Subclinical Aortic Inflammation in Patients with Polymyalgia Rheumatica.

OBJECTIVES: To examine the clinicopathologic features of patients with polymyalgia rheumatica (PMR) who had thoracic aorta repair surgery. Findings were compared with those of a cohort of patients with giant cell arteritis (GCA) requiring thoracic aorta repair. METHODS: All patients evaluated at Mayo Clinic in Rochester, MN, with Current Procedural Terminology (CPT) codes for thoracic aorta repair surgery between 2000- 2021 were identified. All patients were screened for prior PMR diagnosis. Patients with PMR and no signs of GCA were categorized as clinically isolated PMR. The medical records of all patients were manually reviewed, and pathologists re-examined all the aortic tissues. RESULTS: Of the 4621 patients with at least one CPT code for thoracic aorta repair surgery, 43 patients were diagnosed with clinically isolated PMR before the surgery. Detailed histopathological examination of the aortic tissues revealed active inflammation in 30/43 (70%) patients after a median (IQR) of 10.0 (4.7- 13.3) years from the PMR diagnosis. When compared with aortic tissue from patients with a prior diagnosis of GCA, the aorta of patients with PMR had more severe inflammation (Grade 3: 15/30 [50%] vs 5/34 [15%], p= 0.002). Patients with PMR and thoracic aorta repair may experience a 40% increased risk of mortality compared with the general population, but this did not reach statistical significance (standardized mortality ratio: 1.40; 95% CI: 0.91- 2.07). CONCLUSIONS: Some patients with PMR have subclinical aortic inflammation that is detectable many years after initial diagnosis and may contribute to the development of aortic aneurysm.

Transfusion targets and adverse events in pediatric perioperative acute Anemia.

STUDY OBJECTIVE: To evaluate the association between pretransfusion and posttransfusion hemoglobin concentrations and the outcomes of children undergoing noncardiac surgery. DESIGN: Retrospective review of patient records. We focused on initial postoperative hemoglobin concentrations, which may provide a more useful representation of transfusion adequacy than pretransfusion hemoglobin triggers (the latter often cannot be obtained during acute surgical hemorrhage). SETTING: Single-center, observational cohort study. PATIENTS: We evaluated all pediatric patients undergoing noncardiac surgery who received intraoperative red blood cell transfusions from January 1, 2008, through December 31, 2018. INTERVENTIONS: None. MEASUREMENTS: Associations between pre- and posttransfusion hemoglobin concentrations (g/dL), hospital-free days, intensive care unit admission, postoperative mechanical ventilation, and infectious complications were evaluated with multivariable regression modeling. MAIN RESULTS: In total, 113,713 unique noncardiac surgical procedures in pediatric patients were evaluated, and 741 procedures met inclusion criteria (median [range] age, 7 [1-14] years). Four hundred ninety-eight patients (68%) with a known preoperative hemoglobin level had anemia; of these, 14% had a preexisting diagnosis of anemia in their health record. Median (IQR) pretransfusion hemoglobin concentration was 8.1 (7.4-9.2) g/dL and median (IQR) initial postoperative hemoglobin concentration was 10.4 (9.3-11.6) g/dL. Each decrease of 1 g/dL in the initial postoperative hemoglobin concentration was associated with increased odds of transfusion within the first 24 postoperative hours (odds ratio [95% CI], 1.62 [1.37-1.93]; P < .001). No significant relationships were observed between postoperative hemoglobin concentrations and hospital-free days (P = .56), intensive care unit admission (P = .71), postoperative mechanical ventilation (P = .63), or infectious complications (P = .74). CONCLUSIONS: In transfused patients, there was no association between postoperative hemoglobin values and clinical outcomes, except the need for subsequent transfusion. Most transfused patients presented to the operating room with anemia, which suggests a potential opportunity for perioperative optimization of health before surgery.

Preoperative Anemia and Postoperative Outcomes in Cardiac Surgery: A Mediation Analysis Evaluating Intraoperative Transfusion Exposures.

BACKGROUND: Preoperative anemia is associated with adverse outcomes in cardiac surgery, yet it remains unclear what proportion of this association is mediated through red blood cell (RBC) transfusions. METHODS: This is a historical observational cohort study of adults undergoing coronary artery bypass grafting or valve surgery on cardiopulmonary bypass at an academic medical center between May 1, 2008, and May 1, 2018. A mediation analysis framework was used to evaluate the associations between preoperative anemia and postoperative outcomes, including a primary outcome of acute kidney injury (AKI). Intraoperative RBC transfusions were evaluated as mediators of preoperative anemia and outcome relationships. The estimated total effect, average direct effect of preoperative anemia, and percent of the total effect mediated through transfusions are presented with 95% confidence intervals and P -values. RESULTS: A total of 4117 patients were included, including 1234 (30%) with preoperative anemia. Overall, 437 of 4117 (11%) patients went on to develop AKI, with a greater proportion of patients having preoperative anemia (219 of 1234 [18%] vs 218 of 2883 [8%]). In multivariable analyses, the presence of preoperative anemia was associated with increased postoperative AKI (6.4% [4.2%-8.7%] absolute difference in percent with AKI, P < .001), with incremental decreases in preoperative hemoglobin concentrations displaying greater AKI risk (eg, 11.9% [6.9%-17.5%] absolute increase in probability of AKI for preoperative hemoglobin of 9 g/dL compared to a reference of 14 g/dL, P < .001). The association between preoperative anemia and postoperative AKI was primarily due to direct effects of preoperative anemia (5.9% [3.6%-8.3%] absolute difference, P < .001) rather than mediated through intraoperative RBC transfusions (7.5% [-4.3% to 21.1%] of the total effect mediated by transfusions, P = .220). Preoperative anemia was also associated with longer hospital durations (1.07 [1.05-1.10] ratio of geometric mean length of stay, P < .001). Of this total effect, 38% (22%, 62%; P < .001) was estimated to be mediated through subsequent intraoperative RBC transfusion. Preoperative anemia was not associated with reoperation or vascular complications. CONCLUSIONS: Preoperative anemia was associated with higher odds of AKI and longer hospitalizations in cardiac surgery. The attributable effects of anemia and transfusion on postoperative complications are likely to differ across outcomes. Future studies are necessary to further evaluate mechanisms of anemia-associated postoperative organ injury and treatment strategies.

Clinical presentation and outcomes in patients with antiphospholipid syndrome-associated adrenal hemorrhage. A multicenter cohort study and systematic literature review.

BACKGROUND: Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR). METHODS: We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis. RESULTS: We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47-9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30-11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33-9.85). CONCLUSION: AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.

Persistent aortic inflammation in patients with giant cell arteritis.

OBJECTIVES: To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery. METHODS: Patients who had thoracic aorta surgery between January 1, 2000, and December 31, 2021, at the Mayo Clinic, Rochester, Minnesota, were identified with current procedural terminology (CPT) codes. The identified patients were screened for a prior diagnosis of GCA with diagnostic codes and electronic text search. The available medical records of all the patients of interest were manually reviewed. Thoracic aorta tissues obtained during surgery were re-evaluated in detail by pathologists. The clinicopathologic features of these patients were analyzed. Overall observed survival was compared with lifetable rates from the United States population. RESULTS: Of the 4621 patients with a CPT code for thoracic aorta surgery, 49 had a previous diagnosis of GCA. Histopathologic evaluation of the aortic tissue revealed active aortitis in most patients with GCA (40/49, 82%) after a median (IQR) of 6.0 (2.6-10.3) years from GCA diagnosis. All patients were considered in clinical remission at the time of aortic surgery. The overall mortality compared to age and sex-matched general population was significantly increased with a standardized mortality ratio of 1.55 (95% CI, 1.05-2.19). CONCLUSION: Histopathologic evaluation of the thoracic aorta obtained during surgery revealed active aortitis in most patients with GCA despite being considered in clinical remission several years after GCA diagnosis. Chronic, smoldering aortic inflammation likely contributes to the development of aortic aneurysm and dissection in GCA.

Postoperative Transfusions after Administration of Delayed Cold-stored Platelets versus Room Temperature Platelets in Cardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Delayed cold storage of room temperature platelets may extend shelf life from 5 to 14 days. The study hypothesized that the use of delayed cold-stored platelets in cardiac surgery would be associated with decreased postoperative platelet count increments but similar transfusion and clinical outcomes compared to room temperature-stored platelets. METHODS: This is an observational cohort study of adults transfused with platelets intraoperatively during elective cardiac surgery between April 2020 and May 2021. Intraoperative platelets were either room temperature-stored or delayed cold-stored based on blood bank availability rather than clinical features or provider preference. Differences in transfusion and clinical outcomes, including a primary outcome of allogenic transfusion exposure in the first 24 h postoperatively, were compared between groups. RESULTS: A total of 713 patient encounters were included: 529 (74%) room temperature-stored platelets and 184 (26%) delayed cold-stored platelets. Median (interquartile range) intraoperative platelet volumes were 1 (1 to 2) units in both groups. Patients receiving delayed cold-stored platelets had higher odds of allogeneic transfusion in the first 24 h postoperatively (81 of 184 [44%] vs. 169 of 529 [32%]; adjusted odds ratio, 1.65; 95% CI, 1.13 to 2.39; P = 0.009), including both erythrocytes (65 of 184 [35%] vs. 135 of 529 [26%]; adjusted odds ratio, 1.54; 95% CI, 1.03 to 2.29; P = 0.035) and platelets (48 of 184 [26%] vs. 79 of 529 [15%]; adjusted odds ratio, 1.91; 95% CI, 1.22 to 2.99; P = 0.005). There was no difference in the number of units administered postoperatively among those transfused. Platelet counts were modestly lower in the delayed cold-stored platelet group (-9 × 109/l; 95% CI, -16 to -3]) through the first 3 days postoperatively. There were no significant differences in reoperation for bleeding, postoperative chest tube output, or clinical outcomes. CONCLUSIONS: In adults undergoing cardiac surgery, delayed cold-stored platelets were associated with higher postoperative transfusion utilization and lower platelet counts compared to room temperature-stored platelets without differences in clinical outcomes. The use of delayed cold-stored platelets in this setting may offer a viable alternative when facing critical platelet inventories but is not recommended as a primary transfusion approach.

Coagulation Tests and Bleeding Classification After Cardiopulmonary Bypass: A Prospective Study.

OBJECTIVE: No recent prospective studies have analyzed the accuracy of standard coagulation tests and thromboelastography (TEG) to identify patients with excessive microvascular bleeding following cardiopulmonary bypass (CPB). The aim of this study was to assess the value of coagulation profile tests, as well as TEG, for the classification of microvascular bleeding after CPB. DESIGN: A prospective observational study. SETTING: At a single-center academic hospital. PARTICIPANTS: Patients ≥18 years of age undergoing elective cardiac surgery. INTERVENTIONS: Qualitative assessment of microvascular bleeding post-CPB (surgeon and anesthesiologist consensus) and the association with coagulation profile tests and TEG values. MEASUREMENTS AND MAIN RESULTS: A total of 816 patients were included in the study-358 (44%) bleeders and 458 (56%) nonbleeders. Accuracy, sensitivity, and specificity for the coagulation profile tests and TEG values ranged from 45% to 72%. The predictive utility was similar across tests, with prothrombin time (PT) (62% accuracy, 51% sensitivity, 70% specificity), international normalized ratio (INR) (62% accuracy, 48% sensitivity, 72% specificity), and platelet count (62% accuracy, 62% sensitivity, 61% specificity) displaying the highest performance. Secondary outcomes were worse in bleeders versus nonbleeders, including higher chest tube drainage, total blood loss, transfusion of red blood cells, reoperation rates (p < 0.001, respectively), readmission within 30 days (p = 0.007), and hospital mortality (p = 0.021). CONCLUSIONS: Standard coagulation tests and individual components of TEG in isolation agree poorly with the visual classification of microvascular bleeding after CPB. The PT-INR and platelet count performed best but had low accuracy. Further work is warranted to identify better testing strategies to guide perioperative transfusion decisions in cardiac surgical patients.

Non-invasive hemoglobin estimation for preoperative anemia screening.

BACKGROUND: Preoperative anemia is common and associated with adverse postoperative outcomes. Assessment of hemoglobin concentrations may facilitate optimization prior to surgery. However, phlebotomy-based hemoglobin measurement may contribute to patient discomfort and iatrogenic blood loss, which makes non-invasive hemoglobin estimation attractive in this setting. STUDY DESIGN AND METHODS: This is a prospective study of adult patients presenting for preoperative evaluation before elective surgery at a tertiary care medical center. The Masimo Pronto Pulse CO-Oximeter was utilized to estimate blood hemoglobin concentrations (SpHb), which were then compared with hemoglobin concentrations obtained via complete blood count. Receiver operating curves were used to identify SpHb values maximizing specificity for anemia detection while meeting a minimum sensitivity of 80%. RESULTS: A total of 122 patients were recruited with a median (interquartile range) age of 66 (58, 72) years. SpHb measurements were obtained in 112 patients (92%). SpHb generally overestimated hemoglobin with a mean (± 1.96 × standard deviation) difference of 0.8 (-2.2, 3.9) g/dL. Preoperative anemia, defined by hemoglobin <12.0 g/dL in accordance with institutional protocol, was present in 22 patients (20%). The optimal SpHb cut-point to identify anemia was 13.5 g/dL: sensitivity 86%, specificity 81%, negative predictive value 96%, and positive predictive value 53%. Utilizing this cut-point, 60% (73/122) of patients could have avoided phlebotomy-based hemoglobin assessment, while an anemia diagnosis would have been missed in <3% (3/122). CONCLUSION: The use of SpHb devices for anemia screening in surgical patients is feasible with the potential to reliably rule-out anemia despite limited accuracy.

Longitudinal assessment of behaviour in young children undergoing general anaesthesia.

BACKGROUND: Exposure to general anaesthesia in children might increase the risk of long-term behavioural problems. It is unclear if any behavioural changes in the short term after anaesthesia could be associated with long-term problems. The goal of the current study was to evaluate the short-term trajectory of parent-reported behaviour measured by the Behaviour Assessment System for Children, third edition (BASC-3) amongst children aged 2.5-6 yr who underwent general anaesthesia for elective surgery. METHODS: Children who were undergoing general anaesthesia for surgery were recruited for assessment of behaviour on two occasions: preoperatively (from 1 week to 1 day before anaesthesia), and 3 months postoperatively. To assess longitudinal changes in the parent-reported behaviour measured by BASC-3, linear mixed models were built with visit number included as a categorical variable and subject-specific random intercepts. RESULTS: Sixty-eight children (37 girls [54%]) were enrolled in the study and completed both assessments. At 3 months after anaesthesia, statistically significant improvements (decrease in T scores) in internalising problems (-2.7 [95% confidence interval -4.2 to -1.1]), anxiety (-2.5 [-4.4 to -0.5]), and somatisation (-3.0 [-5.2 to -0.9]) were found. There were no significant differences in scores between visits for other composites or scales. The pattern of results did not depend upon prior anaesthesia exposure. CONCLUSIONS: Anaesthesia for elective surgery in young children was associated with a small decrease in internalising problems but no changes in other areas of behavioural problems when assessed at 3 months postoperatively, including in children with prior exposure to anaesthesia.

Hemodynamics in Patients With Pheochromocytoma or Paraganglioma Undergoing Non-neuroendocrine Operations.

INTRODUCTION: Surgical resection of pheochromocytoma and paraganglioma (PPGL) may be associated with excessive hemodynamic variability. Whether hemodynamic variability occurs in patients with undiagnosed PPGL undergoing unrelated, non-neuroendocrine, operations is unknown. METHODS: We identified patients who underwent non-neuroendocrine surgical procedures up to 5 y before pathologic diagnosis of PPGL. For each PPGL, two non-PPGL patients were matched based on sex, age, type, and year of operation. Electronic medical records were reviewed for intraoperative blood pressures, heart rates, and hemodynamic variability was assessed with range (maximum-minimum), standard deviation, coefficient of variation, and average real variability. RESULTS: Thirty-seven PPGL patients underwent operations preceding the diagnosis of PPGL: 25 pheochromocytomas, 11 paragangliomas, and one metastatic pheochromocytoma. Median interquartile range tumor size at diagnosis was 35 mm (23 to 60). The time from index operation to PPGL diagnosis was ≤12 mo in 21 (56.8%) patients. In 23 (62.2%) patients, the subsequently diagnosed PPGL was functional. Fifteen (40.5%) PPGL and 20 (27.0%) control patients were preoperatively treated for hypertension (P = 0.149). Maximum intraoperative systolic BP was >180 mmHg for 4 (10.8%) PPGL patients and 3 (4.1%) controls (P = 0.219). Two PPGL patients had intraoperative systolic BP >230 mmHg. No significant differences were found with all other measures of intraoperative hemodynamic variability. Similarly, in secondary analysis there was no significant difference in intraoperative hemodynamic variability between biochemically active PPGL and their respective controls. CONCLUSIONS: Patients with undiagnosed PPGL undergoing a wide variety of non-neuroendocrine operations had intraoperative hemodynamic variability comparable to non-PPGL patients undergoing the same type of procedures.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

Disparities in Hypoxemia Detection by Pulse Oximetry Across Self-Identified Racial Groups and Associations With Clinical Outcomes.

OBJECTIVES: To assess disparities in hypoxemia detection by pulse oximetry across self-identified racial groups and associations with clinical outcomes. DESIGN: Observational cohort study from May 5, 2018, to December 31, 2020. SETTING: Three academic medical centers in the United States. PATIENTS: Adults greater than or equal to 18 years who self-identified as White, Black, Asian, or American Indian admitted to the ICU or undergoing surgery during inpatient hospitalization with simultaneous measurements of pulse oximetry-estimated oxygen saturation and arterial blood gas-derived oxygen saturation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariable models were employed to assess the relationships between race, occult hypoxemia (i.e., arterial blood gas-derived oxygen saturation < 88% despite pulse oximetry-estimated oxygen saturation ≥ 92%), and clinical outcomes of hospital mortality and hospital-free days. One-hundred twenty-eight-thousand two-hundred eighty-five paired pulse oximetry-estimated oxygen saturation-arterial blood gas-derived oxygen saturation measurements were included from 26,603 patients. Pulse oximetry-estimated oxygen saturation on average overestimated arterial blood gas-derived oxygen saturation by 1.57% (1.54-1.61%). Black, Asian, and American Indian patients were more likely to experience occult hypoxemia during hospitalization (estimated probability 6.2% [5.1-7.6%], 6.6% [4.9-8.8%], and 6.6% [4.4-10.0%], respectively) compared with White patients (3.6% [3.4-3.8%]). Black patients had increased odds of occult hypoxemia compared with White patients after adjustment (odds ratio, 1.65; 1.28-2.14; p < 0.001). Differences in occult hypoxemia between Asian and American Indian patients compared with White patients were not significant after adjustment (odds ratio, 1.53; 0.95-2.47; p = 0.077 and odds ratio, 1.31; 0.80-2.16; p = 0.288, respectively). Occult hypoxemia was associated with increased odds of mortality in surgical (odds ratio, 2.96; 1.20-7.28; p = 0.019) and ICU patients (1.36; 1.03-1.80; p = 0.033). Occult hypoxemia was associated with fewer hospital-free days in surgical (-2.5 d [-3.9 to -1.2 d]; p < 0.001) but not ICU patients (0.4 d [-0.7 to 1.4 d]; p = 0.500). CONCLUSIONS: Occult hypoxemia is more common in Black patients compared with White patients and is associated with increased mortality, suggesting potentially important outcome implications for undetected hypoxemia. It is imperative to validate pulse oximetry with expanded racial inclusion.

Longitudinal assessment of cognitive function in young children undergoing general anaesthesia.

BACKGROUND: Exposure to general anaesthesia in children may be related to deficits in certain areas of cognition. It is unclear if these deficits could be measured in the immediate postoperative period in young children. The goal of the current study was to evaluate the trajectory of cognitive function in the domains of processing speed, working memory, and fine motor skills amongst children aged 2.5-6 yr who underwent general anaesthesia for elective surgery. METHODS: Children who were scheduled to receive general anaesthesia for surgery were recruited for assessment of cognitive function at three times: preoperatively, 1-2 weeks postoperatively, and 3 months postoperatively. Assessments included processing speed, working memory, and fine motor skills. To assess longitudinal changes in the cognitive outcomes, linear mixed models were built with visit number included as a categorical variable and subject-specific random intercepts. RESULTS: Sixty-one children (33 girls [54%]) enrolled in the study. Twenty-three children (38%) had received general anaesthesia previously. Significant improvements in picture memory, cancellation, and the processing speed composite were found at Visit 2. The improvement in cancellation and processing speed composite remained significant at Visit 3. Statistically significant improvement in Mullen fine motor score was noticed at Visit 3 compared with Visit 1. The pattern of results did not depend upon prior anaesthesia exposure. CONCLUSIONS: General anaesthesia for elective surgery in young children was not associated with declines in working memory, processing speed, and fine motor skills in the first 3 months postoperatively, including in children with prior exposure to anaesthesia.

Implementation of a Comprehensive Patient Blood Management Program for Hospitalized Patients at a Large United States Medical Center.

OBJECTIVE: To assess changes in inpatient transfusion utilization and patient outcomes with implementation of a comprehensive patient blood management (PBM) program at a large US medical center. PATIENTS AND METHODS: This is an observational study of graduated PBM implementation for hospitalized adults (age ≥18 years) from January 1, 2010, through December 31, 2017, at two integrated hospital campuses at a major academic US medical center. Allogeneic transfusion utilization and clinical outcomes were assessed over time through segmented regression with multivariable adjustment comparing observed outcomes against projected outcomes in the absence of PBM activities. RESULTS: In total, 400,998 admissions were included. Total allogeneic transfusions per 1000 admissions decreased from 607 to 405 over the study time frame, corresponding to an absolute risk reduction for transfusion of 6.0% (95% confidence interval [CI]: 3.6%, 8.3%; P<.001) and a 22% (95% CI: 6%, 37%; P=.006) decrease in the rate of transfusions over projected. The risk of transfusion decreased for all blood components except cryoprecipitate. Transfusion reductions were experienced for all major surgery types except liver transplantation, which remained stable over time. Hospital length of stay (multiplicative increase in geometric mean 0.85 [95% CI: 0.81, 0.89]; P<.001) and incident in-hospital adverse events (absolute risk reduction: 1.5% [95% CI: 0.1%, 3.0%]; P=.04) were lower than projected at the end of the study time frame. CONCLUSION: Patient blood management implementation for hospitalized patients in a large academic center was associated with substantial reductions in transfusion utilization and improved clinical outcomes. Broad-scale implementation of PBM in US hospitals is feasible without signal for patient harm.

Etiology, incidence, and outcomes of patient-ventilator asynchrony in critically-ill patients undergoing invasive mechanical ventilation.

Patient-ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P < 0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P < 0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P < 0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.

Sex-Specific Associations Between Preoperative Anemia and Postoperative Clinical Outcomes in Patients Undergoing Cardiac Surgery.

BACKGROUND: Preoperative anemia is common in cardiac surgery, yet there were limited data describing the role of sex in the associations between anemia and clinical outcomes. Understanding these relationships may guide preoperative optimization efforts. METHODS: This is an observational cohort study of adults undergoing isolated coronary artery bypass grafting or single- or double-valve surgery from 2008 to 2018 at a large tertiary medical center. Multivariable regression assessed the associations between preoperative hemoglobin concentrations and a primary outcome of postoperative acute kidney injury (AKI) and secondary outcomes of perioperative red blood cell (RBC) transfusion, reoperation, vascular complications (ie, stroke, pulmonary embolism, and myocardial infarction), and hospital length of stay (LOS). Each outcome was a single regression model, using interaction terms to assess sex-specific associations between hemoglobin and outcome. RESULTS: A total of 4117 patients were included (57% men). Linear splines with sex-specific knots (13 g/dL in women and 14 g/dL in men) provided the best overall fit for preoperative hemoglobin and outcome relationships. In women, each 1 g/dL decrease in hemoglobin <13 g/dL was associated with increased odds of AKI (odds ratio = 1.49; 95% confidence interval [CI], [1.23-1.81]; P < .001), and there was no significant association between hemoglobin per 1 g/dL >13 g/dL and AKI (0.90 [0.56-1.45]; P = .67). The association between hemoglobin and AKI in men did not meet statistical significance (1.10 [0.99-1.22]; P = .076, per 1 g/dL decrease <14 g/dL; 1.00 [0.79-1.26]; P = .98 for hemoglobin per 1 g/dL >14 g/dL). In women, lower preoperative hemoglobin (per 1 g/dL decrease <13 g/dL) was associated with increased odds of RBC transfusion (2.90 [2.33-3.60]; P < .001), reoperation (1.27 [1.11-1.45]; P < .001) and a longer hospital LOS (multiplicative increase in geometric mean 1.05 [1.03-1.07]; P < .001). In men, preoperative hemoglobin (per 1 g/dL decrease <14 g/dL) was associated with increased odds of perioperative RBCs (2.56 [2.27-2.88]; P < .001) and longer hospital LOS (multiplicative increase in geometric mean 1.02 [1.01-1.04] days; P < .001) but not reoperation (0.94 [0.85-1.04]; P = .256). Preoperative hemoglobin per 1 g/dL >13 g/dL in women and 14 g/dL in men were associated with lower odds of RBCs transfusion (0.57 [0.47-0.69]; P < .001 and 0.74 [0.60-0.91]; P = .005, respectively). CONCLUSIONS: Preoperative anemia was associated with inferior clinical outcomes after cardiac surgery. The associations between hemoglobin and outcomes were distinct for women and men, with different spline knot points identified (13 and 14 g/dL, respectively). Clinicians should consider data-driven approaches to determine preoperative hemoglobin values associated with increasing risk for adverse perioperative outcomes across sexes.

The Prevalence and Clinical Significance of Preoperative Thrombocytopenia in Adults Undergoing Elective Surgery: An Observational Cohort Study.

BACKGROUND: Preoperative thrombocytopenia is associated with inferior outcomes in surgical patients, though concurrent anemia may obfuscate these relationships. This investigation assesses the prevalence and clinical significance of preoperative thrombocytopenia with thorough consideration of preoperative anemia status. METHODS: This is an observational cohort study of adults undergoing elective surgery with planned postoperative hospitalization from January 1, 2009 to May 3, 2018. Patients were designated into 4 groups: normal platelet and hemoglobin concentrations, isolated thrombocytopenia (ie, platelet count <100 × 109/L), isolated anemia (ie, hemoglobin <12 g/dL women, <13.5 g/dL men), and thrombocytopenia with anemia. Thrombocytopenia was further defined as incidental (ie, previously undiagnosed) or nonincidental. Multivariable regression analyses were utilized to assess the relationships between thrombocytopenia status and clinical outcomes, with a primary outcome of hospital length of stay. RESULTS: A total of 120,348 patients were included for analysis: 72.3% (95% confidence interval [CI], 72.1-72.6) normal preoperative laboratory values, 26.3% (26.1-26.6) isolated anemia, 0.80% (0.75-0.86) thrombocytopenia with anemia, and 0.52% (0.48-0.56) isolated thrombocytopenia (0.38% [0.34-0.41] nonincidental, 0.14% [0.12-0.17] incidental). Thrombocytopenia was associated with longer hospital length of stay in those with concurrent anemia (multiplicative increase of the geometric mean 1.05 [1.00, 1.09] days; P = .034) but not in those with normal preoperative hemoglobin concentrations (multiplicative increase of the geometric mean 1.02 [0.96, 1.07] days; P = .559). Thrombocytopenia was associated with increased odds for intraoperative transfusion regardless of anemia status (nonanemic: 3.39 [2.79, 4.12]; P < .001 vs anemic: 2.60 [2.24, 3.01]; P < .001). Thrombocytopenia was associated with increased rates of intensive care unit (ICU) admission in nonanemic patients (1.56 [1.18, 2.05]; P = .002) but not in those with preoperative anemia (0.93 [0.73, 1.19]; P = .578). CONCLUSIONS: Preoperative thrombocytopenia is associated with clinical outcomes in elective surgery, both in the presence and absence of concurrent anemia. However, isolated thrombocytopenia is rare (0.5%) and is usually identified before preoperative testing. It is unlikely that routine thrombocytopenia screening is indicated for most patients.

Hospital discharge hemoglobin values and posthospitalization clinical outcomes in transfused patients undergoing noncardiac surgery.

BACKGROUND: Red blood cell (RBC) transfusion is common in surgical patients, yet optimal transfusion targets are incompletely defined in the perioperative period. Hemoglobin levels at the time of hospital discharge may provide insight into transfusion practices, anemia management, and patient outcomes. STUDY DESIGN AND METHODS: This is an observational cohort study of adults receiving RBC transfusion during noncardiac surgery from 2010 to 2014. Multivariable regression was used to assess the relationships between hospital discharge hemoglobin concentrations, anemia severity (severe: <8 g/dL; moderate: 8-10 g/dL; mild/none: ≥10 g/dL), and clinical outcomes, including a primary outcome of 30-day hospital readmission and secondary outcomes of posthospitalization RBC transfusion, composite stroke or myocardial infarction, and mortality. RESULTS: A total of 3129 patients were included: 165 (5%) with severe discharge anemia, 1962 (63%) moderate, and 1002 (32%) with mild/none. Five hundred ninety-two (19%) were readmitted, with the highest rates observed with severe anemia (26% vs 19% for mild/none). Readmissions were not significantly different after multivariable adjustment (overall P = .216); however, in those receiving postoperative intensive care, severe anemia was associated with increased readmission rates (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.09-2.71; reference mild/none]. Posthospitalization RBC transfusion rates were highest with severe anemia (25% vs 10% for mild/none; adjusted HR, 2.2; 95% CI, 1.5-3.3; P < .001). There were no significant differences in composite stroke/myocardial infarction, or mortality. RBC transfusion volumes did not modify anemia-outcome relationships. CONCLUSION: Hospital discharge hemoglobin values for transfused surgical patients were not associated with hospital readmission rates except for those receiving postoperative intensive care. Further evaluation is warranted to understand downstream consequences of postsurgical anemia.

Association Between Spine Surgery and Availability of Opioid Medication.

Importance: Prolonged prescribing of opioids after spine surgery is often perceived as a negative outcome, but successful opioid reduction may occur despite continued prescribing. Improved characterization of opioid availability before and after surgery is necessary to identify these successes. Objective: To evaluate the association between spine surgery and modification of opioid availability postoperatively by using consistent definitions to classify opioid availability before and after surgery. Design, Setting, and Participants: This population-based cohort study included 2223 adults (age ≥18 years) who underwent spine surgery in Olmsted County, Minnesota, from January 1, 2005, through December 31, 2016. Data were analyzed from April 1, 2019, to December 1, 2019. Exposures: Preoperative opioid availability based on prescription data in the 180 days before surgery in accordance with Consortium to Study Opioid Risks and Trends (CONSORT) definitions. Main Outcomes and Measures: Successful modification of opioid availability, defined as an improvement in CONSORT status postoperatively (assessed from 181 to 365 days after surgery) compared with preoperative status, or continued absence of opioid availability for patients with no preoperative availability. Multivariable logistic regression was used to assess the association between preoperative opioid availability and successful modification by 1 year after undergoing surgery. Results: Of 2223 patients included in the study, 1214 were male (54.6%), with a median age of 55 years (interquartile range, 43-68) years. Patients were classified as having no (778 [35.0%]), short-term (1118 [50.3%]), episodic (227 [10.2%]), or long-term (100 [4.5%]) preoperative opioid availability. Of the 2148 patients (96.6%) who were alive at 1 year, postoperative opioid availability was classified as no (1583 [73.7%]), short-term (398 [18.5%]), episodic (104 [4.8%]), and long-term (63 [2.9%]). A total of 1672 patients (77.8%) had successful modification of opioid availability, with success of 83.0% for those with no preoperative availability, 74.9% for those with short-term preoperative availability, 79.8% for those with episodic preoperative availability, and 64.4% for those with long-term preoperative opioid availability. In multivariable analysis, success was significantly associated with preoperative opioid availability (odds ratio [OR] for short term, 0.61 [95% CI, 0.48-0.77]; OR for episodic, 0.95 [95% CI, 0.64-1.40]; OR long term, 0.49 [95% CI, 0.30-0.82]; P < .001 overall vs no availability). Conclusions and Relevance: In this study, when following standardized CONSORT definitions, 4 of 5 adults undergoing spine surgery in a population-based cohort met the criteria for a successful pattern of postoperative opioid prescribing. Similar methods to objectively assess changes in opioid prescribing may be clinically useful in other perioperative settings.

Exposure to surgery with general anaesthesia during adult life is not associated with increased brain amyloid deposition in older adults.

BACKGROUND: Exposure to surgery with general anaesthesia (surgery/GA) is associated with cortical atrophy, but the aetiology remains unknown. Amyloid-ß (Aß) deposition is one of the hallmark pathological characteristics of Alzheimer's disease (AD). We examined brain Aß burden in study participants exposed to surgery/GA. METHODS: We performed a cross-sectional analysis of residents of Olmsted County, MN, USA, in the Mayo Clinic Study of Aging who were aged 70-97 yr and underwent measurement of (i) brain Aß with Pittsburgh compound B positron emission tomography (PiB PET), (ii) brain glucose metabolism with 18-fluorodeoxyglucose (FDG) PET, and (iii) temporal cortical thickness with MRI. Separate analyses were performed with exposure to surgery/GA, defined as occurring after age 40 yr, and with exposure to surgery/GA, defined as occurring within 20 yr before neuroimaging. Imaging measurements were compared between participants who were exposed to surgery/GA vs not exposed. RESULTS: Of the 2563 participants, 585 had PET scans. Regardless of the definition used to quantify exposure, no significant associations were detected between exposure and either global PiB PET or FDG PET. In contrast, exposure to surgery/GA was associated with an increased likelihood of abnormal cortical thinning: odds ratio (OR)=1.98 (95% confidence interval [CI]: 1.19-3.31); P=0.010 in those exposed after age 40 yr, and OR=1.64 (95% CI: 1.05-2.55); P=0.029 in those exposed in the prior 20 yr. CONCLUSIONS: Exposure to surgery/GA is not associated with increases in cortical amyloid deposition. This finding suggests that the modest cortical thinning associated with surgery/GA is not related to AD pathology, but rather is caused by other processes.