Daily Anesthesiology Research Analysis

Emotional responses to sensory experience are central to the human condition in health and disease. We hypothesized that principles governing the emergence of emotion from sensation might be discoverable through their conservation across the mammalian lineage. We therefore designed a cross-species neural activity screen, applicable to humans and mice, combining precise affective behavioral measurements, clinical medication administration, and brain-wide intracranial electrophysiology. This screen revealed conserved biphasic dynamics in which emotionally salient sensory signals are swiftly broadcast throughout the brain and followed by a characteristic persistent activity pattern. Medication-based interventions that selectively blocked persistent dynamics while preserving fast broadcast selectively inhibited emotional responses in humans and mice. Mammalian emotion appears to emerge as a specifically distributed neural context, driven by persistent dynamics and shaped by a global intrinsic timescale.

IMPORTANCE: Platelet transfusion is a frequent procedure with benefits and risks. OBJECTIVE: To provide recommendations in adult and pediatric populations in whom platelet transfusions are commonly performed. EVIDENCE REVIEW: Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was applied to findings from 21 randomized trials and 13 observational studies in contexts of limited randomized clinical trial data. Transfusion strategies using fewer (restrictive) vs greater (liberal) amounts of platelets were compared. FINDINGS: Evidence demonstrated that restrictive transfusion strategies probably did not cause increases in mortality or bleeding relative to liberal strategies across predefined clinical populations. Exceedingly low incidence of spinal hematoma was identified in patients with thrombocytopenia undergoing lumbar puncture. Because definitions of restrictive strategies varied across trials, recommendations reflect practical guidance. The following recommendations are strong recommendations with high/moderate-certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding patients receiving chemotherapy or undergoing allogeneic stem cell transplant, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. For consumptive thrombocytopenia in neonates without major bleeding, platelet transfusion is recommended when platelet count is less than 25 × 103/μL. In patients undergoing lumbar puncture, platelet transfusion is recommended when platelet count is less than 20 × 103/μL. In patients with consumptive thrombocytopenia due to Dengue without major bleeding, platelet transfusion is not recommended. The following recommendations are conditional recommendations with low/very low-certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding adults undergoing autologous stem cell transplant or with aplastic anemia, prophylactic platelet transfusion is not recommended. In adults with consumptive thrombocytopenia without major bleeding, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing central venous catheter placement in compressible anatomic sites, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing interventional radiology, platelet transfusion is recommended when platelet count is less than 20 × 103/μL for low-risk procedures and less than 50 × 103/μL for high-risk procedures. For adults undergoing major nonneuraxial surgery, platelet transfusion is recommended when platelet count is less than 50 × 103/μL. For patients without thrombocytopenia undergoing cardiovascular surgery in the absence of major hemorrhage, including those receiving cardiopulmonary bypass, platelet transfusion is not recommended. For nonoperative intracranial hemorrhage in adults with platelet count greater than 100 × 103/μL, including those receiving antiplatelet agents, platelet transfusion is not recommended. CONCLUSIONS AND RELEVANCE: A consistent pattern of evidence supports the implementation of restrictive platelet transfusion strategies. Restrictive strategies reduce risk of adverse reactions, mitigate platelet shortages, and reduce costs. It is good practice to consider overall clinical context and alternative therapies in the decision to perform platelet transfusion.

OBJECTIVES: Proton pump inhibitors have dose-dependent immunomodulatory effects. We tested the hypothesis that mega-dose esomeprazole therapy would reduce organ dysfunction in patients with sepsis or septic shock. DESIGN: A multinational, randomized, double-blind, placebo-controlled clinical trial. SETTING: Seventeen ICUs or emergency departments in three countries. PATIENTS: Adult patients with sepsis or septic shock. INTERVENTIONS: Mega-dose (1024 mg) esomeprazole or placebo over a 72-hour period. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score to day 10. Secondary outcomes included antibiotics-free days, ICU-free days at day 28, and all-cause mortality. We also conducted a mechanistic study of the in vitro effects of esomeprazole in sepsis. We randomized 307 patients and assigned 148 to esomeprazole and 159 to placebo. Mean age was 71 years; 166 patients (54%) had septic shock and median SOFA score at randomization was 7. The median mean daily SOFA score in the first 10 days post-randomization was 5 (interquartile range [IQR], 3-9) in the esomeprazole group and 5 (IQR, 3-8) in the placebo group (risk difference, 0.1; 95% CI, -0.8 to 1.0; p > 0.99). No differences were observed in secondary outcomes. Monocytes isolated from patients' peripheral blood and activated with a toll-like receptor agonist exhibited a pro-inflammatory phenotype, which was not affected by esomeprazole therapy. CONCLUSIONS: Among patients with sepsis or septic shock, mega-dose esomeprazole did not reduce organ dysfunction or other patient-related or biological secondary outcomes.