The relationship between intraoperative surrogates of vascular stiffness, cerebral aneurysms, and surgical outcomes.

OBJECTIVE: Increased arterial stiffness has been linked to aneurysm formation in the systemic and cerebral circulations, though the role played by arterial stiffness in the cerebral vasculature continues to be refined. This study assesses whether intraoperative surrogates of arterial stiffness differ between patients with cerebral aneurysms and controls, and the extend that these indices relate to outcomes following open surgical treatment. METHODS: We evaluated patients in a prospectively maintained database who underwent cerebral aneurysm surgery, and compared them to controls without cerebral aneurysms. Arterial stiffness was estimated using the intraoperative ambulatory arterial stiffness index (AASI) and average pulse pressure (PP). RESULTS: We analyzed 214 cerebral aneurysm patients and 234 controls. Patients in the aneurysm group were predominantly female and had a higher incidence of hypertension, diabetes mellitus, and vascular disease. They also demonstrate elevated AASI and average PP. When stratified by the occurrence of subarachnoid hemorrhage (SAH) or unfavorable neurological outcome, the AASI and average PP were not highly associated with the occurrence of SAH but were highly associated with unfavorable neurological outcomes. After multivariable analysis, both the AASI and average PP were no longer associated with unfavorable neurological outcomes, however elevated age, strongly linked with arterial stiffness, became a key predictive variable. CONCLUSION: Readily obtained intraoperative surrogates of arterial stiffening demonstrates its presence in those with cerebral aneurysm disease and the extent that it does it may meaningfully direct their clinical course. However, multivariable analysis demonstrates limitations of using arterial stiffness measures to predict clinical outcomes.

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.

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.

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.

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.

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.

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.

Pulse wave travel distance as a novel marker of ventricular-arterial coupling.

Each stroke volume ejected by the heart is distributed along the arterial system as a pressure waveform. How far the front of the pressure waveform travels within the arterial system depends both on the pulse wave velocity (PWV) and the ejection time (ET). We tested the hypothesis that ET and PWV are coupled together, in order to produce a pulse wave travel distance (PWTD = PWV × ET) which would match the distance from the heart to the most distant site in the arterial system. The study was conducted in 11 healthy volunteers. We recorded lead II of the ECG along with pulse plethysmography at ear, finger and toe. The ET at the ear and pulse arrival time to each peripheral site were extracted. We then calculated PWV followed by PWTD for each location. Taken into account the individual subject variability PWTDToe in the supine position was 153 cm (95% CI 146-160 cm). It was not different from arterial pathway distance from the heart to the toe (D Toe 153 cm). The PWTDFinger and PWTDEar were longer than the distance from the heart to the finger and ear irrespective of body position. ETEar and PWVToe appear to be coupled in healthy subjects to produce a PWTD that is roughly equivalent to the arterial pathway distance to the toe. We propose that PWTD should be evaluated further to test its potential as a noninvasive parameter of ventricular-arterial coupling in subjects with cardiovascular diseases.

Predictive Modeling of Massive Transfusion Requirements During Liver Transplantation and Its Potential to Reduce Utilization of Blood Bank Resources.

BACKGROUND: Patients undergoing liver transplantation frequently but inconsistently require massive blood transfusion. The ability to predict massive transfusion (MT) could reduce the impact on blood bank resources through customization of the blood order schedule. Current predictive models of MT for blood product utilization during liver transplantation are not generally applicable to individual institutions owing to variability in patient population, intraoperative management, and definitions of MT. Moreover, existing models may be limited by not incorporating cirrhosis stage or thromboelastography (TEG) parameters. METHODS: This retrospective cohort study included all patients who underwent deceased-donor liver transplantation at the Johns Hopkins Hospital between 2010 and 2014. We defined MT as intraoperative transfusion of > 10 units of packed red blood cells (pRBCs) and developed a multivariable predictive model of MT that incorporated cirrhosis stage and TEG parameters. The accuracy of the model was assessed with the goodness-of-fit test, receiver operating characteristic analysis, and bootstrap resampling. The distribution of correct patient classification was then determined as we varied the model threshold for classifying MT. Finally, the potential impact of these predictions on blood bank resources was examined. RESULTS: Two hundred three patients were included in the study. Sixty (29.6%) patients met the definition for MT and received a median (interquartile range) of 19.0 (14.0-27.0) pRBC units intraoperatively compared with 4.0 units (1.0-6.0) for those who did not satisfy the criterion for MT. The multivariable model for predicting MT included Model for End-stage Liver Disease score, whether simultaneous liver and kidney transplant was performed, cirrhosis stage, hemoglobin concentration, platelet concentration, and TEG R interval and angle. This model demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test P = .45) and good discrimination (c statistic: 0.835; 95% confidence interval, 0.781-0.888). A probability cutoff threshold of 0.25 was found to misclassify only 4 of 100 patients as unlikely to experience MT, with the majority such misclassifications within 4 units of the working definition for MT. For this threshold, a preoperative blood ordering schedule that allocated 6 units of pRBCs for those unlikely to experience MT and 15 for those who were likely to experience MT would prevent unnecessary crossmatching of 338 units/100 transplants. CONCLUSIONS: When clinical and laboratory parameters are included, a model predicting intraoperative MT in patients undergoing liver transplantation is sufficiently accurate that its predictions could guide the blood order schedule for individual patients based on institutional data, thereby reducing the impact on blood bank resources. Ongoing evaluation of model accuracy and transfusion practices is required to ensure continuing performance of the predictive model.

The Longitudinal Course of Pain and Analgesic Therapy Following Aneurysmal Subarachnoid Hemorrhage: A Cohort Study.

OBJECTIVE: The purpose of this study was to determine the duration, intensity, location, and usual treatment of pain throughout hospitalization following subarachnoid hemorrhage. BACKGROUND: Headache following subarachnoid hemorrhage can be sudden and severe. Little is known about the longitudinal course of headache or its analgesic therapy following the initial diagnosis of subarachnoid hemorrhage. METHODS: A prospectively maintained database of 564 patients diagnosed with cerebral aneurysms collected from 10/2009 to 2/2013 was searched for conscious patients with subarachnoid hemorrhage. Available electronic records were queried for pain scores (0-10/10), location, and analgesic consumption. RESULTS: Forty-six adults with subarachnoid hemorrhage met eligibility criteria for inclusion. Mean [CI 95] daily pain was 3.8 [3.2, 4.4] and maximal daily pain was 5.8 [5.1, 6.6]. Eighty-nine percent of patients reported severe pain of 7-10/10, and 63% of patients reported 10/10 pain at some point during hospitalization. While mean [CI 95] pain declined over the course of hospital stay at a rate of 0.06 [0.04, 0.07] units/day (P < .001), mean [CI 95] maximal daily pain changed at a rate of -0.03 [-0.06, 0.01] units/day, which is not significantly different than zero (P = .15). Pain was located primarily in the head in 76% of subjects but pain in the back, neck, limbs, and eyes was also reported. All patients received oral acetaminophen with increasing daily doses. All but three patients, received opioids, most commonly intravenous fentanyl and oral oxycodone. The mean [95 CI] intravenous morphine equivalent dose of opioids consumed was 15.7 [10.3, 21.1] mg/day and changed at a rate of -0.11 [-0.37, 0.15] mg/day which is not significantly different than zero (P = .40). CONCLUSION: Despite steady consumption of analgesics, the pain reported by conscious patients while recovering from subarachnoid hemorrhage in the hospital is often severe and persists throughout hospitalization.

The Impact of Incident Postoperative Delirium on Survival of Elderly Patients After Surgery for Hip Fracture Repair.

BACKGROUND: The impact of delirium on survival of elderly patients remains undetermined with conflicting results from clinical studies and meta-analysis. In this study, we assessed the relationship between long-term mortality and incident postoperative delirium in elderly patients undergoing hip fracture repair. METHODS: Patients ≥65 years old who were not delirious before undergoing hip fracture repair were included in a database maintained prospectively from March 1999 to July 2009. All participating patients underwent delirium assessment on the second postoperative day by using the confusion assessment method. Survival of the participants was determined as of October 2012. RESULTS: In 459 patients, the mean (SD) period of evaluation from surgery until death or study closure was 4.1 (3.5) years with patients followed for as long as 13.6 years. Preoperative cognitive impairment was present in 120 patients (26.1%), and delirium on the second postoperative day was observed in 151 (32.9%) of these patients. Although univariate analysis demonstrated a strong association between incident postoperative delirium and survival, this relationship did not persist in a multivariate model. Survival was a function of age at the time of surgery (P < 0.001), illness severity as determined by the ASA physical status score (P < 0.001), and duration of admission to the intensive care unit after surgery (P < 0.001). Incorporation of incident postoperative delirium did not meaningfully (P = 0.22) enhance the final survival model. In such a model, the hazard ratio (95% confidence interval) for incident postoperative delirium was 1.25 (0.92-1.48). CONCLUSIONS: Incident postoperative delirium was not significantly associated with decreased survival in elderly patients undergoing hip fracture repair.

Analgesic therapy for major spine surgery.

Pain following spine surgery is often difficult to control and can persist. Reduction of this pain requires a multidisciplinary approach that depends on contributions of both surgeons and anesthesiologists. The spine surgeon's role involves limiting manipulation of structures contributing to pain sensation in the spine, which requires an in-depth understanding of the specific anatomic etiologies of pain originating along the spinal axis. Anesthesiologists, on the other hand, must focus on preemptive, multimodal analgesic treatment regimens. In this review, we first discuss anatomic sources of pain within the spine, before delving into a specific literature-supported pain management protocol intended for use with spinal surgery.

Far-lateral transcondylar approach for microsurgical trapping of an anterior inferior cerebellar artery aneurysm.

Aneurysms of the posterior circulation remain challenging lesions given their proximity to the brainstem and cranial nerves. Many of these aneurysms may best be approached through a retrosigmoid-suboccipital craniectomy with a far-lateral transcondylar extension. In this narrated video illustration, we present the case of a 37-year-old man with an incidentally discovered right-sided anterior inferior cerebellar artery (AICA) aneurysm. Diagnostic studies included CT angiography and cerebral angiography. A suboccipital craniectomy and far-lateral transcondylar extension were performed for microsurgical trapping and excision of the AICA aneurysm. The techniques of the retrosigmoid craniectomy, C-1 laminectomy, condylectomy and microsurgical trapping of the aneurysm are reviewed. The video can be found here: http://youtu.be/JiM3CXVwXnk.

Physiologic and pathophysiologic consequences of altered sialylation and glycosylation on ion channel function.

Voltage-gated ion channels are transmembrane proteins that regulate electrical excitability in cells and are essential components of the electrically active tissues of nerves, muscle and the heart. Potassium channels are one of the largest subfamilies of voltage sensitive channels and are among the most-studied of the voltage-gated ion channels. Voltage-gated channels can be glycosylated and changes in the glycosylation pattern can affect ion channel function, leading to neurological and neuromuscular disorders and congenital disorders of glycosylation (CDG). Alterations in glycosylation can also be acquired and appear to play a role in development and aging. Recent studies have focused on the impact of glycosylation and sialylation on ion channels, particularly for voltage-gated potassium and sodium channels. The terminal step of sialylation often affects channel activation and inactivation kinetics. The presence of sialic acids on O or N-glycans can alter the gating mechanism and cause conformational changes in the voltage-sensing domains due to sialic acid's negative charges. This manuscript will provide an overview of sialic acids, potassium and sodium channel function, and the impact of sialylation on channel activation and deactivation.

Sedation depth during spinal anesthesia and survival in elderly patients undergoing hip fracture repair.

Low intraoperative Bispectral Index (BIS) values may be associated with increased mortality. In a previously reported trial to prevent delirium, we randomized patients undergoing hip fracture repair under spinal anesthesia to light (BIS >80) or deep (BIS approximately 50) sedation. We analyzed survival of patients in the original trial. Among all patients, mortality was equivalent across sedation groups. However, among patients with serious comorbidities (Charlson score >4), 1-year mortality was reduced in the light (22.2%) vs deep (43.6%) sedation group (hazard ratio [HR], 0.43; 95% confidence interval, 0.19-0.97; P = 0.04) during spinal anesthesia. Similarly, among patients with Charlson score >6, 1-year mortality was reduced in the light (28.6%) vs deep (52.6%) sedation group (HR 0.33; 95% confidence interval, 0.12-0.94; P = 0.04) during spinal anesthesia. Further research on reduced mortality after light sedation during spinal anesthesia is needed.

Comparison of equivolume, equiosmolar solutions of mannitol and hypertonic saline with or without furosemide on brain water content in normal rats.

BACKGROUND: Mannitol and hypertonic saline (HS) are used by clinicians to reduce brain water and intracranial pressure and have been evaluated in a variety of experimental and clinical protocols. Administering equivolume, equiosmolar solutions in healthy animals could help produce fundamental data on water translocation in uninjured tissue. Furthermore, the role of furosemide as an adjunct to osmotherapy remains unclear. METHODS: Two hundred twenty isoflurane-anesthetized rats were assigned randomly to receive equivolume normal saline, 4.2% HS (1,368 mOsm/L 25% mannitol (1,375 mOsm/L), normal saline plus furosemide (8 mg/kg), or 4.2% HS plus furosemide (8 mg/kg) over 45 min. Rats were killed at 1, 2, 3, and 5 h after completion of the primary infusion. Outcome measurements included body weight; urinary output; serum and urinary osmolarity and electrolytes; and brain, lung, skeletal muscle, and small bowel water content. RESULTS: In the mannitol group, the mean water content of brain tissue during the experiment was 78.0% (99.3% CI, 77.9-78.2%), compared to results from the normal saline (79.3% [99.3% CI, 79.1-79.5%]) and HS (78.8% [99.3% CI, 78.6-78.9%]) groups (P < 0.001), whereas HS plus furosemide yielded 78.0% (99.3% CI, 77.8-78.2%) (P = 0.917). After reaching a nadir at 1 h, brain water content increased at similar rates for mannitol (0.27%/h [99.3% CI, 0.14-0.40%/h]) and HS (0.27%/h [99.3% CI, 0.17-0.37%/h]) groups (P = 0.968). CONCLUSIONS: When compared to equivolume, equiosmolar administration of HS, mannitol reduced brain water content to a greater extent over the entire course of the 5-h experiment. When furosemide was added to HS, the brain-dehydrating effect could not be distinguished from that of mannitol.

Infarct volume after hyperacute infusion of hypertonic saline in a rat model of acute embolic stroke.

INTRODUCTION: Hypertonic saline (HS) can treat cerebral edema arising from a number of pathologic conditions. However, physicians are reluctant to use it during the first 24 h after stroke because of experimental evidence that it increases infarct volume when administered early after reperfusion. Here, we determined the effect of HS on infarct size in an embolic clot model without planned reperfusion. METHODS: A clot was injected into the internal carotid artery of male Wistar rats to reduce perfusion in the middle cerebral artery territory to less than 40 % of baseline, as monitored by laser-Doppler flowmetry. After 25 min, rats were randomized to receive 10 mL/kg of 7.5 % HS (50:50 chloride:acetate) or normal saline (NS) followed by a 0.5 mL/h infusion of the same solution for 22 h. RESULTS: Infarct volume was similar between NS and HS groups (in mm(3): cortex 102 ± 65 mm(3) vs. 93 ± 49 mm(3), p = 0.72; caudoputamenal complex 15 ± 9 mm(3) vs. 21 ± 14, p = 0.22; total hemisphere 119 ± 76 mm(3) vs. 114 ± 62, p = 0.88, respectively). Percent water content was unchanged in the infarcted hemisphere (NS 81.6 ± 1.5 %; HS 80.7 ± 1.3 %, p = 0.16), whereas the HS-treated contralateral hemisphere was significantly dehydrated (NS 79.4 ± 0.8 %; HS 77.5 ± 0.8 %, p < 0.01). CONCLUSIONS: HS reduced contralateral hemispheric water content but did not affect ipsilateral brain water content when compared to NS. Infarct volume was unaffected by HS administration at all evaluated locations.

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.