Perioperative changes in neurocognitive and Alzheimer's disease-related cerebrospinal fluid biomarkers in older patients randomised to isoflurane or propofol for anaesthetic maintenance.

BACKGROUND: Animal studies have shown that isoflurane and propofol have differential effects on Alzheimer's disease (AD) pathology and memory, although it is unclear whether this occurs in humans. METHODS: This was a nested randomised controlled trial within a prospective cohort study; patients age ≥60 yr undergoing noncardiac/non-neurological surgery were randomised to isoflurane or propofol for anaesthetic maintenance. Cerebrospinal fluid (CSF) was collected via lumbar puncture before, 24 h, and 6 weeks after surgery. Cognitive testing was performed before and 6 weeks after surgery. Nonparametric methods and linear regression were used to evaluate CSF biomarkers and cognitive function, respectively. RESULTS: There were 107 subjects (54 randomised to isoflurane and 53 to propofol) who completed the 6-week follow-up and were included in the analysis. There was no significant effect of anaesthetic treatment group, time, or group-by-time interaction for CSF amyloid-beta (Aß), tau, or phospho-tau181p levels, or on the tau/Aß or p-tau181p/Aß ratios (all P>0.05 after Bonferroni correction). In multivariable-adjusted intention-to-treat analyses, there were no significant differences between the isoflurane and propofol groups in 6-week postoperative change in overall cognition (mean difference [95% confidence interval]: 0.01 [-0.12 to 0.13]; P=0.89) or individual cognitive domains (P>0.05 for each). Results remained consistent across as-treated and per-protocol analyses. CONCLUSIONS: Intraoperative anaesthetic maintenance with isoflurane vs propofol had no significant effect on postoperative cognition or CSF Alzheimer's disease-related biomarkers within 6 weeks after noncardiac, non-neurological surgery in older adults. CLINICAL TRIAL REGISTRATION: NCT01993836.

Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study.

BACKGROUND: Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients. METHODS: We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aß, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery. RESULTS: There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aß levels than non-carriers (preoperative median CSF Aß [median absolute deviation], APOE4 305 pg ml-1 [65] vs 378 pg ml-1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (ß [95% confidence interval, CI], 0.218 [0.137-0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (ß [95% CI], -0.196 [-0.256 to -0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aß levels. CONCLUSIONS: Postoperative change trajectories for cognition and CSF Aß, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aß-independent mechanisms.

The accuracy of a near-infrared spectroscopy cerebral oximetry device and its potential value for estimating jugular venous oxygen saturation.

BACKGROUND: An intriguing potential clinical use of cerebral oximeter measurements (SctO2) is the ability to noninvasively estimate jugular bulb venous oxygen saturation (SjvO2). Our purpose in this study was to determine the accuracy of the FORE-SIGHT(®) (CAS Medical Systems, Branford, CT), which is calibrated to a weighted average of 70% (SjvO2) and 30% arterial saturation, for Food and Drug Administration pre-market approval 510(k) certification by adapting an industry standard protocol, ISO 9919:2005 (www.ISO.org) (used for pulse oximeters), and to evaluate the use of SctO2 and SpO2 measurements to noninvasively estimate jugular venous oxygen saturation (SnvO2). METHODS: Paired blood gas samples from the radial artery and the jugular venous bulb were collected from 20 healthy volunteers undergoing progressive oxygen desaturation from 100% to 70%. The blood sample pairs were analyzed via co-oximetry and used to calculate the approximate mixed vascular cerebral blood oxygen saturation, or reference SctO2 values (refSctO2), during increasing hypoxia. These reference values were compared to bilateral FORE-SIGHT SctO2 values recorded simultaneously with the blood gas draws to determine its accuracy. Bilateral SctO2 and SpO2 measurements were then used to calculate SnvO2 values which were compared to SjvO2. RESULTS: Two hundred forty-six arterial and 253 venous samples from 18 subjects were used in the analysis. The ipsilateral FORE-SIGHT SctO2 values showed a tolerance interval (TI) of [-10.72 to 10.90] and Lin concordance correlation coefficient (CCC) with standard error (SE) of 0.83 ± 0.073 with the refSctO2 values calculated using arterial and venous blood gases. The ipsilateral data had a CCC of 0.81 + 0.059 with TI of [-9.22 to 9.40] with overall bias of 0.09%, and amplitude of the root mean square of error after it was corrected with random effects analysis was 2.92%. The bias and variability values between the ipsilateral and the contralateral FORE-SIGHT SctO2 measurements varied from person to person. The SnvO2 calculated from the ipsilateral SctO2 and SpO2 data showed a CCC ± SE of 0.79 ± 0.088, TI = [-14.93 to 15.33], slope of 0.98, y-intercept of 1.14% with SjvO2 values with a bias of 0.20% and an Arms of 4.08%. The SnvO2 values calculated independently from contralateral forehead FORE-SIGHT SctO2 values were not as correlated with the SjvO2 values (contralateral side CCC + SE = 0.72 ± 0.118, TI = [-14.86 to 15.20], slope of 0.66, and y-intercept of 20.36%). CONCLUSIONS: The FORE-SIGHT cerebral oximeter was able to estimate oxygen saturation within the tissues of the frontal lobe under conditions of normocapnia and varying degrees of hypoxia (with 95% confidence interval of [-5.60 to 5.78] with ipsilateral blood sample data). These findings from healthy volunteers also suggest that the use of the calculated SnvO2 derived from SctO2 and SpO2 values may be a reasonable noninvasive method of estimating SjvO2 and therefore global cerebral oxygen consumption in the clinical setting. Further laboratory and clinical research is required to define the clinical utility of near-infrared spectroscopy determination of SctO2 and SnvO2 in the operating room setting.

Exploring the impact of augmenting sedation assessment with physiologic monitors.

BACKGROUND: Pharmacological sedation is a necessary tool in the management of critically ill, mechanically ventilated patients. The intensive care unit (ICU) sedation strategy is to use the least amount of medication to meet safety and comfort goals. Titration of pharmacological agents is currently guided by clinical assessment tools. The purpose of this study was to determine whether the addition of a neurophysiological monitor, bispectral index (BIS), aided the ICU nurse in reducing the amount of drug used, compared to a clinical tool alone, in a general critical care population. METHODS: In this prospective clinical trial, mechanically ventilated adults (N=300) were randomised to sedation assessment using only the observational assessment tool (RASS) or a combination of observational and physiologic measures (RASS+BIS). Subjects were enrolled from a medical ICU (N=154), a trauma ICU (N=72) and a general mixed-use ICU (N=74). RESULTS: BIS-augmented sedation was only associated with the reduction of drug use when patients were sedated with propofol or narcotic agents (propofol [1.61 mg/kg/h vs. 1.77 mg/kg/h; p<0.0001], fentanyl [54.73 mcg/h vs. 66.81 mcg/h; p<0.0001], and hydromorphone [0.97 mg/h vs. 4.00 mg/h: p<0.0001] compared to RASS alone. In contrast, patients sedated with dexmedetomidine or benzodiazepines were given higher doses under the BIS-augmented dexmedetomidine [0.46 mcg/kg/h vs. 0.33 mcg/kg/h; p<0.0001], lorazepam [4.13 mg/h vs. 3.29 mg/h p<0.0001], and midazolam [3.73 mg/h vs 2.86 mg/h; p<0.0001]) protocol compared to clinical assessment alone. CONCLUSION: The clinical evaluation of depth of sedation remains the most reliable method for the titration of pharmacological sedation in the critical care unit. However, BIS-augmented assessment is helpful in reducing the amount of propofol and narcotic medication used and may be considered an adjunct when these agents are utilised.

Postoperative changes in cognition and cerebrospinal fluid neurodegenerative disease biomarkers.

OBJECTIVE: Numerous investigators have theorized that postoperative changes in Alzheimer's disease neuropathology may underlie postoperative neurocognitive disorders. Thus, we determined the relationship between postoperative changes in cognition and cerebrospinal (CSF) tau, p-tau-181p, or Aß levels after non-cardiac, non-neurologic surgery in older adults. METHODS: Participants underwent cognitive testing before and 6 weeks after surgery, and lumbar punctures before, 24 h after, and 6 weeks after surgery. Cognitive scores were combined via factor analysis into an overall cognitive index. In total, 110 patients returned for 6-week postoperative testing and were included in the analysis. RESULTS: There was no significant change from before to 24 h or 6 weeks following surgery in CSF tau (median [median absolute deviation] change before to 24 h: 0.00 [4.36] pg/mL, p = 0.853; change before to 6 weeks: -1.21 [3.98] pg/mL, p = 0.827). There were also no significant changes in CSF p-tau-181p or Aß over this period. There was no change in cognitive index (mean [95% CI] 0.040 [-0.018, 0.098], p = 0.175) from before to 6 weeks after surgery, although there were postoperative declines in verbal memory (-0.346 [-0.523, -0.170], p = 0.003) and improvements in executive function (0.394, [0.310, 0.479], p < 0.001). There were no significant correlations between preoperative to 6-week postoperative changes in cognition and CSF tau, p-tau-181p, or Aß42 changes over this interval (p > 0.05 for each). INTERPRETATION: Neurocognitive changes after non-cardiac, non-neurologic surgery in the majority of cognitively healthy, community-dwelling older adults are unlikely to be related to postoperative changes in AD neuropathology (as assessed by CSF Aß, tau or p-tau-181p levels or the p-tau-181p/Aß or tau/Aß ratios). TRIAL REGISTRATION: clinicaltrials.gov (NCT01993836).

Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1-12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; however, the pathways involved remain unclear. Unbiased proteomic analyses have been used to identify neuroinflammatory pathways in multiple neurologic diseases and syndromes but have not yet been applied to POCD. OBJECTIVE: To utilize unbiased mass spectrometry-based proteomics to identify potential neuroinflammatory pathways underlying POCD. METHODS: Unbiased LC-MS/MS proteomics was performed on immunodepleted cerebrospinal fluid (CSF) samples obtained before, 24 hours after, and 6 weeks after major non-cardiac surgery in older adults who did (n = 8) or did not develop POCD (n = 6). Linear mixed models were used to select peptides and proteins with intensity differences for pathway analysis. RESULTS: Mass spectrometry quantified 8,258 peptides from 1,222 proteins in > 50%of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between patients with versus withoutPOCD (q < 0.05), including proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these groups. Among these, pathway analysis revealed that 50 were from 17 proteins mapping to complement and coagulation pathways (q = 2.44*10-13). CONCLUSION: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.

The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.

BACKGROUND: Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in older surgical patients would reduce PND risk or severity. OBJECTIVE: MARBLE is a randomized, blinded, placebo-controlled phase II sequential dose escalation trial designed to evaluate perioperative administration of an apoE mimetic peptide drug, CN-105, in older adults (age≥60 years). The primary aim is evaluating the safety of CN-105 administration, as measured by adverse event rates in CN-105 versus placebo-treated patients. Secondary aims include assessing perioperative CN-105 administration feasibility and its efficacy for reducing postoperative neuroinflammation and PND severity. METHODS: 201 patients undergoing non-cardiac, non-neurological surgery will be randomized to control or CN-105 treatment groups and receive placebo or drug before and every six hours after surgery, for up to three days after surgery. Chart reviews, pre- and postoperative cognitive testing, delirium screening, and blood and CSF analyses will be performed to examine effects of CN-105 on perioperative adverse event rates, cognition, and neuroinflammation. Trial results will be disseminated by presentations at conferences and peer-reviewed publications. CONCLUSION: MARBLE is a transdisciplinary study designed to measure CN-105 safety and efficacy for preventing PND in older adults and to provide insight into the pathogenesis of these geriatric syndromes.

Noninvasive monitoring of tissue hemoglobin using UV-VIS diffuse reflectance spectroscopy: a pilot study.

We conducted a pilot study on 10 patients undergoing general surgery to test the feasibility of diffuse reflectance spectroscopy in the visible wavelength range as a noninvasive monitoring tool for blood loss during surgery. Ratios of raw diffuse reflectance at wavelength pairs were tested as a first-pass for estimating hemoglobin concentration. Ratios can be calculated easily and rapidly with limited post-processing, and so this can be considered a near real-time monitoring device. We found the best hemoglobin correlations were when ratios at isosbestic points of oxy- and deoxyhemoglobin were used, specifically 529/500 nm. Baseline subtraction improved correlations, specifically at 520/509 nm. These results demonstrate proof-of-concept for the ability of this noninvasive device to monitor hemoglobin concentration changes due to surgical blood loss. The 529/500 nm ratio also appears to account for variations in probe pressure, as determined from measurements on two volunteers.

Minimally invasive cardiac output monitoring in the perioperative setting.

With advancing age and increased co-morbidities in patients, the need for monitoring devices during the perioperative period that allow clinicians to track physiologic variables, such as cardiac output (CO), fluid responsiveness and tissue perfusion, is increasing. Until recently, the only tool available to anesthesiologists to monitor CO was either a pulmonary artery catheter or transesophageal echocardiograph. These devices have their limitations and potential for morbidity. Several new devices (including esophageal Doppler monitors, pulse contour analysis, indicator dilution, thoracic bioimpedance and partial non-rebreathing systems) have recently been marketed which have the ability to monitor CO noninvasively and, in some cases, assess the patient's ability to respond to fluid challenges. In this review, we will describe these new devices including the technology, studies on their efficacy and the limitations of their use.

A brief report: the use of high-frequency oscillatory ventilation for severe pulmonary contusion.

BACKGROUND: Severe pulmonary contusions are a common cause of acute respiratory distress syndrome (ARDS) and are associated with significant morbidity. High frequency oscillatory ventilation (HFOV) is a ventilatory mode that employs a lung protective strategy consistent with the ARDSNet low tidal volume ventilation strategy and may result in reduced morbidity. The objective of this report is to examine the impact of HFOV on blunt trauma patients with severe pulmonary contusions who failed or were at a high risk of failing conventional mechanical ventilation. METHODS: We undertook a retrospective chart review of all patients at our institution who received HFOV for severe pulmonary contusions. Patients were placed on HFOV when their mean airway pressure (mP(aw)) surpassed 30 cm H2O and their FIO2 was greater than 0.6. Baseline demographic data including injury severity score (ISS), length of time requiring HFOV, total ventilator days, and inhospital mortality were collected. Serial determinations of oxygenation index (OI) and the PaO2/FIO2 ratio (P/F) were made up to 72 hours after initiation of HFOV. A linear mixed model was used to analyze the slope (beta) of the regression line of P/F versus time and that of OI versus time. RESULTS: Seventeen patients were identified who underwent HFOV for ARDS due primarily to pulmonary contusions. Mean ISS was 36.6, mean APACHE II score was 21.7, and the mean time before initiation of HFOV was 2.0 days. P/F increased significantly after HFOV was initiated (beta = 12.1; 95% confidence interval 7.9 to 16.4, p < 0.001). OI significantly decreased after HFOV implementation (beta = -1.8; 95% confidence interval -2.3 to -1.3, p < 0.001). Mortality rate was 17.6%. CONCLUSIONS: The early use of HFOV appears to be safe and efficacious in blunt trauma patients sustaining pulmonary contusions, and results in a rapid improvement in OI and the P/F ratio.

An Undiagnosed Paraganglioma in a 58-Year-Old Female Who Underwent Tumor Resection.

Paragangliomas and pheochromocytomas are rare neuroendocrine tumors that can have high morbidity and mortality if undiagnosed. Here we report a case of an undiagnosed paraganglioma in a 58-year-old female who underwent tumor resection. The patient became severely hypertensive intraoperatively with paroxysmal swings in blood pressure and then later became acutely hypotensive after tumor removal. She was managed in the surgical intensive care unit (SICU) postoperatively and discharged from the hospital without acute complications. We briefly discuss the epidemiology, clinical presentation, perioperative management, and possible complications of these tumors to assist healthcare providers if one were to encounter them.

Effects of decreased preoperative endotoxin core antibody levels on long-term mortality after coronary artery bypass graft surgery.

HYPOTHESIS: Decreased preoperative levels of antiendotoxin core antibody (EndoCAb) in patients undergoing cardiac surgery with cardiopulmonary bypass are associated with increased long-term mortality. DESIGN: Observational study. SETTING: Academic medical center. PATIENTS: A total of 474 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. INTERVENTIONS: Preoperative serum IgM EndoCAb levels were determined, and established preoperative risk factors were assessed. Patients were assigned a risk score using a validated method. MAIN OUTCOME MEASURES: The primary end point was mortality. Statistical analysis used the Cox proportional hazards regression model with log EndoCAb as the predictor of interest and Parsonnet additive risk score as a covariate. Kaplan-Meier survival curves were generated to visually compare groups with high vs low EndoCAb levels. RESULTS: Forty-six deaths occurred in 5 years. Annual follow-up rates during the 5 years were 100%, 94%, 93%, 98%, and 98% for the 1-, 2-, 3-, 4-, and 5-year periods, respectively. Parsonnet additive risk score (hazard ratio, 1.07; 95% confidence interval [CI], 1.04-1.11; P < .001) and log EndoCAb (hazard ratio, 0.73; 95% CI, 0.53-0.99; P = .04) were independent predictors of long-term mortality in the final model. Kaplan-Meier analysis revealed that the preoperative EndoCAb level was significantly associated with mortality up to 5 years (P = .01 by log-rank test). CONCLUSION: Lower preoperative serum EndoCAb level is a significant predictor of long-term mortality independent of other known risk factors.

Toward Designing Information Display to Support Critical Care. A Qualitative Contextual Evaluation and Visioning Effort.

OBJECTIVES: Electronic health information overload makes it difficult for providers to quickly find and interpret information to support care decisions. The purpose of this study was to better understand how clinicians use information in critical care to support the design of improved presentation of electronic health information. METHODS: We conducted a contextual analysis and visioning project. We used an eye-tracker to record 20 clinicians' information use activities in critical care settings. We played video recordings back to clinicians in retrospective cued interviews and queried: 1) context and goals of information use, 2) impacts of current display design on use, and 3) processes related to information use. We analyzed interview transcripts using grounded theory-based content analysis techniques and identified emerging themes. From these, we conducted a visioning activity with a team of subject matter experts and identified key areas for focus of design and research for future display designs. RESULTS: Analyses revealed four unique critical care information use activities including new patient assessment, known patient status review, specific directed information seeking, and review and prioritization of multiple patients. Emerging themes were primarily related to a need for better representation of dynamic data such as vital signs and laboratory results, usability issues associated with reducing cognitive load and supporting efficient interaction, and processes for managing information. Visions for the future included designs that: 1) provide rapid access to new information, 2) organize by systems or problems as well as by current versus historical patient data, and 3) apply intelligence toward detecting and representing change and urgency. CONCLUSIONS: The results from this study can be used to guide the design of future acute care electronic health information display. Additional research and collaboration is needed to refine and implement intelligent graphical user interfaces to improve clinical information organization and prioritization to support care decisions.

Orthotopic liver transplant patients require less postoperative morphine than do patients undergoing hepatic resection.

STUDY OBJECTIVE: To compare postoperative morphine use, analgesic efficacy, and side effect profiles in patients following orthotopic liver transplantation (OLTx) and liver resection (LR). DESIGN: Retrospective study. SETTING: Liver transplant and liver resection surgery at a university hospital. PATIENTS: 25 ASA physical status I, II, III, and IV patients undergoing OLTx or liver resection. MEASUREMENTS AND MAIN RESULTS: Morphine use was significantly decreased in the OLTx patients at 6,12, 24, 48, and 72 hours following commencement of patient-controlled analgesia. After commencement of patient-controlled analgesia, pain scores were significantly reduced in the OLTx group compared with those in the liver resection group at 6 and 12 hours. CONCLUSIONS: Orthotopic liver transplant patients experienced less pain and used less morphine postoperatively than did liver resection patients.

The relationship between ionized and total serum magnesium concentrations during abdominal surgery.

STUDY OBJECTIVE: To determine the necessity for ionized magnesium (iMg) assay by evaluating the effect of abdominal surgery without massive transfusion on total magnesium (Mg) and iMg concentrations. DESIGN: Prospective, observational study. SETTING: Operating rooms at a university teaching hospital. PATIENTS: 31 patients without electrolyte abnormalities who were scheduled for abdominal surgery. INTERVENTIONS: None. MEASUREMENTS: Serum electrolytes, iMg, ionized calcium, proteins before and after surgery, and urine Mg were recorded. MAIN RESULTS: Total Mg and iMg decreased: Mg 23%, iMg 15%; p < 0.0001. Total and iMg were highly correlated (r = 0.728, p < 0.0001). Urine Mg output remained within normal limits (mean 0.24 mmol/hr). CONCLUSIONS: During abdominal surgery without massive transfusion, both total and ionized hypomagnesemia occur. Changes in iMg and total serum Mg concentrations are closely correlated. Total serum Mg assay, while overestimating the prevalence of ionized hypomagnesemia, is sufficient to screen for hypomagnesemia.

APOE polymorphism is associated with risk of severe sepsis in surgical patients.

OBJECTIVE: To test for an association between apolipoprotein E (APOE) genotypes and the occurrence of severe sepsis in an elective surgical cohort. DESIGN: Prospective, observational, single cohort study. SETTING: Sixteen-bed surgical intensive care unit (ICU) at a university hospital. PATIENTS: Patients were 343 patients with planned admission to the ICU after major elective noncardiac surgery. INTERVENTIONS: Blood samples, together with demographic data, baseline clinical data, and Acute Physiology and Chronic Health Evaluation II scores, were collected on admission to the ICU and on each subsequent ICU day. APOE genotyping was conducted using a polymerase chain reaction-based assay. The primary outcome was diagnosis of severe sepsis; secondary outcomes included time on mechanical ventilation, ICU length of stay, and ICU mortality. MEASUREMENTS AND MAIN RESULTS: Severe sepsis was diagnosed in 34 of 343 patients (9.9%). Carriers of the APOepsilon3 allele (one or two copies) had a lower incidence of severe sepsis than patients with no APOepsilon3 allele (p = .014), with a relative risk of 0.284 (95% confidence interval 0.127-0.635). The protective effect of APOepsilon3 genotype on the incidence of severe sepsis remained significant (p < .01) after adjusting for age, gender, or race in a logistic regression model. Supporting our findings, presence of the APOepsilon3 allele was also associated with fewer days spent in the ICU (p = .007). In contrast, APOE genotypes were not associated with duration of mechanical ventilation or ICU mortality. CONCLUSIONS: In an elective surgical cohort, presence of the APOepsilon3 allele is associated with decreased incidence of severe sepsis and a shorter ICU length of stay.

Changes in hematocrit based on incremental blood sampling: mathematical models perform poorly.

PURPOSE: Excessive blood sampling, with its inherent risks, is of growing concern among clinicians. We performed this study to measure the changes in hematocrit (Hct) during a laboratory investigation where multiple blood samples are collected. The performance of a simple mathematical model, used in clinical practice to predict Hct changes, is evaluated. METHODS: Eight healthy male volunteers participated in this study. The equation Hct(f) = Hct(i)*(EBV-BL)/EBV is used to predict changes in Hct. Where Hct(f) and Hct(i) are, respectively, the final and initial Hct, EBV is the estimated blood volume and BL is the blood loss. RESULTS: Thirty-five pharmacokinetic samples per subject were collected totalling 314 mL of BL. The Hct decreased from 44.2% +/- 2.2% to 39.9% +/- 2.5% (P = 0.001). On average, model predictions tended to have a discrete tendency to underestimate the Hct changes (-0.5% points of bias). While the predictions of the Hct were very accurate in 50% of the subjects, the discrepancy of the Hct predictions was clinically significant in the other 50% of the subjects. CONCLUSION: Consistent with the model prediction, this study demonstrated a significant reduction in the Hct values in healthy subjects undergoing incremental phlebotomy. On average, the model successfully predicted the decrease in Hct. However, the inter- and intra-individual variabilities in the Hct changes are clinically significant. In clinical settings, which are not well controlled environments, the variability is likely to be greater and the clinical use of the model cannot replace the need to monitor the Hct.

Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration.

The debate over colloid versus crystalloid as the best solution for intraoperative fluid resuscitation is not resolved. Published studies have shown that mortality is not related to the specific fluid used for resuscitation. In addition, the quality of postoperative recovery between colloid and crystalloid has not been well investigated. In a prospective, blinded fashion, we investigated the effects of colloid and crystalloid resuscitation on nausea and vomiting and on the postoperative patient recovery profile. Patients undergoing major elective noncardiac surgery were randomized to receive 6% hetastarch in saline (HS-NS), 6% hetastarch in balanced salt (HS-BS), or lactated Ringer's solution (LR) on the basis of a fluid administration algorithm. The anesthetic was standardized. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. A postoperative morbidity survey was performed at baseline and daily after surgery. Ninety patients participated in the study, with 30 patients in each group. The amounts of study fluid (mean +/- SD) administered were 1301 +/- 1079 mL, 1448 +/- 759 mL, and 5946 +/- 1909 mL for the HS-NS, HS-BS, and LR groups, respectively (P < 0.05, HS-NS and HS-BS versus LR). Both the HS-NS and HS-BS (colloid) groups had a significantly less frequent incidence of nausea and vomiting, use of rescue antiemetics, severe pain, periorbital edema, and double vision. We concluded that intraoperative fluid resuscitation with colloid, when compared with crystalloid administration, is associated with an improvement in the quality of postoperative recovery.