Brendan S. Silbert

Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial

BACKGROUND Epidural block is widely used to manage major abdominal surgery and postoperative analgesia, but its risks and benefits are uncertain. We compared adverse outcomes in high-risk patients managed for major surgery with epidural block or alternative analgesic regimens with general anaesthesia in a multicentre randomised trial. METHODS 915 patients undergoing major abdominal surgery with one of nine defined comorbid states to identify high-risk status were randomly assigned intraoperative epidural anaesthesia and postoperative epidural analgesia for 72 h with general anaesthesia (site of epidural selected to provide optimum block) or control. The primary endpoint was death at 30 days or major postsurgical morbidity. Analysis by intention to treat involved 447 patients assigned epidural and 441 control. FINDINGS 255 patients (57.1%) in the epidural group and 268 (60.7%) in the control group had at least one morbidity endpoint or died (p=0.29). Mortality at 30 days was low in both groups (epidural 23 [5.1%], control 19 [4.3%], p=0.67). Only one of eight categories of morbid endpoints in individual systems (respiratory failure) occurred less frequently in patients managed with epidural techniques (23% vs 30%, p=0.02). Postoperative epidural analgesia was associated with lower pain scores during the first 3 postoperative days. There were no major adverse consequences of epidural-catheter insertion. INTERPRETATION Most adverse morbid outcomes in high-risk patients undergoing major abdominal surgery are not reduced by use of combined epidural and general anaesthesia and postoperative epidural analgesia. However, the improvement in analgesia, reduction in respiratory failure, and the low risk of serious adverse consequences suggest that many high-risk patients undergoing major intra-abdominal surgery will receive substantial benefit from combined general and epidural anaesthesia intraoperatively with continuing postoperative epidural analgesia.

Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial.

Background: Nitrous oxide is widely used in anesthesia, often administered at an inspired concentration around 70%. Although nitrous oxide interferes with vitamin B12, folate metabolism, and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations, the consequences of these effects are unclear. Methods: Patients having major surgery expected to last at least 2 h were randomly assigned to nitrous oxide–free (80% oxygen, 20% nitrogen) or nitrous oxide–based (70% N2O, 30% oxygen) anesthesia. Patients and observers were blind to group identity. The primary endpoint was duration of hospital stay. Secondary endpoints included duration of intensive care stay and postoperative complications; the latter included severe nausea and vomiting, and the following major complications: pneumonia, pneumothorax, pulmonary embolism, wound infection, myocardial infarction, venous thromboembolism, stroke, awareness, and death within 30 days of surgery. Results: Of 3,187 eligible patients, 2,050 consenting patients were recruited. Patients in the nitrous oxide–free group had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56–0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31–0.51; P < 0.001), but median duration of hospital stay did not differ substantially between groups (7.0 vs. 7.1 days; P = 0.06). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide–free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05–1.73; P = 0.02). Conclusions: Avoidance of nitrous oxide and the concomitant increase in inspired oxygen concentration decreases the incidence of complications after major surgery, but does not significantly affect the duration of hospital stay. The routine use of nitrous oxide in patients undergoing major surgery should be questioned.

Perioperative epidural analgesia for major abdominal surgery for cancer and recurrence-free survival: randomised trial.

Objective To compare long term recurrence of cancer and survival of patients having major abdominal surgery for cancer. Design Long term follow-up of prospective randomised controlled clinical trial in which patients were randomly assigned to receive general anaesthesia with or without epidural block for at least three postoperative days. Setting 23 hospitals in Australia, New Zealand, and Asia. Participants 503 adult patients who had potentially curative surgery for cancer. Main outcome measure Cancer-free survival (analysis was by intention to treat). Results Long term follow-up data were available for 94% (n=446) of eligible participants. The median time to recurrence of cancer or death was 2.8 (95% confidence interval 0.7 to 8.7) years in the control group and 2.6 (0.7 to 8.7) years in the epidural group (P=0.61). Recurrence-free survival was similar in both epidural and control groups (hazard ratio 0.95, 95% confidence interval 0.76 to 1.17; P=0.61). Conclusion Use of epidural block in abdominal surgery for cancer is not associated with improved cancer-free survival. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000637448

Perioperative Epidural Analgesia and Outcome After Major Abdominal Surgery in High-Risk Patients

In a primary analysis of a large recently completed randomized trial in 915 high-risk patients undergoing major abdominal surgery, we found no difference in outcome between patients receiving perioperative epidural analgesia and those receiving IV opioids, apart from the incidence of respiratory failure. Therefore, we performed a selected number of predetermined subgroup analyses to identify specific types of patients who may have derived benefit from epidural analgesia. We found no difference in outcome between epidural and control groups in subgroups at increased risk of respiratory or cardiac complications or undergoing aortic surgery, nor in a subgroup with failed epidural block (all P > 0.05). There was a small reduction in the duration of postoperative ventilation (geometric mean [SD]: control group, 0.3 [6.5] h, versus epidural group, 0.2 [4.8] h; P = 0.048). No differences were found in length of stay in intensive care or in the hospital. There was no relationship between frequency of use of epidural analgesia in routine practice outside the trial and benefit from epidural analgesia in the trial. We found no evidence that perioperative epidural analgesia significantly influences major morbidity or mortality after major abdominal surgery.

Postoperative cognitive dysfunction is independent of type of surgery and anesthetic.

BACKGROUND: Postoperative cognitive dysfunction (POCD) has been documented after cardiac and noncardiac surgery. The type of surgery and anesthetic has been assumed to be associated with the incidence but there are few prospective data comparing the incidence after different procedures. In this study, we sought to determine the association of the type of surgical procedure and anesthesia on the incidence of POCD after procedures involving light sedation, general anesthesia for noncardiac surgery, and general anesthesia for cardiac surgery involving cardiopulmonary bypass. METHODS: Eight neuropsychological tests were administered at baseline and at 7 days and 3 months postoperatively to subjects from 3 procedure groups and a nonoperative control group. Reliable change index was used to calculate POCD. The study sample consisted of subjects involved in 3 separate trials investigating coronary angiography (CA) (percutaneous diagnostic procedure) under sedation, major noncardiac surgery (total hip joint replacement [THJR] surgery) under general anesthesia, and coronary artery bypass graft (CABG) surgery under general anesthesia. RESULTS: Data were collected from 644 patients in the patient groups and 34 subjects in the control group. Neuropsychological results were available for POCD at day 7 for THJR surgery (n = 162) and CABG surgery (n = 281). The incidence of POCD at day 7 was 17% for THJR surgery and 43% for CABG surgery (adjusted odds ratio = 0.2, 95% confidence interval [CI]: 0.1, 0.4; P < 0.01). At 3 months, the incidence of POCD for all groups combined (n = 636) was 17% (21% for CA under sedation, 16% for THJR surgery, and 16% for CABG surgery). The mean (95% CI) for the difference in proportions of POCD among groups was 0.00 (−0.07, 0.07) (P = 0.91) for CABG versus THJR; −0.05 (−0.12, 0.03) (P = 0.21) for CABG versus CA; and −0.05 (−0.13, 0.03) (P = 0.24) for THJR versus CA. There were no significant differences among groups (adjusted odds ratio = 1.21, 95% CI: 0.94, 1.55; P = 0.13). CONCLUSIONS: The incidence of POCD in old and elderly patients at day 7 was higher after CABG surgery than THJR surgery, but POCD at 3 months was independent of the nature or the type of procedure or anesthetic when comparing CA, THJR, and CABG surgery groups. Cardiovascular risk factors were not predictive of POCD after any procedure.

Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial

BACKGROUND:There is a plausible pathophysiologic rationale for increased long-term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous oxide. However, this relationship has not been established clinically. The ENIGMA trial randomized 2050 patients having noncardiac surgery lasting more than 2 hours to nitrous oxide–based or nitrous oxide–free anesthesia. We conducted a follow-up study of the ENIGMA patients to evaluate the risk of cardiovascular events in the longer term. METHODS:The trial case report forms and medical records of all study patients were reviewed. The date and cause of death and occurrence of myocardial infarction or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary endpoint of the study was survival. RESULTS:The median follow-up time was 3.5 (range: 0 to 5.7) years. Three hundred eighty patients (19%) had died since the index surgery, 91 (4.5%) were recorded as having myocardial infarction, and 44 (2.2%) had a stroke during the entire follow-up period. Nitrous oxide did not significantly increase the risk of death [hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82)]. The adjusted odds ratio for myocardial infarction in patients administered nitrous oxide was 1.59 (95% CI: 1.01 to 2.51; P = 0.04) and for stroke was 1.01 (95% CI: 0.55 to 1.87; P = 0.97). CONCLUSIONS:The administration of nitrous oxide was associated with increased long-term risk of myocardial infarction, but not of death or stroke in patients enrolled in the ENIGMA trial. The exact relationship between nitrous oxide administration and serious long-term adverse outcomes will require confirmation by an appropriately designed large randomized controlled trial.

Preexisting cognitive impairment in patients scheduled for elective coronary artery bypass graft surgery.

BACKGROUND: An accurate assessment of the prevalence of cognitive impairment in patients scheduled for coronary artery bypass graft (CABG) surgery is necessary if valid assumptions regarding cognitive change are to be made. Such an assessment requires the use of a healthy control group free of cardiovascular disease. METHODS: In a retrospective observational study, 349 patients scheduled for CABG surgery underwent neuropsychological testing. We compared the results with those from a group of 170 healthy controls without cardiovascular disease and containing more female patients who were matched for age and IQ score. Cognitive impairment was defined as test scores ≥2 sd less than the controls on two or more of the seven tests. RESULTS: The CABG surgery patients performed significantly worse than the control group on all tests except the Grooved Pegboard test (nondominant). When analyzed by group, performance on the verbal learning test was the most impaired. Cognitive impairment was present in 122 (35%) of CABG surgery patients before their procedure. Prior myocardial infarction, age, and IQ were independent predictors of cognitive impairment. CONCLUSIONS: Cognitive impairment is prevalent in patients presenting for CABG surgery. Impaired cognition before surgery must be considered when assessing the effects of CABG surgery on cognitive performance.

Superficial and deep cervical plexus block for carotid artery surgery: A prospective study of 1000 blocks

Background And Objectives. Cervical plexus blocks are performed for carotid surgery to allow neurological assessment of the awake patient. The aim of this study was to establish the frequency of success, complications, and patient acceptance of the technique. Methods. One thousand superficial and deep cervical blocks were performed in 924 patients having carotid artery surgery. Data about the blocks were recorded prospectively and patients were followed up postoperatively by an independent anesthesiologist to assess patient acceptance of the technique. Results. Lidocaine was the most frequently used anesthetic (88%). Surgical supplementation of the blocks was required in 53% of operations. Six blocks (0.6%) had clinical evidence of intravascular injection of local anesthetic. Sedation was required in 66% of operations and conversion to general anesthesia occurred in 25 (2.5%) of operations. Ninety‐one percent of patients reported no problems with the block, and 93% stated that they would have the same anesthetic for any future similar surgery. Conclusions. We conclude that superficial and deep cervical plexus block has a high success rate, low complication rate, and high patient acceptance rate. Caution should, however, be exercised to ensure a low intravascular injection rate which is of most concern with this technique, because blood was aspirated in 30% of patients during performance of the block.

Stopping vs. Continuing Aspirin before Coronary Artery Surgery

BACKGROUND Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery. METHODS We used a 2-by-2 factorial trial design to randomly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin trial are reported here. Patients were randomly assigned to receive 100 mg of aspirin or matched placebo preoperatively. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS Among 5784 eligible patients, 2100 were enrolled; 1047 were randomly assigned to receive aspirin and 1053 to receive placebo. A primary outcome event occurred in 202 patients in the aspirin group (19.3%) and in 215 patients in the placebo group (20.4%) (relative risk, 0.94; 95% confidence interval, 0.80 to 1.12; P=0.55). Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P=0.75), and cardiac tamponade occurred at rates of 1.1% and 0.4%, respectively (P=0.08). CONCLUSIONS Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo. (Funded by the Australian National Health and Medical Research Council and others; Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.).

A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly.

Background:Postoperative cognitive dysfunction (POCD) after coronary artery bypass graft surgery is a common complication for which, despite many clinical investigations, no definitive etiology has been found. The current use of both high- and low-dose fentanyl as anesthetic techniques allowed us to investigate the effect of fentanyl on the incidence of POCD. Methods:Three hundred fifty patients scheduled to undergo elective coronary artery bypass graft surgery were randomized to receive either high-dose fentanyl (50 &mgr;g/kg) or low-dose fentanyl (10 &mgr;g/kg) as the basis of the anesthetic. All patients underwent neuropsychological testing before surgery and at 1 week, 3 months, and 12 months after surgery. Results:One hundred sixty-eight patients in the low-dose group and 158 patients in the high-dose group were included in the final analysis. Neuropsychological testing was performed on 88%, 93%, and 92% of patients at 1 week, 3 months, and 12 months, respectively. There was no difference between group mean scores at any of the three testing times. Analysis of individual patients by the 20% rule did not detect any differences between groups. The one SD rule, which has fewer false-positive results, detected significantly more patients with POCD in the low-dose group than in the high-dose group at 1 week (23.6% vs. 13.7%; P = 0.03) but not at the other testing times. Patients with POCD spent an average of 1.2 days longer in the hospital than those without POCD (P = 0.021). Conclusions:High-dose fentanyl is not associated with a difference in the incidence of POCD at 3 or 12 months after surgery. Low-dose fentanyl leads to shorter postoperative ventilation times and may be associated with a greater incidence of POCD 1 week after surgery. Early POCD is associated with an increased duration of stay in the hospital.