Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Implementing nitrous oxide cracking technology in the labour ward to reduce occupational exposure and environmental emissions: a quality improvement study.

Nitrous oxide, a potent greenhouse gas, is a common labour analgesic. One method which may reduce its carbon footprint is to 'crack' the exhaled gas into nitrogen and oxygen using catalytic destruction. In this quality improvement project, based on environmental monitoring and staff feedback, we assessed the impact of nitrous oxide cracking technology in the maternity setting. Mean ambient nitrous oxide levels were recorded during the final 30 minutes of uncomplicated labour in 36 cases and plotted on a run chart. Interventions were implemented in four stages, comprising: stage 1, baseline (12 cases); stage 2, cracking with nitrous oxide delivered and scavenged via a mouthpiece (eight cases); stage 3, cracking with nitrous oxide via a facemask with an air-filled cushion (eight cases); stage 4, cracking with nitrous oxide via a low-profile facemask, and enhanced coaching on the use of the technology (eight cases). The median ambient nitrous oxide levels were 71% lower than baseline in stage 2 and 81% lower in stage 4. Staff feedback was generally positive, though some found the technology to be cumbersome; successful implementation relies on effective staff engagement. Our results indicate that cracking technology can reduce ambient nitrous oxide levels in the obstetric setting, with potential for reductions in environmental impacts and occupational exposure.

Test of neural inertia in humans during general anaesthesia.

BACKGROUND: Neural inertia is defined as the tendency of the central nervous system to resist transitions between arousal states. This phenomenon has been observed in mice and Drosophila anaesthetized with volatile anaesthetics: the effect-site concentration required to induce anaesthesia in 50% of the population (C50) was significantly higher than the effect-site concentration for 50% of the population to recover from anaesthesia. We evaluated this phenomenon in humans using propofol or sevoflurane (both with or without remifentanil) as anaesthetic agents. METHODS: Thirty-six healthy volunteers received four sessions of anaesthesia with different drug combinations in a step-up/step-down design. Propofol or sevoflurane was administered with or without remifentanil. Serum concentrations of propofol and remifentanil were measured from arterial blood samples. Loss and return of responsiveness (LOR-ROR), response to pain (PAIN), Patient State Index (PSI) and spectral edge frequency (SEF) were modeled with NONMEM®. RESULTS: For propofol, the C50 for induction and recovery of anaesthesia was not significantly different across the different endpoints. For sevoflurane, for all endpoints except SEF, significant differences were found. For some endpoints (LOR and PAIN) the difference was significant only when sevoflurane was combined with remifentanil. CONCLUSIONS: Our results nuance earlier findings with volatile anaesthetics in mice and Drosophila. Methodological aspects of the study, such as the measured endpoint, influence the detection of neural inertia. A more thorough definition of neural inertia, with a robust methodological framework for clinical studies is required to advance our knowledge of this phenomenon. CLINICAL TRIAL REGISTRATION: NCT 02043938.

Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery.

BACKGROUND: Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival. METHODS: We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012). RESULTS: We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33-0.81, P-value for effect=0.004, number needed to treat 74, I(2)=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14-0.64) and desflurane (OR=0.43, 95% credible interval 0.21-0.82) were individually associated with a reduction in mortality when compared with TIVA. CONCLUSIONS: Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.

Effect of Perioperative Lidocaine, Propofol and Steroids on Pulmonary Metastasis in a Murine Model of Breast Cancer Surgery.

Addressing the hypothesis that anaesthetic-analgesic technique during cancer surgery might influence recurrence or metastatic spread is a research priority. Propofol, which has anti-inflammatory properties in vitro, is clinically associated with reduced risk of cancer recurrence compared with sevoflurane anaesthesia in retrospective studies. Amide local anaesthetics, such as lidocaine, have cancer inhibiting effects in vitro. Steroids have anti-inflammatory and immunosuppressive effects and are associated with improved recovery after major non-cancer surgery. We compared the effects of propofol, lidocaine and methylprednisolone on postoperative metastasis in a murine model of breast cancer surgery under sevoflurane anaesthesia. 4T1 tumour cells were introduced into the mammary fat-pad of female BALB/c mice and the resulting tumour resected seven days later under general anaesthesia with sevoflurane. Mice (n = 72) were randomized to four treatment groups: Sevoflurane alone (control); Propofol group received 5 mg.kg-1; Lidocaine group received 1.5 mg.kg-1 followed by 2 mg.kg-1.h-1 infusion; Methylprednisolone group received 30 mg.kg-1 methylprednisolone. The primary outcome measure was pulmonary metastasis colony count, as assessed by in-vitro proliferation, two weeks post-operatively. This was achieved by treating the post-mortem lung tissue with collagenase IV, straining and culturing for 14 days prior to colony count. Compared with control, lidocaine and propofol each individually reduced pulmonary metastasis colonies; mean (SD) 846 (±581) vs. 88 (±52) vs. 34 (±44) respectively, (p = 0.0001 and p = 0.0001). Methylprednisolone increased lung metastasis, 2555 (±609) vs. 846 (±581), p = 0.0001. Post-operative hepatic metastatic disease and serum interleukin-6 and vascular endothelial growth factor levels were similar in all groups. In conclusion, in a murine model of breast cancer surgery during sevoflurane anaesthesia, propofol and lidocaine each decreased pulmonary metastasis, while methylprednisolone increased it.

Inhalational versus propofol-based total intravenous anaesthesia: practice patterns and perspectives among Australasian anaesthetists.

Increasing evidence suggests that total intravenous anaesthesia (TIVA) may be the preferred anaesthetic for cancer resection surgery. To assist the preparation of a randomised controlled trial (RCT) examining Volatile (versus TIVA) Anaesthesia and Perioperative Outcomes Related to Cancer (VAPOR-C) we developed an 18-question electronic survey to investigate practice patterns and perspectives (emphasising indications, barriers, and impact on cancer outcomes) of TIVA versus inhalational general anaesthesia in Australasia. The survey was emailed to 1,000 (of 5,300 active Fellows) randomly selected Australian and New Zealand College of Anaesthetists (ANZCA) Fellows. The response rate was 27.5% (n=275). Of the respondents, 18% use TIVA for the majority of cases. In contrast, 46% use TIVA 20% of the time or less. Respondents described indications for TIVA as high risk of nausea, neurosurgery, and susceptibility to malignant hyperthermia. Lack of equipment, lack of education and cost were not considered barriers to TIVA use, and a significant proportion (41%) of respondents would use TIVA more often if setup were easier. Of the respondents, 43% thought that TIVA was associated with less cancer recurrence than inhalational anaesthesia, while 46% thought that there was no difference. Yet, only 29% of respondents reported that they use TIVA often or very often for cancer surgery. In Australasia, there is generally a low frequency of TIVA use despite a perception of benefit when compared with inhalational anaesthesia. Anaesthetists are willing to use TIVA for indications where sufficient evidence supports a meaningful level of improvement in clinical outcome. The survey explores attitudes towards use of TIVA for cancer surgery and demonstrates equipoise in anaesthetists' opinions regarding this indication. The inconsistent use of TIVA in Australasia, minimal barriers to its use, and the equipoise in anaesthetists' opinions regarding the effect of TIVA versus inhalational anaesthesia on cancer outcomes support the need for a large prospective RCT.