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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094On-line version ISSN 1806-907X

Rev. Bras. Anestesiol. vol.58 no.3 Campinas May/June 2008 



A comparative study between one and two effective doses (ED95) of rocuronium for tracheal intubation


Estudio comparativo entre una y de los dosis efectivas (DE95) de rocuronio para la intubación traqueal



Luciano Carlos Gomes de MirandaI; Louis BarrucandII; José Costa, TSAIII; Núbia VerçosaIV

IPós-Graduando do Curso de Pós-Graduação em Cirurgia-Geral Área de Concentração: Anestesiologia, Mestrado, Faculdade de Medicina da UFRJ; Anestesiologista do Hospital Naval Marcílio Dias
IIProfessor Titular de Patologia do Departamento de Anatomia Patológica da FM/UFRJ
IIIAnestesiologista Responsável pelo CET/SBA do Serviço de Anestesiologia do Hospital Naval Marcílio Dias
IVProfessora-Associada Mestre e Doutora em Medicina do Departamento de Cirurgia da FM/UFRJ; Coordenadora da Graduação e Pós-Graduação em Anestesiologia FM/UFRJ; Responsável pelo Ambulatório de Avaliação Pré-Anestésica do Hospital Universitário Clementino Fraga Filho UFRJ; Certificado de Área de Atuação em Dor SBA/AMB

Correspondence to




BACKGROUND AND OBJECTIVES: Neuromuscular blockers (NMB) are used to induce relaxation of skeletal muscles and facilitate tracheal intubation (TI). According to the literature, two effective doses (ED95) of NMB are ideal for TI. Rocuronium is a steroid-type, synthetic, non-depolarizing neuromuscular blocker of medium duration. The objective of this study was to evaluate and compare the conditions of tracheal intubation with one and two effective doses (ED95) of rocuronium, following the criteria of the Copenhagen Consensus Conference.
METHODS: Sixty patients of both genders, ages 20 to 60 years, physical status ASA I and II, Mallampati 1 and 2, body mass index (BMI) < 35, who underwent general anesthesia, randomly divided in two groups of 30 patients, were evaluated. Group 1 (G1) received 0.3 of rocuronium (1 ED95), and Group 2 (G2) received 0.6 (2 DE95). Parameters used to evaluate TI were based on the criteria of the Copenhagen Consensus Conference (Good Clinical Research Practice): laryngoscopy, vocal cords (position and movements), reaction to the insertion of the tube and/or filling of the cuff (movements of limbs and cough).
RESULTS: All intubations were considered excellent or good (acceptable); therefore, there were no cases of failure or any intubation considered bad (unacceptable). The results of the statistical analysis were not significant. Consequently, we did not observe any clinically significant differences in the parameters evaluated.
CONCLUSIONS: Both doses of rocuronium, 0.3 and 0.6 ED95, provided clinically satisfactory parameters of TI in elective procedures.



JUSTIFICATIVA Y OBJETIVOS: Los bloqueadores neuromusculares (BNM) son fármacos utilizados para producir el relajamiento de la musculatura esquelética y facilitar la intubación traqueal (IT). La literatura describe que son necesarias de los dosis efectivas (DE95) lo ideal para la IT. El rocuronio es un BNM no despolarizador del tipo esteroide, sintético y de duración intermedia. El objetivo de este estudio fue evaluar y comparar las condiciones de intubación traqueal (IT), utilizando una y de los dosis efectivas (DE95) del rocuronio, secundando los criterios de la Conferencia de Consenso de Copenhague.
MÉTODO: Se estudiaron 60 pacientes divididos aleatoriamente en 2 grupos de 30, de ambos sexos, edades entre 20 y 60 años, estado físico ASA I y II, Mallampati 1 y 2, índice de masa corporal (IMC) < 35, sometidos a anestesia general. En el Grupo 1 (G1) se administró 0,3 (1 DE95) y en el Grupo 2 (G2) 0,6  DE95 (2 DE95) de rocuronio. Los parámetros para la evaluación de la IT fueron en base a los criterios de la Conferencia de Consenso de Copenhague (Good Clinical Research Practice): Laringoscopia, cuerdas vocales (posición y movimiento), reacción a la inserción del tubo y/o a la insuflación del globo (movimiento de los miembros y tos).
RESULTADOS: Todas las intubaciones se consideraron excelentes o buenas boas (aceptables), y no hubo ningún caso en que no se logró el éxito o que no haya sido clasificado como malo (inaceptable). Los resultados del análisis estadístico no arrojaron nada de importante. Por tanto, no hubo diferencia clínica significativa en ninguno de los parámetros evaluados.
CONCLUSIONES: El rocuronio tanto en la dosis de 0,3 como en la de 0,6 DE95 proporcionó condiciones clínicamente aceptables de IT en los procedimientos de elección.




Neuromuscular blockers (NMB) are used in Anesthesiology for relaxation of skeletal muscles, facilitate tracheal intubation (TI), and to provide good surgical conditions. These drugs are quaternary ammonium compounds that have at least one positively charged nitrogen atom. Due to this chemical characteristic, these drugs are attracted by the negative charge of the alpha subunit of postsynaptic cholinergic receptors in the neuromuscular junction (NMJ). Since their structure is similar to acetylcholine, they can, therefore, occupy the cholinergic receptor, leading to changes in ionic permeability 1,2.

Neuromuscular blockers can produce several collateral effects, and among the most clinically important are: autonomic stimulation, ganglionic blockade, release of histamine, and vagolytic and sympatholytic activities3. Those effects lead to cardiovascular changes that, although they may be unnoticed, they can also, in some cases, have severe consequences 4.

The potency of NMB is measured by the dose-response relationship. The ED95 of NMB is the dose that decreases muscle strength of the anesthetized patient by 95% in response to a simple stimulus, obtained by stimulating the ulnar nerve and recording the mechanical response of the adductor pollicis muscle 5.

The literature, in general, indicates that, for an adequate TI, at least two ED95 of any NMB are necessary 5,6. Clinical acceptable conditions of intubation through direct laryngoscopy include: relaxed jaw, open and immobile vocal cords, and absence of diaphragmatic movements 7,8 .

Rocuronium is a synthetic, steroid-type, non-depolarizing NMB with intermediate duration of action, and low potency, with an ED95 of 0.3 Potency is the main factor, besides dose and blood flow in the muscle group, responsible by the speed of installation of a NMB 9,10.

The objective of this study was to evaluate and compare conditions for TI, using 0.3 and 0.6 of rocuronium in elective surgeries, according to the criteria of the Copenhagen Consensus Conference 7 (Good Clinical Practice).



After approval by the Ethics Commission on Research of the Hospital Naval Marcílio Dias and signing of the informed consent, a prospective, double-blind clinical study, with random distribution of patients (Microsoft Excel) was undertaken. Tracheal intubations were performed by an anesthesiologist who was unaware of the dose of rocuronium used. Sixty patients of both genders, ages varying from 20 to 60 years, physical status ASA I and II, Mallampati 1 and 2, BMI < 35, were devided in two groups: in Group 1 (G1), patients received 0.3 of rocuronium, and in Group 2 (G2), 0.6 All patients were scheduled for elective surgeries (ENT, general surgeries, and plastic surgeries) at the Hospital Naval Marcílio Dias. Patients allergic to the drugs used in this study, pregnant women, and patients using drugs that could interfere with rocuronium were excluded from the study.

Pre-anesthetic medication was not administered to any patient. In the operating room a peripheral vein was catheterized and intravenous midazolam (3 mg) was administered. Monitoring consisted of: cardioscope in the DII and V5 derivations, non-invasive blood pressure (NIBP), pulse oximeter (SpO2), capnograph (PETCO2), and peripheral nerve stimulator (TOF Watch), which was placed on the ulnar nerve on the contralateral wrist to the venoclisis to record the response of the adductor pollicis muscle. A sequence of four supramaximal stimuli (TOF), with 0.2-millisecond waves, frequency of 2 Hz, and duration of 2 seconds were applied every 10 seconds.

Patients were oxygenated for three minutes and anesthetics were infused as follows: 3.0 µ of fentanyl, 2.5 of propofol, and 0.3 (G1) or 0.6 (G2) of rocuronium. Patients were ventilated with a mask and, three minutes after administration of the NMB, TI was performed. Heart rate (HR), NIBP, and TOF were measured one minute before and after induction and intubation. Lidocaine gel was applied to all cannulas.

Parameters used to evaluate the quality of TI were based on the criteria of the Copenhagen Consensus Conference7 (Good Clinical Research Practice) and are shown in Chart I.

The Mann-Whitney test was used to evaluate the age of patients, and the Student t test was used to analyze weight, HR, and NIBP. The test of proportion was used for gender, physical status, and conditions of TI. Values of p < 0.05 were considered significant.



Both groups were homogenous for age, weight, gender, and physical status (Table I). Heart rate and NIBP were not significantly different between G1 and G2.



The train-of-four ratio varied between 0.25 and 0.40 at the time of TI in G1. Patients in G2 showed no response to the supramaximal stimuli sequence.

All intubations were considered excellent or good (acceptable); cases of unsuccessful intubation or classified as bad (unacceptable) did not occur. Parameters evaluated showed no statistically significant differences.



Studies have proved that it is possible to perform TI with or without the administration of NMB 11,12. The main motivation of this study was to answer the following question: Why one should use two ED95 of NMB if, by definition, one ED95 causes a 95% reduction in muscle strength, which would allow for an acceptable TI?

This study proved that, in both groups, laryngoscopy and opening of vocal cords provided excellent conditions of exposure of the larynx and for the insertion of the tracheal tube without difficulties. This observation demonstrated that, similar to what is described in the literature on TI with two ED95 5,6,13, the factors required for a good intubation (relaxation of the jaw and vocal cords) were also present in patients who received only one ED95. After conclusion of this step, we observed that three patients in G1 and one in G2 presented mild, self-limited, movement of the diaphragm for a maximal period of three seconds, which did not required the administration of any drugs. The same occurred in four patients in G1 when the tracheal tube cuff was inflated.

According to the experiments of Donatie et al., the neuromuscular blockade of laryngeal muscles and diaphragm is less intense that that of the adductor pollicis, but the onset of action and recovery are faster 14. Besides the morphology, the large blood flow due to the central location of those muscles is the main explanation for this difference. According to the literature, there is no direct relationship between monitoring of the adductor pollicis muscle and laryngeal muscles, which was also observed in the present study 12,13.

Studies comparing the action of NMB on laryngeal muscles and diaphragm demonstrated that it is similar to their actions on the muscles of the vocal cords regarding beginning of action, time of recovery, and peak action 14. Three patients in G1 and one in G2 presented mild diaphragmatic movement after intubation, which, however, did not compromise the quality of the procedure.

According to the literature, relaxation of the masseter muscle occurs before that of the adductor pollicis 13. The relaxation of the jaw was considered excellent in 26 patients in G1 and in 29 patients in G2.


Table II


The different muscle groups show a significant difference in relaxation. Although the adductor pollicis muscle showed elevated TOF values (0.4), the magnitude neuromuscular blockade observed was enough to consider the TI as good or excellent, according to the criteria of the Copenhagen Consensus Conference 12,13,15. Thus, several authors have been using scales that evaluate the clinical criteria for TI.

Heier et al. have described that the use of high doses of rocuronium for fast TI can cause undesirable effects 6. Those effects were not observed in the present study because smaller doses were used.

The residual effect of intermediate action NMBs has been studied extensively. Eikermann et al. warned that patients can develop postoperative dysfunction of the airways, even with TOF of 0.9 16,17. The study infers that the use of only one ED95 decreased the incidence of residual postoperative blockade, but the present study did not evaluate this parameter.

Currently, anesthesiologists are frequently asked to maintain patients at a minimal level of NMB during surgeries in which stimulators are used to monitor neuronal integrity, such as thyroidectomy, parathyroidectomy, and tympanomastoidectomy. One should consider performing intubation with one ED95 in those situations, as well as in surgeries of very short duration, like microsurgeries of the larynx.

The authors agree with the affirmation made by Schlaich et al. that "by reducing the dose of rocuronium from 0.6 to 0.3 for TI, its pharmacodynamic profile changes from fast onset of action and intermediate duration to intermediate onset of action and short duration" 18.

We concluded that all patients were intubated in conditions considered excellent or good, according to the criteria of the Copenhagen Consensus Conference, with both doses of rocuronium 0.3 and 0.6



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Correspondence to:
Dr. Luciano Carlos Gomes Miranda
Rua Domingues de Sá 297/701 – Icaraí
24220-000 Niterói, RJ

Submitted em 7 de novembro de 2007
Accepted para publicação em 14 de fevereiro de 2008



* Received from Hospital Naval Marcílio Dias, Rio de Janeiro, RJ

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