Our study showed no significant difference between a combination of dexmedetomidine 1μg/kg and rocuronium 0.6 mg/kg and suxamethonium 1 mg/kg in respect of the effect on the rate of excellent intubating conditions during RSI in adult patients.
Although this study is the first one to use Dex pretreatment with rocuronium in RSI, multiple studies have experimented with the outcome of different doses of rocuronium either as a sole agent or with adjuvants, on the intubating conditions in RSI, with conflicting results (Alanoğlu et al., 2006; Tran et al., 2015). Contrary to our results, Kown et al. compared suxamethonium with a standard rocuronium dose of 0.6 mg/kg. They reported better intubation conditions in the succinyl group.(Sluga et al., 2005) This could be explained as they used a high dose of suxamethonium 1.5 mg/kg and a relatively low dose of rocuronium and they did not use adjuvants in either group. Similar to our results, higher doses of rocuronium (1–1.2 mg/kg) provided comparable intubating conditions to that of suxamethonium (Kwon et al., 2013; Patanwala et al., 2011; Schreiber et al., 2005a).
Combining DEX with a standard dose of rocuronium 0.6 mg/kg, instead of administering high dose rocuronium (1.2 mg/kg) alone, might be regarded as a suitable choice for RSI, as this high dose results in almost doubled recovery time (Schultz et al., 2001b). Moreover, avoiding high doses of rocuronium may permit spontaneous recovery and mitigate the need to antagonize rocuronium with sugammadex, which is expensive and not usually available in many countries (Murphy, 2018). Indeed, if reversal of rocuronium is required, the efficacy of standard reversal doses of sugammadex is not altered in those with Dex pretreatment (Memiş et al., 2008).
Compared with other studies, that reported as high as 80% of their patients had excellent intubation conditions (Fuchs-Buder et al., 2007; Kim et al., 2015; Naguib et al., 2006), substantial low rates of excellent intubating conditions (less than 50%) were observed among our patients in both control and experimental groups. We cannot offer a clear explanation for this observation, although we have undertaken rigorous measures. Standardized protocol was applied to all patients including random allocation of patients, matching of tested drugs, and concealing labels, and participants (patients, personnel who administered tested drugs and who collected data) were blinded to the identity of the tested medications. In order to avoid observer bias two independent anesthetists were in charge of each patient; one administered all medications and was in charge of the patient throughout the whole surgery, and a second anesthetist was responsible for intubation and collecting intubation condition data. Performance bias was mitigated as only two designated senior consultants were in charge of intubation and collecting intubation conditions. Moreover, our sample size was larger than other studies (Czarnetzki et al., 2020; Alanoğlu et al., 2006; Tran et al., 2015; Sluga et al., 2005; Patanwala et al., 2011; Schreiber et al., 2005a; Schultz et al., 2001b; Murphy, 2018; Memiş et al., 2008; Kim et al., 2015; Naguib et al., 2006; El-Kobbia et al., 2015; Park et al., 2013). However, a possible explanation of the observed lower rates of excellent intubation conditions is “omitted data.” Initially, we randomly allocated 240 patients between the control and experimental groups, 120 each. However, we had to omit data and analyzed only data from 228 patients. The number of withdrawn data was higher in the control group (7 patients) than in the experimental group (5 patients). The reasons for deleting those data, in order of frequency, were as follows: Cormack and Lehan grade 3 or 4 (5 patients), taking more than 80 s for intubation (3 patients), patients asked to terminate the study because they felt pain at the infusion site (2 patients), one patient asked to withdraw from the study with no reason, and one patient that needed supplemental propofol. We might hypothesize that if the deleted data were included in the final analysis, the rate of excellent intubation conditions would have been different.
Our experiment also showed that incidence of excellent intubating conditions was notably higher in females than males. This outcome, although not the principal interest of our research, was not unpredicted as gender has its role on the pharmacodynamics of neuromuscular blocking agents and females are more susceptible to the effects of amino-steroid muscle relaxant, e.g., rocuronium than males (Adamus et al., 2007; Adamus et al., 2008; Adamus et al., 2011). Further clinical trials in the future may explore the assumption that Dex-rocuronium combination has more efficacy in females than males.
The all in all incidence of adverse effects among our study population was 21 %. Most of the adverse effects happened with the control group, 73%. The most frequent suxamethonium associated adverse outcome was muscle aches, at 24 h post-operatively. Indeed, suxamethonium associated muscle ache is well documented self- limiting complaint, and respond to simple analgesics, with no long-term consequences (Schreiber et al., 2005b).
Pretreatment associated complications occurred only with Dex pretreated group (4%), none with saline pretreated control group. The side effects were pain at the injection site (two patients and they asked to withdraw from the study due to pain and they were excluded from the final analysis), erythema, and nausea which responded well to reassurance. Also, unfavorable outcomes on administering the neuromuscular relaxant, mainly erythema, have been observed more often with the suxamethonium group. However, they were mild and did not warrant treatment.
No statistically notable difference between groups was observed as regard systolic and diastolic blood pressure at baseline (before induction), and at induction and after intubation. However, there was significant lower heart rate values in the Dex-pretreated rocuronium group than in the suxamethonium group. This was expected as bradycardia is a well-known association with Dex (Fujii & Tanaka-Mizuno, 2018; Bloor et al., 1992). However, it was self-limiting and did not require intervention.
One limitation of this study was that all our patients were premedicated with midazolam an hour before conducting our research protocol, this might have affected the values of our results as midazolam has got muscle relaxant properties through α2 γ-aminobutyric acid A (GABAA) receptors.(Park et al., 2019)