Scholarly article on topic 'Effects of 2 mg.kg−1 of Intravenous Lidocaine on the Latency of Two Different Doses of Rocuronium and on the Hemodynamic Response to Orotracheal Intubation'

Effects of 2 mg.kg−1 of Intravenous Lidocaine on the Latency of Two Different Doses of Rocuronium and on the Hemodynamic Response to Orotracheal Intubation Academic research paper on "Health sciences"

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Brazilian Journal of Anesthesiology
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Keywords
{Lidocaine / "Neuromuscular Blockade / Neuromuscular Nondepolarizing Agents" / "Intubation / Intratracheal" / "ANESTESICO / Local: lidocaína" / "BLOOQUEADOR NEUROMUSCULAR: Rocurônio" / "INTUBAÇÃO TRAQUEAL" / "FISIOLOGIA / Transmissão neuromusculares ;TÉCNICAS DE MEDIÇÃO: hemodinâmica" / "ANESTESICO / Local: lidocaína" / "COMPLICACIONES / Bloqueo neuromuscular / Intubación endotraqueal" / "FISIOLOGÍA / Transmisión neuromusculares"}

Abstract of research paper on Health sciences, author of scientific article — Gustavo Gameiro Vivancos, Jyrson Guilherme Klamt, Luís Vicente Garcia

Summary Background and objectives Lidocaine potentiates the effects of neuromuscular blockers and attenuates the hemodynamic response to orotracheal intubation. The objective of the present study was to test the effects of lidocaine on the latency of two different doses of rocuronium and on the hemodynamic response to intubation. Methods Eighty patients were distributed in 4 groups: Groups 1 and 2 received 0.6 mg.kg−1 of rocuronium; patients in Group 2 also received 2 mg.kg−1 of lidocaine before intubation. Patients in Groups 3 and 4 received 1.2 mg.kg−1 of rocuronium; patients in Group 4 received additional 2 mg.kg−1 of lidocaine. The latency of the neuromuscular blockade was measured by acceleromyography. Hemodynamic evaluation was performed at baseline, immediately before, and 1 minute after orotracheal intubation (OI). Results Statistically significant differences were not observed between the latency from 0.6 mg.kg−1 and 1.2 mg.kg−1 of rocuronium in patients who received lidocaine before induction and those who did not. The latency in patients who received 0.6 mg.kg−1 of rocuronium with lidocaine was statistically similar to that of those who received 1.2 mg.kg−1 rocuronium independently of whether lidocaine was administered or not. Patients who did not receive lidocaine before induction showed the same increases in systolic, diastolic, and mean arterial pressure and heart rate after OI, which was not observed in those patients who received lidocaine. Conclusions Intravenous lidocaine before anesthetic induction was capable of attenuating the hemodynamic response associated to OI maneuvers, but it did not reduce the latency of the neuromuscular blockade produced by two different doses of rocuronium.

Academic research paper on topic "Effects of 2 mg.kg−1 of Intravenous Lidocaine on the Latency of Two Different Doses of Rocuronium and on the Hemodynamic Response to Orotracheal Intubation"

Rev Bras Anestesio! 2011; 61: 1: 1-12

SCIENTIFIC ARTICLE

Effects of 2 mg.kg-1 of Intravenous Lidocaine on the Latency of Two Different Doses of Rocuronium and on the Hemodynamic Response to Orotracheal Intubation

Gustavo Gameiro Vivancos, TSA 1, Jyrson Guilherme Klamt, TSA 2, Lws Vicente Garcia, TSA 2

Summary: Vivancos GG, Klamt JG, Garcia LV - Effects of 2 mg.kg-1 of Intravenous Lidocaine on the Latency of Two Different Doses of Rocuronium and on the Hemodynamic Response of Orotracheal Intubation.

Background and objectives: Lidocaine potentiates the effects of neuromuscular blockers and attenuates the hemodynamic response to orotracheal intubation. The objective of the present study was to test the effects of lidocaine on the latency of two different doses of rocuronium and on the hemodynamic response to intubation.

Methods: Eighty patients were distributed in 4 groups: Groups 1 and 2 received 0.6 mg.kg-1 of rocuronium; patients in Group 2 also received 2 mg.kg-1 of lidocaine before intubation. Patients in Groups 3 and 4 received 1.2 mg.kg-1 of rocuronium; patients in Group 4 received additional 2 mg.kg-1 of lidocaine. The latency of the neuromuscular blockade was measured by acceleromyography. Hemodynamic evaluation was performed at baseline, immediately before, and 1 minute after orotracheal intubation (OI).

Results: Statistically significant differences were not observed between the latency from 0.6 mg.kg-1 and 1.2 mg.kg-1 of rocuronium in patients who received lidocaine before induction and those who did not. The latency in patients who received 0.6 mg.kg-1 of rocuronium with lidocaine was statistically similar to that of those who received 1.2 mg.kg-1 rocuronium independently of whether lidocaine was administered or not. Patients who did not receive lidocaine before induction showed the same increases in systolic, diastolic, and mean arterial pressure and heart rate after OI, which was not observed in those patients who received lidocaine.

Conclusions: Intravenous lidocaine before anesthetic induction was capable of attenuating the hemodynamic response associated to OI maneuvers, but it did not reduce the latency of the neuromuscular blockade produced by two different doses of rocuronium. Keywords: Lidocaine; Neuromuscular Blockade, Neuromuscular Nondepolarizing Agents; Intubation, Intratracheal.

[Rev Bras Anestesiol 2011;61(1): 1-12] ©Elsevier Editora Ltda.

INTRODUCTION

Intravenous local anesthetics have been used during induction of general anesthesia to decrease hypertension and tachycardia secondary to orotracheal intubation (OI) 1-4. Several authors demonstrated this protective effect of lidocaine when used alone or in association with beta-blockers 5-6, calcium channel blockers 7, and inhalational anesthestics 8. Attenuation of the hemodynamic response can be beneficial and prevent complications, especially in those with coronary isch-emic disease 9. When systemic lidocaine is used it decreases airways reactivity being useful in patients with asthma 10-12, it decreases intraoperative anesthetic consumption 1314, the blockade of the systemic inflammatory response secondary to surgery 1516, postoperative pain 13,14,17, and favors early hospital discharge 18.

Received from Hospital das Clinicas de Ribeirâo Preto da Faculdade de Medicina de Ri-beirao Preto - FMRP, Brazil.

1. Anesthesiologist; Post-Graduate Student at FMRP

2. Assistant Professor, Physician; Anesthesiology Professor of FMRP

Submitted on April 19,2010

Approved on July 27,2010

Correspondence to:

Dr. Luis Vicente Garcia

Rua José da Silva, 624 apt. 94

14090-042 - Ribeirao Preto, SP, Brazil

E-mail: lvgarcia@fmrp.usp.br

Systemic and epidural use of local anesthetics decreases the latency and increases the duration of neuromuscular blockers 1921. The interaction of local anesthetics with pre-and post-synaptic nicotinic receptors in the neuromuscular junction explains this phenomenon 22-24.

Rocuronium, a short-latency non-depolarizing neuromuscular blocker has been used for rapid-sequence intubation of patients as an alternative to succinylcholine 25. Even when used in high doses its latency is greater than that of succinyl-choline 26.

High doses of rocuronium are recommended to shorten its latency, although it increases its duration. The objective of the present study was to test the effects of 2 mg.kg-1 of lidocaine on the latency of two doses of rocuronium and to determine whether the use of high doses of rocuronium is necessary when using lidocaine. This study also intended to confirm the protective effects of lidocaine regarding the hemodynamic response to OI.

METHODS

After analysis and approval by the Ethics Committee of Hospital das Clinicas of Faculdade de Medicina de Ribeirao Preto, patients signed an informed consent. Eighty patients were selected for this study. Patients were randomly divided into four groups, according to the method described by Doig and Simp-

son 27. The following inclusion criteria were used: ages between 18 and 50 years, physical status ASA I or II, body mass index (BMI) between 18 and 27 kg.m-2, absence of medication that could interfere with the neuromuscular blockade, absence of hepatic of renal dysfunction, and absence of neuro-muscular disease. Patients in Groups 1 (Roc 0.6) and 2 (Lido + Roc 0.6) received 0.6 mg.kg-1 of rocuronium and lidocaine was only administered in Group 2. In Groups 3 (Roc 1.2) and

4 (Lido + Roc 1.2), 1.2 mg.kg-1 of rocuronium was used and lidocaine was administered only to patients in Group 4. When used, 2 mg.kg-1 of 2% lidocaine was administered during 5 minutes before anesthetic induction. The standard technique of total intravenous anesthesia was used for general anesthesia. Midazolam 0.05 mg.kg-1 was administered upon arrival to the operating room. Target-controlled infusion of propofol and continuous infusion of remifentanil were used. Anesthetic induction was achieved with a target dose of 4 pg.mL-1 of pro-pofol and infusion of 0.5 pg.kg-1.min"1 of remifentanil, both in

5 minutes. Rocuronium, whose dose varied according to the group, was the neuromuscular blocker used. Neuromuscular function was evaluated by a TOF Watch SX (Organon) monitor by accelerometry. Supramaximal stimulation of the ulnar nerve (60 mA) was performed, and contraction of the adductor pollicis muscle was evaluated in the contralateral arm to the venous cannulation. The monitor was installed upon arrival of the patient to the operating room. After induction and loss of consciousness, the device was calibrated via the automatic system of the monitor for detection of the supramaximal stimulus. After calibration, a simple stimulus was applied every second for 5 minutes until the signal stabilized. Whenever necessary, this time was prolonged. The signal was considered to be stable when the variation was smaller than 5% during 1 minute. The blocker was administered over 5 seconds and the time to determine latency was marked from the beginning of the injection on. Monitoring was through a simple 0.1Hz stimulus until the answer of adductor pollicis was 5% of the initial response, at which time the latency time was recorded.

Patients were also evaluated through a parametric Dix-tal 2010 monitor with a 5-lead electrocardiogram, noninvasive blood pressure through oscillometry, oxygen satura-

tion through pletismography, capnography, and esophageal temperature. Hemodynamic variables, systolic, diastolic, and mean arterial pressure (mmHg), as well as heart rate (beats/ min) were recorded on three moments: 2 minutes after the administration of midazolam (Baseline), immediately before intubation (before OI), and 1 minutes after tracheal intubation (after OI).

The software Graphpad Prism 3.0 was used for the statistical analysis. Categorical variables (gender and physical status ASA) were described as proportions, and the Chi-square test was used for independent samples for in-tergroup analysis. Quantitative variables were described as mean ± standard deviation. The normalcy of distribution was tested for all variables in each group by the non-parametric Kolmogorov-Smirnov test. Analysis of variance (ANOVA) was used for intergroup comparisons with Newman-Keuls posttest for multiple comparisons. For intragroup comparisons of mean, systolic, and diastolic arterial pressure and heart rate, analysis of variance for repeated measurements with New-man-Keuls post-test for multiple comparisons was used. The level of critical significance was 5%.

RESULTS

Regarding the demographic data, statistically significant differences were not observed among groups. Statistical significant differences were not observed for tenar temperature (Table I).

Figure 1 shows the mean and distribution of the latency values for all four groups. Significant differences were not observed between Groups 1 and 2 and Groups 3 and 4, i.e., addition of lidocaine did not decrease the latency of 0.6 mg.kg-1 and 1.2 mg.kg-1 of rocuronium. A statistical significant difference was observed when Group 1 was compared to Groups 3 and 4, i.e., the increase in dose from 0.6 mg.kg-1 to 1.2 mg.kg-1 decreased the latency time of rocuronium. A significant difference was not observed between Group 2 and Groups 3 and 4, i.e., the association of lidocaine and rocuronium at a dose of 0.6 mg.kg-1

Table I - Demographic Characteristics and Temperature in the Tenar Region

Group 1 Group 2 Group 3 Group 4

Age (years) 29.80 ± 9.76 31.55 ± 11.55 30.20 ± 9.74 31.60 ± 10.72

Weight (kg) 65.00 ± 13.90 65.20 ± 14.72 61.10 ± 9.98 64.70 ± 10.51

Height (m) 1.67 ± 0.11 1.68 ± 0.11 1.63 ± 0.08 1.67 ± 0.09

BMI (kg.m-2) 22.98 ± 2.86 22.80 ± 2 60 22.65 ± 2.54 23.11 ± 2.09

Gender

Male 6 (30%) 8 (40%) 4 (20%) 7 (35%)

Female 14 (70%) 12 (60)% 16 (80%) 13 (65%)

Physical status

ASA I 20 (100%) 18 (90%) 20 (100%) 19 (95%)

ASA II 0 (0%) 2 (10%) 0 (0%) 1 (5%)

Peripheral Temperature (°C) 34.22 ± 1.36 33.95 ± 1.02 34.54 ± 0.95 34.67 ± 1.31

Group 1: 0.6 mg.kg-1 of rocuronium; Group 2: 0.6 mg.kg-1 of rocuronium + 2 mg.kg-1 of lidocaine; Group 3: 1.2 mg.kg-1 of rocuronium; Group 4: 1.2 mg.kg-1 of rocuronium + 2 mg.kg-1 of lidocaine.

® 60-

p > 0.005 *p < 0.05

58.50 56.00 46.00 47.00

Roc 0.6 Lido + Roc 0.6 Roc 1.2 Lido + Roc 1.2

Figure 1

produced a latency similar to that of the higher dose of rocuronium.

Figure 2 shows systolic (A), diastolic (B), and mean (C) arterial pressure and heart rate (D) of patients who did not receive lidocaine (Groups 1 and 3) and patients who received lidocaine before anesthetic induction (Groups 2 and 4). Intra-group comparison showed a statistically significant difference in mean values of the four variables before and after intubation (without lidocaine), with an increase in mean pressure and heart rate levels. In patients who received lidocaine (with lido), the levels of all variables before and after OI were statistically similar.

DISCUSSION

The systemic injection of lidocaine before OI is used in clinical practice in an attempt to reduce the cardiovascular response to manipulation of the airways. Hamaya and Dohi 28 demonstrated that the use of intravenous lidocaine is capable of attenuating the increases in heart rate and blood pressure after tactile stimulation of the airways. Yorukoglu et al. 1 demonstrated the prevention of the increase in heart rate after OI in patients who received systemic lidocaine. In the present study, an intragroup analysis was performed to detect differences in the mean levels of hemodynamic variables in three phases (baseline, before OI, and after OI). For this analysis, 80 patients were divided into two groups independently of the dose of rocuronium used, since rocuronium did not cause important hemodynamic changes, even in high doses 29. Patients who received lidocaine presented significant attenuation of tachycardia and they did not show increases in blood pressure after OI. In those patients the mean values of heart rate were statistically similar before and after OI. In patients who did not receive lidocaine, a significant increase in blood pressure levels and heart rate were observed. This effect was demonstrated even with the use of high doses of propofol and

remifentanil in anesthetic induction which by themselves are capable of partially blocking this response 3031. The degree of the blockade of coughing reflexes is associated with the plasma concentration of lidocaine. It is know that lidocaine has sedative and analgesic actions in the central nervous system 32-34, being used as an anesthetic adjunct during general anesthesia 13,14,17,18. Thus, central mechanisms of lidocaine are responsible for this blocking effect on coughing reflexes and attenuation of the hemodynamic response to OI.

To study the latency of rocuronium, we followed the principles described in "Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision" 35. This review is a guide of the main care to guarantee the trustworthiness of the results in the study of neuromuscular blockers. Through those recommendations, the homogenous distribution of the patients in the study groups was possible.

The idea of reducing the latency of a neuromuscular blocker is clearly important when the anesthesiologist is facing the need of rapid-sequence intubation 3637. The main indication of this procedure is the prevention of bronchoaspiration in patients in a full stomach, the so-called Mendelson Syndrome38. Neuromuscular blockers more indicated for rapid sequence intubation are succinylcholine and rocuronium due to their lower latency 26. The interaction between local anesthetics and neuromuscular blockers is known and demonstrated in different models 19,23,24,39,40. Local anesthetics have a strong capability of inhibiting several subtypes of nicotinic receptors of acetylcholine, including muscular 22,41-43. The hypothesis that lidocaine could potentiate the neuromuscular blockade of rocuronium, decreasing its latency, was not demonstrated in the present study. The results were able to demonstrate statistical significance of the comparison among the latencies of two different doses of rocuronium, 0.6 mg.kg-1 and 1.2 mg.kg-1, which has been widely divulgated in the literature 29 44. Using the dose of 1.2 mg.kg-1, indicated for rapid-sequence intubation, the latencies obtained were 47.40 seconds in the group that did not receive lidocaine, and 48.60 seconds in the group that received lidocaine, i.e., nearly ident i cal. For the dose of 0.6 mg.kg-1, despite the mean differences between Groups 1 (Roc 0.6) and 2 (Lido + Roc 0.6) of 59.30 and 55.30 seconds, respectively, statistically significant differences were not observed. Cardoso et al. 19 also did not observe differences in the latency of rocuronium 0.6 mg.kg-1 when it was administered after lidocaine. Those results go against the results of Nonaka et al. 20 who demonstrated a 35%-reduction in the latency of vecuronium, from 174 to 115 seconds, after pre-treatment intravenous lidocaine,1.5 mg.kg-1. The explanation for the difference in the latencies of rocuronium and vecuronium has not been established. It is believed that the lower latency of rocuronium is related to its lower potency; therefore, when it is used in high doses an important gradient between the plasma and the biophase is generated leading to more rapid diffusion of rocuronium molecules for the neuromuscular junction 45 46. Pharmacokinetic differences between both blockers with a lower volume of distribution, decreased protein binding, and greater Keo of rocuronium in relation to

Without lido; With lido;

Baseline Before OI After OI

Lido: lidocaine; OI: orotracheal intubation. Figure 2

100 и

Without lido; With lido;

Baseline Before OI After OI

vecuronium could also explain the lower latency for the same reason above. It has been speculated that the lower latency of rocuronium is associated to the rapid occupation of 100% of nicotinic receptors due to the rapid diffusion of a large number of molecules of the anesthetic due to the excessively high gradient 45-46. This mechanism could hinder a greater reduction of the already low latency. The use of lower doses of rocuronium could detect a significant difference, since the gradient would be lower. In the present study, the latency of 0.6 mg.kg-1 of rocuronium (lower dose) associated with lidocaine (Group 2) was statistically similar to 1.2 mg.kg-1 with and without lidocaine (Groups 3 and 4, respectively). This result shows that the latency of the lower dose could be closer to that of the higher dose when using lidocaine, which does not demonstrate, but it could indicate a potentiation of the neuromuscular blocker by lidocaine. Another factor associated to this difference could be the muscle group involved. The adductor pollicis muscle is more sensitive to neuromus-cular blockers than the diaphragm and laryngeal muscles 47-49, for example. In this more resistance musculature a larger absolute amount of nicotinic receptors needs to be blocked, and it is possible that in those muscle groups the reduction in latency with the administration of lidocaine could be detected due to the need of greater diffusion of anesthetic molecules. Yorukoglu et al. 1 without monitoring the muscular blockade, compared intubation conditions of patients who received 0.6 mg.kg-1 of rocuronium with and without lidocaine with those who received succinylcholine. He demonstrated that conditions for OI after the use of lidocaine before rocuronium were

comparable to those of succinylcholine over 60 seconds, which was not observed in patients who did not receive lidocaine 1. Although the neuromuscular blocker is not the only factor responsible for good intubation conditions, more adequate muscle relaxation in other muscles other than adductor pollicis could have contributed for this result. Intubation conditions after a low dose of rocuronium (0.3 mg.kg-1) associated with lidocaine was compared to the conditions obtained after the administration of succinylcholine with similar results; however, intubation was performed in 90 seconds with the combination rocuronium-lidocaine, and 60 seconds with succinylcholine 50.

The present study has some limitations. Intubation and la-ryngoscopy conditions were not tested. It is possible that the use of lidocaine could have facilitated OI independently of the latency of rocuronium in the adductor pollicis. The latency of the neuromuscular blocker was not evaluated in other groups of muscles more resistant to neuromuscular blockers and whose relaxation could be involved in facilitating OI maneuvers is another limiting factor.

Thus, the results obtained allow the conclusion that 2 mg.kg-1 of lidocaine IV before anesthetic induction is capable of attenuating the hemodynamic response, i.e., tachycardia and hypertension associated with OI maneuvers. However, this dose of lidocaine is not capable of potentiating the effects of 0.6 mg.kg-1 and 1.2 mg.kg-1 of rocuronium neither decrease its latency, despite the latency of patients who received 0.6 mg.kg-1 being similar to that of patients who received 1.2 mg.kg-1 of rocuronium with or without lidocaine.

Rev Bras Anestesio! 2011; 61: 1: 1-12

ARTIGO CIENTÍFICO

Efeito da Utilizagao de 2 mg.kg"1de Lidocaína Endovenosa na Latencia de duas Doses Diferentes de Rocuronio e na Resposta Hemodinámica a Intubagao Traqueal

Gustavo Gameiro Vivancos, TSA 1, Jyrson Guilherme Klamt, TSA 2, Luís Vicente Garcia, TSA 2

Resumo: Vivancos GG, Klamt JG, Garcia LV - Efeito da Utilizagao de 2 mg.kg-1de Lidocaína Endovenosa na Latencia de duas Doses Diferentes de Rocuronio e na Resposta Hemodinámica a Intubagao Traqueal.

Justificativa e objetivos: A lidocaína potencializa o efeito dos bloqueadores neuromusculares e atenua a resposta hemodinámica a intubagao. O objetivo do presente estudo foi testar o efeito da lidocaína sobre a latencia de duas doses diferentes do rocuronio e sobre a resposta hemodinámica a intubagao orotraqueal (IOT).

Método: 80 pacientes foram distribuídos em quatro grupos: os dos Grupos 1 e 2 receberam 0,6 mg.kg-1 de rocuronio, sendo que os do Grupo 2 receberam também 2 mg.kg-1 de lidocaína antes da indugao; os dos Grupos 3 e 4 receberam 1,2 mg.kg-1 de rocuronio, sendo que os do Grupo 4 receberam 2 mg.kg-1 de lidocaína. A latencia do bloqueio neuromuscular foi medida por meio da aceleromiografia. A avaliagao hemodinámica foi feita no momento basal, imediatamente antes e um minuto depois da IOT.

Resultados: Nao se encontrou diferenga estatística significativa entre a latencia do rocuronio nas doses de 0,6 mg.kg-1 e 1,2 mg.kg-1 nos pacientes que receberam ou nao a lidocaína antes da indugao. A latencia dos pacientes que receberam rocuronio 0,6 mg.kg-1 com lidocaína foi estatisticamente igual a dos pacientes que receberam 1,2 mg.kg-1de rocuronio, independentemente da administragao ou nao de lidocaína. Os pacientes que nao receberam lidocaína antes da indugao apresentaram aumento dos valores de pressao arterial sistólica, diastólica e média e da frequencia cardíaca após a IOT, o que nao ocorreu nos que receberam lidocaína.

Conclusoes: Assim, a lidocaína por via venosa antes da indugao anestésica foi capaz de atenuar a resposta hemodinámica associada as manobras de IOT, mas nao de diminuir a latencia do bloqueio neuromuscular produzido por duas doses diferentes de rocuronio. Unitermos: ANESTESICO, Local: lidocaína; BLOOQUEADOR NEUROMUSCULAR: Rocuronio; INTUBAQÁO TRAQUEAL; FISIOLOGIA, Trans-missao neuromusculares;TÉCNICAS DE MEDIQÁO: hemodinámica.

[Rev Bras Anestesiol 2011;61(1): 1-12] ©Elsevier Editora Ltda.

INTRODUQÁO

Os anestésicos locais tem sido utilizados pela via venosa durante a indugao de anestesia geral com o intuito de reduzir a hiperten-sao e a taquicardia decorrentes da intubagao orotraqueal 1-4. Diversos autores conseguiram demonstrar esse efeito protetor da lidocaína quando utilizada sozinha ou em associagao com beta-bloqueadores 56, bloqueadores de canal de cálcio 7 e anestésicos inalatórios 8. A atenuagao da resposta hemodinámica pode ser benéfica e prevenir complicagoes, em especial nos portadores de doenga isquémica coronariana 9. Quando utilizada por via sis-temica, ela diminui a reatividade das vias aéreas sendo útil nos portadores de asma 10-12 , diminui o consumo de anestésicos no período intraoperatório 1314 o bloqueio da resposta ¡nflamatória sistemica cirúrgica 1516, diminui a dor pós-operatória 13,14,17 e favorece a alta hospitalar precoce 18.

Recebido do Hospital das Clínicas de Ribeirao Preto da Faculdade de Medicina de Ri-beirao Preto - FMRP.

1. Anestesiologista; Pós-Graduando da FMRP

2. Professor-Assistente Doutor; Professor da Disciplina de Anestesiologia da FMRP

Submetido em 19 de abril de 2010

Aprovado para publicaçâo em 27 de julho de 2010

Correspondência para:

Dr. Luís Vicente Garcia

Rua José da Silva, 624, apt°. 94

14090-042 - Ribeirao Preto, SP

E-mail: lvgarcia@fmrp.usp.br

O uso de anestésicos locais por via sistemica e via peridural diminui a latencia e aumenta a duragao farmacológica dos blo-queadores neuromusculares 19-21. A interagao dos anestésicos locais com receptores nicotínicos pré e os sinápticos na jungao neuromuscular é a explicagao para esse fenómeno 22-24.

O rocuronio, um bloqueador neuromuscular adespolari-zante de latencia curta, vem sendo utilizado para a intubagao de pacientes em sequencia rápida, como uma alternativa a succinilcolina 25. Mesmo quando utilizado em altas doses, sua latencia é maior do que a da succinilcolina 26.

A utilizagao de altas doses de rocuronio é recomendada para se encurtar a latencia, embora isso aumente sobremaneira sua duragao. O presente estudo pretende testar o efeito da utilizagao de uma dose de 2 mg.kg-1 sobre duas doses diferentes de rocuronio no tocante a latencia e verificar se existe ou nao a necessidade de se usarem altas doses de rocuronio quando se aplica lidocaína. O estudo também pretende confirmar o efeito protetor da lidocaína na resposta hemodinámica a IOT.

MÉTODO

Após a análise e a aprovagao pelo Comite de Ética do Hospital das Clínicas da Faculdade de Medicina de Ribeirao Preto e a assinatura do termo de consentimento livre e esclarecido, 80 pacientes foram selecionados para o estudo.

EFEITO DA UTILIZAQÁO DE 2 MG.KG"1DE LIDOCAÍNA ENDOVENOSA NA LATÉNCIA DE DUAS DOSES DIFERENTES DE ROCURONIO E NA

RESPOSTA HEMODINÁMICA A INTUBAQÁO TRAQUEAL

Os pacientes foram casualisados pelo método descrito por Doig e Simpson 27 e divididos em quatro grupos. Foram utilizados os seguintes critérios de inclusao: idade entre 18 e 50 anos, estado físico ASA I ou II, índice de massa corporal (IMC) entre 18 e 27 kg.m-2, ausencia de utilizagao de medicamentos que pudessem influenciar no bloqueio neuromus-cular, ausencia de disfungao hepática, renal ou doenga neu-romuscular. Os pacientes dos Grupos 1 (Roc 0,6) e 2 (Lido + Roc 0,6) receberam na indugao anestésica rocurónio na dose 0,6 mg.kg-1, sendo que a administragao de lidocaína ocorreu apenas no Grupo 2. Já nos Grupos 3 (Roc 1,2) e 4 (Lido + Roc 1,2), a dose de rocurónio foi de 1,2 mg.kg-1 e apenas nos pacientes do Grupo 4 foi administrada lidocaína. Quando utilizada, a lidocaína a 2%, na dose de 2 mg.kg-1, foi administrada durante cinco minutos antes da indugao anestésica. Para a realizagao da anestesia geral, foi padronizada a técnica de anestesia venosa total. Midazolam 0,05 mg.kg-1 era administrado na chegada dos pacientes a sala de ope-ragao. Foi utilizado propofol em infusao alvo-controlada e remifentanil em infusao contínua. A indugao anestésica foi feita com dose-alvo de propofol de 4 pg.mL-1 e infusao de remifentanil 0,5 |jg.kg-1.min-1, ambos em 5 minutos. O blo-queador neuromuscular foi o rocurónio, cuja dose variou de acordo com o grupo de estudo. A fungao neuromuscular foi avaliada por meio do monitor TOF Watch SX (Organon), pelo método da acelerometria. Foi realizada estimulagao su-pramáxima do nervo ulnar (60 mA) e avaliada a contragao do músculo adutor do polegar no brago oposto a pungao venosa. O monitor foi instalado na chegada do paciente a sala de cirurgia. Após a administragao do agente indutor e a perda da consciencia, o aparelho foi calibrado por meio do sistema automático do monitor para a detecgao do estímulo supramáximo. Após a calibragao, um estímulo simples a cada segundo foi utilizado por 5 minutos até a estabilizagao do sinal. Quando necessário, esse tempo foi estendido. O sinal era considerado estável quando a variagao era inferior a 5% durante 1 minuto. O bloqueador foi administrado em injegao de 5 segundos e o tempo para a determinagao da latencia foi marcado a partir do início da injegao. A monito-ragao foi realizada através de um estímulo simples de 0,1 Hz

até a resposta do adutor do polegar diminuir a 5% da res-posta inicial quando, entao, era anotado o valor da latencia.

Os pacientes também foram avaliados através de monitor multiparamétrico Dixtal 2010 com eletrocardiografia de cinco vias, pressao arterial nao invasiva pelo método da oscilometria, saturagao arterial de oxigenio com pletismo-grafia, capnografia e temperatura esofágica. As variáveis hemodinámicas: pressao arterial sistólica, diastólica e média (mmHg), e a frequencia cardíaca (batimentos/minuto) foram registradas e anotadas em tres momentos distintos: 2 minutos após a administragao de midazolam (Basal), pouco antes da intubagao (antes de IOT) e 1 minuto após a intuba-gao traqueal (após IOT).

A análise estatística foi realizada com a ajuda do programa Graphpad Prism 3.0. As variáveis categóricas (sexo e estado físico ASA) foram descritas sob a forma de proporgoes e, para a análise estatística, utilizou-se o teste Qui-quadrado para amostras independentes em análise intergrupos. As variáveis quantitativas foram descritas sob a forma de média ± des-vio-padrao. A normalidade das distribuigoes foi testada para todas as variáveis, em cada um dos grupos, utilizando-se o teste nao paramétrico de Kolmogorov-Smirnov. Recorreu-se a Análise de Variáncia (ANOVA) para a comparagao intergrupos, com pós-teste de Newman-Keuls para comparagoes múltiplas. Na comparagao intragrupos das variáveis pressao arterial média, sistólica e diastólica e frequencia cardíaca, utilizou-se a análise da variáncia para medidas repetidas com pós-teste de Newman-Keuls para comparagoes múltiplas. O nível de significáncia crítico foi de 5%.

RESULTADOS

Com relagao aos dados demográficos dos pacientes, nao se encontrou diferenga estatística significativa entre os grupos em todas as variáveis analisadas. Nao houve diferenga significativa entre os grupos para a variável temperatura tenar (Tabela I).

A Figura1 mostra a média e a distribuigao dos valores da variável latencia para os quatro grupos. Nao foi encontrada

Tabela I - Características Demográficas e Temperatura da Regiao Tenar da Mao

Grupo 1 Grupo 2 Grupo 3 Grupo 4

Idade (anos) 29,80 ± 9,76 31,55 ± 11,55 30,20 ± 9,74 31,60 ± 10,72

Peso (kg) 65,00 ± 13,90 65,20 ± 14,72 61,10 ± 9,98 64,70 ± 10,51

Altura (m) 1,67 ± 0,11 1,68 ± 0,11 1,63 ± 0,08 1,67 ± 0,09

IMC (kg.m-2) 22,98 ± 2,86 22,80 ± 2,60 22,65 ± 2,54 23,11 ± 2,09

Masculino 6 (30%) 8 (40%) 4 (20%) 7 (35%)

Feminino 14 (70%) 12 (60)% 16 (80%) 13 (65%)

Estado Físico

ASA I 20 (100%) 18 (90%) 20 (100%) 19 (95%)

ASA II 0 (0%) 2 (10%) 0 (0%) 1 (5%)

Temperatura periférica (°C) 34,22 ± 1,36 33,95 ± 1,02 34,54 ± 0,95 34,67 ± 1,31

Grupo 1: 0,6 mg.kg-1 de rocurónio; Grupo 2: 0,6 mg.kg-1 de rocurónio + 2 mg.kg-1 de lidocaína ; Grupo 3: 1,2 mg.kg-1 de rocurónio; Grupo 4: 1,2 mg.kg-1 de rocurónio + 2 mg.kg-1 de lidocaína.

Média

p > 0,005 *p < 0,05

58,50 56,00 46,00 47,00

Roc 0,6 Lido + Roc 1,2 Lido + Roc 0,6 Roc 1,2

Figura 1

diferenga significativa entre os Grupos 1 e 2 ou entre os Grupos 3 e 4, ou seja, a adigao de lidocaína nao diminuiu a la-tencia das doses de 0,6 mg.kg-1 e 1,2 mg.kg-1 de rocurónio. Houve diferenga estatística quando se comparou o Grupo 1 com os Grupos 3 e 4, ou seja, o aumento da dose de 0,6 mg.kg-1 para 1,2 mg.kg-1 diminuiu a latencia do rocurónio. Nao houve diferenga estatística entre o Grupo 2 e os Grupos 3 e 4, ou seja, a associagao de lidocaína ao rocurónio na dose de 0,6 mg.kg-1 produziu latencia semelhante a produzida pela dose maior de rocurónio.

Na Figura 2, estao os valores de pressao arterial sistóli-ca (A), diastólica (B) e média (C) e de frequéncia cardíaca (D) dos pacientes que nao receberam lidocaína (Grupos 1 e 3 juntos) e dos pacientes que receberam lidocaína antes da indugao anestésica (Grupos 2 e 4 juntos). A comparagao intragrupos mostrou que há diferenga estatística significativa entre os valores médios das quatro variáveis estudadas antes e depois da intubagao quando os pacientes nao receberam lidocaína (sem lido), com aumento dos valores médios de pressao e frequencia cardíaca. Já nos pacientes que rece-beram lidocaína (com lido), os valores de todas as variáveis, antes e depois da IOT, foram estatisticamente iguais.

DISCUSSAO

A injegao sistemica de lidocaína antes da IOT é usada na prá-tica clínica, na tentativa de reduzir a resposta cardiovascular a manipulagao das vias aéreas. Hamaya e Dohi 28 demonstra-ram que o uso de lidocaína por via venosa é capaz de atenuar o aumento de frequencia cardíaca e pressao arterial após a es-timulagao táctil das vias aéreas. Yorukoglu e col. 1 mostraram prevengao do aumento da frequencia cardíaca após a IOT em pacientes que receberam lidocaína sistemica. No presente estudo, fez-se uma análise dentro dos grupos para detectar diferengas nos valores médios das variáveis hemodinámicas nas tres fases de medida (basal, antes da IOT e depois da

IOT). Para essa análise, os 80 pacientes foram divididos em dois grupos, independentemente da dose de rocurónio utilizada, uma vez que o rocurónio nao provoca alteragóes hemodinámicas importantes, mesmo em doses elevadas 29. Os pacientes que receberam lidocaína apresentaram significativa atenuagáo da taquicardia e náo tiveram aumento dos valores pressóricos após a IOT. Nesses pacientes, os valores médios de frequéncia cardíaca foram estatisticamente iguais antes e depois da IOT. Nos pacientes que náo receberam lidocaína, houve aumento significativo dos valores de pressáo arterial e da frequéncia cardíaca. Esse efeito foi demonstrado mesmo com a utilizagáo de doses elevadas de propofol e remifenta-nil na indugáo anestésica, as quais, por si, já sáo capazes de bloquear parte dessa resposta 3031. O grau de bloqueio dos reflexos e tosse está associado á concentragáo plasmática de lidocaína. Sabe-se que a lidocaína tem agáo sedativa e analgésica no sistema nervoso central, 32-34 sendo usada como adjunto anestésico durante anestesia geral 13,14,17,18. Dessa forma, atribui-se a mecanismos centrais da lidocaína esse efeito de bloqueio dos reflexos da tosse e atenuagáo da resposta hemodinámica á IOT.

Para estudar a laténcia do rocurónio, procuramos seguir os princípios descritos no Good clinical research practice in pharmacodynamics studies of neuromuscular blocking agents II: the Stockholm revision 35. Essa revisáo é um guia com os principais cuidados a serem tomados para garantir a confiabilidade dos resultados no estudo de bloqueadores neuromusculares. Seguindo essas recomendagóes, foi pos-sível a distribuigáo homogénea dos pacientes nos grupos de estudo.

A ideia de reduzir a laténcia de um bloqueador neuromuscular se faz realmente importante quando o anestesiologista se defronta com a necessidade de intubagáo em sequéncia rápida 3637. A principal indicagáo desse procedimento é a prevengáo de broncoaspiragáo em pacientes com o estómago cheio, a chamada Síndrome de Mendelson 38. Os bloque-adores neuromusculares mais indicados na intubagáo em sequéncia rápida sáo a succinilcolina e o rocurónio, devi-do ás baixas laténcias 26. A interagáo entre os anestésicos locais e os bloqueadores neuromusculares é conhecida e demonstrada em diferentes modelos 19,23,24,39,40. Os anestésicos locais tém a grande capacidade de inibir vários subtipos de receptores nicotínicos de acetilcolina, inclusive os musculares 22,41-43. A hipótese de que a lidocaína pudesse potencializar o bloqueio neuromuscular do rocurónio, redu-zindo sua laténcia, náo foi demonstrada no presente estudo. Os resultados conseguiram demonstrar significáncia esta-tística na comparagáo entre as laténcias das duas diferentes dose de rocurónio utilizadas, 0,6 mg.kg-1 e 1,2 mg.kg-1, como já é amplamente difundido na literatura 29 44. Utilizando a dose de 1,2 mg.kg-1, indicada para intubagáo em sequén-cia rápida, as laténcias obtidas foram de 47,40 segundos para o grupo que náo recebeu lidocaína e 48,60 segundos para o grupo que recebeu lidocaína, ou seja, valores quase idénticos. Para a dose 0,6 mg.kg-1, apesar da diferenga de médias constatada entre os Grupos 1 (Roc 0,6) e 2 (Lido + Roc 0,6) de 59,30 e 55,30 segundos, respectivamente,

EFEITO DA UTILIZAQÄO DE 2 MG.KG"1DE LIDOCAÍNA ENDOVENOSA NA LATÉNCIA DE DUAS DOSES DIFERENTES DE ROCURONIO E NA

RESPOSTA HEMODINÄMICA A INTUBAQÄO TRAQUEAL

Sem lido; Com lido;

100 п

Sem lido; Com lido;

Basal Antes IOT Depois IOT

Antes IOT

Depois IOT

Lido: Lidocaína; IOT: intubagao orotraqueal. Figura 2

nao foi encontrada significáncia estatística. Cardoso e col. 19 também nao encontraram diferenga na latencia do rocurónio na dose de 0,6 mg.kg-1 após o uso de lidocaína. Esses resultados confrontam o estudo realizado por Nonaka e col. 20 o que demonstraram redugao de cerca de 35% na latencia do vecurónio de 174 para 115 segundos após um pré-tratamento com 1,5 mg.kg-1 de lidocaína por via venosa. A explicagao para a diferenga de latencia entre o rocurónio e o vecurónio ainda nao foi totalmente estabelecida. Acredita-se que a menor latencia do rocurónio esteja relacionada a sua baixa potencia; dessa forma, quando usado em altas doses, gera-se um importante gradiente entre o plasma e a biofase, levando a uma difusao mais rápida das moléculas de rocuró-nio para a jungao neuromuscular 45 46. Diferengas farmacoci-néticas entre os dois bloqueadores, como menor volume de distribuigao, menor ligagao proteica e maior Keo do rocurónio em relagao ao vecurónio, também explicariam essa menor latencia, pelo mesmo motivo já citado. Especula-se, entao, que a baixa latencia do rocurónio esteja associada a rápida ocupagao de 100% dos receptores nicotínicos, devido a di-fusao rápida de um grande número de moléculas do anestésico, pelo gradiente excessivamente alto 45 46. Esse mecanismo pode tornar difícil uma maior diminuigao da já baixa latencia. O uso de menores de doses de rocurónio poderia detectar uma diferenga significativa, uma vez que o gradiente seria menor. No estudo, a latencia dos pacientes em que foram administrados 0,6 mg.kg-1 de rocurónio (menor dose) associado a lidocaína (Grupo 2) foi estatisticamente igual a dos pacientes que receberam a dose de 1,2 mg.kg-1 do bloqueador, sem e com a lidocaína (Grupos 3 e 4, respectivamente). Esse resultado mostra que a dose menor pode ter sua latencia mais próxima a dose maior quando usada a lidocaína, o que nao demonstra - mas pode indicar -potencializagao do bloqueador pela lidocaína. Outro fator associado a essa diferenga pode ser o grupo muscular envolvido. O músculo adutor do polegar é mais sensível aos bloqueadores neuromusculares do que o diafragma ou os laríngeos 47-49, por exemplo. Nessa musculatura mais resistente, maior quantidade absoluta de receptores nicotínicos precisa ser bloqueada e é possível que nesses grupos musculares a diminuigao da latencia com o uso da lidocaína possa ser detectada pela necessidade de maior difusao de moléculas do anestésico. Yorukoglu e col. 1 sem monitorar o bloqueio neuromuscular, compararam as condigoes de intubagao de pacientes que receberam 0,6 mg.kg-1 rocurónio com ou sem lidocaína com as de pacientes que receberam succinilcolina. Demonstraram que o uso de lidocaína antes do rocurónio oferece condigoes para IOT comparáveis a da succinilcolina em 60 segundos, o que nao ocorreu nos pacientes que nao receberam lidocaína 1. Embora o bloqueador neuromuscular nao seja o único fator responsável pelas boas condigoes de intubagao, um relaxamento muscular mais adequado em outros músculos que nao o adutor do polegar pode ter contribuído para esse resultado. As con-digoes de intubagao traqueal após uma dose baixa de rocurónio (0,3 mg.kg-1) associado a lidocaína também foram comparadas as condigoes obtidas após a succinilcolina,

com resultados equivalentes, porém a intubagao era realizada em 90 segundos com a combinagao rocurónio-lidocaína e 60 segundos com a succinilcolina 50.

Algumas limitagoes podem ser encontradas no presente estudo. As condigoes de intubagao e laringoscopia nao fo-ram testadas. É possível que o uso de lidocaína pudesse ter facilitado a IOT, independentemente da latencia do rocurónio no adutor do polegar. Outro fator limitante foi que a latencia do bloqueador neuromuscular também nao foi avaliada em outros grupos musculares mais resistentes aos bloqueadores neuromusculares, cujo relaxamento muscular poderia estar envolvido na facilitagao das manobras de IOT.

Dessa maneira, os resultados obtidos permitem concluir que a lidocaína na dose de 2 mg.kg-1 por via venosa, antes da indugao anestésica, é capaz de atenuar a resposta hemodi-námica de taquicardia e hipertensao associadas as manobras de IOT. Entretanto, essa dose de lidocaína nao é capaz de potencializar o efeito do rocurónio nas doses de 0,6 mg.kg-1 e 1,2 mg.kg-1 ou de diminuir sua latencia, embora a latencia dos pacientes que receberam 0,6 mg.kg-1 de rocurónio com lidocaína seja igual a daqueles que receberam 1,2 mg.kg-1 de rocurónio com ou sem lidocaína.

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RESPOSTA HEMODINÂMICA À INTUBAÇÂO TRAQUEAL

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Resumen: Vivancos GG, Klamt JG, Garcia LV- Efecto de la Utilización de 2 mg.kg-1 de Lidocaína Endovenosa en la Latencia de dos Dosis Diferentes de Rocuronio y en la Respuesta Hemodinámica a la Intubación Traqueal.

Justificativa y objetivos: La lidocaína potencia el efecto de los bloqueantes neuromusculares y atenúa la respuesta hemodinámica a la intubación. El objetivo del presente estudio fue comprobar el efecto de la lidocaína sobre la latencia de dos dosis diferentes del rocuronio y sobre la respuesta hemodinámica a la intubación.

Método: 80 pacientes fueron distribuidos en 4 grupos: los dos Grupos 1 y 2 recibieron 0,6 mg.kg-1 de rocuronio, siendo que los del

Grupo 2 recibieron también 2 mg.kg-1 de lidocaína antes de la inducción; los dos Grupos 3 y 4 recibieron 1,2 mg.kg-1 de rocuronio siendo que los del Grupo 4 recibieron 2 mg.kg-1 de lidocaína. La latencia del bloqueo neuromuscular se midió por medio de la aceleromiografía. La evaluación hemodinámica se hizo en el momento basal, inmediatamente antes y un minuto después de la IOT.

Resultados: No se encontró diferencia estadística significativa entre la latencia del rocuronio en las dosis de 0,6 mg.kg-1 y 1,2 mg.kg-1 en los pacientes que recibieron o no la lidocaína antes de la inducción. La latencia de los pacientes que recibieron rocuronio 0,6 mg.kg-1 con lidocaína fue estadísticamente igual a la de los pacientes que recibieron 1,2 mg.kg-1de rocuronio, independientemente de la administración o no de lidocaína. Los pacientes que no recibieron lido-

caína antes de la inducción, presentaron aumentos de los valores de presión arterial sistólica, diastólica y promedio, y de la frecuencia cardíaca después de la IOT, pero eso no se dio en los que recibieron la lidocaína.

Conclusiones: Así, la lidocaína por vía venosa antes de la inducción anestésica fue capaz de atenuar la respuesta hemodinámica asociada a las maniobras de IOT, pero no de reducir la latencia del bloqueo neuromuscular producido por dos dosis diferentes de rocuronio.

Descriptores: ANESTESICO, Local: lidocaína; COMPLICACIONES, Bloqueo neuromuscular, Intubación endotraqueal; FISIOLOGÍA, Transmisión neuromusculares.