleeding provide specific management algorithms for the treatment of microvascular bleeding and reversal of coagulation abnormalities and emphasize the use of viscoelastic testing and the potential of targeted hemostatic resuscitation with coagulation factor concentrates. The strengths and limitations of the evidence behind current coagulopathy diagnostic and therapeutic strategies are discussed. The review ends with a call for the implementation of evidence from well-conducted randomized clinical trials into multimodal algorithms for patient blood management.