We performed a systematic review and meta-analysis of RCTs to evaluate intubating conditions and apnoea times with different succinylcholine regimens. As a gold standard, we have chosen succinylcholine 1.0 mg kg− 1, which is probably the most widely used regimen for RSI. We analysed data from six trials including relevant data of 864 patients.
If we consider the outcome "excellent intubating conditions" as the most relevant in the context of RSI (Figure 2), we may conclude that regimens equal or lower than 0.5 mg kg− 1 produced less often excellent conditions, whereas 2.0 mg kg− 1 performed significantly better that 1 mg kg− 1. With succinylcholine 2.0 mg kg− 1, the number needed to treat suggested that four to five patients needed to be intubated for one to have excellent intubating conditions during RSI who would not have had such excellent conditions had they all received 1 mg kg− 1 only. This result must be interpreted cautiously mainly for two reasons. Firstly, 2.0 mg kg− 1 was tested in one single trial only with a limited number of patients. Secondly, in that single trial, only 63% of patients had excellent intubating conditions with the standard regimen, 1.0 mg kg− 1. This "baseline" incidence was lower compared with the other trials. It can, therefore, not be excluded that 2.0 mg kg− 1 performed well since in the only trial that tested this regimen, the gold standard regimen performed relatively badly. Thus, it remains unknown whether 2.0 mg kg− 1 further improves "excellent intubating conditions" in a patient population with a high baseline incidence of "excellent intubating conditions".
Alternatively, the outcome "unacceptable intubating conditions" may be regarded as the most relevant in the context of RSI (Figure 3). Contrary to the outcome "excellent intubating conditions", the result was much more dichotomous; regimens below 0.5 mg kg− 1 were clearly less efficacious compared with the gold standard, 1 mg kg− 1, whereas regimens above 0.5 mg kg− 1 were no different from 1 mg kg− 1. Based on this outcome, it may be deduced that regimens below 0.5 mg kg− 1 should be avoided for RSI. Interestingly, with the gold standard regimen 1 mg kg− 1, the incidence of "unacceptable intubating conditions" showed much less variability between trials (0% to 6.7%) compared with the outcome "excellent intubating conditions". This suggests that indirect comparisons between different succinylcholine regimens are more reliable when the outcome "unacceptable intubating conditions" is chosen. It also suggests that the outcome "unacceptable intubating conditions" is not ideal to test various degrees of efficacy of experimental regimens compared with the gold standard regimen; with regimens above 0.6 mg kg− 1, unacceptable intubating conditions were virtually absent.
Additionally to the outcomes "excellent" and "unacceptable" intubating conditions, apnoea time may be used for rational decision-making (Figure 4). With regimens below 0.8 mg kg− 1, median apnoea times became constantly shorter, and consequently, mean differences compared with the gold standard regimen increased. There is thus an argument in favour of using lower than standard succinylcholine regimens for RSI. This must however be weighted against the increased risk of having less often excellent intubating conditions and more frequently unacceptable intubating conditions. Data on apnoea times with regimens above 1 mg kg− 1 were lacking. Thus, clinically relevant prolongation of apnoea times with 1.5 or 2.0 mg kg− 1 needs to be formally shown. Also, the primary factor determining return of spontaneous respiration may not be the depth of neuromuscular block, but the degree of centrally mediated respiratory depression induced by the opioids and hypnotics used for induction of anaesthesia.
Strengths and Limitations
The strength of this meta-analysis is the rigorous systematic review of the literature. Also, we included exclusively RCTs comparing different experimental regimens of succinylcholine with the gold standard regimen, 1 mg kg− 1, for RSI and using the same validated intubation score. However, the number of retrieved valid studies was small, the number of included patients limited, and statistical heterogeneity was relatively high. Thus, the evidence base remains weak and the interpretation of the data is not straightforward. Additionally, all trials were performed in low risk patients undergoing elective surgery, although succinylcholine is mainly used for RSI in patients undergoing emergency surgery. Some studies were using a modified RSI technique and in one, sevoflurane was used for induction. This may have introduced clinical heterogeneity. The observed variability of the baseline incidences of excellent intubating conditions suggests that the study populations were not similar or that intubation scores were interpreted differently. Finally, succinylcholine-related adverse effects were not systematically reported and for regimens above 1.0 mg kg− 1, data on apnoea times were lacking. For rational decision-making, adverse effects and apnoea times with all tested regimens should be known.
It is surprising that efficacy and potential of harm of a drug that has been widely used for almost 60 years in the perioperative setting including anaesthesia, intensive care and emergency medicine, is so poorly documented. This begs the question as to the need for further high quality trials to better understand the role of succinylcholine in patients needing RSI. Specific high-risk patient populations have not be studied, including pregnant women, patients undergoing emergency surgery, and children. Also, the optimal succinylcholine regimen in obese patients remains controversial,[13,14] and needs further investigation. Trials should report on drug-related adverse effects and apnoea times.
BMC Anesthesiol. 2020;20(54) © 2020 BioMed Central, Ltd.