Miller David, Lewis Sharon R, Pritchard Michael W, Schofield-Robinson Oliver J, Shelton Cliff L, Alderson Phil, Smith Andrew F
Academic Unit, North Cumbria University Hospitals, Cumberland Infirmary, Newtown Road, Carlisle, UK, CA2 7HY.
Cochrane Database Syst Rev. 2018 Aug 21;8(8):CD012317. doi: 10.1002/14651858.CD012317.pub2.
The use of anaesthetics in the elderly surgical population (more than 60 years of age) is increasing. Postoperative delirium, an acute condition characterized by reduced awareness of the environment and a disturbance in attention, typically occurs between 24 and 72 hours after surgery and can affect up to 60% of elderly surgical patients. Postoperative cognitive dysfunction (POCD) is a new-onset of cognitive impairment which may persist for weeks or months after surgery.Traditionally, surgical anaesthesia has been maintained with inhalational agents. End-tidal concentrations require adjustment to balance the risks of accidental awareness and excessive dosing in elderly people. As an alternative, propofol-based total intravenous anaesthesia (TIVA) offers a more rapid recovery and reduces postoperative nausea and vomiting. Using TIVA with a target controlled infusion (TCI) allows plasma and effect-site concentrations to be calculated using an algorithm based on age, gender, weight and height of the patient.TIVA is a viable alternative to inhalational maintenance agents for surgical anaesthesia in elderly people. However, in terms of postoperative cognitive outcomes, the optimal technique is unknown.
To compare maintenance of general anaesthesia for elderly people undergoing non-cardiac surgery using propofol-based TIVA or inhalational anaesthesia on postoperative cognitive function, mortality, risk of hypotension, length of stay in the postanaesthesia care unit (PACU), and hospital stay.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE (1946 to November 2017), Embase (1974 to November 2017), PsycINFO (1887 to November 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles.
We included randomized controlled trials (RCTs) with participants over 60 years of age scheduled for non-cardiac surgery under general anaesthesia. We planned to also include quasi-randomized trials. We compared maintenance of anaesthesia with propofol-based TIVA versus inhalational maintenance of anaesthesia.
Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and synthesized findings.
We included 28 RCTs with 4507 randomized participants undergoing different types of surgery (predominantly cardiovascular, laparoscopic, abdominal, orthopaedic and ophthalmic procedures). We found no quasi-randomized trials. Four studies are awaiting classification because we had insufficient information to assess eligibility.All studies compared maintenance with propofol-based TIVA versus inhalational maintenance of anaesthesia. Six studies were multi-arm and included additional TIVA groups, additional inhalational maintenance or both. Inhalational maintenance agents included sevoflurane (19 studies), isoflurane (eight studies), and desflurane (three studies), and was not specified in one study (reported as an abstract). Some studies also reported use of epidural analgesia/anaesthesia, fentanyl and remifentanil.We found insufficient reporting of randomization methods in many studies and all studies were at high risk of performance bias because it was not feasible to blind anaesthetists to study groups. Thirteen studies described blinding of outcome assessors. Three studies had a high of risk of attrition bias, and we noted differences in the use of analgesics between groups in six studies, and differences in baseline characteristics in five studies. Few studies reported clinical trials registration, which prevented assessment of risk of selective reporting bias.We found no evidence of a difference in incidences of postoperative delirium according to type of anaesthetic maintenance agents (odds ratio (OR) 0.59, 95% confidence interval (CI) 0.15 to 2.26; 321 participants; five studies; very low-certainty evidence); we noted during sensitivity analysis that using different time points in one study may influence direction of this result. Thirteen studies (3215 participants) reported POCD, and of these, six studies reported data that could not be pooled; we noted no difference in scores of POCD in four of these and in one study, data were at a time point incomparable to other studies. We excluded one large study from meta-analysis because study investigators had used non-standard anaesthetic management and this study was not methodologically comparable to other studies. We combined data for seven studies and found low-certainty evidence that TIVA may reduce POCD (OR 0.52, 95% CI 0.31 to 0.87; 869 participants).We found no evidence of a difference in mortality at 30 days (OR 1.21, 95% CI 0.33 to 4.45; 271 participants; three studies; very low-certainty evidence). Twelve studies reported intraoperative hypotension. We did not perform meta-analysis for 11 studies for this outcome. We noted visual inconsistencies in these data, which may be explained by possible variation in clinical management and medication used to manage hypotension in each study (downgraded to low-certainty evidence); one study reported data in a format that could not be combined and we noted little or no difference between groups in intraoperative hypotension for this study. Eight studies reported length of stay in the PACU, and we did not perform meta-analysis for seven studies. We noted visual inconsistencies in these data, which may be explained by possible differences in definition of time points for this outcome (downgraded to very low-certainty evidence); data were unclearly reported in one study. We found no evidence of a difference in length of hospital stay according to type of anaesthetic maintenance agent (mean difference (MD) 0 days, 95% CI -1.32 to 1.32; 175 participants; four studies; very low-certainty evidence).We used the GRADE approach to downgrade the certainty of the evidence for each outcome. Reasons for downgrading included: study limitations, because some included studies insufficiently reported randomization methods, had high attrition bias, or high risk of selective reporting bias; imprecision, because we found few studies; inconsistency, because we noted heterogeneity across studies.
AUTHORS' CONCLUSIONS: We are uncertain whether maintenance with propofol-based TIVA or with inhalational agents affect incidences of postoperative delirium, mortality, or length of hospital stay because certainty of the evidence was very low. We found low-certainty evidence that maintenance with propofol-based TIVA may reduce POCD. We were unable to perform meta-analysis for intraoperative hypotension or length of stay in the PACU because of heterogeneity between studies. We identified 11 ongoing studies from clinical trials register searches; inclusion of these studies in future review updates may provide more certainty for the review outcomes.
在老年外科手术人群(60岁以上)中,麻醉剂的使用正在增加。术后谵妄是一种急性病症,其特征为对环境的意识降低和注意力障碍,通常发生在术后24至72小时之间,可影响高达60%的老年外科手术患者。术后认知功能障碍(POCD)是一种新发的认知障碍,可能在术后持续数周或数月。传统上,手术麻醉一直使用吸入剂维持。呼气末浓度需要调整,以平衡老年人意外知晓和用药过量的风险。作为替代方案,丙泊酚全静脉麻醉(TIVA)恢复更快,并可减少术后恶心和呕吐。使用目标控制输注(TCI)的TIVA可根据患者的年龄、性别、体重和身高,通过算法计算血浆和效应室浓度。TIVA是老年患者手术麻醉中吸入维持剂的一种可行替代方案。然而,在术后认知结果方面,最佳技术尚不清楚。
比较基于丙泊酚的TIVA或吸入麻醉用于老年非心脏手术患者全身麻醉维持时,对术后认知功能、死亡率、低血压风险、麻醉后监护病房(PACU)停留时间和住院时间的影响。
我们检索了Cochrane对照试验中心注册库(CENTRAL;2017年第11期)、MEDLINE(1946年至2017年11月)、Embase(1974年至2017年11月)、PsycINFO(1887年至2017年11月)。我们检索了临床试验注册库以查找正在进行的研究,并对相关文章进行了前后向引文检索。
我们纳入了年龄超过60岁、计划在全身麻醉下进行非心脏手术的参与者的随机对照试验(RCT)。我们还计划纳入半随机试验。我们比较了基于丙泊酚的TIVA麻醉维持与吸入麻醉维持。
两位综述作者独立评估纳入研究、提取数据、评估偏倚风险并综合研究结果。
我们纳入了28项RCT,共4507名随机参与者,他们接受了不同类型的手术(主要是心血管、腹腔镜、腹部、骨科和眼科手术)。我们未找到半随机试验。四项研究等待分类,因为我们没有足够的信息来评估其合格性。所有研究均比较了基于丙泊酚的TIVA维持与吸入麻醉维持。六项研究为多臂研究,包括额外的TIVA组、额外的吸入维持组或两者皆有。吸入维持剂包括七氟烷(19项研究)、异氟烷(8项研究)和地氟烷(3项研究),一项研究未明确说明(作为摘要报告)。一些研究还报告了硬膜外镇痛/麻醉、芬太尼和瑞芬太尼的使用情况。我们发现许多研究中随机化方法的报告不足,并且所有研究都存在较高的实施偏倚风险,因为麻醉师对研究组进行盲法操作不可行。13项研究描述了结果评估者的盲法。三项研究存在较高的失访偏倚风险,我们注意到六项研究中两组之间在镇痛药使用上存在差异,五项研究中基线特征存在差异。很少有研究报告临床试验注册情况,这妨碍了对选择性报告偏倚风险的评估。我们没有发现证据表明根据麻醉维持剂类型,术后谵妄的发生率存在差异(比值比(OR)0.59,95%置信区间(CI)0.15至2.26;321名参与者;五项研究;极低确定性证据);我们在敏感性分析中注意到,一项研究中使用不同的时间点可能会影响该结果的方向。13项研究(3215名参与者)报告了POCD,其中六项研究报告的数据无法合并;我们注意到其中四项研究中POCD评分没有差异,并且在一项研究中,数据的时间点与其他研究不可比。我们从荟萃分析中排除了一项大型研究,因为研究调查人员使用了非标准的麻醉管理方法,并且该研究在方法上与其他研究不可比。我们合并了七项研究的数据,发现低确定性证据表明TIVA可能会降低POCD(OR 0.52,95%CI 0.31至0.87;869名参与者)。我们没有发现证据表明30天死亡率存在差异(OR 1.21,95%CI 0.33至4.45;271名参与者;三项研究;极低确定性证据)。12项研究报告了术中低血压情况。我们未对11项该结果的研究进行荟萃分析。我们注意到这些数据存在视觉上的不一致,这可能是由于每项研究中临床管理和用于治疗低血压的药物可能存在差异所解释(降级为低确定性证据);一项研究报告的数据格式无法合并,并且我们注意到该研究中两组在术中低血压方面几乎没有差异。八项研究报告了在PACU的停留时间,我们未对七项研究进行荟萃分析。我们注意到这些数据存在视觉上的不一致,这可能是由于该结果的时间点定义可能存在差异所解释(降级为极低确定性证据);一项研究的数据报告不清晰。我们没有发现证据表明根据麻醉维持剂类型,住院时间存在差异(平均差(MD)0天,95%CI -1.32至1.32;175名参与者;四项研究;极低确定性证据)。我们使用GRADE方法对每个结果的证据确定性进行降级。降级的原因包括:研究局限性,因为一些纳入研究随机化方法报告不足、存在高失访偏倚或高选择性报告偏倚风险;不精确性,因为我们找到的研究很少;不一致性,因为我们注意到各研究之间存在异质性。
由于证据的确定性非常低,我们不确定基于丙泊酚的TIVA维持或吸入剂维持是否会影响术后谵妄的发生率、死亡率或住院时间。我们发现低确定性证据表明基于丙泊酚的TIVA维持可能会降低POCD。由于研究之间存在异质性,我们无法对术中低血压或在PACU的停留时间进行荟萃分析。我们从临床试验注册库搜索中识别出11项正在进行的研究;将这些研究纳入未来的综述更新中可能会为综述结果提供更高的确定性。