Polderman Jorinde Aw, Farhang-Razi Violet, Van Dieren Susan, Kranke Peter, DeVries J Hans, Hollmann Markus W, Preckel Benedikt, Hermanides Jeroen
Department of Anaesthesiology, Academic Medical Center (AMC) University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands, 1105 AZ.
Cochrane Database Syst Rev. 2018 Aug 28;8(8):CD011940. doi: 10.1002/14651858.CD011940.pub2.
In the perioperative period, dexamethasone is widely and effectively used for prophylaxis of postoperative nausea and vomiting (PONV), for pain management, and to facilitate early discharge after ambulatory surgery.Long-term treatment with steroids has many side effects, such as adrenal insufficiency, increased infection risk, hyperglycaemia, high blood pressure, osteoporosis, and development of diabetes mellitus. However, whether a single steroid load during surgery has negative effects during the postoperative period has not yet been studied.
To assess the effects of a steroid load of dexamethasone on postoperative systemic or wound infection, delayed wound healing, and blood glucose change in adult surgical patients (with planned subgroup analysis of patients with and without diabetes).
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, and the Web of Science for relevant articles on 29 January 2018. We searched without language or date restriction two clinical trial registries to identify ongoing studies, and we handsearched the reference lists of relevant publications to identify all eligible trials.
We searched for randomized controlled trials comparing an incidental steroid load of dexamethasone versus a control intervention for adult patients undergoing surgery. We required that studies include a follow-up of 30 days for proper assessment of the number of postoperative infections, delayed wound healing, and the glycaemic response.
Two review authors independently screened studies for eligibility, extracted data from relevant studies, and assessed all included studies for bias. We resolved differences by discussion and pooled included studies in a meta-analysis. We calculated Peto odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Our primary outcomes were postoperative systemic or wound infection, delayed wound healing, and glycaemic response within 24 hours. We created a funnel plot for the primary outcome postoperative (wound or systemic) infection. We used GRADE to assess the quality of evidence for each outcome.
We included in the meta-analysis 38 studies that included adults undergoing a large variety of surgical procedures (i.e. abdominal surgery, cardiac surgery, neurosurgery, and orthopaedic surgery). Age range of participants was 18 to 80 years. There is probably little or no difference in the risk of postoperative (wound or systemic) infection with dexamethasone compared with no treatment, placebo, or active control (ramosetron, ondansetron, or tropisetron) (Peto OR 1.01, 95% confidence interval (CI) 0.80 to 1.27; 4931 participants, 27 studies; I² = 27%; moderate-quality evidence). The effects of dexamethasone on delayed wound healing are unclear because the wide confidence interval includes both meaningful benefit and harm (Peto OR 0.99, 95% CI 0.28 to 3.43; 1072 participants, eight studies; I² = 0%; low-quality evidence). Dexamethasone may produce a mild increase in glucose levels among participants without diabetes during the first 12 hours after surgery (MD 13 mg/dL, 95% CI 6 to 21; 10 studies; 595 participants; I² = 50%; low-quality evidence). We identified two studies reporting on glycaemic response after dexamethasone in participants with diabetes within 24 hours after surgery (MD 32 mg/dL, 95% CI 15 to 49; 74 participants; I² = 0%; very low-quality evidence).
AUTHORS' CONCLUSIONS: A single dose of dexamethasone probably does not increase the risk for postoperative infection. It is uncertain whether dexamethasone has an effect on delayed wound healing in the general surgical population owing to imprecision in trial results. Participants with increased risk for delayed wound healing (e.g. participants with diabetes, those taking immunosuppressive drugs) were not included in the randomized studies reporting on delayed wound healing included in this meta-analysis; therefore our findings should be extrapolated to the clinical setting with caution. Furthermore, one has to keep in mind that dexamethasone induces a mild increase in glucose. For patients with diabetes, very limited evidence suggests a more pronounced increase in glucose. Whether this influences wound healing in a clinically relevant way remains to be established. Once assessed, the three studies awaiting classification and two that are ongoing may alter the conclusions of this review.
在围手术期，地塞米松被广泛且有效地用于预防术后恶心和呕吐（PONV）、疼痛管理以及促进门诊手术后的早期出院。长期使用类固醇有许多副作用，如肾上腺功能不全、感染风险增加、高血糖、高血压、骨质疏松以及糖尿病的发生。然而，手术期间单次给予类固醇负荷在术后是否有负面影响尚未得到研究。
评估地塞米松类固醇负荷对成年手术患者术后全身或伤口感染、伤口愈合延迟以及血糖变化的影响（对有糖尿病和无糖尿病患者进行计划亚组分析）。
我们于2018年1月29日在MEDLINE、Embase、Cochrane对照试验中心注册库（CENTRAL）、Cochrane图书馆以及科学网中检索相关文章。我们检索了两个临床试验注册库，无语言或日期限制以识别正在进行的研究，并手工检索了相关出版物的参考文献列表以识别所有符合条件的试验。
我们检索了比较地塞米松偶然类固醇负荷与成年手术患者对照干预的随机对照试验。我们要求研究包括30天的随访，以适当评估术后感染的数量、伤口愈合延迟以及血糖反应。
两位综述作者独立筛选研究的合格性，从相关研究中提取数据，并评估所有纳入研究的偏倚。我们通过讨论解决分歧，并将纳入研究汇总进行荟萃分析。我们计算二分结果的Peto比值比（OR）和连续结果的平均差（MD）。我们的主要结局是术后全身或伤口感染、伤口愈合延迟以及24小时内的血糖反应。我们为主要结局术后（伤口或全身）感染创建了漏斗图。我们使用GRADE评估每个结局的证据质量。
我们将38项研究纳入荟萃分析，这些研究包括接受各种手术（即腹部手术、心脏手术、神经外科手术和骨科手术）的成年人。参与者的年龄范围为18至80岁。与未治疗、安慰剂或活性对照（雷莫司琼、昂丹司琼或托烷司琼）相比，地塞米松术后（伤口或全身）感染风险可能几乎没有差异或无差异（Peto OR 1.01，95%置信区间（CI）0.80至1.27；4931名参与者，27项研究；I² = 27%；中等质量证据）。地塞米松对伤口愈合延迟的影响尚不清楚，因为宽置信区间既包括有意义的益处也包括危害（Peto OR 0.99，95% CI 0.28至3.43；1072名参与者，8项研究；I² = 0%；低质量证据）。地塞米松可能会使无糖尿病参与者在术后前12小时内血糖水平轻度升高（MD 13 mg/dL，95% CI 6至21；10项研究；595名参与者；I² = 50%；低质量证据）。我们确定了两项研究报告了糖尿病参与者术后24小时内地塞米松后的血糖反应（MD 32 mg/dL，95% CI 15至49；74名参与者；I² = 0%；极低质量证据）。
单次剂量的地塞米松可能不会增加术后感染风险。由于试验结果不精确，地塞米松对普通外科人群伤口愈合延迟是否有影响尚不确定。本荟萃分析中报告伤口愈合延迟的随机研究未纳入伤口愈合延迟风险增加的参与者（如糖尿病患者、服用免疫抑制药物者）；因此，我们的研究结果应谨慎外推至临床环境。此外，必须记住地塞米松会使血糖轻度升高。对于糖尿病患者，非常有限的证据表明血糖升高更为明显。这是否以临床相关方式影响伤口愈合仍有待确定。一旦评估，三项等待分类的研究和两项正在进行的研究可能会改变本综述的结论。
