Residual neuromuscular block after rocuronium or cisatracurium

Abstracts

JUSTIFICATIVA E OBJETIVOS: O bloqueio neuromuscular residual na sala de recuperação pós-anestésica (SRPA) é um fenômeno que pode aumentar a morbidade pós-operatória, com incidência variando entre 0% e 93%. O objetivo deste estudo foi avaliar a incidência do bloqueio neuromuscular residual na SRPA. MÉTODO: Foram estudados 93 pacientes submetidos à cirurgia geral com o uso de cisatracúrio ou rocurônio. Após a admissão na SRPA foi realizada a monitorização objetiva da função neuromuscular (aceleromiografia - TOF GUARD). O bloqueio neuromuscular residual foi definido como SQE < 0,9. RESULTADOS: Do total de 93 pacientes, 53 receberam cisatracúrio e 40 rocurônio. As características demográficas, duração do procedimento e o uso de antagonista foram comparáveis em ambos os grupos. O bloqueio neuromuscular residual foi de 32% no subgrupo C (cisatracúrio) e 30% no subgrupo R (rocurônio). O bloqueio neuromuscular residual não foi associado à dose, idade, ou uso de antagonista, porém apresentou relação com a duração do procedimento cirúrgico. No subgrupo C o tempo médio de cirurgia foi 135 minutos nos pacientes com bloqueio neuromuscular e 161 minutos nos pacientes sem bloqueio, p < 0,029. No subgrupo R o tempo médio de cirurgia foi 122 e 150 minutos, respectivamente, p < 0,039. CONCLUSÕES: Os pacientes de ambos os grupos apresentaram incidência elevada de bloqueio neuromuscular residual na SRPA. A curarização residual pós-operatória continua um problema mesmo com os novos bloqueadores neuromusculares de ação intermediária. É de suma importância a monitorização objetiva de todos os pacientes submetidos à anestesia geral com uso de bloqueador neuromuscular.

BLOQUEADORES NEUROMUSCULARES; BLOQUEADORES NEUROMUSCULARES; MONITORIZAÇÃO; MONITORIZAÇÃO; RECUPERAÇÃO PÓS- ANESTÉSICA

SCIENTIFIC ARTICLE

Residual neuromuscular block after rocuronium or cisatracurium^*

Bloqueo neuromuscular residual después del uso de rocuronio o cisatracúrio

Bruno Salomé de Morais, M.D.^I; Carlos Henrique Viana de Castro, TSA, M.D.^II; Vera Coelho Teixeira, TSA, M.D.^III; Alexandre Silva Pinto, M.D.^IV

^IAnestesiologista do Hospital Lifecenter e Hospital das Clínicas da UFMG

^IIDiretor Clínico e Anestesiologista do Hospital Lifecenter. Especialista em Terapia Intensiva e Clínica Médica.

^IIIAnestesiologista e Responsável pelo CET/SBA do Hospital Felício Rocho. Especialista em Terapia Intensiva e Clínica Médica

^IVAnestesiologista do Hospital Márcio Cunha

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Residual neuromuscular block in the post-anesthetic recovery unit (PACU) may increase postoperative morbidity from 0% to 93%. This study aimed at evaluating the incidence of residual neuromuscular block in the PACU.

METHODS: Participated in this study 93 patients submitted to general anesthesia with cisatracurium or rocuronium. After PACU admission, neuromuscular function was objectively monitored (acceleromyography - TOF GUARD). Residual neuromuscular block was defined as TOF < 0.9.

RESULTS: From 93 patients, 53 received cisatracurium and 40 rocuronium. Demographics, procedure length and the use of antagonists were comparable between groups. Residual neuromuscular block was 32% in subgroup C (cisatracurium) and 30% in subgroup R (rocuronium). Residual neuromuscular block was unrelated to dose, age and use of antagonists, but was related to procedure length. In subgroup C, mean procedure length was 135 minutes for patients with neuromuscular block and 161 minutes for patients without (p < 0.029). In subgroup R, mean surgery length was 122 and 150 minutes, respectively (p < 0.039).

CONCLUSIONS: Both groups had high incidence of residual neuromuscular block in the PACU. Residual postoperative curarization is still a problem even with new intermediary action neuromuscular blockers. It is highly important to objectively monitor all patients submitted to general anesthesia with neuromuscular blockers.

Key words: MONITORING: acceleromyography, neuromuscular function; NEUROMUSCULAR BLOCKERS: cisatracurium, rocuronium; POST-ANESTHETIC RECOVERY: residual neuromuscular block

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: El bloqueo neuromuscular residual en la sala de recuperación posanestésica (SRPA) es un fenómeno que puede aumentar la morbidez posoperatoria, con incidencia variando entre 0% y 93%. La finalidad de este estudio fue evaluar la incidencia del bloqueo neuromuscular residual en la SRPA.

MÉTODO: Fueron estudiados 93 pacientes sometidos a cirugía general con el uso de cisatracúrio o rocuronio. Después de la admisión en la SRPA fue realizada la monitorización objetiva de la función neuromuscular (aceleromiografia - TOF-GUARD). El bloqueo neuromuscular residual fue definido como TOF < 0,9.

RESULTADOS: Del total de 93 pacientes, 53 recibieron cisatracúrio y 40 rocuronio. Las características demográficas, duración del procedimiento y el uso de antagonista fueron comparables en ambos grupos. El bloqueo neuromuscular residual fue del 32% en el subgrupo C (cisatracúrio) y 30% en el subgrupo R (rocuronio). El bloqueo neuromuscular residual no fue asociado a la dosis, a la edad, o al uso de antagonista, sin embargo presentó relación con la duración del procedimiento quirúrgico. En el subgrupo C el tiempo medio de cirugía fue de 135 minutos en los pacientes con bloqueo neuromuscular y 161 minutos en los pacientes sin bloqueo, p < 0,029. En el subgrupo R el tiempo medio de cirugía fue 122 y 150 minutos, respectivamente, p < 0,039.

CONCLUSIONES: Los pacientes de ambos grupos presentaron incidencia elevada de bloqueo neuromuscular residual en la SRPA. La curarización residual posoperatoria continúa un problema, lo mismo con los nuevos bloqueadores neuromusculares de acción intermediaria. Es de suma importancia la monitorización objetiva de todos los pacientes sometidos a la anestesia general con el uso del bloqueador neuromuscular.

INTRODUCTION

Postoperative paralysis or muscle weakness due to lack of, or incomplete antagonism of don-depolarizing muscle relaxants is known as residual postoperative curarization (RPOC). RPOC is associated to major morbidity and mortality ^1,2. The incidence of post-anesthetic residual neuromuscular block has been evaluated by different authors for decades, with broad difference in results (0% to 93%) ^3-6. A multicenter study has observed that half the deaths associated to anesthesia were due to post-anesthetic respiratory depression ⁷.

This study aimed at evaluating the incidence of residual neuromuscular block in the post-anesthetic recovery unit in patients receiving rocuronium or cisatracurium during general anesthesia.

METHODS

After the Research Ethics Committee approval and their informed consent, participated in this study all patients of both genders, physical status ASA I or II, aged above 18 years, admitted to the PACU after general anesthesia with rocuronium or cisatracurium for general, thoracic, plastic, urologic, gynecologic, ENT, orthopedic or neurologic surgery in the period Feb-Jun/2003. Exclusion criteria were patients with neuromuscular function intraoperatively monitored or those with any neuromuscular function disorder. Patients admitted to the PACU intubated, hypothermal (probe positioned at the tenar eminence recording temperatures below 32 ºC) or receiving any other neuromuscular blocker were also excluded from the study. Additional exclusion criteria were patients receiving additional NMB dose during surgery, those with altered potassium, calcium or magnesium levels, and those refusing to be part of the study.

Patients were divided in two subgroups according to the neuromuscular blocker: rocuronium (subgroup R) and cisatracurium (subgroup C). All patients were monitored at PACU arrival with cardioscopy, pulse oximetry and peripheral nerve stimulator, in addition to receiving oxygen under facial mask in 3 L.min^-1 flow.

Neuromuscular function monitoring was performed by investigator not participating in the anesthetic induction and blind to the drugs used. This investigator was a physician specializing in Anesthesiology allocated to the PACU. All physicians participating in data collection knew how to handle peripheral nerve stimulators and were familiar with the research protocol. These investigators have not participated in the anesthetic induction, so they have not chosen the neuromuscular blocker or the anesthetic approach.

No recommendation was made to anesthesiologists in order not to influence anesthetic technique, neuromuscular monitoring or intraoperative blockade reversal.

TOF stimulation with intensity of 40 mA was used to monitor neuromuscular function (acceleromyography - TOF-GUARD Organon Teknika, NY). Patients were evaluated at PACU arrival. TOF was applied three times with 30-second intervals between stimulations and the mean of these three values was calculated.

Patients with residual neuromuscular block were those with T₄/T₁ < 0.9. After TOF measurement in the PACU, all patients with T₄/T₁ between 0.7 and 0.3 received 20 µg.kg^-1 neostigmine and 10 µg.kg^-1 atropine. Patients with T₄/T₁ < 0.3 received 40 µg.kg^-1 neostigmine and 20 µg.kg^-1 atropine. Patients with less than two TOF responses (T₂) were re-intubated.

Patients' weight, age, period between NMB and TOF, neuromuscular blocker dose, use of drugs interfering with neuromuscular block and administration of neostigmine during surgery were also evaluated. Mann-Whitney test was used for comparisons between groups with regard to continuous variables. Chi-square test was used for categorical variables. Fisher Exact test was used when expected values were below 5. Statistical significance level was 5%.

RESULTS

The study consisted in the evaluation of 93 patients in the period 02/27/03 to 06/02/03, being 45 males and 48 females. From these, 47 patients were physical status ASA I and 46 were ASA II. Cisatracurium was administered to 53 patients and rocuronium to 40. All patients were submitted to balanced general anesthesia to be submitted to surgical procedures as shown in table I.

Brazilian Journal of Anesthesiology, 2005; 55: 6: 622-630

Residual neuromuscular block after rocuronium or cisatracurium

Bruno Salomé de Morais; Carlos Henrique Viana de Castro; Vera Coelho Teixeira; Alexandre Silva Pinto

Mean patients' age was 47.8 years and mean weight was 66.7 kg. Only 28 patients (30%) received neostigmine at the end of surgery.

Table II shows the comparison between groups in age, weight, gender, physical status (ASA), number of DE95 used, procedure length, use of neostigmine and any drug potentially exacerbating NMB.

Brazilian Journal of Anesthesiology, 2005; 55: 6: 622-630

Residual neuromuscular block after rocuronium or cisatracurium

Bruno Salomé de Morais; Carlos Henrique Viana de Castro; Vera Coelho Teixeira; Alexandre Silva Pinto

In subgroup C, 17 patients (32%) presented residual neuromuscular block, while in subgroup R the incidence was 12 patients (30%) (p = 0.83). Mean neuromuscular block dose for subgroup C was 0.1575 mg.kg-1 (SD 0.048). This dose is equivalent to 3.15 DE95 for cisatracurium. In subgroup R, mean dose was 0.66 mg.kg-1 (SD 0.157). This dose is equivalent to 2.20 DE95 for rocuronium. Patients receiving neostigmine at the end of anesthesia were 30.2% in subgroup C and 30% in subgroup R. Among patients receiving neostigmine, mean dose for subgroup C was 0.027 mg.kg-1 (SD 0.0078) and 0.029 mg.kg-1 for subgroup R (SD 0.0068) with p = 0.625. Bolus NMB dose was not related to residual curarization as shown in table III.

Brazilian Journal of Anesthesiology, 2005; 55: 6: 622-630

Residual neuromuscular block after rocuronium or cisatracurium

Bruno Salomé de Morais; Carlos Henrique Viana de Castro; Vera Coelho Teixeira; Alexandre Silva Pinto

Table IV shows time elapsed between NMB administration and TOF measurement in both groups. Table V represents the ratio between TOF and use of neostigmine in different subgroups.

Brazilian Journal of Anesthesiology, 2005; 55: 6: 622-630

Residual neuromuscular block after rocuronium or cisatracurium

Bruno Salomé de Morais; Carlos Henrique Viana de Castro; Vera Coelho Teixeira; Alexandre Silva Pinto

Brazilian Journal of Anesthesiology, 2005; 55: 6: 622-630

Residual neuromuscular block after rocuronium or cisatracurium

Bruno Salomé de Morais; Carlos Henrique Viana de Castro; Vera Coelho Teixeira; Alexandre Silva Pinto

Among patients receiving neostigmine at the end of surgery there has been no difference in mean dose with regard to patients with or without residual neuromuscular block. In subgroup C, patients with RPOC received 0.21 mg.kg^-1 (SD 0.0049) neostigmine and those without residual curarization received 0.029 mg.kg^-1 (SD 0.0077) neostigmine, with p = 0.059. In subgroup R, patients with RPOC received 0.025 mg.kg^-1 (SD 0.0002) neostigmine while those without RPOC received 0.03 mg.kg^-1 (SD 0.0072) with p = 0.449. However, when patients were subdivided with regard to neostigmine dose, there has been a lower incidence of residual curarization among those receiving more than 0.03 mg.kg^-1, as shown in table VI.

Brazilian Journal of Anesthesiology, 2005; 55: 6: 622-630

Residual neuromuscular block after rocuronium or cisatracurium

Bruno Salomé de Morais; Carlos Henrique Viana de Castro; Vera Coelho Teixeira; Alexandre Silva Pinto

Table VII shows the relation between TOF values and concomitant use of some drug exacerbating competitive neuromuscular blocker effect.

Brazilian Journal of Anesthesiology, 2005; 55: 6: 622-630

Residual neuromuscular block after rocuronium or cisatracurium

Bruno Salomé de Morais; Carlos Henrique Viana de Castro; Vera Coelho Teixeira; Alexandre Silva Pinto

Three subgroup C patients and two subgroup R patients presented TOF between 0.3 and 0.7 and were medicated with 0.002 mg neostigmine and 0.02 mg.kg^-1 atropine. After 10 minutes a new measurement was performed and all patients presented TOF above 0.9. No patient needed re-intubation.

DISCUSSION

In 1942, Griffith and Johnson described, in a pioneer publication, the use of curare in general anesthesia ⁸. Today, more than 60 years after the introduction of curare in anesthesiology, neuromuscular blockers are a landmark for modern anesthesia since they help tracheal intubation, provide operating field relaxation, allow for immobilization and help ventilation control. However, a major side effect of this group of drugs is the possibility of residual neuromuscular block.

Close and continuous observation after reversal is critical. Residual neuromuscular block should always be reminded in the post-anesthetic recovery unit (PACU), since it is seldom possible to show total neuromuscular recovery based on clinical parameters only. Clinical signs of lack of residual curarization (raise and maintain the head for 5 seconds, show the tongue, open eyes, cough and deeply breathe) have provided false-negative results in all groups when compared to peripheral nerve stimulation ³. In dubious situations it is critical to use more objective methods.

According to what is to be analyzed, several stimulation methods may be applied: isolated stimulation (IS), train of four (TOF), stimulation with post-tetanus count (PTC), double burst stimulation (DBS) and tetanus post-tetanus bursts (TPT). The following may be used for postoperative neuromuscular function monitoring: TOF and DBS. Train of four is the most common for the following advantages: it is painless, does not require control measures and adequately reflects neuromuscular block level.

Residual neuromuscular block is a risk factor for postoperative pulmonary complications such as aspiration, pneumonia and atelectasis ^2,9.

Although the trend for more frequent use of neuromuscular blockers (NMB) of intermediary action, the incidence of residual neuromuscular block is still high, even with the administration of anti-cholinesterase drugs ^4,5.

A recent study has shown that 24.7% of patients receiving vecuronium and 14.7% of those receiving rocuronium had TOF < 0.07 in the PACU after attempt to revert neuromuscular block with pyridostigmine ⁵.

Simpler stimulators allow for visual or tactile evaluation of muscle contraction only. However, several studies have suggested that even on experienced hands, it may be difficult to detect fatigue with those methods when T₄/T₁ > 0,3 ^10,11. Double burst stimulation helps visual or tactile detection of fatigue, but also have limitations ¹¹. T₄/T₁ > 0,3 suggests that patient will not develop significant respiratory difficulty; however this is not enough to prevent gastric content aspiration or airways obstruction ¹². Swallowing difficulty disappears only with T₄/T₁ > 0.9 ¹³. With TOF < 0.9 on adductor pollicis, airways protection is impaired, increasing four to five times the risk of aspiration ⁹. To assure normal muscular function and ventilatory regulation, TOF > 0.9 on adductor pollicis should be reached before extubation ⁹.

Many studies standardizing residual curarization as TOF < 0.7 have shown the incidence of 8% to 42% with vecuronium ¹, 24% with mivacurium ¹⁴, and up to 65% with atracurium. Considering that the safe TOF value for extubation is above 0.9, the incidence of residual neuromuscular block is even higher than that found in those studies.

Subgroup C has received the highest relative NMB dose (3.15 DE95) as compared to subgroup R (2.2 DE95). This difference may be due to longer cisatracurium onset as compared to rocuronium, with higher relative dose to obtain satisfactory intubation conditions in a short period of time.

There has been a high incidence of postoperative neuromuscular block in both groups, without statistically significant differences in residual neuromuscular block between cisatracurium and rocuronium. The incidence of neuromuscular block in the PACU was 32% in subgroup C and 30% in subgroup R. The incidence of residual neuromuscular block was kept high, in levels equivalent to results obtained by recent studies.

There has been no statistically significant difference in NMB dose among RPOC patients, showing that bolus neuromuscular blocker has not determined residual neuromuscular block. Increasing cisatracurium dose prolongs deep neuromuscular block (without response to neurostimulation). However, at the beginning of spontaneous recovery, there is a similar profile, in spite of the difference in dose, thus allowing the calculation of the recovery period ¹⁵. A similar study has concluded that atracurium dose is not associated to RPOC ⁴. Another author has observed that higher vecuronium doses were associated to higher risk of RPOC ¹, however multiple NMB doses were used in this study.

There is statistically significant difference between NMB administration and TOF in both groups (Table IV). Shorter interval between NMB administration and procedure completion is related to higher incidence of residual neuromuscular block, so patients submitted to short procedures are at higher risk. Similar results were found with vecuronium ¹, atracurium ⁴ and rocuronium ⁵.

There was no statistical difference in neuromuscular block among patients receiving or not neostigmine (Table V). Neostigmine effectively antagonizes neuromuscular block ¹⁶. There are controversies with regard to neostigmine doses needed for total reversal, because they depend on the drug, its dose, time elapsed since its administration and on the concomitant use of drugs which may interfere with neuromuscular blockers.

For all patients, time elapsed between neostigmine administration and residual neuromuscular block evaluation was above 10 minutes.

Mean neostigmine dose for cisatracurium and rocuronium subgroups was relatively low: 0.027 mg.kg^-1 and 0.029 mg.kg^-1, respectively. Mean neostigmine doses were not enough to revert neuromuscular block induced by cisatracurium and rocuronium, since there has been no statistically significant difference in TOF values among patients receiving or not the antagonist. Studies suggest that 0.05 mg.kg^-1 neostigmine is effective to revert vecuronium-induced neuromuscular block ^1,16.

When patients were subdivided by neostigmine dose, it was observed that doses above 0.03 mg.kg^-1 were effective to revert neuromuscular block and all patients receiving this dose arrived to the PACU with TOF above 0.9 (Table VI).

Many drugs may interact with neuromuscular blockers, changing blockade pattern. Our study was not sensitive to show this drug interaction since there has been no statistically significant difference in TOF values among patients using or not these drugs.

Neostigmine sub-doses and shorter procedures are associated to higher risk of RPOC. Careful and continuous observation in the PACU is critical even after reversal.

Objective neuromuscular function monitoring should always be adopted because it allows for the correct decision on the need for reversal, the reversal dose and the effectiveness of the antagonism.

Patients of both groups presented high incidence of residual neuromuscular block in the PACU. Postoperative residual curarization is still a problem, even with new intermediary action neuromuscular blockers.

REFERENCES

Submitted for publication February 9, 2005

Accepted for publication August 11, 2005

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*

Received fro) CET/SBA de Anestesiologia do Hospital Felício Rocho, Belo Horizonte, MG

Publication Dates

• Publication in this collection
  13 Mar 2006
• Date of issue
  Dec 2005

History

• Received
  09 Feb 2005
• Accepted
  11 Aug 2005