Day case anaesthesia aims at providing good operating conditions while assuring a reliably rapid recovery. Drugs used must have the lowest possible risk of a prolonged duration of action or any other adverse reactions. Optimal intubation conditions allowing atraumatic, rapid tracheal intubation are essential. Mivacurium and rocuronium are non-depolarizing neuromuscular blocking drugs of short and intermediate durations of action, respectively. They are useful in day case anaesthesia for providing rapid onset of muscle relaxation and recovery [1-3].
Mivacurium is a benzylisoquinolinium derivative with a relative short duration of action at doses from 0.15 to 0.2 mg kg−1. It is inactivated through enzymatic breakdown by plasma cholinesterases [4,5]. Rocuronium is an aminosteroid non-depolarizing neuromuscular blocking agent of intermediate duration of action. It is eliminated by the liver and kidneys. It provides good or excellent intubating conditions with a short onset of time at doses from 0.6 to 1.2 mg kg−1 [6-10]. Wierda has estimated doses to produce identical duration at 0.15 mg kg−1 for mivacurium and 0.3 mg kg−1 for rocuronium .
We compared intubation conditions and time-course of action with those smaller doses of mivacurium and rocuronium, in the context of day case anaesthesia or for short procedures.
After institutional approval and informed patient consent, 50 patients, ASA I or II were enrolled prospectively. Patients with expected difficult intubation or taking medication known to interact with neuromuscular blocking agents were excluded. Patients were randomly allocated to receive either mivacurium or rocuronium according to a randomization list (25 in each group).
Anaesthesia was induced with propofol using a target controlled infusion (TCI) (target 6–8 μg mL−1) and sufentanil (0.25 μg kg−1) and maintained with propofol (target 3.5–4.5 μg mL−1) and 50% nitrous oxide in oxygen. We used the diprifusor TCI system, which assumes a three-compartment pharmacokinetic model with a specific set of pharmacokinetic parameters for propofol and two independent infusion control algorithms to provide a fail-safe mechanism to enhance patient safety.
Following induction, the right arm was positioned comfortably on an arm board and well strapped to allow proper monitoring. A TOF-WATCH SXTM was stabilized and calibrated. Patients were ventilated with oxygen via a face-mask during this procedure, which took around 6 min. After that, the muscular relaxant was administered.
Neuromuscular blockade (NMB) was monitored every 15 s by acceleromyography using the TOF-WATCH SX (BiometerTM/; Denmark) with supramaximal train-of-four (TOF) stimulation of the ulnar nerve. Propofol at a target of 6–8 μg mL−1 was continued until tracheal intubation was performed.
T1 (first twitch of the TOF) expressed as percentage of control response and the TOF ratio (T4 : T1) were used for the evaluation of neuromuscular block. NMB was achieved with either mivacurium 0.15 mg kg−1 or rocuronium 0.3 mg kg−1. Neuromuscular blockade was assessed from the time of induction of anaesthesia until full recovery from muscle relaxation (TOF ratio >90%). Tracheal intubation was performed at the maximal achieved block and carried out by an experienced anaesthetist blinded to the agent used. Intubation conditions were evaluated according to a standard scheme taking into account the ease of laryngoscopy, the position of the vocal cords, airway reaction and limb movement. They were graded as excellent, good or poor.
Other parameters recorded in this study included:
- time of onset of NMB;
- percentage of patients reaching complete blockade or ≥95%;
- time at which laryngoscopy followed by intubation was performed;
- duration of time for 10% and 25% recovery of T1 (clinical duration);
- time required for T1 to recover from 25% to 70% and from 25% to 90%;
- time required for TOF ratio (T4 : T1) to reach 70% and 90%.
When TOF ratio was over 90%, patients were ventilated with 100% oxygen and extubated.
A t-test was used for parametric data and Fisher's exact test was used to compare intubation grades among groups. Analysis of variance was used to determine changes in onset and recovery times between the groups. Data were expressed as means ± SD. P < 0.05 was considered statistically significant.
The two groups were comparable with respect to sex, age, weight and height (Table 1).
One patient in the rocuronium group was withdrawn from the study due to failed data. Patients whose NMB was less than 95% were excluded from analysis to allow comparable groups. Complete blockade (100%) was reached in 8/24 patients in the rocuronium group and in 18/24 patients in the mivacurium group. Greater than 95% block was achieved in 24/25 patients in the mivacurium group and in 23/24 patients in the rocuronium group. The doses defined by Wierda as having identical duration did not necessarily induce a complete block in all patients.
The onset time of NMB was 211 ± 16 s for mivacurium and 237 ± 17 s for rocuronium. There was no significant difference concerning the times to intubation (Table 2).
T1 reached 25% recovery (clinical duration) within 889 ± 45 s in the mivacurium group and 913 ± 64 s in the rocuronium group. No difference was found in the time required for TOF ratio to reach 70% or 90% recovery; the time to 70% recovery was 1356 s with mivacurium and 1562 s with rocuronium, and 90% recovery was attained in 1595 s with mivacurium and 1841 s with rocuronium (Table 2).
Intubation conditions were described as excellent in 92% of patients in the mivacurium group and in 100% of patients in the rocuronium group. The intubation conditions of the other 8% to whom mivacurium was given were considered as good. There were no poor intubation conditions.
During laryngoscopy, 12% of patients in the mivacurium group had intermediately abducted vocal cords. The vocal cords of the other 88% were fully abducted and all patients in the rocuronium group had fully abducted vocal cords at the time of intubation. Slight limb movement was noticed in only one patient in the mivacurium group.
There was no significant difference between the two groups concerning airway reactions during intubation. In the rocuronium group, 74% of patients had no reaction, and 26% had a brief diaphragmatic reaction. These results are comparable with the mivacurium group in which 48% of patients had no airway reaction during intubation, 44% had a brief diaphragmatic movement and 8% had a sustained cough or breathing reaction, which did not impede the intubation (Table 3).
During general anaesthesia for short procedures, tracheal intubation may be accomplished after concurrent injection of alfentanil, remifentanil or sufentanil and propofol without a neuromuscular blocking agent. Nevertheless, relatively high doses, which may not be suitable for short procedures and haemodynamic stability, are required to obtain reliably satisfactory conditions.
This study was designed to examine if injection of low doses of rocuronium or mivacurium during induction of anaesthesia improved intubation conditions [1,2,11]. Our results demonstrate that waiting for maximal suppression of twitch response, rather than attempting tracheal intubation at a predetermined time, yields similar onset times and intubation conditions following administration of these doses of mivacurium or rocuronium.
Satisfactory intubation conditions were obtained with both neuromuscular blocking agents within 261 ± 14 s for mivacurium and within 245 ± 20 s for rocuronium despite the fact that complete blockade was not observed in all patients. In the mivacurium group, 18 patients reached complete blockade compared to only eight patients in the rocuronium group.
These results are in accordance with previous studies where mechanomyograph recordings were used [5-7,12,13]. These findings suggest that waiting for optimal twitch suppression might be a better indicator to achieve the best intubation conditions.
The clinical duration (T1 25% recovery) classifies rocuronium as an intermediate duration neuromuscular blocking agent after a bolus of 0.6 mg kg−1 (2×ED 95) while mivacurium has a shorter duration of action after 0.15 mg kg−1 (2× ED 95%). Therefore, mivacurium is frequently used for short procedures and in ambulatory anaesthesia.
In this study, duration 25% and all other pharmacodynamic variables are equivalent in the two groups and are also in accordance with the literature following the administration of 0.15 mg kg−1 mivacurium or 0.3 mg kg−1 rocuronium [4,6,9,13,14]. Timelines for rocuronium and mivacurium are illustrated in Figure 1. Only the late phase of recovery is longer for rocuronium but the difference is not significant.
Therefore, rocuronium 0.3 mg kg−1 could be an adequate alternative to mivacurium concerning intubating conditions as well as duration of action. Studies have demonstrated a significant increase in histamine plasma concentrations (200% or more) from the first to the third minute following rapid administration of mivacurium 0.2 mg kg−1. In contrast, administration of increasing doses of rocuronium induces no significant changes . This histamine release is present in approximately 30% of the patients and is associated with erythema, haemodynamic variations or rare bronchospasm.
The second problem with mivacurium is linked to its metabolism depending on pseudocholinesterases. In heterozygotes for the atypical enzyme (incidence 1 in 480), the duration is lengthened by 30–50%. In atypical homozygotes (incidence 1 in 3000), the duration is markedly prolonged, such that full paralysis after an intubating dose of 0.2 mg kg−1 will last 3–4 h [16,17]. The duration of action of mivacurium is also lengthened in renal and hepatic failure . In patients with reduced renal function, rocuronium has the same or a slightly prolonged time course of neuromuscular blockade compared to patients with normal renal function [19,20]. Recently, Robertson and colleagues concluded that rocuronium 0.3 mg kg−1 is suitable for use in patients with renal failure when endotracheal intubation and neuromuscular blockade for a short period of time are needed . In contrast, patients with liver failure have prolonged clinical duration of block and increased recovery time with a wide inter-individual variation due to a decreased elimination rate [22,23]. Studies from France and Norway have suggested a frequent rate of anaphylaxis with rocuronium [24-26]. A study concerning allergy testing by Garvey and colleagues  in Denmark does not suggest a more frequent incidence of sensitivity to rocuronium. The lack of immunoglobulin E-specific antibodies raises the possibility that some of the reports of apparent anaphylaxis actually represent a confluence of relatively common clinical findings (hypotension, vasodilatation and bronchospasm) that do not have an immunologic basis. In a recent publication, Bhananker and colleagues showed that the incidence of reports containing anaphylaxis terms did not differ between vecuronium and rocuronium in the US and suggested that reports may be significantly influenced by the area from which the reports originate .
In summary, this study demonstrates that adequate intubation conditions with rapid recovery from neuromuscular blockade can be achieved equally well with mivacurium or rocuronium.
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