General anaesthesia abolishes spontaneous respiration. Use of general anaesthesia is frequently unavoidable during surgical procedures. The ability to maintain breathing by placing a tube in the windpipe of patients undergoing general anaesthesia is therefore crucial. A neuromuscular blocking agent (NMBA) is used for relaxation of muscles of the throat and is traditionally used to ease correct placement of the tube. However, use of an NMBA may cause unwanted side effects. On the other hand, large observational studies have indicated that avoiding NMBA may cause difficulties when the tube is placed during anaesthesia.
In the present systematic review, we assessed the effect of avoiding NMBA instead of using NMBA on difficulties associated with placing a tube in the windpipe of patients undergoing general anaesthesia. Further, we evaluated the consequences of using or avoiding NMBA on events of pain or injury in the upper part of the throat following placement of a tube in the windpipe.
We identified 34 randomized controlled trials that met our inclusion criteria. These trials included 3565 patients who were undergoing various surgical procedures in hospital departments. Most trials were conducted in high-income countries, and most patients were undergoing elective surgery. Trials included patients of both sexes; most were healthy and non-obese, and staff members did not expect difficulty when placing the tube in the windpipe.
This review supports that use of NMBA may ensure the best conditions for placing a tube in the windpipe during general anaesthesia. When an NMBA is avoided, risk for pain or injury in the throat is increased following placement of a tube in the windpipe.
Quality of the evidence
Conditions for which a tube is placed in the windpipe are defined in individual trials and may not reflect a situation that many clinicians would consider to be clinically serious. Regarding events of injury and sore throat, only sparse data are available from trials with low risk of bias, although among all included trials, avoiding NMBA increased the risk of pain or injury. We therefore consider our overall findings to reflect evidence of moderate quality.
This review supports that use of an NMBA may create the best conditions for tracheal intubation and may reduce the risk of upper airway discomfort or injury following tracheal intubation. Study results were characterized by indirectness, heterogeneity, and high or uncertain risk of bias concerning our primary outcome describing difficult tracheal intubation. Therefore, we categorized the GRADE classification of quality of evidence as moderate to low. In light of defined outcomes of individual included trials, our primary outcomes may not reflect a situation that many clinicians consider to be an actual difficult tracheal intubation by which the patient's life or health may be threatened.
Tracheal intubation during induction of general anaesthesia is a vital procedure performed to secure a patient's airway. Several studies have identified difficult tracheal intubation (DTI) or failed tracheal intubation as one of the major contributors to anaesthesia-related mortality and morbidity. Use of neuromuscular blocking agents (NMBA) to facilitate tracheal intubation is a widely accepted practice. However, because of adverse effects, NMBA may be undesirable. Cohort studies have indicated that avoiding NMBA is an independent risk factor for difficult and failed tracheal intubation. However, no systematic review of randomized trials has evaluated conditions for tracheal intubation, possible adverse effects, and postoperative discomfort.
To evaluate the effects of avoiding neuromuscular blocking agents (NMBA) versus using NMBA on difficult tracheal intubation (DTI) for adults and adolescents allocated to tracheal intubation with direct laryngoscopy. To look at various outcomes, conduct subgroup and sensitivity analyses, examine the role of bias, and apply trial sequential analysis (TSA) to examine the level of available evidence for this intervention.
We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, LILACS, advanced Google, CINAHL, and the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and www.centerwatch.com, up to January 2017. We checked the reference lists of included trials and reviews to look for unidentified trials.
We included randomized controlled trials (RCTs) that compared the effects of avoiding versus using NMBA in participants 14 years of age or older.
Two review authors extracted data independently. We conducted random-effects and fixed-effect meta-analyses and calculated risk ratios (RRs) and their 95% confidence intervals (CIs). We used published data and data obtained by contacting trial authors. To minimize the risk of systematic error, we assessed the risk of bias of included trials. To reduce the risk of random errors caused by sparse data and repetitive updating of cumulative meta-analyses, we applied TSA.
We identified 34 RCTs with 3565 participants that met our inclusion criteria. All trials reported on conditions for tracheal intubation; seven trials with 846 participants described ‘events of upper airway discomfort or injury’, and 13 trials with 1308 participants reported on direct laryngoscopy. All trials used a parallel design. We identified 18 dose-finding studies that included more interventions or control groups or both. All trials except three included only American Society of Anesthesiologists (ASA) class I and II participants, 25 trials excluded participants with anticipated DTI, and obesity or overweight was an excluding factor in 13 studies. Eighteen trials used suxamethonium, and 18 trials used non-depolarizing NMBA.
Trials with an overall low risk of bias reported significantly increased risk of DTI with no use of NMBA (random-effects model) (RR 13.27, 95% CI 8.19 to 21.49; P < 0.00001; 508 participants; four trials; number needed to treat for an additional harmful outcome (NNTH) = 1.9, I2 = 0%, D2 = 0%, GRADE = moderate). The TSA-adjusted CI for the RR was 1.85 to 95.04. Inclusion of all trials resulted in confirmation of results and of significantly increased risk of DTI when an NMBA was avoided (random-effects model) (RR 5.00, 95% CI 3.49 to 7.15; P < 0.00001; 3565 participants; 34 trials; NNTH = 6.3, I2 = 70%, D2 = 82%, GRADE = low). Again the cumulative z-curve crossed the TSA monitoring boundary, demonstrating harmful effects of avoiding NMBA on the proportion of DTI with minimal risk of random error. We categorized only one trial reporting on upper airway discomfort or injury as having overall low risk of bias. Inclusion of all trials revealed significant risk of upper airway discomfort or injury when an NMBA was avoided (random-effects model) (RR 1.37, 95% CI 1.09 to 1.74; P = 0.008; 846 participants; seven trials; NNTH = 9.1, I2 = 13%, GRADE = moderate). The TSA-adjusted CI for the RR was 1.00 to 1.85. None of these trials reported mortality. In terms of our secondary outcome 'difficult laryngoscopy', we categorized only one trial as having overall low risk of bias. All trials avoiding NMBA were significantly associated with difficult laryngoscopy (random-effects model) (RR 2.54, 95% CI 1.53 to 4.21; P = 0.0003; 1308 participants; 13 trials; NNTH = 25.6, I2 = 0%, D2= 0%, GRADE = low); however, TSA showed that only 6% of the information size required to detect or reject a 20% relative risk reduction (RRR) was accrued, and the trial sequential monitoring boundary was not crossed.