Liposomal bupivacaine provides superior pain control compared to bupivacaine with adjuvants in interscalene block for total shoulder replacement: a prospective double-blinded, randomized controlled trial.

INTRODUCTION: Optimal pain control methods after total shoulder arthroplasty (TSA) achieve reduced opioid consumption, shortened hospital stay, and improved patient satisfaction in addition to adequate analgesia. Interscalene brachial plexus block is the gold standard for TSA, yet it typically does not provide pain relief lasting beyond 24 hours. Liposomal bupivacaine (LB) purportedly provides prolonged analgesia, yet it has been minimally explored for interscalene block, and it is significantly more expensive than standard bupivacaine. METHODS: This is a prospective, 2-arm, double-blinded randomized controlled trial. Subjects presenting for anatomic or reverse TSA were randomized in a 1:1 ratio to receive interscalene brachial plexus block with either LB plus bupivacaine (LBB group) or bupivacaine plus dexamethasone and epinephrine (BDE group). The primary outcome was 120-hour postoperative opioid consumption. Secondary outcomes were pain scores up to 96 hours postoperatively, pain control satisfaction, complications, level of distress from block numbness, and hospital stay. RESULTS: Ninety patients, 45 per group, were included in the intention-to-treat analysis and randomized. Because of withdrawal of consent and loss to follow-up, 40 in each group completed enrollment through postoperative day 60. Total 120-hour postoperative opioid consumption was similar between groups (P = .127), with no differences within 24- or 48-hour time intervals. Postoperative pain scores at 24-48 hours, 48-72 hours, 72-96 hours, and day 60 were significantly lower for the LBB group. DISCUSSION: LB interscalene brachial plexus block before total shoulder arthroplasty did not reduce 120-hour postoperative opioid consumption but significantly reduced postoperative pain between 24 and 96 hours and at postoperative day 60.

Rectus Sheath Block Improves Patient Recovery Following Open Aortic Surgery.

BACKGROUND: Postoperative pain management remains a barrier to recovery following aortic surgery. Although epidural catheters help in adjunctive pain management, less is known about the use of rectus sheath blocks. We compared patient recovery following open abdominal aortic surgery (OAS) with and without adjunctive rectus block. METHODS: Adult patients undergoing open abdominal aortic aneurysm repair and aortobifemoral or aortoiliac bypass for occlusive disease were identified and stratified by use of general anesthesia alone (GA) versus adjunctive use of a rectus sheath block (GA + RB). A small number of patients with GA and concomitant epidural analgesia, along with patients that had retroperitoneal repairs, were not included in further analysis. Outcomes included time to extubation, intraoperative and postoperative morphine milligram equivalents (MME) utilization, length of stay, discharge MME, and postoperative complications. Categorial data were compared with Person Chi-Square tests or Fisher's exact tests. Continuous data were tested with independent t-tests or Mann-Whitney U-tests. RESULTS: From January 2017 to April 2022, there were 106 patients who underwent open aortic surgery, 55 patients with GA alone, 39 with GA + RB, and 12 patients who had a GA with concomitant epidural analgesia. Between GA and GA + RB, patients were comparable in both groups in terms of age, BMI (body mass index), smoking history, hypertension, diabetes, CAD (coronary artery disease), COPD (chronic obstructive pulmonary disease), and ASA (American Society of Anesthesiologists) class and prior opioid use. Patients with GA + RB were more likely to have scheduled elective procedures (80% GA cohort vs. 94.9% RB, P = 0.040), and a lower incidence of retroperitoneal exposure (14.5% GA cohort vs. 0% RB, P = 0.019). Patients with GA + RB had shorter time to extubation than GA (84.6% < 12 hr vs. 44.4%, P < 0.001), greater rate of procedural ketamine usage (GA + RB: 61.5% vs. GA: 40.0%, P = 0.049), lower MME at first postoperative day (median MME GA + RB: 25.0 vs. GA: 67.5, P = 0.002), lower discharge MME (median MME GA + RB: 142.5 vs. GA: 225.0, P = 0.036), and overall shorter length of stay (median stay GA + RB: 5 vs. GA: 6 days, P = 0.006). Postoperative complications were similar between groups. Similar findings were found in the comparison between elective-only GA and GA + RB patients and after exclusion of patients who only had a single shot of regional anesthesia. CONCLUSIONS: Patients that receive adjunctive rectus sheath blocks for pain control following OAS utilize fewer opioid medications during hospital stay and at discharge. Rectus sheath blocks represent an alternative option to other periprocedural analgesia following open aortic surgery.

Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II.

OBJECTIVE: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. DESIGN: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. SETTING: ICUs. PATIENTS: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). INTERVENTIONS: IV angiotensin II or placebo. MEASUREMENTS AND MAIN RESULTS: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. CONCLUSIONS: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Rates for HEDIS Screening for Diabetic Nephropathy Quality Measure May Be Overstated.

The Healthcare Effectiveness Data and Information Set (HEDIS) is used by health plans to measure and report on quality and performance. This study evaluated the appropriateness of the prescription drug compliance step for the Medical Attention for Nephropathy quality measure for patients with diabetes. Data from national commercial claims for 28,348,363 persons were reviewed. The study applied the standard HEDIS specifications for compliance in medical attention for nephropathy for diabetic patients. Evaluation of the third and final process (evidence of angiotensin-converting enzyme [ACE] inhibitors or angiotensin II receptor blockers [ARBs]) found that the addition of this step contributed 14% to 16% of the numerator, bringing the final rate to the >80% range. Yet, presence of a prescription for an ACE inhibitor or ARB did not confirm microalbuminuria. Only 1% of the persons satisfying Step 3 had evidence of microalbuminuria in years prior and none in the reporting year. Use of these medications does not obviate the need for a nephropathy screening in diabetics. Inclusion of these medications as numerator compliance leads to overreporting and may contribute to underscreening of a population at risk.

Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety.

OBJECTIVE: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II. DATA SOURCES: PubMed, Medline, Scopus, and Cochrane. STUDY SELECTION: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed. DATA EXTRACTION: In total, 18,468 studies were screened by two reviewers and one arbiter. One thousand one hundred twenty-four studies, in which 31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected. Data recorded included number of subjects, comorbidities, angiotensin II dose and duration, pressor effects, other physiologic and side effects, and adverse events. DATA SYNTHESIS: The most common nonpressor effects included changes in plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse events were infrequent and included headache, chest pressure, and orthostatic symptoms. The most serious side effects were exacerbation of left ventricular failure in patients with congestive heart failure and bronchoconstriction. One patient with congestive heart failure died from refractory left ventricular failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated with angiotensin II in case studies, cohort studies, and one placebo-controlled study. One healthy subject died after a pressor dose of angiotensin II was infused continuously for 6 days. No other serious adverse events attributable to angiotensin II were reported. Heterogeneity in study design prevented meta-analysis. CONCLUSION: Adverse events associated with angiotensin II were infrequent; however, exacerbation of asthma and congestive heart failure and one fatal cerebral hemorrhage were reported. This systematic review supports the notion that angiotensin II has an acceptable safety profile for use in humans.

Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy.

BACKGROUND: Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. METHODS: In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. RESULTS: Of 817 participants, 36.5% were RRT independent and 50.8% died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70-0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16-1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95% confidence interval (95% CI) 0.70-0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95% CI 0.50-0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95% CI 1.14-1.39, P < 0.001); MIF (AHR, 1.18, 95% CI 1.08-1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95% CI 1.02-1.56, P < 0.03) were associated with mortality. CONCLUSIONS: Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve outcomes.

Treatment of acute kidney injury with cast nephropathy.

Nearly 50% of patients with multiple myeloma develop renal disease; acute kidney injury (AKI) from cast nephropathy, or "myeloma kidney" is the most common type. Development of AKI is associated with worse 1-year survival and reduces the therapeutic options available to patients. Therefore, there is a great need to develop more effective therapies. Cast nephropathy is due to the interaction and aggregation of filtered free light chains (FLCs) and Tamm- Horsfall protein (THP) causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of FLCs as this correlates with renal recovery. Newer chemotherapy agents lower FLCs and have been referred to as "renoprotective". However there remains great interest in using various extracorporeal therapies to remove serum FLCs. Initially, therapeutic plasma exchange (TPE) was thought to improve renal outcomes in cast nephropathy based on small trials. The largest randomized trial of TPE, however, failed to show any benefit. A newer technique is extended high cut-off hemodialysis (HCO-HD). This modality uses a high molecular weight cut-off filter to remove FLCs. To date, trials with HCO-HD in patients with cast nephropathy have been encouraging. However, there are no randomized trials demonstrating the benefit of HCOHD when used in addition to newer chemotherapeutic regimens. Until these studies are available, HCO-HD cannot be recommended as standard of care.

Attitudes Towards Conflicts of Interest in Medical Research: A Survey of US Medical Students.

Industry funds nearly two-thirds of US healthcare research, and industry-sponsorship may produce more favorable research results and conclusions. Medical students report feeling inadequately prepared to avoid negative industry influence. Research of educational interventions that educate students on the potential effects of industry influence is lacking, and no interventions have demonstrated long-term benefit. Surveying and assessing student opinions of the relationship between industry and research may help improve future educational interventions. We surveyed preclinical and clinical students at seven US medical schools regarding their attitudes towards industry conflicts of interest (COIs) in medical research. A total of 466 medical students including 232 preclinical and 234 clinical students completed the survey. Of those who had research experience, clinical students were more likely than preclinical students to look for COIs (62.0% v 45.9%, p = .014) and to consider whether author COIs are pertinent to the article (68.1% v 54.1%, p = .023). Many disagreed that they felt adequately educated on the issue of COIs (42.7%), but most agreed that medical school should take a role in guiding student interactions with industry (65.0%). Students responded that all listed financial relationships between industry and investigator, except for providing food and/or beverage, would likely bias the investigator's research. Many students feel inadequately educated on industry issues in biomedical research, and most believe medical schools should help guide interactions with industry. Our findings support further development of educational interventions that prepare students to navigate the relationship between industry and medical research during and after medical school.

The effect of the selective cytopheretic device on acute kidney injury outcomes in the intensive care unit: a multicenter pilot study.

Acute kidney injury (AKI) is characterized by deterioration in kidney function resulting in multisystem abnormalities. Much of the morbidity and mortality associated with AKI result from a systemic inflammatory response syndrome (SIRS). This study described herein is a prospective, single-arm, multicenter US study designed to evaluate the safety and efficacy of the Selective Cytopheretic Device (SCD) treatment on AKI requiring continuous renal replacement therapy (CRRT) in the ICU. The study enrolled 35 subjects. The mean age was 56.3±15. With regard to race, 71.4% of the subjects were Caucasian, 22.9% were Black, and 5.7% were Hispanic. Average SOFA score was 11.3±3.6. Death from any cause at Day 60 was 31.4%. Renal recovery, defined as dialysis independence, was observed in all of the surviving subjects at Day 60. The results of this pilot study indicate the potential for a substantial improvement in patient outcomes over standard of care therapy, which is associated with a greater than 50% 60-day mortality in the literature. The SCD warrants further study in scientifically sound, pivotal trial to demonstrate reasonable assurance of safety and effectiveness.

Myoglobin removal using high-volume high-flux hemofiltration in patients with oliguric acute kidney injury.

BACKGROUND: Rhabdomyolysis can cause acute kidney injury (AKI). It remains controversial whether or not myoglobin can be removed from the circulation with extracorporeal therapy and decrease the incidence of AKI. Therefore, we examined myoglobin removal in a series of 11 patients with oliguric AKI treated with high-volume hemofiltration. METHODS: Patients received prefilter hemofiltration using a polysulphone filter with a molecular size cutoff of 65 kDa and a surface area of 1.7 m(2). Sieving coefficients and myoglobin clearances were calculated at 6, 12, and 24 h after the start of hemofiltration. RESULTS: The mean sieving coefficient was 0.158, and the mean myoglobin clearance was 8.7 ml/min. CONCLUSION: Despite the use of high-volume hemofiltration, the removal of myoglobin was negligible. In patients with normal renal function, the anticipated amount of extracorporeal removal would not significantly impact renal exposure to myoglobin.

Clinical utility of gray scale renal ultrasound in acute kidney injury.

BACKGROUND: Acute kidney injury occurs commonly in hospitalized patients and is associated with significant morbidity and mortality. Although renal ultrasound is often performed, its clinical utility in determining of the cause of acute kidney injury, particularly the detection of urinary tract obstruction, is not established. METHODS: Retrospective cohort study of all adult inpatients that underwent renal ultrasound for acute kidney injury over a 3-year period at a large university teaching hospital. The frequency of renal ultrasound abnormalities and clinical characteristics that predicted the finding of urinary tract obstruction was determined. RESULTS: Over the 3-year period, 1471 renal ultrasounds were performed of which 55% (810) were for evaluation of acute kidney injury. Renal ultrasound was normal in 62% (500 of 810) of patients. Hydronephrosis was detected in only 5% (42 of 810) of studies and in only 2.3% (19 of 810) of the cases was obstructive uropathy considered the cause of acute kidney injury. The majority of these patients (14 of 19) had a medical history suggestive of urinary tract obstruction. Less than 1% of patients (5 of 810) had urinary tract obstruction on ultrasound without a suggestive medical history. Most other ultrasound findings were incidental and did not establish an etiology for the acute kidney injury. CONCLUSIONS: Renal ultrasound for evaluation of acute kidney injury is indicated if there is medical history suggestive of urinary tract obstruction. Otherwise, renal ultrasound is unlikely to yield useful results and should be used more selectively based on patients' medical history.

Utility of Erector Spinae Plane Blocks for Postoperative Pain Management and Opioid Reduction Following Lumbar Fusions.

STUDY DESIGN: Retrospective. OBJECTIVE: The purpose of this study was to determine the utility of the erector spinae plane regional anesthesia (ESP) block in reducing opioid medication usage and postanesthesia care unit length of stay (PACU-LOS) for patients undergoing either a posterior or transforaminal lumbar interbody fusions (PLIF/TLIF). SUMMARY OF BACKGROUND DATA: Posterior lumbar spine fusion is a common surgical procedure typically associated with significant postoperative pain. Poorly controlled postoperative pain can lead to a number of poor outcomes. Although opioids are a mainstay for pain control, they are associated with adverse effects and a risk of dependence. Therefore, multimodal pain control has become more prevalent in orthopedics and combines traditional opioid and nonopioid pain mediation with general anesthesia protocols and regional nerve blocks. MATERIALS AND METHODS: A retrospective chart review was conducted for patients undergoing PLIFs or TLIFs between 2019 and 2021. Patients were placed into 2 groups, those receiving an ESP block and those that did not. T tests assuming unequal variances were used to assess differences in pain scores, opioid consumption, and PACU-LOS between groups. RESULTS: The study group demonstrated a 35% reduction in opioid use ( P =0.016), a 16% reduction in pain with activity ( P =0.042), and a 9.7% reduction in pain at rest ( P =0.219) compared with the control group. There were no significant differences in PACU-LOS between groups ( P =0.314). CONCLUSION: The use of an ESP block for patients undergoing PLIFs and TLIFs appears to be a safe and effective means to manage postoperative pain and reduce opioid consumption.

Utility of the transversus abdominis plane and rectus sheath blocks in patients undergoing anterior lumbar interbody fusions.

BACKGROUND CONTEXT: Anterior lumbar interbody fusion (ALIF) is a well-established technique to address numerous pathological conditions of the spine and to restore sagittal spine balance. Improving patient comfort and reducing opioid consumption following lumbar fusions is a significant goal for spine surgeons. Therefore, there is a growing need to explore multimodal options for pain management post-surgery. PURPOSE: Determine the effectiveness of combined transversus abdominis plane (TAP) and rectus sheath (RS) blocks in those undergoing (ALIF) as compared to a historical control. STUDY DESIGN/SETTING: Retrospective comparative cohort performed at a tertiary referral orthopedic specialty hospital. PATIENT SAMPLE: Of the 175 patients (88 patients received a combined regional block) who underwent an ALIF between January 1, 2018 and August 1, 2021. OUTCOME MEASURES: Pain scores both during activity and at rest, opioid consumption during the first 72 hours postoperatively, total postoperative anesthesia care unit length of stay (PACU LOS), 30-day emergency department visits, 30-day readmissions, and unplanned returns to the operating room. METHODS: Charts of patients undergoing an ALIF during the open period for this study were placed into two groups: those that received combined regional anesthesia and those that did not. A t test assuming unequal variances was used to determine if there were differences in outcome variables between the two groups. RESULTS: The study group, those receiving the combine block, demonstrated a statistically significant reduction in opioid pain medicine (24.8%), reported pain (10-13%), and PACU LOS (18.7%). There were no differences in complication rates between the two groups. CONCLUSIONS: The combined use of TAP and RS blocks appears to be a well-tolerated and effective means of pain management in this patient cohort.

Anesthesia awareness and the bispectral index.

BACKGROUND: Awareness during anesthesia is a serious complication with potential long-term psychological consequences. Use of the bispectral index (BIS), developed from a processed electroencephalogram, has been reported to decrease the incidence of anesthesia awareness when the BIS value is maintained below 60. In this trial, we sought to determine whether a BIS-based protocol is better than a protocol based on a measurement of end-tidal anesthetic gas (ETAG) for decreasing anesthesia awareness in patients at high risk for this complication. METHODS: We randomly assigned 2000 patients to BIS-guided anesthesia (target BIS range, 40 to 60) or ETAG-guided anesthesia (target ETAG range, 0.7 to 1.3 minimum alveolar concentration [MAC]). Postoperatively, patients were assessed for anesthesia awareness at three intervals (0 to 24 hours, 24 to 72 hours, and 30 days after extubation). RESULTS: We assessed 967 and 974 patients from the BIS and ETAG groups, respectively. Two cases of definite anesthesia awareness occurred in each group (absolute difference, 0%; 95% confidence interval [CI], -0.56 to 0.57%). The BIS value was greater than 60 in one case of definite anesthesia awareness, and the ETAG concentrations were less than 0.7 MAC in three cases. For all patients, the mean (+/-SD) time-averaged ETAG concentration was 0.81+/-0.25 MAC in the BIS group and 0.82+/-0.23 MAC in the ETAG group (P=0.10; 95% CI for the difference between the BIS and ETAG groups, -0.04 to 0.01 MAC). CONCLUSIONS: We did not reproduce the results of previous studies that reported a lower incidence of anesthesia awareness with BIS monitoring, and the use of the BIS protocol was not associated with reduced administration of volatile anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG concentrations were within the target ranges. Our findings do not support routine BIS monitoring as part of standard practice. (ClinicalTrials.gov number, NCT00281489 [ClinicalTrials.gov].).

Intensity of renal support in critically ill patients with acute kidney injury.

BACKGROUND: The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial. METHODS: We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. RESULTS: Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P=0.47). There was no significant difference between the two groups in the duration of renal-replacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. CONCLUSIONS: Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)

Bispectral index monitoring, duration of bispectral index below 45, patient risk factors, and intermediate-term mortality after noncardiac surgery in the B-Unaware Trial.

BACKGROUND: Postoperative mortality has been associated with cumulative anesthetic duration below an arbitrary processed electroencephalographic threshold (bispectral index [BIS] <45). This substudy of the B-Unaware Trial tested whether cumulative duration of BIS values lower than 45, cumulative anesthetic dose, comorbidities, or intraoperative events were independently associated with postoperative mortality. METHODS: The authors studied 1,473 patients (mean ± SD age, 57.9 ± 14.4 yr; 749 men) who underwent noncardiac surgery at Barnes-Jewish Hospital in St. Louis, Missouri. Multivariable Cox regression analysis was used to determine whether perioperative factors were independently associated with all-cause mortality. RESULTS: A total of 358 patients (24.3%) died during a follow-up of 3.2 ± 1.1 yr. There were statistically significant associations among various perioperative risk factors, including malignancy and intermediate-term mortality. BIS-monitored patients did not have lower mortality than unmonitored patients (24.9 vs. 23.7%; difference = 1.2%, 95% CI, -3.3 to 5.6%). Cumulative duration of BIS values less than 45 was not associated with mortality (multivariable hazard ratio, 1.03; 95% CI, 0.93-1.14). Increasing mean and cumulative end-tidal anesthetic concentrations were not associated with mortality. The multivariable Cox regression model showed a good discriminative ability (c-index = 0.795). CONCLUSIONS: This study found no evidence that either cumulative BIS values below a threshold of 40 or 45 or cumulative inhalational anesthetic dose is injurious to patients. These results do not support the hypothesis that limiting depth of anesthesia either by titration to a specific BIS threshold or by limiting end-tidal volatile agent concentrations will decrease postoperative mortality.

Relationship between bispectral index values and volatile anesthetic concentrations during the maintenance phase of anesthesia in the B-Unaware trial.

BACKGROUND: Hypnotic depth during anesthesia affects electroencephalography waveforms and electroencephalogram-derived indices, such as the bispectral index (BIS). Titrating anesthetic administration against the BIS assumes reliable relationships between BIS values, electroencephalogram waveforms, and effect site concentration, beyond loss of responsiveness. Associations among BIS, end-tidal anesthetic concentrations (ETAC), and patient characteristics were examined during anesthetic maintenance, using B-Unaware trial data. METHODS: Pharmacokinetically stable ETAC epochs during intraoperative anesthetic maintenance were analyzed. A generalized estimating equation determined independent relationships among BIS, ETAC (in age-adjusted minimum alveolar concentration equivalents), patient characteristics, and 1-yr mortality. Further individual and population characteristics were explored graphically. RESULTS: A total of 3,347,523 data points from 1,100 patients were analyzed over an ETAC range from 0.42 to 1.51 age-adjusted minimum alveolar concentration. A generalized estimating equation yielded a best predictive equation: BIS = 62.9-1.6 (if age younger than 60 yr) -1.6 (if female) -2.5 (if American Society of Anesthesiologists physical status more than 3) -2.6 (if deceased at 1 yr) -2.5 (if N2O was not used) -1.4 (if midazolam dose more than 2 mg) -1.3 (if opioid dose more than 50 morphine equivalents) -15.4 × age-adjusted minimum alveolar concentration. Although a population relationship between ETAC and BIS was apparent, interindividual variability in the strength and reliability of this relationship was large. Decreases in BIS with increasing ETAC were not reliably observed. Individual-patient linear regression yielded a median slope of -8 BIS/1 age-adjusted minimum alveolar concentration (interquartile range -30, 0) and a median correlation coefficient of -0.16 (interquartile range -0.031, -0.50). CONCLUSIONS: Independent of pharmacokinetic confounding, BIS frequently correlates poorly with ETAC, is often insensitive to clinically significant changes in ETAC, and is vulnerable to interindividual variability. BIS is therefore incapable of finely guiding volatile anesthetic titration during anesthetic maintenance.