Additional predictors of the lower limit of cerebral autoregulation during cardiac surgery.

OBJECTIVES: The lower limit of autoregulation (LLA) of cerebral blood flow was previously shown to vary directly with the Ambulatory Arterial Stiffness Index (AASI) redefined as 1-regression slope of DBP-versus-SBP readings invasively measured from the radial artery before the bypass. We aimed expanding the predictive capacity of the LLA with AASI by combining it with additional predictors and provide new indications whether mean arterial pressure (MAP) is above/below the LLA. DESIGN AND METHOD: In 181 patients undergoing cardiac surgery, mean (SD) age 71 (8) years), we identified from the demographic, preoperative and intraoperative characteristics independent and statistically significant 'single predictors' of the LLA (including AASI). This was achieved using multivariate linear regression with a backward-elimination technique. The single predictors combined with 1-AASI generated new multiplicative and additive composite predictors of the LLA. Indicators for the MAP-to-LLA difference (DIF) were determined using DIF-versus-predictor plots. The odds ratio (OR) for the DIF sign (Outcome = 1 for DIF≤0) and predictor-minus-median sign (Exposure = 1 for Predictor  ≤ Median) were calculated using logistic regression. RESULTS: BMI, 1-AASI and systolic coefficient of variation were identified single predictors that correlated similarly with the LLA ( r  = -0.26 to -0.27, P  < 0.001). The multiplicative and additive composite predictors displayed higher correlation with LLA ( r  = -0.41 and r  = -0.43, respectively, P  < 0.001) and improved LLA estimation. The adjusted OR for the composite predictors was nearly twice that of the single predictors. CONCLUSION: The novel composite predictors may enhance the LLA estimation and the ability to maintain MAP in the cerebral autoregulatory range during cardiac surgery.

Comprehensive quality initiative leads to immediate postoperative extubation following liver transplant.

BACKGROUND: Immediate postoperative extubation (IPE) can reduce perioperative complications and length of stay (LOS), however it is performed variably after liver transplant across institutions and has historically excluded high-risk recipients from consideration. In late 2012, we planned and implemented a single academic institution structured quality improvement (QI) initiative to standardize perioperative care of liver transplant recipients without exceptions. We hypothesized that such an approach would lead to a sustained increase in IPE after primary (PAC) and delayed abdominal closure (DAC). METHODS: We retrospectively studied 591 patients from 2013 to 2018 who underwent liver transplant after initiative implementation. We evaluated trends in incidence of IPE versus delayed extubation (DE), and reintubation, LOS, and mortality. RESULTS: Overall, 476/591 (80.5%) recipients underwent PAC (278 IPE, 198 DE) and 115/591 (19.5%) experienced DAC (39 IPE, 76 DE). When comparing data from 2013 to data from 2018, the incidence of IPE increased from 9/67 (13.4%) to 78/90 (86.7%) after PAC and from 1/12 (8.3%) to 16/23 (69.6%) after DAC. For the same years, the incidence of IPE after PAC for recipients with MELD scores ≥30 increased from 0/19 (0%) to 12/17 (70.6%), for recipients who underwent simultaneous liver-kidney transplant increased from 1/8 (12.5%) to 4/5 (80.0%), and for recipients who received massive transfusion (>10 units of packed red blood cells) increased from 0/17 (0%) to 10/13 (76.9%). Reintubation for respiratory considerations <48 h after IPE occurred in 3/278 (1.1%) after PAC and 1/39 (2.6%) after DAC. IPE was associated with decreased intensive care unit (HR of discharge: 1.92; 95% CI: 1.58, 2.33; P < 0.001) and hospital LOS (HR of discharge: 1.45; 95% CI: 1.20, 1.76; P < 0.001) but demonstrated no association with mortality. CONCLUSION: A structured QI initiative led to sustained high rates of IPE and reduced LOS in all liver transplant recipients, including those classified as high risk.

Measurement of Information Transfer During Simulated Sequential Complete Shift-to-Shift Intraoperative Handoffs.

Objective: To determine information transfer during simulated shift-to-shift intraoperative anesthesia handoffs and the benefits of using a handoff tool. Patients and Methods: Anesthesiology residents and faculty participating in simulation-based education in a simulation center on April 6 and 20, 2017, and April 11 and 25, 2019. We used a fixed clinical scenario to compare information transfer in multiple sequential simulated handoff chains conducted from memory or guided by an electronic medical record generated tool. For each handoff, 25 informational elements were assessed on a discrete 0-2 scale generating a possible information retention score of 50. Time to handoff completion and number of clarifications requested by the receiver were also determined. Results: We assessed 32 handoff chains with up to 4 handoffs per chain. When both groups were combined, the mean information retention score was 31 of 50 (P<.001) for the first clinician and declined by an average of 4 points per handoff (P<.001). The handoff tool improved information retention by almost 7 points (P=.002), but did not affect the rate of information degradation (P=.38). Handoff time remained constant for the intervention group (P=.67), but declined by 2 minutes/handoff (P<.001) in the control group, which required 7 more clarifications/handoff (P=.003). In the control group, 7 of 16 (44%) handoff chains contained one or more information retention scores below the lowest score of the entire intervention group (P=.007). Conclusion: Clinical handoffs are accompanied by degradation of information that is only partially reduced by use of a handoff tool, which appears to prevent extremes of information degradation.

Prophylactic Recombinant Factor VIIa for Preventing Massive Transfusion During Orthotopic Liver Transplantation.

OBJECTIVES: RecombinanthumanactivatedfactorVIIahas been usedprophylactically to mitigate requirements for transfusion in liver transplant. We explored its effectiveness andrisks amonglivertransplantrecipients at high risk for massive transfusion. MATERIALS AND METHODS: We performed a retrospective study of recipients who underwent liver transplant from 2012 to 2015. Patients considered at risk for massive transfusion received up to two 20 µg/kg doses of recombinant human activated factor VIIa, with rescue use permitted for other patients. We used propensity matching to determine the average treatment effectson patients who received recombinant human activated factor VIIa prophylactically to prevent massive transfusion. We determined thromboembolic events from medical record review. RESULTS: Of 234 liver transplant recipients, 38 received prophylactic and 2 received rescue recombinant human activated factor VIIa. We used a prediction model to readily identify those who would receive prophylactic recombinant human activated factorVIIa (C statistic = 0.885; 95% CI, 0.835-0.935). Propensity matching achieved balance, particularly for massive transfusion. Twenty-three of 38 patients (60.5%) who received recombinant human activated factorVIIa and 47 of 76 matched controls (61.8%) experienced massive transfusion. The coefficient for the average treatment effect of prophylactic administration was - 0.013 (95% CI, -0.260 to 0.233; P = .92). The cohorts exhibited no difference in number ofthromboembolic events (P > .99), although fatal events occurred in 1 patient who had prophylactic and 1 patient who had rescue recombinant human activated factor VIIa. CONCLUSIONS: Prophylactic recombinanthumanactivated factor VIIa use in patients at elevated risk of massive transfusion did not affect incidence of massive transfusion and was not associated with an increase in thromboembolic events overall. The lack of clinical benefit and the potential for fatal throm-boembolic events observed with recombinant human activated factor VIIa precluded its prophylactic use in liver transplant recipients.

Case Series in the Utility of Invasive Blood Pressure Monitoring in Microvascular Decompression.

BACKGROUND: The utility of arterial lines in microvascular decompression (MVD) is not well described. OBJECTIVE: To examine the safety and costs of arterial lines compared with noninvasive blood pressure (NIBP) monitoring in MVDs. METHODS: We retrospectively reviewed patients undergoing MVD from 2012 to 2020. Patients were grouped by procedure date from 2012 to 2014 and 2015 to 2020, reflecting our institution's decreasing trend in arterial line placement around 2014 to 2015. Patient features, intraoperative characteristics, and postoperative complications were collected for all cases. Statistical differences were evaluated using chi-squared analyses and t-tests. RESULTS: Eight hundred fifty-eight patients underwent MVDs, with 204 between 2012 and 2014 and 654 between 2015 and 2020. Over time, the frequency of arterial line placement decreased from 64.2% to 30.1%, P < .001. Arterial lines involved 11 additional minutes of preincision time, P < .001. Patients with arterial lines required both increased doses and costs of vasoactive medications intraoperatively. Patients receiving arterial lines demonstrated no significant differences in complications compared with patients with NIBP monitoring. On average, patients with arterial lines incurred $802 increased costs per case compared with NIBP monitoring. CONCLUSION: NIBP monitoring in MVDs provides neurologically and hemodynamically safe outcomes compared with invasive blood pressure monitoring. For patients without significant cardiopulmonary risk factors, NIBP monitoring may be a cost-effective alternative in MVDs.

Brain water as a function of age and weight in normal rats.

Rats are frequently used for studying water content of normal and injured brain, as well as changes in response to various osmotherapeutic regimens. Magnetic resonance imaging in humans has shown that brain water content declines with age as a result of progressive myelination and other processes. The purpose of this study was to quantify changes in brain water content during rat development and aging. Brain water content was measured by standard techniques in 129 normal male Sprague-Dawley rats that ranged in age (weight) from 13 to 149 days (18 to 759 g). Overall, the results demonstrated a decrease in water content from 85.59% to 76.56% with increasing age (weight). Nonlinear allometric functions relating brain water to age and weight were determined. These findings provide age-related context for prior rat studies of brain water, emphasize the importance of using similarly aged controls in studies of brain water, and indicate that age-related changes in brain water content are not specific to humans.

Effects of Volume Replacement for Urinary Losses from Mannitol Diuresis on Brain Water in Normal Rats.

BACKGROUND/OBJECTIVE: It is frequently recommended that urine output following perioperative mannitol administration be replaced 1:1 with an isotonic crystalloid solution. It is possible that this strategy could increase brain water by reducing the serum osmolality achieved with prior mannitol administration. Therefore, brain water content of rats treated with mannitol alone or mannitol plus normal saline (NS) was studied over a range of urinary replacement ratios. METHODS: Male Wister rats received mannitol 3.2 gm/100 gm infused over 45 min followed by hourly determinations of urine output (UO). Control animals received no additional therapy, whereas animals undergoing intervention received hourly replacement of their urinary losses with 0.9% NS in decreasing NS:UO ratios (1:1, 1:2, 1:3). Three hours after completion of the mannitol infusion, a final tally of UO was made. At that time in all animals, blood was obtained for determination of hemoglobin and electrolyte concentrations and plasma osmolality. Following that, the animals were sacrificed to determine brain water content. Additional groups underwent the same protocol but for 5 h with 1:1 urinary replacement, or received a volume of NS equal to that of the mannitol administered to all other control and intervention animals. RESULTS: 1:1 replacement of urinary loss with NS following mannitol administration was associated with brain water content indistinguishable from control animals receiving only a volume of NS equal to that of the mannitol administered to all other groups. Regression analysis demonstrated a decrease in the final brain water content of 0.67% (CI95 0.43-0.92, p < 0.001) per replacement level as NS:UO replacement ratios were decreased from 1:1 to 1:2 and, finally to 1:3. At the final NS:UO replacement ratio of 1:3, brain water content was indistinguishable from the control group receiving mannitol without NS replacement (p = 0.48) For 1:1 replacement following mannitol, brain water did not differ between experiments of 3 or 5 h duration (p = 0.52). CONCLUSIONS: In rats, NS replacement of UO 1:1 following mannitol administration leads to brain water content no different than if NS had been given in place of mannitol. Only when the NS:UO replacement ratio was 1:3, brain water was similar to that of control animals receiving mannitol alone. The recommendation to replace UO 1:1 with an equal volume of isotonic crystalloid following perioperative mannitol administration must recognize how this strategy could elevate brain water content compared to less vigorous replacement of UO.

Altered neuronal excitability in a Hodgkin-Huxley model incorporating channelopathies of the delayed rectifier potassium channel.

Channelopathies involving acquired or genetic modifications of the delayed rectifier K+ channel Kv1.1 include phenotypes characterized by enhanced neuronal excitability. Affected Kv1.1 channels exhibit combinations of altered expression, voltage sensitivity, and rates of activation and deactivation. Computational modeling and analysis can reveal the potential of particular channelopathies to alter neuronal excitability. A dynamical systems approach was taken to study the excitability and underlying dynamical structure of the Hodgkin-Huxley (HH) model of neural excitation as properties of the delayed rectifier K+ channel were altered. Bifurcation patterns of the HH model were determined as the amplitude of steady injection current was varied simultaneously with single parameters describing the delayed rectifier rates of activation and deactivation, maximal conductance, and voltage sensitivity. Relatively modest changes in the properties of the delayed rectifier K+ channel analogous to what is described for its channelopathies alter the bifurcation structure of the HH model and profoundly modify excitability of the HH model. Channelopathies associated with Kv1.1 can reduce the threshold for onset of neural activity. These studies also demonstrate how pathological delayed rectifier K+ channels could lead to the observation of the generalized Hopf bifurcation and, perhaps, other variants of the Hopf bifurcation. The observed bifurcation patterns collectively demonstrate that properties of the nominal delayed rectifier in the HH model appear optimized to permit activation of the HH model over the broadest possible range of input currents.

Opioid-Sparing Cardiac Anesthesia: Secondary Analysis of an Enhanced Recovery Program for Cardiac Surgery.

BACKGROUND: Cardiac anesthetics rely heavily on opioids, with the standard patient receiving between 70 and 105 morphine sulfate equivalents (MSE; 10-15 µg/kg of fentanyl). A central tenet of Enhanced Recovery Programs (ERP) is the use of multimodal analgesia. This study was performed to assess the association between nonopioid interventions employed as part of an ERP for cardiac surgery and intraoperative opioid administration. METHODS: This study represents a post hoc secondary analysis of data obtained from an institutional ERP for cardiac surgery. Consecutive patients undergoing cardiac surgery received 5 nonopioid interventions, including preoperative gabapentin and acetaminophen, intraoperative dexmedetomidine and ketamine infusions, and regional analgesia via serratus anterior plane block. The primary objective, the association between intraoperative opioid administration and the number of interventions provided, was assessed via a linear mixed-effects regression model. To assess the association between intraoperative opioid administration and postoperative outcomes, patients were stratified into high (>50 MSE) and low (≤50 MSE) opioids, 1:1 propensity matched based on 15 patients and procedure covariables and assessed for associations with postoperative outcomes of interest. To investigate the impact of further opioid restriction, ultralow (≤25 MSE) opioid participants were then identified, 1:3 propensity matched to high opioid patients, and similarly compared. RESULTS: A total of 451 patients were included in the overall analysis. Analysis of the primary objective revealed that intraoperative opioid administration was inversely related to the number of interventions employed (estimated -7.96 MSE per intervention, 95% confidence interval [CI], -9.82 to -6.10, P < .001). No differences were detected between low (n = 136) and high (n = 136) opioid patients in postoperative complications, postoperative pain scores, time to extubation, or length of stay. No differences were found in outcomes between ultralow (n = 63) and high (n = 132) opioid participants. CONCLUSIONS: Nonopioid interventions employed as part of an ERP for cardiac surgery were associated with a reduction of intraoperative opioid administration. Low and ultralow opioid use was not associated with significant differences in postoperative outcomes. These findings are hypothesis-generating, and future prospective studies are necessary to establish the role of opioid-sparing strategies in the setting of cardiac surgery.

Validation of predictive models identifying patients at risk for massive transfusion during liver transplantation and their potential impact on blood bank resource utilization.

BACKGROUND: Intraoperative massive transfusion (MT) is common during liver transplantation (LT). A predictive model of MT has the potential to improve use of blood bank resources. STUDY DESIGN AND METHODS: Development and validation cohorts were identified among deceased-donor LT recipients from 2010 to 2016. A multivariable model of MT generated from the development cohort was validated with the validation cohort and refined using both cohorts. The combined cohort also validated the previously reported McCluskey risk index (McRI). A simple modified risk index (ModRI) was then created from the combined cohort. Finally, a method to translate model predictions to a population-specific blood allocation strategy was described and demonstrated for the study population. RESULTS: Of the 403 patients, 60 (29.6%) in the development and 51 (25.5%) in the validation cohort met the definition for MT. The ModRI, derived from variables incorporated into multivariable model, ranged from 0 to 5, where 1 point each was assigned for hemoglobin level of less than 10 g/dL, platelet count of less than 100 × 109 /dL, thromboelastography R interval of more than 6 minutes, simultaneous liver and kidney transplant and retransplantation, and a ModRI of more than 2 defined recipients at risk for MT. The multivariable model, McRI, and ModRI demonstrated good discrimination (c statistic [95% CI], 0.77 [0.70-0.84]; 0.69 [0.62-0.76]; and 0.72 [0.65-0.79], respectively, after correction for optimism). For blood allocation of 6 or 15 units of red blood cells (RBCs) based on risk of MT, the ModRI would prevent unnecessary crossmatching of 300 units of RBCs/100 transplants. CONCLUSIONS: Risk indices of MT in LT can be effective for risk stratification and reducing unnecessary blood bank resource utilization.

Effect of baseline cognitive impairment on association between predicted propofol effect site concentration and Bispectral index or sedation score.

BACKGROUND: This study determined whether the relationship between predicted propofol effect site concentration (Ce) and observer's assessment of alertness/sedation scale (OAA/S) or Bispectral Index (BIS) was similar comparing cognitively intact vs impaired patients undergoing hip fracture repair with spinal anesthesia and sedation. METHODS: Following informed consent baseline mini-mental status exam (MMSE), Clinical Dementia Rating (CDR) and geriatric depression scale (GDS) were obtained. Intraoperatively OAA/S, BIS, and propofol (timing and exact amounts) administered were recorded. Cerebrospinal fluid was collected for Alzheimer's (AD) biomarkers. Mean Ce level (AvgCe) during surgery was calculated using the area under the Ce measurement series from incision to closure, divided by surgical time. Average OAA/S (AvgOAA/S), and BIS (AvgBIS) were similarly calculated. Pearson correlations of AvgCe with AvgOAA/S and AvgBIS were calculated overall and by CDR. Nonparametric locally weighted scatterplot smoothing (LOWESS) fits of AvgOAA/S and AvgBIS on AvgCe were produced, stratified by CDR. Multivariable regression incorporating baseline cognitive measurements or AD biomarkers assessed AvgOAA/S or AvgBIS associations with AvgCe. RESULTS: In 186 participants AvgBIS and AvgOAA/S correlated with AvgCe (Pearson ρ = - 0.72; p < 0.0001 and Pearson ρ = - 0.81; p < 0.0001, respectively), and remained unchanged across CDR levels. Association patterns of AvgOAA/S or AvgBIS on AvgCe guided by LOWESS fits and modeled through regression, were similar when stratified by CDR (p = 0.16). Multivariable modeling found no independent effect on AvgBIS or AvgOAA/S by MMSE, CDR, GDS, or AD biomarkers after accounting for AvgCe. CONCLUSIONS: When administering sedation in conjunction with spinal anesthesia, cognitive impairment does not affect the relationship between predicted propofol AvgCe and AvgOAA/S or AvgBIS.

General Anesthesia Alters Intracranial Venous Pressures During Transverse Sinus Stenting.

INTRODUCTION: Pressure gradients across venous stenosis are used as a marker for physiologically significant narrowing in idiopathic intracranial hypertension. Performing such measurements under conscious sedation (CS) more likely reflects physiologic conditions, but can be uncomfortable, leading some operators to perform measurement under general anesthesia (GA), though this may not be equivalent. METHODS: We performed a retrospective analysis of patients who received endovascular transverse sinus stenting due to idiopathic intracranial hypertension between August 2013 and May 2017. Patients' demographics and anesthetic parameters were collected along with venous pressure measurements. RESULTS: We identified 15 patients (14 women). The mean (SD) age was 30.5 (9.0) years and the mean body mass index (SD) was 39.5 (9.6) kg/m2. After measurements during CS, GA was induced with propofol and maintained with a volatile anesthetic. The median [IQR; range] transverse sinus pressure gradient under CS was 18 [12, 25; 6-38] mmHg compared with 14 [8, 21; 3-26] mm Hg under GA. The median [IQR; range] pressure gradient change after initiation of GA was -3 [-12, 0; -22 to 9] mm Hg (P = 0.014). After correction for increases in internal jugular vein pressures associated with assumption of GA, the median [IQR; range] gradient change was -11 [-12.5, -5; -22 to 0] mm Hg (P < 0.001). CONCLUSIONS: The transition from CS to GA results in clinically meaningful reductions in transverse sinus gradients in idiopathic intracranial hypertension. Correction for increases in the internal jugular vein pressures reveals even more dramatic reductions in transverse sinus gradients.

Anesthesia Simulation Boot Camp-a Decade of Experience Enhancing Self-efficacy in First-year Residents.

BACKGROUND: Novice anesthesiology residents must acquire new technical, cognitive, and behavioral skills as they transition into the high-stakes perioperative environment. Simulation-based education improves procedural skill and behavior, and it permits deliberate practice with feedback; exposure to uncommon, high-consequence events; assessment; reproducibility; and zero risk to patients. We introduced a 5-day, high-fidelity Simulation Boot Camp (SBC) in 2006 for first-year clinical anesthesia residents (CA-1s) and report over a decade of experience assessing its impact on self-efficacy, value, feasibility, and sustainability. METHODS: All CA-1s in our residency program participated in the SBC as part of orientation. Participants completed 2 individual high-fidelity simulations per day, each with a private debriefing session from an attending anesthesiologist in our simulation center. We measured their self-reported confidence, which we report as self-efficacy (SE), the belief in one's own ability to successfully execute a skill or behavior necessary for a desired outcome, for 25 basic anesthesia skills before and after course completion. Participants also completed a postcourse evaluation. RESULTS: Of the 281 CA-1s who participated in the course from 2006 to 2016, we collected data on 267 (95%). SE improved over the course of SBC for all 25 individual skills (P < .001) and remained stable over the decade-long period of study. Univariate analysis revealed a strong association between increased SE and male sex (P < .001), video gaming experience (P < .001), and completion of a prior residency (P = .018). Males were also more likely to report video gaming experience (P < .001). Multivariable analysis revealed that although women had lower SE than did men, they had a greater increase in SE attributed to participation in SBC (P = .041). Participants strongly agreed SBC was a realistic and nonjudgmental learning tool, built confidence, and should be mandatory. Most comments were positive, reflecting overall satisfaction with SBC. CONCLUSIONS: SBC increases SE, is feasible, valuable to participants, and sustainable with remarkably consistency over the study period.

Ventilator Alarms in Intensive Care Units: Frequency, Duration, Priority, and Relationship to Ventilator Parameters.

Ventilator alarms have long been presumed to contribute substantially to the overall alarm burden in the intensive care unit. In a prospective observational study, we determined that each ventilator triggered an alarm cascade of up to 8 separate notifications once every 6 minutes. In 1 intensive care unit with different ventilator manufacturers, the distribution of high-priority alarms was manufacturer dependent with 8.6% of alarms from 1 type and 89.8% of alarms from another type of ventilator. Alarm limits were not a function of patient-specific ventilator settings.

Day-Night Activity in Hospitalized Children after Major Surgery: An Analysis of 2271 Hospital Days.

OBJECTIVES: To characterize the day-night activity patterns of children after major surgery and describe differences in children's activity patterns between the pediatric intensive care unit (PICU) and inpatient floor setting. STUDY DESIGN: In this prospective observational study, we characterized the daytime activity ratio estimate (DARE; ratio between mean daytime activity [08:00-20:00] and mean 24-hour activity [00:00-24:00]) for children admitted to the hospital after major surgery. The study sample included 221 infants and children ages 1 day to 17 years admitted to the PICU at a tertiary, academic children's hospital. Subjects were monitored with continuous accelerometry from postoperative day 1 until hospital discharge. The National Health and Nutrition Examination Survey accelerometry data were utilized for normative data to compare DARE in a community sample of US children to hospitalized children. RESULTS: The mean DARE over 2271 hospital days was 57.8%, with a significant difference between the average DARE during PICU days and inpatient floor days (56% vs 61%, P < .0001). The average subject DARE ranged from 43% to 73%. In a covariate-adjusted mixed effects model, PICU location, lower age, orthopedic or urologic surgery, and intubation time were associated with decreased DARE. Hospitalized children had significantly lower DARE than the National Health and Nutrition Examination Survey subjects in all age groups studied, with the largest difference in the youngest PICU group analyzed (6-9 years; 59% vs 75%, P < .0001). A subset analysis of children older than 2 years (n = 144) showed that DARE was <50% on 15% of hospital days. CONCLUSIONS: Children hospitalized after major surgery experience disruptions in day-night activity patterns during their hospital stay that may reflect disturbances in circadian rhythm.

Depth of sedation as an interventional target to reduce postoperative delirium: mortality and functional outcomes of the Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients randomised clinical trial.

BACKGROUND: The Strategy to Reduce the Incidence of Postoperative Delirium in the Elderly trial tested the hypothesis that limiting sedation during spinal anaesthesia decreases in-hospital postoperative delirium after hip fracture repair. This manuscript reports the secondary outcomes of this trial, including mortality and function. METHODS: Two hundred patients (≥65 yr) undergoing hip fracture repair with spinal anaesthesia were randomised to heavier [modified Observer's Assessment of Alertness/Sedation score (OAA/S) 0-2] or lighter (OAA/S 3-5) sedation, and were assessed for postoperative delirium. Secondary outcomes included mortality and return to pre-fracture ambulation level at 1 yr. Kaplan-Meier analysis, multivariable Cox proportional hazard model, and logistic regression were used to evaluate intervention effects on mortality and odds of ambulation return. RESULTS: One-year mortality was 14% in both groups (log rank P=0.96). Independent risk factors for 1-yr mortality included: Charlson comorbidity index [hazard ratio (HR)=1.23, 95% confidence interval (CI), 1.02-1.49; P=0.03], instrumental activities of daily living [HR=0.74, 95% CI, 0.60-0.91; P=0.005], BMI [HR=0.91, 95% CI 0.84-0.998; P=0.04], and delirium severity [HR=1.20, 95% CI, 1.03-1.41; P=0.02]. Ambulation returned to pre-fracture levels, worsened, or was not obtained in 64%, 30%, and 6% of 1 yr survivors, respectively. Lighter sedation did not improve odds of ambulation return at 1 yr [odds ratio (OR)=0.76, 95% CI, 0.24-2.4; P=0.63]. Independent risk factors for ambulation return included Charlson comorbidity index [OR=0.71, 95% CI, 0.53-0.97; P=0.03] and delirium [OR=0.32, 95% CI, 0.10-0.97; P=0.04]. CONCLUSIONS: This study found that in elderly patients having hip fracture surgery with spinal anaesthesia supplemented with propofol sedation, heavier intraoperative sedation was not associated with significant differences in mortality or return to pre-fracture ambulation up to 1 yr after surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00590707.

Effect of Depth of Sedation in Older Patients Undergoing Hip Fracture Repair on Postoperative Delirium: The STRIDE Randomized Clinical Trial.

Importance: Postoperative delirium is the most common complication following major surgery in older patients. Intraoperative sedation levels are a possible modifiable risk factor for postoperative delirium. Objective: To determine whether limiting sedation levels during spinal anesthesia reduces incident delirium overall. Design, Setting, and Participants: This double-blind randomized clinical trial (A Strategy to Reduce the Incidence of Postoperative Delirum in Elderly Patients [STRIDE]) was conducted from November 18, 2011, to May 19, 2016, at a single academic medical center and included a consecutive sample of older patients (≥65 years) who were undergoing nonelective hip fracture repair with spinal anesthesia and propofol sedation. Patients were excluded for preoperative delirium or severe dementia. Of 538 hip fractures screened, 225 patients (41.8%) were eligible, 10 (1.9%) declined participation, 15 (2.8%) became ineligible between the time of consent and surgery, and 200 (37.2%) were randomized. The follow-up included postoperative days 1 to 5 or until hospital discharge. Interventions: Heavier (modified observer's assessment of sedation score of 0-2) or lighter (observer's assessment of sedation score of 3-5) propofol sedation levels intraoperatively. Main Outcomes and Measures: Delirium on postoperative days 1 to 5 or until hospital discharge determined via consensus panel using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria. The incidence of delirium was compared between intervention groups with and without stratification by the Charlson comorbidity index (CCI). Results: Of 200 participants, the mean (SD) age was 82 (8) years, 146 (73%) were women, 194 (97%) were white, and the mean (SD) CCI was 1.5 (1.8). One hundred participants each were randomized to receive lighter sedation levels or heavier sedation levels. A good separation of intraoperative sedation levels was confirmed by multiple indices. The overall incident delirium risk was 36.5% (n = 73) and 39% (n = 39) vs 34% (n = 34) in heavier and lighter sedation groups, respectively (P = .46). Intention-to-treat analyses indicated no statistically significant difference between groups in the risk of incident delirium (log-rank test χ2, 0.46; P = .46). However, in a prespecified subgroup analysis, when stratified by CCI, sedation levels did effect the delirium risk (P for interaction = .04); in low comorbid states (CCI = 0), heavier vs lighter sedation levels doubled the risk of delirium (hazard ratio, 2.3; 95% CI, 1.1- 4.9). The level of sedation did not affect delirium risk with a CCI of more than 0. Conclusions and Relevance: In the primary analysis, limiting the level of sedation provided no significant benefit in reducing incident delirium. However, in a prespecified subgroup analysis, lighter sedation levels benefitted reducing postoperative delirium for persons with a CCI of 0. Trial Registration: clinicaltrials.gov Identifier: NCT00590707.

Relationship Between the Ambulatory Arterial Stiffness Index and the Lower Limit of Cerebral Autoregulation During Cardiac Surgery.

BACKGROUND: Pulse pressure, the ambulatory arterial stiffness index (AASI), and the symmetric AASI are established predictors of adverse cardiovascular outcomes. However, little is known about their relationship to cerebral autoregulation. This study evaluated whether these markers of vascular properties relate to the lower limit of cerebral autoregulation (LLA). METHODS AND RESULTS: The LLA was determined during cardiac surgery with transcranial Doppler ultrasonography in 181 patients. All other variables were calculated from continuous intraoperative readings obtained before cardiopulmonary bypass. The LLA varied directly with the AASI (ß=3.12 per 0.1 change in AASI, P<0.001) and to a lesser extent the symmetric AASI (ß=2.02 per 0.1 change in symmetric AASI, P≤0.022), while peripheral pulse pressure was not significantly related (ß=0.0, P>0.99). Logistic regression revealed that the likelihood of LLA being >65 mm Hg increased by 50% (95% confidence interval, 11%-102%, P=0.008) for every 0.1 increase in the AASI. The AASI was able to predict a LLA above certain thresholds (area under the curve receiver operating characteristic for AASI predicting an LLA >65 mm Hg: 0.60; 95% confidence interval, 0.51%-0.68%, P=0.043). Incorporating additional variables improved the model's predictive ability (area under the curve for AASI predicting a LLA >65 mm Hg: 0.75; 95% confidence interval, 0.68-0.82, P=0.036). CONCLUSIONS: These data indicate that the LLA is related to the mechanical properties of the vasculature as represented by the AASI. The AASI can be used to predict LLA threshold levels during cardiac surgery. It is now possible to link elevations in the LLA with an increased AASI as determined from readily accessible intraoperative variables.