Services on Demand
Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.54 no.1 Campinas Jan./Feb. 2004
Influence of stimulation frequency on rocuronium and pancuronium-induced neuromuscular block onset. Acceleromyography evaluation*
Influencia de la frecuencia de estímulos en la instalación del bloqueo neuromuscular producido por el rocuronio y pancuronio. Evaluación por el método acelerográfico
Derli da Conceição Munhóz, M.D.I; Angélica de Fátima de Assunção Braga, TSA, M.D.II; Glória Maria Braga Potério, TSA, M.D.II
IAnestesiologista do Hospital de Clínicas
IIProfessora Doutora do Departamento de Anestesiologia da Faculdade de Ciências Médicas da UNICAMP
BACKGROUND AND OBJECTIVES: Factors associated
to patients and neuromuscular blockers (NMB), as well as others inherent to
neuromuscular function monitoring, may affect neuromuscular block onset. This
study aimed at the influence of two different stimulation frequencies on rocuronium
and pancuronium-induced neuromuscular block.
METHODS: Participated in this study 120 patients, physical status ASA I and II, submitted to elective procedures under general anesthesia, who were randomly allocated in two groups, according to the stimulation frequency employed to monitor neuromuscular block: Group I - 0.1 Hz (n = 60) and Group II - 1 Hz (n = 60). Two subgroups were formed within each group (n = 30), according to the neuromuscular blocker: Subgroup P (pancuronium) and Subgroup R (rocuronium). Patients were premedicated with muscular midazolam (0.1 mg.kg-1), 30 minutes before surgery. Anesthesia was induced with propofol (2.5 mg.kg-1) preceded by alfentanil (50 µg.kg-1) and followed by pancuronium or rocuronium. Patients were ventilated under mask with 100% oxygen until 75% or more decrease in adductor pollicis muscle response, when laryngoscopy and tracheal intubation were performed. Neuromuscular function was monitored by acceleration transducer. The following parameters were evaluated: pancuronium and rocuronium onset time; time for complete block and tracheal intubation conditions.
RESULTS: Mean times (seconds) for pancuronium-induced neuromuscular block onset and for complete neuromuscular block were: Group I (159.33 ± 35,22 and 222 ± 46.56) and Group II (77.83 ± 9.52 and 105.96 ± 15.58); rocuronium-induced values were: Group I (83 ± 17.25 and 125.33 ± 20.12) and Group II (48.96 ± 10.16 and 59.83 ± 10.36) with statistical difference between groups. Tracheal intubation conditions were satisfactory in 117 patients (97.5%) and unsatisfactory in 3 (2.5%).
CONCLUSIONS: Rocuronium and pancuronium-induced neuromuscular block onset and time required for complete adductor pollicis muscle neuromuscular block are shorter when higher stimulation frequencies are applied.
Key Words: MONITORING: acceleromyography; NEUROMUSCULAR BLOCKERS, Nondepolarizing: pancuronium; rocuronium
JUSTIFICATIVA Y OBJETIVOS: Factores relacionados
al paciente y al bloqueador neuromuscular (BNM), así como otros inherentes
a la monitorización de la función neuromuscular pueden influenciar
en la instalación del bloqueo neuromuscular. El objetivo de este estudio
fue evaluar la influencia de dos frecuencias diferentes de estímulos
sobre el tiempo de instalación del bloqueo producido por el pancuronio
y por el rocuronio.
MÉTODO: Fueron incluidos en el estudio 120 pacientes, estado físico ASA I y II, sometidos a cirugías electivas bajo anestesia general, distribuidos aleatoriamente en dos grupos, de acuerdo con la frecuencia de estímulo empleada, para la monitorización del bloqueo neuromuscular: Grupo I - 0,1 Hz (n = 60) y Grupo II - 1 Hz (n = 60). En cada grupo se formaron dos subgrupos (n = 30) de acuerdo con el bloqueador neuromuscular empleado: Subgrupo P (pancuronio) y Subgrupo R (rocuronio). La medicación pre-anestésica consistió de midazolam (0,1 mg.kg-1) por vía muscular, 30 minutos antes de la cirugía. La inducción anestésica fue obtenida con propofol (2,5 mg.kg-1) precedido de alfentanil (50 µg.kg-1) y seguido de pancuronio o rocuronio. Los pacientes fueron ventilados bajo máscara con oxígeno a 100% hasta la obtención de reducción de 75% o más en la amplitud de la respuesta del músculo aductor del pulgar, cuando fueron realizadas las maniobras de laringoscopia e intubación traqueal. La función neuromuscular fue monitorizada con aceleromiografia. Fueron evaluados: tiempo de inicio de acción del pancuronio y del rocuronio; tiempo para instalación del bloqueo total y condiciones de intubación traqueal.
RESULTADOS: Los tiempos medios (segundos) para el inicio de acción e instalación de bloqueo neuromuscular total producido por el pancuronio fueron: Grupo I (159,33 ± 35,22 y 222 ± 46,56) y Grupo II (77,83 ± 9,52 y 105,96 ± 15,58); para el rocuronio: Grupo I (83 ± 17,25 y 125,33 ± 20,12) y Grupo II (48,96 ± 10,16 y 59,83 ± 10,36) con diferencia significativa entre los grupos. Las condiciones de intubación traqueal fueron satisfactorias en 117 pacientes (97,5%) e insatisfactorias en 3 (2,5%).
CONCLUSIONES: El inicio de acción y el tiempo para la obtención del bloqueo neuromuscular total en el músculo aductor del pulgar, producidos por el rocuronio y por el pancuronio, son más cortos cuando hay empleo de mayores frecuencias de estímulos.
Neuromuscular junction monitoring (NMJ) through a nerve stimulator is useful during anesthetic procedures involving neuromuscular blockers. These devices allow for the administration of additional neuromuscular blocker doses to maintain adequate surgical relaxation, not empirically, but according to patients' needs 1,2. In optimal conditions, muscles to be monitored would be those to be relaxed during surgery or those involved in laryngoscopy and tracheal intubation maneuvers. Since this is not always feasible, an approximation would be to choose a muscle with similar response to the target muscle. For example, orbicularis oculi muscle monitoring is a good indicator of intubation conditions. In theory, any superficial muscle is susceptible to be stimulated for neuromuscular block monitoring. However, in the clinical practice and in investigation studies, the ulnar nerve is the most widely used for being accessible since the elbow, for innervating hypothenar eminentia, interosseous and adductor pollicis muscles. The latter is unquestionably the most widely used because its contraction strength reflects other peripheral muscles relaxation with good approximation 3. In addition to factors related to patients and the neuromuscular blocker (NMB), other factors inherent to neuromuscular function monitoring may affect neuromuscular block onset, such as stimulation frequency 4,5.
This study aimed at comparing the influence of two different stimulation frequencies on pancuronium and rocuronium-induced neuromuscular block onset.
After the Hospital's Ethics Committee approval and their informed consent, participated in this study 120 patients of both genders, physical status ASA I and II, aged 18 to 57 years, weighing 45 to 88 kg, scheduled for elective procedures under general anesthesia with tracheal intubation and mechanically controlled ventilation, who were randomly distributed in two groups, according to the stimulation frequency used for neuromuscular block monitoring: Group I - 0.1 Hz (n = 60) and Group II - 1 Hz (n = 60). Two subgroups were formed within each group (n = 30) according to the neuromuscular blocker: Subgroup P (pancuronium - 0.1 mg.kg-1) and Subgroup R (rocuronium - 0.6 mg.kg-1). Exclusion criteria were patients with neuromuscular, renal or liver diseases, hydroelectrolytic and acid-base changes, history of gastric reflux, under drugs interacting with neuromuscular blockers and with indications of difficult laryngoscopy and tracheal intubation (Mallampati III and IV) 6. Patients were premedicated with muscular midazolam (0.1 mg.kg-1) 30 minutes before anesthetic induction. A peripheral vein was catheterized in the operating room for hydration and drug administration. Anesthesia was induced with alfentanil (50 µg.kg-1), followed by propofol (2.5 mg.kg-1) and pancuronium or rocuronium in the preconized doses and administered in 5 seconds. Patients were ventilated under mask with 100% oxygen and laryngoscopy and tracheal intubation maneuvers were performed when there was 75% or more decrease in adductor pollicis muscle response amplitude.
Continuous monitoring consisted of cardioscopy at DII lead, pulse oximetry and noninvasive blood pressure. Neuromuscular transmission monitor (Acceleromyograph - TOF-GUARD) was used to evaluate neuromuscular block. Alfentanil was administered before propofol, which was followed by supramaximal stimulations (0.1 or 1 Hz) according to the study group for five minutes to stabilize control response. Surface electrodes were placed on the ulnar nerve path on the wrist. An acceleration transducer (piezoelectric) was fixed on the distal phalanx of the monitored limb thumb and a temperature sensor was placed on the thenar region. During and after anesthetic induction, neuromuscular function was continuously monitored with isolated stimulations (0.1 or 1 Hz) until complete neuromuscular block. Adductor pollicis responses shown in bar charts and digital figures were stored in a memory card and then reproduced in compatible pre-programmed computer. Muscle responses tracings (Figures 1 and 2) show: 1) propofol injection; 2) neuromuscular blocker injection; 3) neuromuscular block onset (tracheal intubation time); 4) complete neuromuscular block.
The following parameters were evaluated: 1) neuromuscular parameters - pancuronium or rocuronium onset; time elapsed (in seconds) between neuromuscular blocker injection and 75% or more decrease in adductor pollicis muscle response amplitude; time for complete neuromuscular block; time (in seconds) between beginning of neuromuscular blocker injection and 100% adductor pollicis muscle blockade; 2) tracheal intubation conditions using the method proposed by Helbon-Hansen et al. 7, considering laryngoscopy difficulty level, presence and intensity of cough and vocal cords position and movement, attributing scores from 1 to 4 to each parameter (Table I).
Score equal to or lower than 2 in three parameters corresponded to satisfactory tracheal intubation conditions, and scores above 2 in one of the three parameters were considered unsatisfactory; 3) hemodynamic parameters - mean blood pressure (MBP) and heart rate (HR) evaluated in the following moments: immediately before anesthetic induction (M0), after anesthetic induction and before laryngoscopy and tracheal intubation (M1) and 1 minute after tracheal intubation (M2).
Student's t test, Fisher's Exact test and Wilcoxon test were used for statistical analysis considering significant 5% (p < 0.05).
There have been no statistically significant differences in demographics data between groups and subgroups, which were considered homogeneous (Table II).
Neuromuscular block onset and time for complete neuromuscular block were significantly shorter in both Group II subgroups (p < 0.01) as compared to Group I (Table III).
As to laryngoscopy, vocal cords position and movement, all patients of all groups have received score 1. As to presence or intensity of cough, 58 Group I (0.1 Hz) patients (96.66%) had score 1, and 2 patients (3.33%) had score 2. In Group II (1 Hz), 49 patients (81.66%) had score 1, 8 patients (13.33%) had score 2, and 3 patients (5%) had score 3. Tracheal intubation conditions were satisfactory in 117 patients (97.5%) and unsatisfactory in 3 (2.5%). Patients with unsatisfactory intubation conditions belonged to Group II Subgroup P. Fisher's Exact test used to compare between groups and subgroups, has not shown significant differences. There were no significant hemodynamic changes in both groups and subgroups.
Neuromuscular block onset and degree produced by neuromuscular blockers may be affected by several factors, among them the stimulation mode, being these effects more important with the use of higher frequencies 8-12. Previous studies 2 on the effects of ulnar nerve stimulation frequency on blockade induced by different rocuronium doses have resulted in approximately 50% decrease in onset when frequencies were increased from 0.1 Hz to 1 Hz, being this shortening possibly related to rocuronium pre-synaptic effect. Early pre-junctional cholinergic receptors occupation interferes with acethylcholine displacement from reserve deposits to promptly releasable deposits and consequent decrease in neurotransmitter release.
Similar results were reported by other authors 13 who have studied the effects of different ulnar nerve stimulation patterns on the installation of rocuronium-induced blockade. They have compared the effects of isolated 0.1 Hz and 1 Hz stimulations and TOF stimulation with 2 Hz at 15-second intervals, and have concluded that rocuronium onset on adductor pollicis is affected by stimulation pattern, becoming shorter with higher frequencies. So, they considered inadequate the ulnar nerve stimulation with 1 Hz to monitor relaxation conditions for tracheal intubation. However, De Mey et al. 14 have studied neuromuscular block installation in masseter and adductor pollicis using different frequency stimulations. They have used 0.1 Hz frequency to monitor the mandible muscle and 1 Hz to monitor the ulnar nerve and have observed no significant differences between mean onset times for both muscles blockade. So, they have recommended ulnar nerve stimulation with 1 Hz frequency to determine the correspondence between adductor pollicis onset and optimal tracheal intubation conditions. This stimulation frequency has been also studied by other authors 15 who have recommended its use until tracheal intubation.
Our study has shown that onset and time for complete neuromuscular block induced by both neuromuscular blockers are significantly shorter when higher stimulation frequencies (1 Hz) are used. These results are in line with the literature 13,14 and emphasize the need for prudence when comparing neuromuscular block onset and degree in studies with different stimulation frequencies and modes. A non apparent effect when the motor nerve is stimulated with 0.1 Hz frequency may be partially revealed with 2 Hz and totally revealed with higher frequencies 2.
Most probable explanation for faster block in these cases is that the succession of contractions caused by nerve stimulation with high frequency stimulations increases muscle metabolic activity and blood flow, resulting in more drug transportation to the stimulated muscle 1,15,16. Factors related to the type of monitor may also interfere in blockade onset. The use of preload in the adductor pollicis, mandatory in mechanomyography, increases regional metabolism leading to more blood flow to the monitored muscle and, as a consequence, a higher number of neuromuscular blocker molecules may reach neuromuscular junction in a shorter period of time 4,8,16. The importance of muscle blood flow is also shown by the fact that muscles close to central circulation and with better perfusion, such as the diaphragm, tend to be more rapidly paralyzed than peripheral and less perfused muscles, such as adductor pollicis 17,18.
Another explanation is that more frequent stimulations may lead to neurotransmitter depletion at stimulation site, causing deeper and earlier muscle responses blockade 19,20.
The importance of mandible relaxation to obtain optimal tracheal intubation conditions and maintain patent airways has been considered by Smith et al. 21 who have evaluated, in humans, masseter sensitivity to pancuronium as compared to adductor pollicis sensitivity. They have observed that mandible relaxation was obtained with low pancuronium doses and have stressed that the masseter may be the only muscle more sensitive than the adductor pollicis to nondepolarizing neuromuscular blockers. Such sensitive muscle makes us think about the possibility that even low nondepolarizing neuromuscular blocker doses may compromise airways patency, so the earlier the tracheal intubation, the higher the safety margin for the risk of gastric content aspiration.
Considering the discrepancy between masseter and adductor pollicis blockade installation, we decided to perform laryngoscopy maneuvers when there was 75% decrease in adductor pollicis contractile responses amplitude. Previous studies 4,22 have resulted in satisfactory tracheal intubation conditions without total disappearance of adductor pollicis responses. The possibility of performing tracheal intubation when rocuronium was used in a dose equivalent to twice DE95 without maximum adductor pollicis blockade had been already reported by other authors 23. De Mey et al. 24 have evaluated rocuronium-induced blockade and have observed that in the same stimulation conditions (0.1 Hz) there was earlier masseter muscle blockade as compared to the adductor pollicis. Although different sensitivities between both muscles have an important role in nondepolarizing neuromuscular blockers onset, this alone does not explains shorter onset of masseter block. The additional explanation is that the masseter is closer to central circulation and receives more blood flow.
In our study using as reference for laryngoscopy and tracheal intubation maneuvers 75% or more decrease in adductor pollicis response amplitude, tracheal intubation was possible in all patients. The possible explanation is that, simultaneously, there was blockade of muscles responsible for mandible strength and of laryngeal muscles, sufficient for intubation. Satisfactory tracheal intubation conditions in most patients may have also been affected by propofol used for anesthetic induction. The hypnotic of choice for anesthetic induction affects tracheal intubation conditions in several ways: by depressing laryngeal and pharyngeal reflexes to tracheal intubation and also by potentiating the effects of some neuromuscular blockers 25-28. Among hypnotics, propofol is widely used for anesthetic induction because it significantly depresses laryngeal and pharyngeal reflexes and may even do without neuromuscular blockers for tracheal intubation. This effect confirms the superiority of propofol as compared to other hypnotics, expressed by higher incidence of vocal cords immobility, even observed in studies where no blockers were used 29-34. In our study, most patients (97.5%) had satisfactory tracheal intubation conditions and so we may admit that laryngoscopy and intubation maneuvers have not exacerbated reflex autonomic activity to sufficient levels to cause significant blood pressure changes. Another hypothesis would be propofol protecting effect as a consequence of reflexes depressing activity, which has contributed to cardiocirculatory parameters stability.
Our conclusion was that onset and time for complete neuromuscular block in the adductor pollicis muscle produced by rocuronium and pancuronium are affected by stimulation frequencies used during monitoring. Onset of both blockers was significantly shortened when frequencies were increased from 0.1 Hz to 1 Hz.
01. McCoy EP, Mirakhur RK, Connolly FM et al - The influence of the duration of control stimulation on the onset and recovery of neuromuscular block. Anesth Analg, 1995;80:364-367. [ Links ]
02. Feldman SA, Khaw K - The effect of dose and the rate of stimulation on the action of rocuronium. Eur J Anaesth, 1995;12:15-17. [ Links ]
03. Donati F, Plaud B, Meistelman C - A method to measure elicited contraction of laryngeal adductor muscles during anesthesia. Anesthesiology, 1991;74:827-832. [ Links ]
04. Donati F - Onset of action of relaxants. Can J Anaesth, 1988;35:S52-S58. [ Links ]
05. Bowman WC, Rodger IW, Houston J et al - Structure action relationships among some desacetoxy analogues of pancuronium and vecuronium in the anesthetized cat. Anesthesiology, 1988;69:57-62. [ Links ]
06. Mallampati SR, Gatt SP, Gugino LD et al - A clinical sign to predict difficult tracheal intubation: a prospective study. Can J Anaesth, 1985;32:429-434. [ Links ]
07. Helbo-Hansen S, Ravlo O, Trap-Andersen S - The influence of alfentanil on the intubating conditions after priming with vecuronium. Acta Anaesthesiol Scand, 1988;32:41-44. [ Links ]
08. Curran MJ, Donati F, Bevan DR - Onset and recovery of atracurium and suxamethonium-induced neuromuscular blockade with simultaneous train-of-four and single twitch stimulation. Br J Anaesth, 1987;59:989-994. [ Links ]
09. Bell PF, Gibson FM, Mirakhur RK et al - Comparison of single twitch and train-of-four modes of stimulation for measurement of non-depolarizing neuromuscular block. Br J Anaesth, 1988; 60:343P. [ Links ]
10. Cooper RA, Mirakhur RK, Elliott P et al - Estimation of the potency of ORG 9426 using two different modes of nerve stimulation. Can J Anaesth, 1992;39:139-142. [ Links ]
11. Maddineni VR, Mirakhur RK, Cooper R et al - Potency estimation of mivacurium: comparison of two different modes of nerve stimulation. Br J Anaesth, 1993;70:694-695. [ Links ]
12. Viby-Mogensen J, Engbaek J, Eriksson LI et al - Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents. Acta Anaesthesiol Scand, 1996;40:59-74 [ Links ]
13. Hans P, Dewé W, Albert A - Onset time on neuromuscular block and intubating conditions: influence of different stimulation patterns. Acta Anaesthesiol Belg, 1997;48:15-21. [ Links ]
14. De Mey JC, De Laat M - Factors influencing the profile of onset of relaxation. Acta Anaesthesiol Belg, 1997;48:7-10. [ Links ]
15. Goat VA, Yeung ML, Blakeney C et al - The effect of blood flow upon the activity of gallamine triethiodide. Br J Anaesth, 1976;48:69-73. [ Links ]
16. Saxena PR, Dhasmana KM, Prakash O - A comparison of systemic and regional haemodynamic effects of d-tubocurarine, pancuronium and vecuronium. Anesthesiology, 1983;59: 102-108. [ Links ]
17. Chauvin M, Lebreault C, Duvaldestin P - The neuromuscular blocking effect of vecuronium on the human diaphragm. Anesth Analg, 1987;66:117-122. [ Links ]
18. Pansard JL, Chauvin M, Lebreault C et al - Effect of an intubating dose of succinylcholine and atracurium on the diaphragm and adductor pollicis muscle in humans. Anesthesiology, 1987;67:326-330. [ Links ]
19. Girling KJ, Mahajan RP - The effect of stabilization on the onset of neuromuscular block when assessed using accelerometry. Anesth Analg, 1996;82:1257-1260. [ Links ]
20. Galindo A - Procaine, pentobarbital and halothane: effects at the mammalian myoneural junction. J Pharmacol Exp Ther, 1971; 177:360-368. [ Links ]
21. Smith CE, Donati F, Bevan DR - Differential effects of pancuronium on masseter and adductor pollicis muscles in humans. Anesthesiology, 1989;71:57-61. [ Links ]
22. Carnie JC, Street MK, Kumar B - Emergency intubation on the trachea facilitated by suxamethonium. Br J Anaesth, 1986;58:498-501. [ Links ]
23. Huizinga AC, Vandenbrom RH, Wierda JM et al - Intubating conditions and onset time of neuromuscular block of ORG 9426 (rocuronium), a new nondepolarizing neuromuscular blocking agent: a comparison with suxamethonium. Acta Anaesthesiol Scand, 1992;36:463-468. [ Links ]
24. De Mey JC, De Baerdemaeker L, De Laat M et al - The onset of neuromuscular block at the masseter muscle as a predictor of optimal intubating conditions with rocuronium. Eur J Anaesthesiol, 1999;16:387-389. [ Links ]
25. Bali IM, Dundeee JW - Effect of I.V. induction regimens on endotracheal intubation with alcuronium and atracurium. Br J Anaesth, 1985;57:830-831. [ Links ]
26. Fuchs-Buder T, Sparr HJ, Ziegenfuss T - Thiopental or etomidate for rapid sequence induction with rocuronium. Br J Anaesth, 1998;80:504-506. [ Links ]
27. McCourt KC, Salmela L, Mirakhur RK et al - Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia. Anaesthesia, 1998;53:867-871. [ Links ]
28. Skinner HJ, Biswas A, Mahajan RP - Evaluation of intubating conditions with rocuronium and either propofol or etomidate for rapid sequence induction. Anaesthesia, 1998;53:702-710. [ Links ]
29. Keaveny JP, Knell PJ - Intubation under induction doses of propofol. Anaesthesia, 1988;43:S80-S81. [ Links ]
30. McKeating K, Bali IM, Dundee JW - The effects of thiopentone and propofol on upper airway integrity. Anaesthesia, 1988;43:638-640. [ Links ]
31. Braga A FA, Potério GMB, Braga FSS et al - Intubação traqueal sem relaxantes musculares, utilizando propofol como agente de indução. Rev Bras Anestesiol, 1991;41:(Supl13):CBA130. [ Links ]
32. Scheller MS, Zornow MH, Saidman LJ - Tracheal intubation without the use of muscle relaxants: A technique using propofol and varying doses of alfentanil. Anesth Analg, 1992;75: 788-793. [ Links ]
33. Braga AFA, Braga FSS, Potério GMB et al - The effect of different doses of propofol on tracheal intubating conditions without muscle relaxant in children. Eur J Anaesth, 2001;18:384-388. [ Links ]
34. Dobson AP, McCluskey A, Meakin G et al - Effective time to satisfactory intubation conditions after administration of rocuronium in adults. Comparison of propofol and thiopentone for rapid sequence induction of anaesthesia. Anaesthesia, 1999;54: 172-197. [ Links ]
Submitted for publication January 24, 2003
Accepted for publication May 6, 2003
* Received from Departamento de Anestesiologia da Faculdade de Ciências Médicas da UNICAMP, Campinas, SP