We reviewed the evidence from randomized controlled trials comparing high initial concentrations of sevoflurane with low initial concentrations to see whether the evidence supports use of high initial concentrations to reduce induction times and complications for inhalational induction of anaesthesia. This update of a review first published in 2013 is current to February 2016.
General anaesthesia for surgery can be induced by having patients breathe a mixture of sevoflurane (a sweet-smelling inhaled anaesthetic vapour or drug) and oxygen through a mask. This technique has been reported to be safe, reliable and well accepted by patients. The initial concentration of sevoflurane used for induction can be low or high. The low initial concentration technique involves administering a low concentration of sevoflurane (less than 4%), then gradually increasing the concentration until the patient is anaesthetized. The high initial concentration technique involves administering high concentrations of sevoflurane (from 4% to 8%) from the beginning, then continuing until the patient is anaesthetized. Immediately following loss of consciousness and before anaesthesia is deep enough to allow surgery, patients can go through a stage where they cough, their breathing and heart rate become irregular and they may hold their breath and make uncontrolled movements. A high concentration might shorten this stage.
We included in our review 11 randomized controlled trials (829 participants). These trials were conducted between 1997 and 2014 and differed with regard to participants (adults vs children), concentrations of sevoflurane used, addition of nitrous oxide and opioids and other factors. Some elements of the methods suggested low-quality evidence would be obtained. The studies could not always be combined, and study results cannot be stated with certainty.
The high initial concentration technique shortened induction time (six studies, 443 participants, low-quality evidence) and led to similar rates of cough (eight studies, 589 participants, low-quality evidence), sudden sustained closure of the vocal cords that prevented breathing (seven studies, 588 participants, low-quality evidence), breath holding (five studies, 389 participants, low-quality evidence), sudden movements (five studies, 445 participants, low-quality evidence) and slow heart rate (three studies, 199 participants, low-quality evidence). The high initial concentration technique showed greater suspension of breathing when compared with the low initial concentration technique (two studies, 160 participants, low-quality evidence).
Quality of the evidence
The included studies provided low-quality evidence, and study results should be interpreted with caution. More studies are needed to enable firm conclusions.
A high initial concentration sevoflurane technique probably offers more rapid induction of anaesthesia and a similar rate of complications, except for apnoea, which may be more common with a high initial concentration. However, this conclusion is not definitive because the included studies provided evidence of low quality.
Sevoflurane induction for general anaesthesia has been reported to be safe, reliable and well accepted by patients. Sevoflurane induction uses either low or high initial concentrations. The low initial concentration technique involves initially administering a low concentration of sevoflurane and gradually increasing the concentration of the dose until the patient is anaesthetized. The high initial concentration technique involves administering high concentrations from the beginning, then continuing with those high doses until the patient is anaesthetized. This review was originally published in 2013 and has been updated in 2016.
We aimed to compare induction times and complication rates between high and low initial concentration sevoflurane anaesthetic induction techniques in adults and children who received inhalational induction for general anaesthesia. We defined 'high' as greater than or equal to and 'low' as less than a 4% initial concentration.
For the updated review, we searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (1950 to February 2016), EMBASE (1980 to February 2016), Latin American Caribbean Health Sciences Literature (LILACS) (1982 to February 2016) and the Institute for Scientific Information (ISI) Web of Science (1946 to February 2016). We also searched the reference lists of relevant articles and conference proceedings and contacted the authors of included trials. The original search was run in September 2011.
We sought all published and unpublished, randomized controlled trials comparing high versus low initial sevoflurane concentration inhalational induction. Our primary outcomes included two measures of anaesthesia (time to loss of the eyelash reflex (LOER) and time until a weighted object held in the patient's hand was dropped), time to successful insertion of a laryngeal mask airway (LMA) and time to endotracheal intubation. Other outcomes were complications of the technique.
We used standardized methods for conducting a systematic review as described in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently extracted details of trial methods and outcome data from reports of all trials considered eligible for inclusion. We conducted all analyses on an intention-to-treat basis, when possible. We estimated overall treatment effects by using a fixed-effect model when we found no substantial heterogeneity, whereas we applied the random-effects model in the presence of considerable heterogeneity.
We reran the searches and included one new study (100 participants) in this updated review. In total, we included 11 studies with 829 participants, although most analyses were based on data from fewer participants and evidence of low quality. We noted substantial heterogeneity in the included trials. Thus, our results should be read with caution. It was not possible to combine trials for the primary outcome (LOER), but individual trials reported faster induction times (typically 24 to 82 seconds faster, 41 seconds (31.37 to 50.62)) with high initial concentration sevoflurane (six studies, 443 participants, low-quality evidence). Apnoea appeared to be more common in the high initial concentration sevoflurane group (risk ratio (RR) 3.14, 95% confidence interval (CI) 1.72 to 5.7, two studies, 160 participants, low-quality evidence). We found no evidence of differences between the two groups in the incidence of cough (odds ratio (OR) 1.23, 95% CI 0.53 to 2.81, eight studies, 589 participants, low-quality evidence), laryngospasm (OR 1.59, 95% CI 0.16 to 15.9, seven studies, 588 participants, low-quality evidence), breath holding (OR 1.16, 95% CI 0.47 to 2.83, five studies, 389 participants, low-quality evidence), patient movement (RR 1.14, 95% CI 0.69 to 1.89, five studies, 445 participants, low-quality evidence) or bradycardia (OR 0.8, 95% CI 0.22 to 2.88, three studies, 199 participants, low-quality evidence), and the overall incidence of complications was low.