Laryngoscopy and endotracheal intubation during induction of general anaesthesia are extremely strong nociceptive stimuli, which often lead to unintended stimulation of the sympathetic nervous system manifested by increased arterial pressure and tachycardia [1]. In general, haemodynamic cardiovascular changes accompanying intubation are transient and do not result in severe sequels. However, in patients with concomitant coronary disease, arterial hypertension or intracranial pathology, increased values of these circulatory parameters may lead to myocardial ischaemia or secondary brain damage. To minimize effectively these adverse changes, it is suggested to administer opioids blocking ß-receptors or stimulating a2 – adrenergic receptors, local or general lignocaine or to deepen the general anaesthesia with intravenous or inhaled agents [2].

The extent of circulatory response depends on the type and depth of general anaesthesia, age of patients, concomitant diabetes or cardiovascular diseases and drugs used [2]. Moreover, the duration and possible difficult laryngoscopy and intubation are involved [3]. Adequate intubation conditions are more common in relaxed patients [4]. Therefore, proper assessment of neuromuscular block with a relaxant is of utmost importance. The time of achieving optimal conditions for intubation depends on the type and dose of a relaxant, individual characteristics of patients, and some other factors [5].  Thus, monitoring of neuromuscular conduction appears to be necessary for proper timing of induction.

The methods providing the best assessment of the extent of neuromuscular block include mechanomiography and acceleromiography [6]. In clinical practice, on the other hand, visual assessment of the reaction of the thumb adductor to train-of-four (TOF) stimulation of the ulnar nerve at the wrist is commonly used [6].

Cisatracurium, one of the most potent atracurium isomers, does not release histamine in the doses used clinically, which is its advantage over the parent agent speaking in favour of its use for endotracheal intubation [7].

The aim of the present study was to assess the usefulness of monitoring of neuromuscular block induced with cisatracurium to provide optimal endotracheal intubation conditions and to minimize cardiovascular reactions.

METHODS

The study design was approved by the Independent Bioethical Committee for Scientific Research, Gdansk Medical University.  The study encompassed ASA I patients scheduled for lumbosacral discoidectomy. The exclusion criteria included hepatic, renal, cardiovascular, nervous and muscular diseases, tobacco smoking, alcohol abuse and drugs potentially affecting neuromuscular conduction. Moreover, patients with preoperative assessment indicating possible difficult intubation and those with infeasible laryngoscopic visualisation of the true glottis during induction of anaesthesia were excluded.

Patients were randomly allocated to two groups. In group I, the moment of intubation was chosen based on clinical assessment and experience of an attending anaesthesiologist, who had never used a peripheral nerve stimulator. In group II, an anaesthesiologist performed intubation when he visually assessed complete loss of all 4 reactions to TOF stimulation carried out  every 15 sec. Patients were orally premedicated with midazolam 0.2 mg kg-1 45 min before induction of anaesthesia. Anaesthesia was induced with fentanyl 2 µg kg-1 and thiopentone 5 mg kg-1; once the ciliary reflex disappeared, cisatracurium 0.15 mg kg-1 was administered. If required, additional thiopentone (33% of the initial dose) was given to  maintain the bispectral index <50 throughout the procedure. After the administration of a relaxant, female patients were intubated with the 7 mm endotracheal tubes whereas male patients with the 8 mm ones. Artificial lung ventilation was carried out using 100% O2 in the semi-closed system with ETCO2 ranging 37-40 mm Hg.

The neuromuscular junction block was monitored by observing the reactions of the thumb adductor to stimulation of the ulnar nerve at the wrist with the 60 mA, 2 Hz current (each stimulus lasting 0. 2ms) induced with the peripheral nerve stimulator.

HR and MAP values were analysed at the following stages of induction of anaesthesia: T0 – initiation of the procedure, T1 – fentanyl administration, T2 – 1 min after fentanyl administration, T3 – thiopentone administration, T4 – cisatracurium administration, T5 – 1 min after cisatracurium administration, T6 – intubation, T7 – 1 min after intubation, T8 – 2 min after intubation. Moreover, intubation conditions were assessed based on easiness of laryngoscopy, opening and mobility of vocal cords, reactions to insertion of the endotracheal tube and inflation of its cuff according to generally accepted criteria [6]. Furthermore, we evaluated the time between the administration of a relaxant (end of 5-second infusion) and endotracheal intubation (end of 5-second inflation of the sealing cuff).

The results were statistically analysed using the Shapiro-Wilk W test, ANOVA, Wilcoxon and Mann-Whitney U tests.  Data were presented as a mean and standard deviation. P<0.05 was considered statistically significant.

RESULTS

The study population included 45 patients, 21 in group I and 24 in group II. The study groups were comparable in terms of age, weight, BMI, height, deep and superficial body temperature (Table 1).

The mean time required for intubation was significantly shorter in group I compared to group II (162±35 sec vs 339±74 sec, p<0.001).

Excellent and good intubation conditions were observed in all group II patients and only in 13 group I patients (53%, p=0.003).

There were no intergroup differences in bispectral index values at the successive stages of the study (Table 2).

In group I, significantly increased HR and MAP (p<0.05) were observed during and after intubation. In group II, HR and MAP during intubation and at 1min and 2 min after intubation were significantly lower (p<0.001) compared to group I (Table 2).

DISCUSSION

Monitoring of neuromuscular conduction substantially prolonged the cisatracurium-intubation time yet increased the percentage of clinically acceptable intubation conditions. Timing of intubation in the group without stimulation was based on experiences of anaesthesiologists and recommendations of producers of muscle relaxants. Habits of anaesthesiologists seem important, as with the majority of agents used in clinical practice 2.5 min is enough to achieve the desirable effect [7, 8].

On average, intubation in the group with stimulation was performed at 5 min after cisatracurium administration. It is known that the maximum effect of cisatracurium is observed much later compared to equipotent doses of atracurium, mivacurium, vecuronium and rocuronium [8]. Unlike atracurium, which is the mixture of 10 stereoisomers, cisatracurium is a “pure” 1R-cis isomer constituting about 15% of the parent agent. The comparison of properties of various stereoisomers of atracurium confirms the hypothesis that the time of neuromuscular block is inversely proportional to the potency of an agent. Cisatracurium is four-fold more potent than atracurium and its effective dose inducing the 95% neuromuscular block (ED95 ) is 0.05 mg kg-1 [7]. The maximum action of cisatracurium following 2×ED95, however, occurs markedly later compared to atracurium (5.2±0.3 min vs 3.2±0.3 min) [8, 9].

Generally, maximum neuromuscular block was demonstrated to occur 7.7 min after 0.1 mg kg-1 of cisatracurium [10]. To shorten this time, it is recommended to increase its single dose or use a small priming dose [7]. With the majority of agents blocking neuromuscular conduction, 2×ED95 is sufficient to enable endotracheal intubation; for cisatracurium, 3 or 4×ED95 (0.15-0.2 mg kg-1) is suggested [7]. It was shown that only large priming doses of cisatracurium (0.015 mg kg-1, and the basic dose of 0.085 mg kg-1) substantially shorten the time of neuromuscular block [11]. However, routine clinical use of this method is not recommended due to possible adverse effects.

In our study, excellent intubation conditions were observed in all patients with the moment of intubation chosen after complete loss of the reaction to TOF stimulation assessed visually.  According to other authors, 95% of patients were provided with excellent intubation conditions using the same assessment of the reaction to supramaximum TOF stimulation of the ulnar nerve [12]. Thus, the method seems suitable and simple ensuring optimal conditions for intubation in the majority of cases.

Moreover, conditions for intubation may be improved by modifying the anaesthetic technique. In our study, anaesthesia was induced with thiopentone, as it is well known that its effects on intubation conditions are lesser compared to those of propofol or etomidate [13]. Intubation without relaxation is also possible yet requires large doses of thiopentone, which cannot be used in clinical practice due to their adverse side effects [14]. A high proportion of clinically acceptable intubation conditions may be achieved using propofol with remifentanil without relaxants, which is associated, however, with the risk of hypotension and bradycardia [15, 16]. Such a method may be used when neuromuscular block is not necessary or when relaxants are contraindicated.

Laryngoscopy and subsequent endotracheal intubation are one of the most potent nociceptive stimuli. Nociceptive stimulation induces numerous reactions, e.g. motor response, characteristic electroencephalographic picture of CNS stimulation or stimulation of the sympathetic nervous system manifested by increased arterial pressure and accelerated heart rate [17,18]. The patient`s movements may be effectively blocked with muscle relaxants; increased reactions of the circulatory system to intubation, on the other hand, appear to depend largely on the kind and dose of opioids or hypnotics used [15,17]. Fentanyl in the dose of 5-8 µg kg-1 is suggested for complete loss of circulatory reaction to intubation [2].

Patients anaesthetized without neuromuscular conduction monitoring showed higher mean values of arterial pressure and heart rate during and after intubation. Moreover, a high proportion of those patients was characterized by bad intubation conditions resulting from insufficient block of neuromuscular conduction. Muscle relaxants administered during sedation were demonstrated to increase the stability of haemodynamic parameters [19], which is likely to result from the lack of afferent stimulation of CNS by muscle fibres. It seems that in patients with incomplete neuromuscular block, laryngoscopy and intubation cause stronger nociceptive stimulation, hence stronger reflex cardiovascular reactions. In our study the comparable values of bispectral index found in both groups of patients contradict any impact of an additional dose of thiopentone (administered in the group where TOF with stimulation was used) on the intergroup haemodynamic differences.

CONCLUSIONS

Monitoring of neuromuscular block induced with cisatracurium prolongs the endotracheal intubation time, improves intubation conditions and minimizes cardiovascular reactions.

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REFERENCES

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Address:

*Malgorzata Witkowska
Zaklad Neuroanestezjologii UM Gdansk
ul. Debinki 7, 80-211 Gdansk
tel./fax: 0-58 349 23 35

Received: 14.04.2009
Accepted: 29.05.2009