Postoperative cognitive dysfunction (POCD) is common in elderly patients after noncardiac surgery, but the consequences are unknown. The authors' aim was to determine the effects of POCD on long-term ...prognosis.
This was an observational study of Danish patients enrolled in two multicenter studies of POCD between November 1994 and October 2000. The cohort was followed up from the date of surgery until August 2007. Cognitive function was assessed by a neuropsychological test battery at three time points: before, at 1 week after, and at 3 months after noncardiac surgery. Data on survival, labor market attachment, and social transfer payments were obtained from administrative databases. The Cox proportional hazards regression model was used to compute relative risk estimates for mortality and disability, and the relative prevalence of time on social transfer payments was assessed by Poisson regression.
A total of 701 patients were followed up for a median of 8.5 yr (interquartile range, 5.3-11.4 yr). POCD at 3 months, but not at 1 week, was associated with increased mortality (hazard ratio, 1.63 95% confidence interval, 1.11-2.38; P = 0.01, adjusted for sex, age, and cancer). The risk of leaving the labor market prematurely because of disability or voluntary early retirement was higher among patients with 1-week POCD (hazard ratio, 2.26 1.24-4.12; P = 0.01). Patients with POCD at 1 week received social transfer payments for a longer proportion of observation time (prevalence ratio, 1.45 1.03-2.04; P = 0.03).
Cognitive dysfunction after noncardiac surgery was associated with increased mortality, risk of leaving the labor market prematurely, and dependency on social transfer payments.
Available evidence on the effects of a high fraction of inspired oxygen (FIO2) of 60% to 90% compared with a routine fraction of inspired oxygen of 30% to 40%, during anaesthesia and surgery, on ...mortality and surgical site infection has been inconclusive. Previous trials and meta-analyses have led to different conclusions on whether a high fraction of supplemental inspired oxygen during anaesthesia may decrease or increase mortality and surgical site infections in surgical patients.
To assess the benefits and harms of an FIO2 equal to or greater than 60% compared with a control FIO2 at or below 40% in the perioperative setting in terms of mortality, surgical site infection, respiratory insufficiency, serious adverse events and length of stay during the index admission for adult surgical patients.We looked at various outcomes, conducted subgroup and sensitivity analyses, examined the role of bias and applied trial sequential analysis (TSA) to examine the level of evidence supporting or refuting a high FIO2 during surgery, anaesthesia and recovery.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, BIOSIS, International Web of Science, the Latin American and Caribbean Health Science Information Database (LILACS), advanced Google and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) up to February 2014. We checked the references of included trials and reviews for unidentified relevant trials and reran the searches in March 2015. We will consider two studies of interest when we update the review.
We included randomized clinical trials that compared a high fraction of inspired oxygen with a routine fraction of inspired oxygen during anaesthesia, surgery and recovery in individuals 18 years of age or older.
Two review authors extracted data independently. We conducted random-effects and fixed-effect meta-analyses, and for dichotomous outcomes, we calculated risk ratios (RRs). We used published data and data obtained by contacting trial authors.To minimize the risk of systematic error, we assessed the risk of bias of the included trials. To reduce the risk of random errors caused by sparse data and repetitive updating of cumulative meta-analyses, we applied trial sequential analyses. We used Grades of Recommendation, Assessment, Development and Evaluation (GRADE) to assess the quality of the evidence.
We included 28 randomized clinical trials (9330 participants); in the 21 trials reporting relevant outcomes for this review, 7597 participants were randomly assigned to a high fraction of inspired oxygen versus a routine fraction of inspired oxygen.In trials with an overall low risk of bias, a high fraction of inspired oxygen compared with a routine fraction of inspired oxygen was not associated with all-cause mortality (random-effects model: RR 1.12, 95% confidence interval (CI) 0.93 to 1.36; GRADE: low quality) within the longest follow-up and within 30 days of follow-up (Peto odds ratio (OR) 0.99, 95% CI 0.61 to 1.60; GRADE: low quality). In a trial sequential analysis, the required information size was not reached and the analysis could not refute a 20% increase in mortality. Similarly, when all trials were included, a high fraction of inspired oxygen was not associated with all-cause mortality to the longest follow-up (RR 1.07, 95% CI 0.87 to 1.33) or within 30 days of follow-up (Peto OR 0.83, 95% CI 0.54 to 1.29), both of very low quality according to GRADE. Neither was a high fraction of inspired oxygen associated with the risk of surgical site infection in trials with low risk of bias (RR 0.86, 95% CI 0.63 to 1.17; GRADE: low quality) or in all trials (RR 0.87, 95% CI 0.71 to 1.07; GRADE: low quality). A high fraction of inspired oxygen was not associated with respiratory insufficiency (RR 1.25, 95% CI 0.79 to 1.99), serious adverse events (RR 0.96, 95% CI 0.65 to 1.43) or length of stay (mean difference -0.06 days, 95% CI -0.44 to 0.32 days).In subgroup analyses of nine trials using preoperative antibiotics, a high fraction of inspired oxygen was associated with a decrease in surgical site infections (RR 0.76, 95% CI 0.60 to 0.97; GRADE: very low quality); a similar effect was noted in the five trials adequately blinded for the outcome assessment (RR 0.79, 95% CI 0.66 to 0.96; GRADE: very low quality). We did not observe an effect of a high fraction of inspired oxygen on surgical site infections in any other subgroup analyses.
As the risk of adverse events, including mortality, may be increased by a fraction of inspired oxygen of 60% or higher, and as robust evidence is lacking for a beneficial effect of a fraction of inspired oxygen of 60% or higher on surgical site infection, our overall results suggest that evidence is insufficient to support the routine use of a high fraction of inspired oxygen during anaesthesia and surgery. Given the risk of attrition and outcome reporting bias, as well as other weaknesses in the available evidence, further randomized clinical trials with low risk of bias in all bias domains, including a large sample size and long-term follow-up, are warranted.
Objective
Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described ...this systemic‐to‐brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short‐ and long‐term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function.
Methods
Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using 11CPBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed.
Results
Patients showed a global downregulation of gray matter 11CPBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS‐induced release of the proinflammatory marker tumor necrosis factor‐α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in 11CPBR28 distribution volume. Change in Stroop Color‐Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in 11CPBR28 binding (p = 0.027).
Interpretation
This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572–582
Postoperative cognitive dysfunction is common, but it remains unclear whether there are long-term adverse cognitive effects of surgery combined with anesthesia. The authors examined the association ...between exposure to surgery and level of cognitive functioning in a sample of 8,503 middle-aged and elderly twins.
Results from five cognitive tests were compared in twins exposed to surgery, classified as major, minor, hip and knee replacement, or other, with those of a reference group without surgery using linear regression adjusted for sex and age. Genetic and shared environmental confounding was addressed in intrapair analyses of 87 monozygotic and 124 dizygotic same-sexed twin pairs in whom one had a history of major surgery and the other did not.
Statistically significantly lower composite cognitive score was found in twins with at least one major surgery compared with the reference group (mean difference, -0.27; 95% CI, -0.48 to -0.06), corresponding to one tenth of an SD, that is, a negligible effect size. In the intrapair analysis, the surgery-exposed co-twin had the lower cognitive score in 49% (95% CI, 42 to 56%) of the pairs. None of the other groups differed from the reference group except the knee and hip replacement group that tended to have higher cognitive scores (mean difference, 0.35; 95% CI, -0.18 to 0.87).
A history of major surgery was associated with a negligibly lower level of cognitive functioning. The supplementary analyses suggest that preoperative cognitive functioning and underlying diseases were more important for cognitive functioning in mid- and late life than surgery and anesthesia.
To investigate the association between markers of acute endothelial glycocalyx degradation, inflammation, coagulopathy, and mortality after trauma.
Hyperinflammation and acute coagulopathy of trauma ...predict increased mortality. High catecholamine levels can directly damage the endothelium and may be associated with enhanced endothelial glycocalyx degradation, evidenced by high circulating syndecan-1.
Prospective cohort study of trauma patients admitted to a Level 1 Trauma Centre in 2003 to 2005. Seventy-five patients were selected blindly post hoc from 3 predefined injury severity score (ISS) groups (<16, 16-27, >27). In all patients, we measured 17 markers of glycocalyx degradation, inflammation, tissue and endothelial damage, natural anticoagulation, and fibrinolysis (syndecan-1, IL-6, IL-10, histone-complexed DNA fragments, high-mobility group box 1 (HMGB1), thrombomodulin, von Willebrand factor, intercellular adhesion molecule-1, E-selectin, protein C, tissue factor pathway inhibitor (TFPI), antithrombin, D-dimer, tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), soluble uPA receptor, and plasminogen activator inhibitor-1), hematology, coagulation, catecholamines, and assessed 30-day mortality. Variables were compared in patients stratified according to syndecan-1 median.
Patients with high circulating syndecan-1 had higher catecholamines, IL-6, IL-10, histone-complexed DNA fragments, HMGB1, thrombomodulin, D-dimer, tPA, uPA (all P < 0.05), and 3-fold increased mortality (42% vs. 14%, P = 0.006) despite comparable ISS (P = 0.351). Only in patients with high glycocalyx degradation was higher ISS correlated with higher adrenaline, IL-6, histone-complexed DNA fragments, HMGB1, thrombomodulin, and APTT, lower protein C (all P < 0.05), unchanged TFPI and blunted D-dimer response (P < 0.001) because D-dimer was profoundly increased even at low ISS. After adjusting for age and ISS, syndecan-1 was an independent predictor of mortality (OR: 1.01 95%CI, 1.00-1.02; P = 0.043).
In trauma patients, high circulating syndecan-1, a marker of endothelial glycocalyx degradation, is associated with inflammation, coagulopathy and increased mortality.
Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected ...by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients.
In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min
·m
. The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions.
Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group (
=0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm
(interquartile range, 0-118 mm
; range, 0-25 261 mm
) in the low-target group versus 29 mm
(interquartile range, 0-143 mm
; range, 0-22 116 mm
) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028;
=0.99), as was the secondary outcome of number of new lesions (1 interquartile range, 0-2; range, 0-24 versus 1 interquartile range, 0-2; range, 0-29 respectively; median difference estimate, 0; 95% confidence interval, 0-0;
=0.71). No significant difference was observed in frequency of severe adverse events.
Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02185885.
Purpose: The neuromuscular blocking agent rocuronium can be administered to facilitate tracheal intubation. We hypothesized that rocuronium 0.9 mg/kg provided a larger proportion of patients with ...vocal cords in abducted position compared to rocuronium 0.6 mg/kg at train-of-four (TOF) 0. Methods: This secondary analysis was based on 52 elderly surgical patients of which 36 patients received rocuronium 0.6 mg/kg and 16 patients received rocuronium 0.9 mg/kg. Neuromuscular block was monitored with acceleromyography with TOF stimulation at the ulnar nerve. The primary outcome was the proportion of patients with vocal cords in abducted position at TOF 0. Secondary outcomes were intubating conditions evaluated by the Fuchs-Buder scale, the Intubating Difficulty Score (IDS), onset time, and duration of action of rocuronium. Results: At TOF 0, a significantly larger proportion of patients had vocal cords in abducted position in the rocuronium 0.9 mg/kg group (81%) compared with the rocuronium 0.6 mg/kg group (53%); difference (%) 28, 95% Cl 3–53, P = 0.05. Excellent intubating conditions (Fuchs-Buder) were more common in the rocuronium 0.9 mg/kg group (62.5%); difference (%) 32.5, 95% Cl 4–61), P = 0.03. No significant difference was found in IDS or onset time of rocuronium (difference 19 s, 95% Cl: -5–43). Duration of action was significantly longer (difference 29 min, 95% Cl: 10–47) in the 0.9 mg/kg group. Conclusion: The proportion of patients with vocal cords in abducted position was significantly larger after rocuronium 0.9 mg/kg compared to rocuronium 0.6 mg/kg at TOF 0 monitored at the ulnar nerve.
A high perioperative inspiratory oxygen fraction (80%) has been recommended to prevent postoperative wound infections. However, the most recent and one of the largest trials, the PROXI trial, found ...no reduction in surgical site infection, and 30-day mortality was higher in patients given 80% oxygen. In this follow-up study of the PROXI trial we assessed the association between long-term mortality and perioperative oxygen fraction in patients undergoing abdominal surgery.
From October 8, 2006, to October 6, 2008, 1386 patients underwent elective or emergency laparotomy and were randomized to receive either 80% or 30% oxygen during and for 2 hours after surgery. The follow-up date was February 24, 2010. Survival was analyzed using Kaplan-Meier statistics and the Cox proportional hazards model.
Vital status was obtained in 1382 of 1386 patients after a median follow-up of 2.3 years (range 1.3 to 3.4 years). One hundred fifty-nine of 685 patients (23.2%) died in the 80% oxygen group compared to 128 of 701 patients (18.3%) assigned to 30% oxygen (HR, 1.30 95% confidence interval, 1.03 to 1.64, P = 0.03). In patients undergoing cancer surgery, the HR was 1.45; 95% confidence interval, 1.10 to 1.90; P = 0.009; and after noncancer surgery, the HR was 1.06; 95% confidence interval, 0.69 to 1.65; P = 0.79.
Administration of 80% oxygen in the perioperative period was associated with significantly increased long-term mortality and this appeared to be statistically significant in patients undergoing cancer surgery but not in noncancer patients.
Immediate consequences of trauma include a rapid and immense activation of the immune system, whereas long-term outcomes include premature death, physical disability, and reduced workability.
To ...investigate if moderate to severe trauma is associated with long-term increased risk of death or immune-mediated or cancer disease.
This registry-based, matched, co-twin control cohort study linked the Danish Twin Registry and the Danish National Patient Registry to identify twin pairs in which 1 twin had been exposed to severe trauma and the other twin had not from 1994 to 2018. The co-twin control design allowed for matching on genetic and environmental factors shared within twin pairs.
Twin pairs were included if 1 twin had been exposed to moderate to severe trauma and the other twin had not (ie, co-twin). Only twin pairs where both twins were alive 6 months after the trauma event were included.
Twin pairs were followed up from 6 months after trauma until 1 twin experienced the primary composite outcome of death or 1 of 24 predefined immune-mediated or cancer diseases or end of follow-up. Cox proportional hazards regression was used for intrapair analyses of the association between trauma and the primary outcome.
A total of 3776 twin pairs were included, and 2290 (61%) were disease free prior to outcome analysis and were eligible for the analysis of the primary outcome. The median (IQR) age was 36.4 (25.7-50.2) years. The median (IQR) follow-up time was 8.6 (3.8-14.5) years. Overall, 1268 twin pairs (55%) reached the primary outcome; the twin exposed to trauma was first to experience the outcome in 724 pairs (32%), whereas the co-twin was first in 544 pairs (24%). The hazard ratio for reaching the composite outcome was 1.33 (95% CI, 1.19-1.49) for twins exposed to trauma. Analyses of death or immune-mediated or cancer disease as separate outcomes provided hazard ratios of 1.91 (95% CI, 1.68-2.18) and 1.28 (95% CI, 1.14-1.44), respectively.
In this study, twins exposed to moderate to severe trauma had significantly increased risk of death or immune-mediated or cancer disease several years after trauma compared with their co-twins.
Background
The number of elderly is increasing, and a large proportion of these people will require surgery and anaesthesia. However, little data exist regarding rocuronium in patients above 80 years ...of age. The aim of this study was to determine the onset time and duration of action for rocuronium 0.6 mg/kg in patients above 80 years compared with young adults.
Methods
This prospective observational study included 16 young (18‐40 years) and 16 elderly (>80 years) patients scheduled for total intravenous anaesthesia. Neuromuscular block following rocuronium 0.6 mg/kg was monitored with acceleromyography using train‐of‐four (TOF) stimulation. The primary outcome was onset time (from administration of rocuronium until TOF count = 0). Secondary outcomes were duration of action (from administration to TOF ratio >0.9) and intubating conditions according to Intubation Difficulty Score.
Results
Elderly patients, median age of 84 years, had significantly prolonged onset time compared to younger patients; median 135 seconds (135‐158) vs 90 seconds (90‐105), respectively, a mean difference of 82 seconds (40‐124) and Wilcoxon Mann‐Whitney odds (WMW) of 19.48 (7.48‐X). Duration of action in elderly patients was significantly longer, with a median time of 81 minute (71‐97) vs 53 minute (42‐73), respectively, a mean difference of 31 minute (14‐48), and WMW odds of 6.35 (2.59‐X). There was no significant difference in intubating conditions.
Conclusions
Patients above 80 years had significantly prolonged onset time and duration of action after rocuronium 0.6 mg/kg compared with patients aged 18‐40 years.
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