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Context Hyperglycemia is common in deceased donors, and provokes numerous adverse events in hepatocytic mitochondria. Objective To determine whether hyperglycemia in deceased donors is associated with graft dysfunction after orthotopic liver transplant. Methods Charts on 572 liver transplants performed at the Cleveland Clinic between January 2005 and October 2010 were reviewed. The primary measure was time-weighted averages of donors' glucose measurements. Liver graft dysfunction was defined as (1) primary nonfunction as indicated by death or retransplant or (2) liver graft dysfunction as indicated by an aspartate amino transferase level greater than 2000 U/L or prothrombin time greater than 16 seconds during the first postoperative week. The relationship of interest was estimated by using a multivariable logistic regression. Results The incidence of graft dysfunction was 25%. No significant relationship was found between the range of donor glucose measurements and liver graft dysfunction after donor characteristics were adjusted for (P = .14, Wald test, adjusted odds ratio [95% CI] for liver graft dysfunction corresponding to a relative doubling in time-weighted average for donor glucose of 1.43 [0.89–2.30]). The results thus do not suggest that strict glucose control in donors is likely to improve graft quality.

Three perioperative factors impair host defence against recurrence during cancer surgery: the surgical stress response, use of volatile anaesthetic, and opioids for analgesia. All factors are ameliorated by regional anaesthesia-analgesia. We tested the primary hypothesis that breast cancer recurrence after potentially curative surgery is lower with regional anaesthesia-analgesia using paravertebral blocks and the anaesthetic propofol than with general anaesthesia with the volatile anaesthetic sevoflurane and opioid analgesia. A second hypothesis was that regional anaesthesia-analgesia reduces persistent incisional pain. We did a randomised controlled trial at 13 hospitals in Argentina, Austria, China, Germany, Ireland, New Zealand, Singapore, and the USA. Women (age <85 years) having potentially curative primary breast cancer resections were randomised by computer to either regional anaesthesia-analgesia (paravertebral blocks and propofol) or general anaesthesia (sevoflurane) and opioid analgesia. The primary outcome was local or metastatic breast cancer recurrence. The secondary outcome was incisional pain at 6 months and 12 months. Primary analyses were done under intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT00418457. The study was stopped after a preplanned futility boundary was crossed. Between Jan 30, 2007, and Jan 18, 2018, 2132 women were enrolled to the study, of whom 24 were excluded before surgery. 1043 were assigned to regional anaesthesia-analgesia and 1065 were allocated to general anaesthesia. Baseline characteristics were well balanced between study groups. Median follow-up was 36 (IQR 24–49) months. Among women assigned regional anaesthesia-analgesia, 102 (10%) recurrences were reported, compared with 111 (10%) recurrences among those allocated general anaesthesia (hazard ratio 0·97, 95% CI 0·74–1·28; p=0·84). Incisional pain was reported by 442 (52%) of 856 patients assigned to regional anaesthesia-analgesia and 456 (52%) of 872 patients allocated to general anaesthesia at 6 months, and by 239 (28%) of 854 patients and 232 (27%) of 852 patients, respectively, at 12 months (overall interim-adjusted odds ratio 1·00, 95% CI 0·85–1·17; p=0·99). Neuropathic breast pain did not differ by anaesthetic technique and was reported by 87 (10%) of 859 patients assigned to regional anaesthesia-analgesia and 89 (10%) of 870 patients allocated to general anaesthesia at 6 months, and by 57 (7%) of 857 patients and 57 (7%) of 854 patients, respectively, at 12 months. In our study population, regional anaesthesia-analgesia (paravertebral block and propofol) did not reduce breast cancer recurrence after potentially curative surgery compared with volatile anaesthesia (sevoflurane) and opioids. The frequency and severity of persistent incisional breast pain was unaffected by anaesthetic technique. Clinicians can use regional or general anaesthesia with respect to breast cancer recurrence and persistent incisional pain. Sisk Healthcare Foundation (Ireland), Eccles Breast Cancer Research Fund, British Journal of Anaesthesia International, College of Anaesthetists of Ireland, Peking Union Medical College Hospital, Science Fund for Junior Faculty 2016, Central Bank of Austria, and National Healthcare Group.

Abstract Background Animal models of serious infection suggest that 24 hours of induced hypothermia improves circulatory and respiratory characteristics and enhances survival, but whether therapeutic mild hypothermia in such conditions is of clinical benefit remains unknown. We, therefore, tested whether reducing core temperature to 32–34oC in critically ill patients with septic shock and ventilator-demanding respiratory failure improves survival and reduces organ dysfunction. Methods In this multi-national trial, patients with septic shock were enrolled within 6 hours of onset of septic shock and ventilator-demanding respiratory failure and randomized 1:1, stratified by site (target sample = 560), to routine thermal management or 24 hours of induced hypothermia (target 32–34°C) followed by 48 hours of normothermia. Other aspects of care were per routine in each participating center. The primary endpoint was 30-day all-cause mortality. Results At the third ordinary interim analysis, after recruitment of 432 participants, the Data and Safety Monitoring Board recommended the trial be terminated for futility; the conditional power for rejection of the null hypothesis in favor of efficacy was null. In the induced hypothermia group, target temperature was reached within median 3.2 hours [IQR: 2.2, 4.8], and maintained for 24 hours [IQR: 24, 24] (Figure 1). There was no evidence for a difference in 30-day mortality risk in patients randomized to hypothermia (96/217) vs. routine thermal management (77/215): relative risk 1.24 [95% CI: 0.98, 1.56] (Figure 2). At the end of the temperature intervention (72 hours), more patients assigned to hypothermia were in continued shock (vasoactive medication 71% vs. 58%; P = 0.01), and fewer cooled patients had inflammatory control (32% vs. 47% had CRP decline of >30%, P = 0.005). More harm from cooling was seen in patients entering the trial with normal renal function and with normal platelet count (P for interaction < 0.05). Conclusion Among patients with septic shock and ventilator-demanding respiratory failure, induced hypothermia did not improve survival, but adversely affected the duration of shock, and inflammatory control. Induced hypothermia should not routinely be used in patients with septic shock. Disclosures All authors: No reported disclosures.

Background Patients with dementia are thought to be more sensitive to anesthesia, although volatile anesthetic requirement has not specifically been evaluated in this population. We tested the hypothesis that patients with dementia having non-cardiac surgery have a lower ratio of bispectral index (BIS) to minimal alveolar concentration (MAC) during the five minutes immediately preceding incision, thus exhibiting deeper hypnotic levels at a given MAC fraction. Methods We obtained records from our database registry on patients who had volatile general anesthesia during their most recent operation. We excluded patients premedicated with midazolam. Patients with dementia were identified and their diagnosis was confirmed by chart review. Each patient with dementia was successfully matched with a maximum of five patients without dementia using a multivariate nearest-neighbor distance-matching algorithm restricted to the following criteria: American Society of Anesthesiologists physical status, age, five-minute pre-incision time-weighted average (TWA) estimated effect-site concentration of propofol and fentanyl, and use of remifentanil. Our primary outcome was the TWA BIS-to-MAC ratio during the five minutes immediately preceding incision. Results We analyzed 31 patients with dementia matched with 151 patients without dementia. Median [quartiles] TWA BIS-to-MAC ratios for the matched patients were 85 [73, 100] for the patients with dementia and 78 [73, 84] for the patients without dementia. The percent difference in mean BIS-to-MAC ratios between patients with dementia and patients without dementia was 9% (95% confidence interval: −9% to 29%) ( P  = 0.35, Wald test). Conclusions Our results do not support the hypothesis that patients with dementia are more sensitive to volatile anesthetics than patients without dementia.