Science, Medicine, and the Anesthesiologist

Key Papers from the Most Recent Literature Relevant to AnesthesiologistsPatients with Alzheimer’s disease and Alzheimer’s disease–related dementias are more likely to develop postoperative delirium, and patients with delirium have a 12.5-fold increased likelihood of being newly diagnosed with Alzheimer’s disease or Alzheimer’s disease–related dementias. Despite this bidirectional relationship between delirium and dementia, no clinical plasma biomarkers exist to identify those patients at risk of postoperative delirium. Specific phosphorylated amino acids on the tau protein (Tau-PT217 and Tau-PT181) are new Alzheimer’s disease biomarkers but have not been previously evaluated in postoperative delirium. The presence and severity of postoperative delirium and the preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were prospectively measured in 139 patients, age 65 and older, undergoing knee or hip replacement or laminectomy. Due to the very low concentrations of these targeted phosphorylated proteins in plasma, a special technique of nanoneedle technology was employed with an array of more than 20,000 nanoneedles on a silicon substrate assigned to detect one analyte. Thirteen percent of the studied patients developed postoperative delirium that was associated with higher preoperative plasma levels of Tau-PT217 and Tau-PT181 independent of age, education, or preoperative Mini-Mental State score. The preoperative plasma concentrations of the Alzheimer’s disease biomarkers were also associated with the severity of postoperative delirium.Take home message: In this prospective observational cohort study, preoperative plasma concentrations of phosphorylated tau proteins, new biomarkers for Alzheimer’s disease, were predictive of the presence and severity of postoperative delirium in patients older than 65 undergoing knee and hip replacement or laminectomy surgeries. This novel approach to preoperatively identify those patients at increased risk of postoperative delirium may assist perioperative management to decrease its incidence and severity.In 2007, the Universal Definition of Myocardial Infarction (MI) defined type 2 MI as myocardial ischemia from mismatched oxygen supply and demand. Myocardial infarction carries a poor prognosis and may be undertreated compared to type 1 MI (plaque rupture). This retrospective observational cohort study evaluated whether management and outcomes of type 2 MI have changed between 2010 and 2022 using a Swedish national registry (SWEDEHEART) of patients admitted to coronary care units (14,833 with type 2 MI; 184,329 with type 1 MI). The primary outcome was 1-yr all-cause mortality. Differences in diagnostic imaging and medication were assessed by logistic regression comparing 2010–2012 to 2020–2022. The primary outcome was 25% overall without temporal changes (odds ratio, 1.0 [95% CE, 0.97 to 1.03]; P = 0.992). Increases in echocardiography or coronary imaging were smaller than for type 1 MI (8% vs. 13%, P < 0.001; 6% vs. 12%, P < 0.001, respectively). β-blocker use decreased (6%; P < 0.001) as did renin-angiotensin-aldosterone-system inhibitor provision (3%; P = 0.021).Take home message: In this retrospective cohort study, all-cause mortality 1 yr after type 2 MI did not change over a 10-yr period and was associated with less diagnostic imaging or cardioprotective medications compared to type 1 MI.Underuse of evidence-based therapies in individuals with type 2 diabetes and atherosclerotic cardiovascular disease (1: high-intensity statins; 2: angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs]; and 3: sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide 1 receptor agonists [GLP-1RaA]) are common. The investigators hypothesized that a coordinated team intervention in a cardiology clinic (a cardiologist, an endocrinologist, and an implementation specialist) providing education and feedback would enhance guideline compliance. The primary endpoint was the proportion of participants with prescription of all three groups of therapies at 6 to 12 months after enrollment. Secondary outcomes included alteration in atherosclerotic cardiovascular disease risk factors and major cardiovascular outcomes or their composite. One thousand ninety-four subjects (32% female, median age 70 yr, 25% Black or Hispanic) at 43 U.S. cardiology clinics not already receiving all three therapies were randomized to either 20 intervention clinics (n = 459) or 23 usual care clinics (n = 590). The primary outcome was significantly increased in the intervention group (38% vs. 15%; 23% difference; adjusted odds ratio, 4.38 [95% CI, 2.49 to 7.71]; P < 0.001) after adjustment for site and participant baseline characteristics. No differences in the secondary outcomes were observed.Take home message: This cluster randomized clinical trial found that a coordinated, multifaceted intervention over 12 months increased prescription of all three groups of evidence-based therapies (statins, ACEI/ARBs, SGLT2/GLP-1RaAs) in adult patients with type 2 diabetes and atherosclerotic cardiovascular disease.As opioid-related morbidity and mortality continue to rise nationally, particularly in the Black population, efforts have been made to increase access to medications used to treat opioid use disorder. This retrospective cohort analysis of Medicare disability claims data (n = 23,370; 40% random sample; 2016 to 2019; Black, Hispanic, or White subjects) with an index event related to opioid use disorder (nonfatal overdose, hospitalization for injection drug use-related infection, or inpatient/residential rehabilitation or detoxification care). The primary outcomes were receipt of buprenorphine, naltrexone, naloxone, and high-risk medications (opioid analgesics and benzodiazepines) in the 180 days after the index event; secondary outcomes included health care use and outcomes. Methadone was not captured as the data preceded the 2020 Medicare coverage expansion. Risk-adjusted outcomes were stratified by race and ethnic group. Buprenorphine prescription was significantly lower in Black (13%) relative to White (23%) or Hispanic subjects (19%) as well as lower days’ supply and treatment retention. Naloxone fulfillment was also significantly lower in Black but not in Hispanic subjects (23% White vs. 14% Black vs. 21% Hispanic). Naltrexone fulfillment was rare and did not differ between groups. Opioid analgesic prescription did not differ between groups (approximately 23%), although benzodiazepine prescription was less likely. Ambulatory visits did not vary significantly between groups.Take home message: In a retrospective cohort analysis of Medicare beneficiaries, Black and Hispanic subjects were significantly less likely to have buprenorphine prescription fulfillment compared to White beneficiaries, and Black subjects were also less likely to have naloxone prescription fulfillment.Associations between the intensity of surgeon opioid prescribing and later persistent opioid use among surgical patients is unclear. This retrospective cohort study (112,744 surgical patients 2012 to 2016; Ontario, Canada) examined opioid-naive adults undergoing laparoscopic cholecystectomy or appendectomy, knee arthroscopy, or partial breast excision. Opioid prescribing intensity was categorized into quartiles based on the median daily dose of morphine equivalents dispensed within 7 days of surgery for each surgeons’ patients. The primary outcome was persistent opioid use in the year after surgery. Secondary outcomes included refills within 30 days and for emergency department visits or hospitalizations. Patients with surgeons in the highest prescribing intensity quartile were more likely to fill an opioid prescription within 7 days after surgery (83%) compared with those in the lowest quartile (65%). The primary outcome was low in both highest and lowest quartiles (0.3% quartile 4 vs. 0.3% quartile 1; adjusted odds ratio, 1.18; 95% CI, 0.83 to 1.66). Analyses incorporating stricter definitions of the primary outcome (e.g., a prescription filled within 7 days of discharge) demonstrated significant association with surgeon quartile (as high as adjusted odds ratio, 1.36; 95% CI, 1.25 to 1.47). Patients in quartile 4 were more likely to refill a prescription within 30 days (5% quartile 4 vs. 4% quartile 1; adjusted odds ratio, 1.14; 95% CI, 1.04 to 1.24).Take home message: This retrospective cohort analysis suggests that the surgeon’s overall prescribing practices may contribute to persistent opioid use in the year after surgery, although the strength of the association was sensitive to the precise definition of persistent use.Although subanesthetic dosing of intravenous ketamine is increasingly used for treatment-resistant major depression, its effectiveness relative to electroconvulsive therapy (ECT) is uncertain. This open-label, noninferiority trial randomized 403 patients (5 sites, 38 patients withdrawn prior to treatment) with treatment-resistant major depression without psychosis to receive ketamine or ECT. Over an initial 3-week treatment phase, subjects received either ECT (3×/week) or ketamine (0.5 mg/kg body weight over 40 min) 2×/week. The primary outcome was a treatment response (reduction of at least 50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report; 0 to 27, higher scores indicating greater depression). The noninferiority margin was −10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. Patients with a favorable response were followed over a 6-month period. The primary outcome was met in similar numbers of patients (55% ketamine vs. 41% ECT, difference, 14.2 percentage points; 95% CI, 3.9 to 24.2; P < 0.001 for the noninferiority of ketamine to ECT). Of the secondary outcomes, ECT was associated with a decrease in memory recall after 3 weeks of treatment with gradual recovery during follow-up. No differences were noted in patient-reported quality of life between groups.Take home message: This randomized open-label trial of patients with treatment-resistant major depression without psychosis demonstrated that ketamine was noninferior to ECT when used over a 3-week treatment period.Single-chamber ventricular leadless pacemakers do not support atrial pacing or consistent atrioventricular synchrony. Dual-chamber leadless pacing has not been previously reported. A prospective, multicenter, single-group industry-sponsored study enrolled 300 patients across 55 centers in the United States, Canada, and Europe to evaluate the safety and performance of a dual-chamber leadless pacemaker system. Sinus-node dysfunction was the primary pacing indication in 63% and atrioventricular block in 33% of subjects. Leadless pacemakers were successfully implanted in 98% of subjects. The first primary performance end point was a combination of adequate atrial capture threshold and atrial sensing amplitude at the 3-month visit, which was met in 90% of the patients (95% CI, 86.8 to 93.6) and exceeded the performance goal of 83% (P < 0.001). At least 70% atrioventricular synchrony was achieved in 97% of the patients (95% CI, 95.4 to 99.3), which was a secondary performance goal, exceeding the performance goal of 83% (P < 0.001). The primary safety end point was freedom from complications through 90 days after implantation and was achieved in 90% of patients (95% CI, 87.0 to 93.7), which exceeded the performance goal of 78% (P < 0.001). Serious adverse events occurred in 29 patients (35 device- or procedure-related events).Take home message: This industry-sponsored, single-group, prospective study demonstrated that a dual-chamber leadless pacemaker system was safe and provided atrial pacing and atrioventricular synchrony for 3 months.Platelet transfusion guidelines prior to placement of a central venous catheter (CVC) in thrombocytopenic patients are controversial and were often developed prior to the routine use of ultrasound guidance. This multicenter (10 Dutch centers), controlled noninferiority trial randomized 338 patients with 373 CVC placements who had severe thrombocytopenia (platelet count, 10,000 to 50,000/mm3), treated on hematology wards or an intensive care unit to either one unit of prophylactic platelet transfusion or none prior to ultrasound-guided CVC placement assessed grades of catheter related bleeding (0 to 4; 0 = no bleeding, 4 = hemodynamic stability requiring transfusion or fatal outcome). The primary outcome was grade 2 to 4 bleeding; the secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% CI of 3.5 for the relative risk. The primary outcome was significantly improved in transfused patients (5% vs. 12%, relative risk for withholding platelets, 2.45; 90% CI, 1.27 to 4.70) as well as the secondary outcome (2% vs. 5%, relative risk, 2.43; 95% CI, 0.75 to 7.93).Take home message: This randomized trial of preprocedure platelet transfusion in severely thrombocytopenic patients failed to meet the predefined margin for noninferiority, resulting in more CVC-related bleeding events in patients not receiving prophylactic platelet transfusion.Myocardial infarction (MI) is a leading cause of morbidity and mortality. While early high-sensitivity troponin testing is important for effective treatment, current practice using diagnostic pathways with fixed troponin thresholds has not accounted for differences in age, sex, and comorbidities (particularly renal dysfunction) as well as timing of onset of symptoms and require multiple timepoints for testing. To improve diagnosis of MI, the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) probability score (0 to 100) was developed using machine learning on data of 10,038 consecutive patients (48% female) including high-sensitivity troponin measurements and clinical features. CoDE-ACS was externally validated, using data of 10,286 patients (35% female) from seven cohorts of different healthcare systems. It showed excellent discrimination for the diagnosis of MI (area under the curve, 0.953; 95% CI, 0.947 to 0.958; CoDE-ACS score less than 3 with MI risk of 0.4%, CoDE-ACS score 3 to 60 with MI risk of 13% MI, and CoDE-ACS score higher than 61 with MI risk of 71% MI). The new score more reliably identified patients with low probability for MI at presentation than when using fixed troponin thresholds (61% vs. 27%) with similar negative predictive values and a higher positive predictive value.Take home message: The Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) probability score based on machine learning is a promising tool to reduce the time spent in emergency departments, prevent unnecessary hospital admissions, and improve the timely treatment of MI.

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