Hanson, Andrew C.

OBJECTIVES: To provide a comparative analysis of conventional heparin-versus bivalirudin-based systemic anticoagulation in adult and pediatric patients supported on extracorporeal membrane oxygenation. DESIGN: Retrospective chart review study of adult and pediatric patients receiving extracorporeal membrane oxygenation from January 1, 2014, to October 1, 2019. SETTING: A large, high-volume tertiary referral adult and pediatric extracorporeal membrane oxygenation center. PATIENTS: Four hundred twenty-four individuals requiring extracorporeal membrane oxygenation support and systemically anticoagulated with either unfractionated heparin (223 adult and 65 pediatric patients) or bivalirudin (110 adult and 24 pediatric patients) were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Digital data abstraction was used to retrospectively collect patient details. The majority of both groups were cannulated centrally (67%), and the extracorporeal membrane oxygenation type was predominantly venoarterial (84%). The adult bivalirudin group had a greater occurrence of heparin-induced thrombocytopenia (12% vs 1%; p < 0.01) and was more likely to require postcardiotomy extracorporeal membrane oxygenation (36% vs 55%; p < 0.01). There were no statistical differences between the groups in regards to age, sex, and extracorporeal membrane oxygenation initiation location. The main finding was a reduced mortality in the adult bivalirudin group (odds ratio, 0.39; p < 0.01), whereas no difference was noted in the pediatric group. A significant reduction in the composite transfusion requirement in the first 24 hours was noted in the pediatric bivaluridin group with an odds ratio of 0.28 (p = 0.02). Groups did not differ in regard to laboratories per day, anticoagulant dose adjustments, or ischemic complications. CONCLUSIONS: When compared with heparin-based systemic anticoagulation, bivalirudin demonstrated feasibility and safety as established by the absence of increases in identifiable adverse outcomes while manifesting substantial improvements in hospital mortality in adult patients. Further studies are necessary to corroborate these findings and further elucidate the role of bivalirudin during extracorporeal membrane oxygenation support.

Abstract Background Hospitalization can impair physical and functional status of older adults, but it is unclear whether these deficits are transient or chronic. This study determined the association between hospitalization of older adults and changes in long-term longitudinal trajectories of 2 measures of physical and functional status: gait speed (GS) and instrumental activities of daily living measured with Functional Activities Questionnaire (FAQ). Method Linear mixed-effects models assessed the association between hospitalization (nonelective vs elective, and surgical vs medical) and outcomes of GS and FAQ score in participants (older than 60 years) enrolled in the Mayo Clinic Study of Aging who had longitudinal assessments. Results Of 4902 participants, 1879 had ≥1 hospital admission. Median GS at enrollment was 1.1 m/s. The slope of the annual decline in GS before hospitalization was −0.015 m/s. The parameter estimate (95% CI) for additional annual change in GS trajectory after hospitalization was −0.009 (−0.011 to −0.006) m/s, p &lt; .001. The accelerated GS decline was greater for medical versus surgical hospitalizations (−0.010 vs −0.003 m/s, p = .005), and nonelective versus elective hospitalizations (−0.011 vs −0.006 m/s, p = .067). The odds of a worsening FAQ score increased on average by 4% per year. Following hospitalization, odds of FAQ score worsening further increased (multiplicative annual increase in odds ratio per year [95% CI] following hospitalization was 1.05 [1.03, 1.07], p &lt; .001). Conclusions Hospitalization of older adults is associated with accelerated long-term decline in GS and functional limitations, especially after nonelective admissions and those for medical indications. However, for most well-functioning participants, these changes have little clinical significance.

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.

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 × 10 9 /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.

AbstractBackgroundThe potential adverse effects of exposures to general anesthesia on the developing human brain remain controversial. It has been hypothesized that hypotension accompanying anesthesia could be contributory. We hypothesized that among children exposed to multiple anesthetics prior to age 3, children developing adverse neurodevelopmental outcomes would be more likely to have intraoperative hypotension.MethodsTwo previously published study cohorts were utilized for analysis: the retrospective and prospective Mayo Anesthesia Safety in Kids cohorts. The two lowest consecutive systolic blood pressure measurements were abstracted and standardized by calculating a z‐score for noninvasive blood pressure reference ranges for children. The lowest systolic blood pressure z‐score (continuous variable) and intraoperative hypotension (lowest systolic blood pressure z‐score <−1.0) were used to assess the association of intraoperative hypotension with the incidence of learning disabilities or attention‐deficit/hyperactivity disorder(retrospective cohort) and factor scores/cluster membership (prospective cohort).ResultsOne hunderd and sixteen and 206 children with multiple exposures to general anesthesia were analyzed in the retrospective and prospective cohorts with mean lowest systolic blood pressure z‐scores −0.26 (SD 1.02) and −0.62 (SD 1.10), respectively. There was no overall association of the lowest z‐score or hypotension with learning disabilities or attention‐deficit/hyperactivity disorder in the retrospective cohort. In the prospective cohort, there was no overall association of the lowest systolic blood pressure or hypotension with factor scores or cluster membership.ConclusionsWe did not find evidence to support the hypothesis that, among children exposed to multiple anesthetics prior to age 3, children developing adverse neurodevelopmental outcomes would be more likely to have intraoperative hypotension compared with those who did not.

Abstract Background: 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.Methods: A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥12 hours.Results: 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).Conclusion: 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.

Abstract BackgroundAcute respiratory failure associated with sepsis contributes to higher in-hospital mortality. Intubation and invasive mechanical ventilation is a common rescue procedure. However, the 2016 International Guidelines for Management of Sepsis and Septic Shock does not provide any recommendation on indication nor timing of intubation. Timely intubation may improve outcome. The decision to intubate those patients is often hampered by the fear of further hemodynamic deterioration following intubation. MethodsThis study aimed at evaluating the impact of timely intubation on outcome in sepsis associated respiratory failure. We conducted an ancillary analysis of a prospective registry od adult ICU patients with septic shock admitted to the medical ICU in a tertiary medical center, between April 30th, 2014 and December 31st, 2017. All cases of sepsis with lactate >4 mmol/L, mean arterial pressure <65 mmHg, or vasopressor use after 30 mL/kg fluid boluses and suspected or confirmed infection. Patients who remained hospitalized at 24 hours following sepsis onset were separated into intubated and non-intubated groups. The primary outcome was hospital mortality. Univariate and multivariable analyses were used, adjusted for admission characteristics and stabilization of shock within 6 hours. In a secondary analysis, time-dependent propensity score matching was used to match intubated and non-intubated patients.ResultsWe identified 345 (33%) patients intubated within 24 hours and 707 (67%) not intubated. Intubated patients were younger, transferred more often from an outside facility, had higher severity of illness scores, more lung infection, achieved blood pressure goals more often but less often lactate normalization within 6 hours. The crude in-hospital mortality was higher, 89 (26%) vs. 82 (12%), p<0.001, as were ICU mortality, and ICU and hospital length of stay. After adjustment, intubation showed no effect on hospital mortality but fewer hospital-free days through day 28. After 1:1 propensity score matching, there was no difference in hospital mortality, but fewer hospital-free days in the intubated group. ConclusionsIntubation within 24 hours of sepsis onset was safe and not associated with hospital mortality, but was associated with less 28-day hospital-free days. Intubation should not be discouraged in appropriate patients with septic shock.

IMPORTANCE Hospitalizations are associated with cognitive decline in older adults. OBJECTIVE To determine the association between hospitalization characteristics and the trajectory of cognitive function in older adults. DESIGN Population‐based longitudinal study of cognitive aging. SETTING Olmsted Medical Center and Mayo Clinic, the only centers in Olmsted County, Minnesota, with hospitalization capacity. PARTICIPANTS Individuals without dementia at baseline, with consecutive cognitive assessments from 2004 through 2017, and at least one visit after the age of 60. MEASUREMENTS The primary outcome was longitudinal changes in global cognitive z ‐score. Secondary outcomes were changes in four cognitive domains: memory, attention/executive function, language, and visuospatial skills. Hospitalization characteristics analyzed included elective versus nonelective, medical versus surgical, critical care versus no critical care admission, and long versus short duration admissions. RESULTS Of 4,587 participants, 1,622 had 1 and more hospital admission. Before hospitalization, the average slope of the global z ‐score was −0.031 units/year. After hospitalization, the rate of annual global z ‐score accelerated by −0.051 (95% CI = −0.057, −0.045) units, P < .001, resulting in an estimated annual slope after the first hospitalization of −0.082. The accelerated decline was found in all four cognitive domains (memory, visuospatial, language, and executive, all P < .001). The acceleration of the decline in global z ‐score following hospitalization was greater for medical compared to surgical hospitalizations (slope change following hospitalization = −0.064 vs −0.034 for medical vs surgical, P < .001), and nonelective compared to elective admissions (slope change following hospitalization = −0.075 vs −0.037 for nonelective vs elective, P < .001). The acceleration of cognitive decline was not different for hospitalization with intensive care unit admission versus not. CONCLUSIONS Hospitalization of older adults is associated with accelerated decline of global and domain‐specific cognitive domains, with the rate of decline dependent upon type of admission. The clinical impact of this accelerated decline will depend on the individual's baseline cognitive reserve and expected longevity.

AbstractBackground and ObjectivesOptimizing perioperative analgesia for patients undergoing major lower‐extremity amputation remains a considerable challenge. The utility of liposomal bupivacaine as a component of peripheral nerve blockade for lower‐extremity amputation is unknown.MethodsWe conducted an observational study comparing three different perioperative analgesic techniques for adults undergoing major lower‐extremity amputation under general anesthesia between 2012 and 2017 at an academic medical center: (1) no regional anesthesia, (2) peripheral nerve blockade with standard bupivacaine, and (3) peripheral nerve blockade with a mixture of standard and liposomal bupivacaine. The primary outcome of cumulative opioid oral morphine milligram equivalent utilization in the first 72 hours postoperatively was compared across groups utilizing multivariable linear regression.ResultsA total of 631 unique anesthetics were included for 578 unique patients, including 416 (66%) without regional anesthesia, 131 (21%) with peripheral nerve blockade with a mixture of standard and liposomal bupivacaine, and 84 (13%) with peripheral nerve blockade with standard bupivacaine alone. Cumulative morphine equivalents were lower in those receiving peripheral nerve blockade with combined standard and liposomal bupivacaine compared with those not receiving regional anesthesia (multiplicative increase 0.67; 95% CI 0.50 to 0.90; P = 0.007). There were no significant differences in opioid utilization between peripheral nerve blockade groups (P = 0.59).ConclusionsPeripheral nerve blockade is associated with reduced opioid requirements after lower‐extremity amputation compared with general anesthesia alone. However, the incorporation of liposomal bupivacaine is not significantly different to blockade employing only standard bupivacaine.