Neuromuscular blockers in Brazil

Almeida, Maria Cristina Simões de

doi:10.1590/S0034-70942004000600016

Abstracts

BACKGROUND AND OBJECTIVES: There are no statistical data on the use of neuromuscular blockers in Brazil. This study aimed at statistically analyzing this topic. METHODS: Our study has compiled 831 answers to a questionnaire filled by anesthesiologists attending the 48th Brazilian Congress of Anesthesiology in Recife, 2001, and via Internet by anesthesiologists whose e-mail addresses are in the Brazilian Society of Anesthesiology web page (<A HREF="http://www.sba.com.br/">www.sba.com.br</A>). The following data were evaluated: years of experience with the specialty, region where anesthesiologists practice, neuromuscular blockers (NMB) usage in order of preference, indications for succinylcholine, neuromuscular transmission monitor usage, blockade recovery criteria, neostigmine usage, NMB administration routes and description of observed complications. RESULTS: Most anesthesiologists practice for more than 11 years and the highest number of answers have come from the Southeastern region of Brazil. Most common NMB is atracurium, followed by pancuronium and succinylcholine. Succinylcholine is more frequently used for rapid sequence induction and in children (80% and 25%, respectively). Neuromuscular transmission monitors are never used by 53% of anesthesiologists, and 92% of them use clinical signs as blockade recovery criteria. Neostigmine is routinely used by 45% of professionals and 94% of them administer NMB in bolus. Approximately 30% have referred NMB-related complications. Most frequent complications were prolonged blockade, severe bronchospasm and residual curarization. CONCLUSIONS: Atracurium is the most popular neuromuscular blocker in Brazil; there is a high percentage of succinylcholine usage in non-emergency situations; neuromuscular transmission monitors are seldom used and, as a corollary, there is a significant percentage of clinical criteria to consider patients recovered. We have observed that approximately 30% of anesthesiologists had some type of NMB-related complication.

NEUROMUSCULAR BLOCKERS

JUSTIFICATIVA E OBJETIVOS: Dados estatísticos referentes ao uso de bloqueadores neuromusculares no Brasil são desconhecidos. Este trabalho se propõe a análise estatística desse tópico. MÉTODO: Foram compiladas 831 respostas de um questionário preenchido em parte por anestesiologistas presentes ao 48º Congresso Brasileiro de Anestesiologia em Recife, 2001 e em parte via Internet, por anestesiologistas cujos endereços eletrônicos constam na página da Sociedade Brasileira de Anestesiologia (<A HREF="http://www.sba.com.br/">www.sba.com.br</A>). Foram analisados os seguintes dados: tempo de contato com a especialidade, região onde atuam os anestesiologistas, uso de bloqueadores neuromusculares (BNM) em ordem de preferência, indicações do uso de succinilcolina, uso do monitor da transmissão neuromuscular, critérios para se considerar o paciente descurarizado, uso de neostigmina, forma de administração dos BNM e descrição de complicações observadas. RESULTADOS: A maioria dos anestesiologistas em questão exerce a profissão há mais de 11 anos e o maior número de respostas foi proveniente da região sudeste do Brasil. O BNM mais empregado é o atracúrio, seguido de pancurônio e succinilcolina. A succinilcolina é mais empregada na indução rápida e em crianças (80% e 25% respectivamente). Monitores da transmissão neuromuscular, 53% dos anestesiologistas nunca usam, e como critério de recuperação, 92% consideram o paciente descurarizado mediante sinais clínicos. Em 45% das vezes os profissionais empregam a neostigmina de forma rotineira, e 94% administra os BNM sob forma de bolus. Cerca de 30% registra ter havido complicação decorrente do uso de BNM. As complicações mais apontadas foram o bloqueio prolongado, o broncoespasmo grave e a curarização residual. CONCLUSÕES: O atracúrio é o bloqueador neuromuscular mais empregado no Brasil, há percentual alto de uso da succinilcolina em situações não emergenciais, o uso de monitores da transmissão neuromuscular é raro, e, como um corolário, um percentual significativo de uso de critérios eminentemente clínicos para considerar o paciente descurarizado. Registrou-se que, cerca de 30% dos anestesiologistas teve algum tipo de complicação decorrente do uso desses fármacos.

BLOQUEADORES NEUROMUSCULARES

JUSTIFICATIVA Y OBJETIVOS: Dados estadísticos referentes al uso de bloqueadores neuromusculares en Brasil son desconocidos. Este trabajo se propone el análisis estadístico de ese tópico. MÉTODO: Fueron compiladas 831 respuestas de un cuestionario llenado en parte por anestesiologistas presentes al 48º Congreso Brasileño de Anestesiologia en la ciudad de Recife, 2001 y en parte vía Internet, por anestesiologistas cuyas direcciones electrónicas constan en la página de la Sociedad Brasileña de Anestesiologia (<A HREF="http://www.sba.com.br/">www.sba.com.br</A>). Fueron analizados los siguientes datos: tiempo de contacto con la especialidad, región donde actúan los anestesiologistas, uso de bloqueadores neuromusculares (BNM) en orden de preferencia, indicaciones del uso de succinilcolina, uso del monitor de transmisión neuromuscular, criterios para considerar el paciente descurarizado, uso de neostigmina, forma de administración de los BNM y descripción de complicaciones observadas. RESULTADOS: La mayoría de los anestesiologistas en cuestión ejerce la profesión hace más de 11 años y el mayor número de respuestas fue proveniente de la región sudeste de Brasil. El BNM más empleado es el atracúrio, seguido de pancurónio y succinilcolina. La succinilcolina es más empleada en la inducción rápida y en niños (80% y 25% respectivamente). Monitores de la transmisión neuromuscular, 53% de los anestesiologistas nunca usan, y como criterio de recuperación, 92% consideran el paciente descurarizado mediante señales clínicas. En un 45% de las veces los profesionales emplean la neostigmina de forma rutinaria, y 94% administra los BNM bajo forma de bolus. Cerca del 30% registra que tuvieron complicación consecuente del uso de BNM. Las complicaciones más apuntadas fueron el bloqueo prolongado, el broncoespasmo grave y la curarización residual. CONCLUSIONES: El atracúrio es el bloqueador neuromuscular más empleado en Brasil, hay alto percentual del uso de la succinilcolina en situaciones no emergenciales, el uso de monitores de la transmisión neuromuscular es raro, y, como un corolario, un percentual significativo de uso de criterios eminentemente clínicos para considerar el paciente descurarizado. Se registró que, cerca del 30% de los anestesiologistas tuvo algún tipo de complicación consecuente del uso de eses fármacos.

MISCELLANEOUS

Neuromuscular blockers in Brazil^* * Received from Hospital Governador Celso Ramos, CET Integrado da SES/SC, Florianópolis, SC

El uso de bloqueadores neuromusculares en Brasil

Maria Cristina Simões de Almeida, TSA, M.D.

Doutor em Medicina pela Universidade Johannes Gutenberg-Alemanha, Professora Adjunta da Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC

^{Correspondence} Correspondence to Dra. Maria Cristina Simões de Almeida Address: Rua Renato Barbosa, 227 Jurerê Tradicional ZIP: 88053-640 City: Florianópolis, Brazil

SUMMARY

BACKGROUND AND OBJECTIVES: There are no statistical data on the use of neuromuscular blockers in Brazil. This study aimed at statistically analyzing this topic.

METHODS: Our study has compiled 831 answers to a questionnaire filled by anesthesiologists attending the 48^th Brazilian Congress of Anesthesiology in Recife, 2001, and via Internet by anesthesiologists whose e-mail addresses are in the Brazilian Society of Anesthesiology web page (www.sba.com.br). The following data were evaluated: years of experience with the specialty, region where anesthesiologists practice, neuromuscular blockers (NMB) usage in order of preference, indications for succinylcholine, neuromuscular transmission monitor usage, blockade recovery criteria, neostigmine usage, NMB administration routes and description of observed complications.

RESULTS: Most anesthesiologists practice for more than 11 years and the highest number of answers have come from the Southeastern region of Brazil. Most common NMB is atracurium, followed by pancuronium and succinylcholine. Succinylcholine is more frequently used for rapid sequence induction and in children (80% and 25%, respectively). Neuromuscular transmission monitors are never used by 53% of anesthesiologists, and 92% of them use clinical signs as blockade recovery criteria. Neostigmine is routinely used by 45% of professionals and 94% of them administer NMB in bolus. Approximately 30% have referred NMB-related complications. Most frequent complications were prolonged blockade, severe bronchospasm and residual curarization.

CONCLUSIONS: Atracurium is the most popular neuromuscular blocker in Brazil; there is a high percentage of succinylcholine usage in non-emergency situations; neuromuscular transmission monitors are seldom used and, as a corollary, there is a significant percentage of clinical criteria to consider patients recovered. We have observed that approximately 30% of anesthesiologists had some type of NMB-related complication.

Key Words: NEUROMUSCULAR BLOCKERS

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Dados estadísticos referentes al uso de bloqueadores neuromusculares en Brasil son desconocidos. Este trabajo se propone el análisis estadístico de ese tópico.

MÉTODO: Fueron compiladas 831 respuestas de un cuestionario llenado en parte por anestesiologistas presentes al 48º Congreso Brasileño de Anestesiologia en la ciudad de Recife, 2001 y en parte vía Internet, por anestesiologistas cuyas direcciones electrónicas constan en la página de la Sociedad Brasileña de Anestesiologia (www.sba.com.br). Fueron analizados los siguientes datos: tiempo de contacto con la especialidad, región donde actúan los anestesiologistas, uso de bloqueadores neuromusculares (BNM) en orden de preferencia, indicaciones del uso de succinilcolina, uso del monitor de transmisión neuromuscular, criterios para considerar el paciente descurarizado, uso de neostigmina, forma de administración de los BNM y descripción de complicaciones observadas.

RESULTADOS: La mayoría de los anestesiologistas en cuestión ejerce la profesión hace más de 11 años y el mayor número de respuestas fue proveniente de la región sudeste de Brasil. El BNM más empleado es el atracúrio, seguido de pancurónio y succinilcolina. La succinilcolina es más empleada en la inducción rápida y en niños (80% y 25% respectivamente). Monitores de la transmisión neuromuscular, 53% de los anestesiologistas nunca usan, y como criterio de recuperación, 92% consideran el paciente descurarizado mediante señales clínicas. En un 45% de las veces los profesionales emplean la neostigmina de forma rutinaria, y 94% administra los BNM bajo forma de bolus. Cerca del 30% registra que tuvieron complicación consecuente del uso de BNM. Las complicaciones más apuntadas fueron el bloqueo prolongado, el broncoespasmo grave y la curarización residual.

CONCLUSIONES: El atracúrio es el bloqueador neuromuscular más empleado en Brasil, hay alto percentual del uso de la succinilcolina en situaciones no emergenciales, el uso de monitores de la transmisión neuromuscular es raro, y, como un corolario, un percentual significativo de uso de criterios eminentemente clínicos para considerar el paciente descurarizado. Se registró que, cerca del 30% de los anestesiologistas tuvo algún tipo de complicación consecuente del uso de eses fármacos.

INTRODUCTION

The introduction of neuromuscular blockers in the clinical practice in 1942 has fostered advances in surgical techniques and patients care in intensive care units. There agents, however, are not free from side effects and already during the 50s, an increase in morbidity-mortality of patients receiving such drugs has been recognized ¹. A lot has been written to date about these drugs, explaining from pharmacological aspects, to indications, to the presence of complications or undesirable effects, among them residual curarization and prolonged muscular block with consequent hypoxemia, airway obstruction and postoperative lung complications ^2-4.

The actual situation of neuromuscular blockers (NMB) usage in Brazil is still unknown. This study aimed at pointing objective items about NMB usage in Brazil.

METHODS

Our study has evaluated 831 answers to a questionnaire (^{Attachment 1}) filled by attendees of the 48^th Brazilian Congress of Anesthesiology in Recife, 2001, and received via Internet from anesthesiologists whose e-mail addresses are in the Brazilian Society of Anesthesiology web page (www.sba.com.br).

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

The following data were evaluated: years of professional practice and region where anesthesiologists practice, choice of neuromuscular blockers (NMB) in daily practice in order of preference (1^st, 2^nd, 3^rd, etc), indications for succinylcholine, neuromuscular transmission monitor usage, blockade recovery criteria, neostigmine usage, NMB administration routes and observed complications. This latter item, if positively answered, has been descriptively analyzed in a case-by-case basis and grouped in 8 more frequent complications.

The term "usage index" has been created and used in the statistical analysis whenever "NMB choice" variable was considered, and is mathematically represented:

IU A= S⁶_{i = 1}x_i(7-i)

Where:

IU: usage index (for each studied NMB)

A: used NMB (atracurium, pancuronium etc.)

x = number of anesthesiologists choosing the blocker in position i

i: order of most frequently used NMB (1 = first place, 2 = second place, and so on)

Results were analyzed by simple percentage and are presented in figures.

RESULTS

Years of professional practice are shown in figure 1. Most respondents practice the specialty for more than 11 years.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Most answers came from the Southeastern region, followed by Southern and Northeastern regions. Northern and Mid-West regions have contributed with a low percentage of answers (Figure 2).

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Most frequently used NMB in Brazil and the distribution of their usage by region are shown in figures 3, 4, 5, 6, 7 and 8. Most commonly used NMB was atracurium, followed by pancuronium and succinylcholine. Atracurium is the most widely used NMB in all Brazilian states, except for Northern and Northeastern regions where pancuronium is number one.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Figure 9 shows NMB choice as a function of years of professional practice. In general, there are no differences in comparing both variables.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Succinylcholine usage is shown in figure 10. A large number of Brazilian anesthesiologists use succinylcholine for rapid sequence induction and in children (80% and 25%, respectively). It has also been observed significant indication of this blocker for adults and elective surgeries (15% for both) and 5% of anesthesiologists never use it. In 1% of cases, anesthesiologists use it for emergencies.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Neuromuscular transmission monitors usage is shown in figure 11. Most anesthesiologists (53%) never use this type of monitor in their clinical practice. By grouping those using it always and using it frequently, we have reached 10%.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Figure 12 shows the use of monitors according to years of professional practice. There is a slight trend to more frequent use by professionals with less years of professional practice.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Recovery criteria, as well as neostigmine usage, are shown in figures 13 and 14, respectively. From all respondents, 92% consider that patients are recovered when presenting solely clinical signs suggestive of reversion, such as satisfactory breathing, ability to open eyes, grasp hand and lift legs. A low percentage (3%) routinely uses the monitor, while 5% of respondents evaluate recovery by clinical signs and monitor data.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Relationship between years of professional practice and blockade recovery criteria is shown in figure 15. There were no significant differences.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

Neostigmine usage is shown in figure 16. It is routinely used in 45% of times, and 42% of anesthesiologists use it "sometimes". Only 10% indicate it based on objective monitor data.

Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

As to administration regimen, 94% use NMB in bolus and a low percentage also use it in continuous infusion.

Aproximately one third of respondents have reported one or more moderate to severe complications. Major complications are shown in Table I. Most common complications were prolonged blockade (7.1%), bronchospasm (6.9%), residual neuromuscular block (5.6%), prolonged post- succinylcholine apnea (4.4%), recurarization (2.7%), allergic reactions (2.6%), severe arrhythmias (2.4%) and malignant hyperthermia (1.2%).

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Brazilian Journal of Anesthesiology, 2004; 54: 6: 850-864

Neuromuscular blockers in Brazil

Maria Cristina Simões de Almeida

DISCUSSION

Data most calling the attention in this survey were highest atracurium use followed by pancuronium and succinylcholine, the high percentage of succinylcholine use in elective situations and in children, seldom use of neuromuscular transmission monitors, use of clinical criteria for motor block recovery and high percentage of moderate to severe complications. The comparison of these data with other published data was impaired because no study was found in the literature analyzing statistical aspects of the use of these drugs.

To not impair interpretation of the item "most frequently used NMB" the term "usage index" was created to attribute weights to NMB according to the order of choice (first most frequently used, 7, second 6, and so on). Otherwise, regions with lower number of answers would show very low percentages as compared to those with higher number of answers. With weights attributed to NMB by region analyzed criteria has similar weights when the region was analyzed, helping the interpretation of figures showing this variable.

One may speculate that the high percentage of atracurium use is due to the evidence of benefits, especially in terms of cardiovascular stability, recovery rate and conditions^5-9. The expressive use of succinylcholine and pancuronium could be interpreted as the lack of optimal drugs to replace succinylcholine, as lower vial/bottle cost and as acquired habit.

Reasons for succinylcholine popularity are fast onset and recovery ¹⁰. However, there is a world trend to increasingly restrict its indication, sparing its administration for emergency situations, especially in patients with full stomach and in the presence of laryngospasm ^11,12. Similarly to succinylcholine, pancuronium has also been restricted to procedures where there is programmed postoperative ventilation assistance ^13,14.

The reason for replacing succinylcholine whenever possible is the recording of a large number of severe complications, including deaths, especially related to acute hyperkalemia, malignant hyperthermia or other neuromuscular diseases ^15-19. The introduction of rapacuronium, a short-acting neuromuscular blocker promoting muscle relaxation similar to succinylcholine has not been solidified ²⁰. This agent was withdrawn from the market after short-term use in Europe and the USA, due to severe complications, especially bronchospasm ^20-22.

Rocuronium, pointed by some as an option for fast intubation, is the fourth most frequently used NMB by Brazilian anesthesiologists. Its highest use was recorded in the Southeastern region. Although with major advantages, such as fast onset and lack of metabolites with relaxing effects, it is no longer considered a substitute for succinylcholine ^23,24. Reasons are that even with 1.2 mg.kg^-1, there might not be total larynx abductors paralysis, in addition to wide variation in onset, in some cases reaching 2 minutes ²³.

Succinylcholine itself cannot be considered for rapid sequence induction because in situations where lungs cannot be ventilated, its recovery is not sufficiently fast to prevent oxygen hemoglobin desaturation ^25,26. However, while new drugs such as TAAC-3 are not introduced in the market, we may still consider succinylcholine as the drug of choice for fast intubation ²⁴.

The high percentage of succinylcholine administration in elective situations and in children, observed in this survey, is a reason for concern. It is already established that both mivacurium and rocuronium induce a faster onset in children as compared to adults, justifying the fact that larger centers have replaced succinylcholine by these NMB ^27-31.

Intermediate action neuromuscular blockers are considered agents of choice for their higher safety, in spite of their higher price per vial as compared, for example, to pancuronium ³². Several pharmaco-economic studies have shown that the cost of prolonged action agents is higher as compared to short or intermediate action neuromuscular blockers ^33,34.

As an example, one may mention post-anesthetic care unit stay, which contributes to approximately 3.7% of hospital costs ³⁵. This stay is increased with prolonged action neuromuscular blockers. Increased cost is undoubtedly related to personnel, and anesthesia itself contributes to 1/3 of the hospital bill ³⁶.

The seldom use of neuromuscular transmission monitors is a known fact verbally recorded worldwide. In a recent survey with a small number of respondents, 41% usage has been recorded. A different publication has observed 50% of use when there was the option for intermediate agents in bolus ³⁷. Although these studies have not directly focused on statistical aspects, and so the comparison with our study should be cautiously performed, there is an expressive difference between the use in Brazil and in Europe.

There are publications clearly showing that intraoperative monitors decrease the incidence of residual neuromuscular block ^26,28. However, there are questions whether they significantly contribute to decrease such complication ¹³. Major argument is that there is little information about the presence of NMB residue when nerve stimulator is used alone without instrumental recording. It is emphasized that the lower incidence of this complication is not determined by the device alone, but rather by the association of the understanding of neuromuscular blockers and their antagonists pharmacology and the correct interpretation of monitor data ¹³.

As a consequence of the seldom use of neuromuscular transmission monitors, 92% of Brazilian anesthesiologists are based on clinical criteria to determine motor block recovery.

Good motor activity, such as adequate breathing, full eye opening, good hand grasping and legs movement, although useful in the clinical practice, is inadequate to detect NMB residue in any situation ^26,39. Good ventilation capacity, representing adequate tidal volume, is an insensible test to detect NMB residue and is already normal with T₄/T₁ratio in 0.6 ^40,41. Inability to freely open eyes, together with blurred vision is present even with "acceptable" T₄/T₁ levels, that is, approximately 0.9 ⁴². Active leg movement is also not a safe criterium for adults recovery, but is valued in children ⁴³.

Important data was the presence of moderate to severe complications in 1/3 of the answers.

Prolonged blockade after mivacurium or succinylcholine is related to low plasma cholinesterase activity ^44-48. However, this complication has also been observed with other NMB not depending on pseudocholinesterase enzyme for the end of their effect. This prolonged recovery in most cases is related to pharmacokinetic changes of neuromuscular blockers, often observed during organs failure, such as kidneys, or the administration of the drug to patients with multiple organs failure during intensive treatment ^49-54.

Clearly, residual neuromuscular block is still a major complication, especially with prolonged action blockers, such as pancuronium. Emphasis given by the international literature to this complication is justified by its consequences, especially hypoxemia and postoperative lung complications ^2,55,56. This seems important since pancuronium is the third most widely used NMB in Brazil.

A report from 1985 informed that one third of deaths in anesthesia were due to allergic reactions ⁵⁷. In fact, in spite of new anesthetic techniques and control equipment, the incidence of allergic reactions has barely changed since the first report in 1949 ⁵⁸.

The increasing number of reactions with neuromuscular blockers may be explained by crossed reactions, today approximately 70% of cases ⁵⁹, especially with substances containing ammonium ions ⁶⁰. More flexible molecules, such as succinylcholine, may further stimulate sensory cells, although there are reports on allergic reactions with all types of NMB and antagonists ^61-65.

During anesthesia, the release of endogenous substances may produce many symptoms. The most common is non-immune histamine release promoting effects mostly confined to skin and blood vessels. However, there may be more severe manifestations such as cardiovascular collapse and cardiac arrest, bronchospasm and pulmonary edema ^60,66,67.

Bronchospasm, considered a severe manifestation of histamine release, was present in 6.9% of cases. Among the incidence of severe events in the world literature it is present in approximately 25% to 39% of cases ⁶⁸. Bronchospasm may also be caused by anticholinesterase drugs. This effect may be prevented with glycopyrrolate and atropine ⁶⁹.

The term "recurarization" is not accepted by many investigators, especially by those advocating the existence of the biophase. Some reports of patients with worsening of their respiratory condition in the post-anesthetic care unit after satisfactory recovery have been related to the presence of renal failure ⁷⁰.

Severe arrhythmias, including ventricular fibrillation, have been described with the use of NMB and anticholinesterase drugs ⁷¹. Major arrhythmias are related to the use of succinylcholine, reason why it has been withdrawn from the market for a certain period of time ^15,17,72. Pancuronium promotes arrhythmias by vagolytic action and sympathetic stimulation ⁷³.

Rhythm changes are also present with the administration of bensoisoquinolitic drugs, in general related to histamine release ^73,74. Changes are more uncommon with newer neuromuscular blockers, especially vecuronium and pipecuronium, for not having acetylcholine fragments in the A ring of their molecule ^75,76.

Malignant hyperthermia was reported in 1.2% of cases, incidence which may be considered high taking into account all compiled answers. The incidence in the USA is 1:15.000 anesthetic procedures and, if considering only adult patients, this ratio is lower (1:50.000) ⁷⁷.

There is a higher incidence of this disease during anesthesia and in the post-anesthetic care unit but it is decreasing with halothane-free techniques and succinylcholine ⁷⁷.

As a final conclusion, most commonly used NMB in Brazil is atracurium; succinylcholine is significantly used for rapid sequence induction, in children and in elective surgeries.

Equally important were data related to the seldom use of neuromuscular transmission monitors and, as a consequence, recovery criteria were just clinical aspects. It was also possible to show that neostigmine administration follows a routine and that bolus is the most widely used administration regimen for neuromuscular blockers. Aspects of concern are related to the high incidence of complications, especially prolonged blockade, bronchospasm, residual neuromuscular block and malignant hyperthermia.

REFERENCES

Submitted for publication October 30, 2003

Accepted for publication April 27, 2004

^{Attachment 1}

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17. Rosenberg H, Gronert GA - Intractable cardiac arrest in children given succinylcholine. Anesthesiology, 1992;77:1054.
18. Gronert G - Succinylcholine hyperkalemia after burns. Anesthesiology, 1999;91:320-322.
19. Gronert GA - Cardiac arrest after succinylcholine: mortality greater with rhabdomyolysis than receptor upregulation. Anesthesiology, 2001;94:523-529.
20. Goudsouzian NG - Rapacuronium and bronchospasm. Anesthesiology, 2001;94:727-728.
21. Meakin GH, Pronske EH, Lerman J et al - Bronchospasm after rapacuronium in infants and children. Anesthesiology, 2001;94:926-927.
22. White PF - Rapacuronium: why did it fail as a replacement for succinylcholine? Br J Anaesth, 2002;88:163-165.
23. Caldwell JE - Rapid sequence intubation : is rocuronium an alternative? Seminars in Anaesthesia, Perioperative Medicine and Pain, 2002;212:99-103.
24. Meistelman C - Update on neuromuscular pharmacology. Curr Opin Anaesthesiol, 2001;14:399-404.
25. Heier T, Feiner JR, Lin J et al - Hemoglobin desaturation after succinylcholine-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers. Anesthesiology, 2001;94:754-759.
26. Hayes AH, Mirakhur RK, Breslin DS et al - Postoperative residual block after intermediate-acting neuromuscular blocking drugs. Anaesthesia, 2001;56:312-318.
27. Fisher DM - Neuromuscular blocking agents in paediatric anaesthesia. Br J Anaesth, 1999;83:58-64.
28. Plaud B, Goujard E, Orliaguet G et al - [Pharmacodynamics and safety of mivacurium in infants and children under halothane-nitrous oxide anesthesia]. Ann Fr Anesth Reanim, 1999;18:1047-1053.
29. Brandom BW, Gavin FF - Neuromuscular clocking drugs in pediatric anesthesia. Anesthesiology Clinics of North America, 2002;30:45-59.
30. Sarner JB, Brandom BW, Woelfel SK - Clinical pharmacology of mivacurium chloride (BW B1090U) in children during nitrous oxide-halothane and nitrous oxide-narcotic anesthesia. Anesth Analg, 1989;68:116-121.
31. Goudsouzian NG, Alifimoff JK, Eberly C et al - Neuromuscular and cardiovascular effects of mivacurium in children. Anesthesiology, 1989;70:237-242.
32. Miller RD, Rupp SM, Fisher DM et al - Clinical pharmacology of vecuronium and atracurium. Anesthesiology, 1984;61:444-453.
33. Splinter WM, Isaac LA -The pharmacoeconomics of neuromuscular blocking drugs: a perioperative cost- minimization strategy in children. Anesth Analg, 2001;93: 339-344.
34. Caldwell JE - The problem with long-acting muscle relaxants? They cost more! Anesth Analg, 1997;85:473-475.
35. Macario A, Vitez TS, Dunn B et al - Where are the costs in perioperative care? Analysis of hospital costs and charges for inpatient surgical care. Anesthesiology, 1995;83:1138-1144.
36. Bevan D - The hidden cost of anesthesia. Can J Anaesth, 2002;49:533-535.
37. Fawcett WJ, Dash A, Francis GA et al - Recovery from neuromuscular blockade: residual curarisation following atracurium or vecuronium by bolus dosing or infusions. Acta Anaesthesiol Scand, 1995;39:288-293.
38. Shorten GD, Merk H, Sieber T - Perioperative train-of-four monitoring and residual curarization. Can J Anaesth, 1995;42: 711-715.
39. Brull SJ, Silverman DG - Neuromuscular monitoring and clinical applications: what to do, when, and why? Seminars in Anesthesia, Perioperative Medicine and Pain, 2002;21:104-119.
40. Brand JB, Cullen DJ, Wilson NE et al - Spontaneous recovery from nondepolarizing neuromuscular blockade: correlation between clinical and evoked responses. Anesth Analg, 1977;56:55-58.
41. Ali HH, Wilson RS, Savarese JJ et al -The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans. Br J Anaesth, 1975;47:570-574.
42. Kopman AF, Yee PS, Neuman GG - Relationship of the train-of-four fade ratio to clinical signs and symptoms of residual paralysis in awake volunteers. Anesthesiology, 1997;86: 765-771.
43. Mason LJ, Betts EK - Leg lift and maximum inspiratory force, clinical signs of neuromuscular blockade reversal in neonates and infants. Anesthesiology, 1980;52:441-442.
44. Whittaker M - Plasma cholinesterase variants and the anaesthetist. Anaesthesia, 1980;35:174-197.
45. Goudsouzian NG, dHollander AA, Viby-Mogensen J - Prolonged neuromuscular block from mivacurium in two patients with cholinesterase deficiency. Anesth Analg, 1993;77: 183-185.
46. Benzer A, Luz G, Oswald E et al - Succinylcholine-induced prolonged apnea in a 3-week-old newborn: treatment with human plasma cholinesterase. Anesth Analg, 1992;74:137-138.
47. Rodriguez-Gonzalez MM, Arribas-Carrion C, Torre-Aznar C et al - Prolonged neuromuscular block with mivacurium. Rev Esp Anestesiol Reanim, 1997;44:328-329.
48. Naguib M, el-Gammal M, Daoud W et al - Human plasma cholinesterase for antagonism of prolonged mivacurium-induced neuromuscular blockade. Anesthesiology, 1995;82: 1288-1292.
49. Vanderheyden BA, Reynolds HN, Gerold KB et al - Prolonged paralysis after long-term vecuronium infusion. Crit Care Med, 1992;20:304-307.
50. Partridge BL, Abrams JH, Bazemore C et al - Prolonged neuromuscular blockade after long-term infusion of vecuronium bromide in the intensive care unit. Crit Care Med, 1990;18: 1177-1179.
51. Booij LH - The use of muscle relaxants in the intensive care unit. Acta Anaesthesiol Belg, 1997;48:35-44.
52. Sharpe MD - The use of muscle relaxants in the intensive care unit. Can J Anaesth, 1992;39:949-962.
53. Rossiter A, Souney PF, McGowan S et al - Pancuronium-induced prolonged neuromuscular blockade. Crit Care Med, 1991;19:1583-1587.
54. Head-Rapson AG, Devlin JC, Parker CJ et al - Pharmacokinetics of the three isomers of mivacurium and pharmacodynamics of the chiral mixture in hepatic cirrhosis. Br J Anaesth, 1994;73:613-618.
55. Eriksson LI, Lennmarken C, Wyon N et al - Attenuated ventilatory response to hypoxaemia at vecuronium-induced partial neuromuscular block. Acta Anaesthesiol Scand, 1992;36:710-715
56. Pedersen T, Viby-Mogensen J, Ringsted C - Anaesthetic practice and postoperative pulmonary complications. Acta Anaesthesiol Scand, 1992;36:812-818.
57. Watkins J - Investigation of allergic and hypersensitivity reactions to anaesthetic agents. Br J Anaesth, 1987;59:104-111.
58. Watkins J, Wild G, Bex S et al - A case for co-ordinated investigation and reporting of hypersensitivity-type drug reactions in the UK. Anaesthesia, 2000;55:1127-1128.
59. Laxenaire MC - Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994-December 1996). Ann Fr Anesth Reanim, 1999;18:796-809.
60. Mertes PM, Laxenaire MC - Allergic reactions occurring during anaesthesia. Eur J Anaesthesiol, 2002;19:240-262.
61. Seed MJ, Ewan PW - Anaphylaxis caused by neostigmine. Anaesthesia, 2000;55:574-575.
62. McNicholas JJ, Harban FM - Anaphylaxis caused by neostigmine. Anaesthesia, 2000;55:1039.
63. Laake JH, Rottingen JA - Rocuronium and anaphylaxis - a statistical challenge. Acta Anaesthesiol Scand, 2001;45: 1196-1203.
64. Heier T, Guttormsen AB - Anaphylactic reactions during induction of anaesthesia using rocuronium for muscle relaxation: a report including 3 cases. Acta Anaesthesiol Scand, 2000;44: 775-781.
65. Barthelet Y, Ryckwaert Y, Plasse C et al - Severe anaphylactic reactions after administration of rocuronium. Ann Fr Anesth Reanim, 1999;18:896-900.
66. Moss J, Rosow CE - Histamine release by narcotics and muscle relaxants in humans. Anesthesiology, 1983;59:330-339.
67. Watkins J - Adverse reaction to neuromuscular blockers: frequency, investigation, and epidemiology. Acta Anaesthesiol Scand, 1994;102:(Suppl):6-10.
68. Escolano F, Sierra P - Allergic reactions during anesthesia. Rev Esp Anestesiol Reanim, 1996;43:17-26.
69. Naguib M, Magbou M - Adverse effects of neuromuscular blockers and their antagonists. M E J Anesth, 1998;14:341-373.
70. Bevan DR - Neuromuscular blockade. Inadvertent extubation of the partially paralyzed patient. Anesthesiol Clin North America, 2001;19:913-922.
71. Pleym H, Bathen J, Spigset O et al - Ventricular fibrillation related to reversal of the neuromuscular blockade in a patient with long QT syndrome. Acta Anaesthesiol Scand, 1999;43: 352-355.
72. Delphin E, Jackson D, Rothstein P - Use of succinylcholine during elective pediatric anesthesia should be reevaluated. Anesth Analg, 1987;66:1190-1192.
73. Bowman WC - Non-relaxant properties of neuromuscular blocking drugs. Br J Anaesth, 1982;54:147-160.
74. Naguib M, Samarkandi AH, Bakhamees HS et al - Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine. Br J Anaesth, 1995;75:588-592.
75. Durant NN, Marshall IG, Savage DS et al - The neuromuscular and autonomic blocking activities of pancuronium, Org NC 45, and other pancuronium analogues, in the cat. J Pharm Pharmacol, 1979;31:831-836.
76. Tassonyi E, Neidhart P, Pittet JF et al - Cardiovascular effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting. Anesthesiology, 1988;69:793-796.
77. Strazis KP, Fox AW - Malignant hyperthermia: a review of published cases. Anesth Analg, 1993;77:297-304.

Correspondence to

Dra. Maria Cristina Simões de Almeida

Address: Rua Renato Barbosa, 227 Jurerê Tradicional

ZIP: 88053-640 City: Florianópolis, Brazil

*

Received from Hospital Governador Celso Ramos, CET Integrado da SES/SC, Florianópolis, SC

Publication Dates

Publication in this collection
26 Jan 2005
Date of issue
Dec 2004

History

Accepted
27 Apr 2004
Received
30 Oct 2003

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

[1] 01. Beecher HK, Todd DP - A study of the deaths associated with anesthesia and surgery. Annals of Surgery, 1954;140:2-34.

[2] 02. Berg H, Roed J, Viby-Mogensen J et al - Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand, 1997;41:1095-1103.

[3] 03. Viby-Mogensen J - Why should I change my practice of anaesthesia: neuromuscular blocking agents. Minerva Anestesiol, 2000;66:273-277.

[4] 04. Baillard C, Gehan G, Reboul-Marty J et al - Residual curarization in the recovery room after vecuronium. Br J Anaesth, 2000;84:394-395.

[5] 05. Basta SJ, Ali HH, Savarese JJ et al - Clinical pharmacology of atracurium besylate (BW 33A): a new non-depolarizing muscle relaxant. Anesth Analg, 1982;61:723-729.

[6] 06. Fisher DM, Canfell PC, Fahey MR et al - Elimination of atracurium in humans: contribution of Hofmann elimination and ester hydrolysis versus organ-based elimination. Anesthesiology, 1986;65:6-12.

[7] 07. 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.

[8] 08. Payne JP, Hughes R - Evaluation of atracurium in anaesthetized man. Br J Anaesth, 1981;53:45-54.

[9] 09. Hughes R, Chapple DJ - The pharmacology of atracurium: a new competitive neuromuscular blocking agent. Br J Anaesth, 1981;53:31-44.

[10] 10. Moore EW, Hunter JM - The new neuromuscular blocking agents: do they offer any advantages? Br J Anaesth, 2001;87: 912-925.

[11] 11. Warner DO - Intramuscular succinylcholine and laryngospasm. Anesthesiology, 2001;95:1039-1040.

[12] 12. Larson Jr CP - Laryngospasm - the best treatment. Anesthesiology, 1998;89:1293-1294.

[13] 13. Kopman AF - Neuromuscular blocking agents: new insights and old controversies. Seminars in Anesthesia, Perioperative Medicine and Pain, 2002;21:75-85.

[14] 14. Viby-Mogensen J - Is postoperative residual curarization still a problem? Seminars in Anesthesia, Perioperative Medicine and Pain, 2002;21:130-134.

[15] 15. Sullivan M, Thompson WK, Hill GD - Succinylcholine-induced cardiac arrest in children with undiagnosed myopathy. Can J Anaesth, 1994;41:497-501.

[16] 16. Haeseler G, Petzold J, Hecker H et al -Succinylcholine metabolite succinic acid alters steady state activation in muscle sodium channels. Anesthesiology, 2000;92:1385-1391.

[17] 17. Rosenberg H, Gronert GA - Intractable cardiac arrest in children given succinylcholine. Anesthesiology, 1992;77:1054.

[18] 18. Gronert G - Succinylcholine hyperkalemia after burns. Anesthesiology, 1999;91:320-322.

[19] 19. Gronert GA - Cardiac arrest after succinylcholine: mortality greater with rhabdomyolysis than receptor upregulation. Anesthesiology, 2001;94:523-529.

[20] 20. Goudsouzian NG - Rapacuronium and bronchospasm. Anesthesiology, 2001;94:727-728.

[21] 21. Meakin GH, Pronske EH, Lerman J et al - Bronchospasm after rapacuronium in infants and children. Anesthesiology, 2001;94:926-927.

[22] 22. White PF - Rapacuronium: why did it fail as a replacement for succinylcholine? Br J Anaesth, 2002;88:163-165.

[23] 23. Caldwell JE - Rapid sequence intubation : is rocuronium an alternative? Seminars in Anaesthesia, Perioperative Medicine and Pain, 2002;212:99-103.

[24] 24. Meistelman C - Update on neuromuscular pharmacology. Curr Opin Anaesthesiol, 2001;14:399-404.

[25] 25. Heier T, Feiner JR, Lin J et al - Hemoglobin desaturation after succinylcholine-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers. Anesthesiology, 2001;94:754-759.

[26] 26. Hayes AH, Mirakhur RK, Breslin DS et al - Postoperative residual block after intermediate-acting neuromuscular blocking drugs. Anaesthesia, 2001;56:312-318.

[27] 27. Fisher DM - Neuromuscular blocking agents in paediatric anaesthesia. Br J Anaesth, 1999;83:58-64.

[28] 28. Plaud B, Goujard E, Orliaguet G et al - [Pharmacodynamics and safety of mivacurium in infants and children under halothane-nitrous oxide anesthesia]. Ann Fr Anesth Reanim, 1999;18:1047-1053.

[29] 29. Brandom BW, Gavin FF - Neuromuscular clocking drugs in pediatric anesthesia. Anesthesiology Clinics of North America, 2002;30:45-59.

[30] 30. Sarner JB, Brandom BW, Woelfel SK - Clinical pharmacology of mivacurium chloride (BW B1090U) in children during nitrous oxide-halothane and nitrous oxide-narcotic anesthesia. Anesth Analg, 1989;68:116-121.

[31] 31. Goudsouzian NG, Alifimoff JK, Eberly C et al - Neuromuscular and cardiovascular effects of mivacurium in children. Anesthesiology, 1989;70:237-242.

[32] 32. Miller RD, Rupp SM, Fisher DM et al - Clinical pharmacology of vecuronium and atracurium. Anesthesiology, 1984;61:444-453.

[33] 33. Splinter WM, Isaac LA -The pharmacoeconomics of neuromuscular blocking drugs: a perioperative cost- minimization strategy in children. Anesth Analg, 2001;93: 339-344.

[34] 34. Caldwell JE - The problem with long-acting muscle relaxants? They cost more! Anesth Analg, 1997;85:473-475.

[35] 35. Macario A, Vitez TS, Dunn B et al - Where are the costs in perioperative care? Analysis of hospital costs and charges for inpatient surgical care. Anesthesiology, 1995;83:1138-1144.

[36] 36. Bevan D - The hidden cost of anesthesia. Can J Anaesth, 2002;49:533-535.

[37] 37. Fawcett WJ, Dash A, Francis GA et al - Recovery from neuromuscular blockade: residual curarisation following atracurium or vecuronium by bolus dosing or infusions. Acta Anaesthesiol Scand, 1995;39:288-293.

[38] 38. Shorten GD, Merk H, Sieber T - Perioperative train-of-four monitoring and residual curarization. Can J Anaesth, 1995;42: 711-715.

[39] 39. Brull SJ, Silverman DG - Neuromuscular monitoring and clinical applications: what to do, when, and why? Seminars in Anesthesia, Perioperative Medicine and Pain, 2002;21:104-119.

[40] 40. Brand JB, Cullen DJ, Wilson NE et al - Spontaneous recovery from nondepolarizing neuromuscular blockade: correlation between clinical and evoked responses. Anesth Analg, 1977;56:55-58.

[41] 41. Ali HH, Wilson RS, Savarese JJ et al -The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans. Br J Anaesth, 1975;47:570-574.

[42] 42. Kopman AF, Yee PS, Neuman GG - Relationship of the train-of-four fade ratio to clinical signs and symptoms of residual paralysis in awake volunteers. Anesthesiology, 1997;86: 765-771.

[43] 43. Mason LJ, Betts EK - Leg lift and maximum inspiratory force, clinical signs of neuromuscular blockade reversal in neonates and infants. Anesthesiology, 1980;52:441-442.

[44] 44. Whittaker M - Plasma cholinesterase variants and the anaesthetist. Anaesthesia, 1980;35:174-197.

[45] 45. Goudsouzian NG, dHollander AA, Viby-Mogensen J - Prolonged neuromuscular block from mivacurium in two patients with cholinesterase deficiency. Anesth Analg, 1993;77: 183-185.

[46] 46. Benzer A, Luz G, Oswald E et al - Succinylcholine-induced prolonged apnea in a 3-week-old newborn: treatment with human plasma cholinesterase. Anesth Analg, 1992;74:137-138.

[47] 47. Rodriguez-Gonzalez MM, Arribas-Carrion C, Torre-Aznar C et al - Prolonged neuromuscular block with mivacurium. Rev Esp Anestesiol Reanim, 1997;44:328-329.

[48] 48. Naguib M, el-Gammal M, Daoud W et al - Human plasma cholinesterase for antagonism of prolonged mivacurium-induced neuromuscular blockade. Anesthesiology, 1995;82: 1288-1292.

[49] 49. Vanderheyden BA, Reynolds HN, Gerold KB et al - Prolonged paralysis after long-term vecuronium infusion. Crit Care Med, 1992;20:304-307.

[50] 50. Partridge BL, Abrams JH, Bazemore C et al - Prolonged neuromuscular blockade after long-term infusion of vecuronium bromide in the intensive care unit. Crit Care Med, 1990;18: 1177-1179.

[51] 51. Booij LH - The use of muscle relaxants in the intensive care unit. Acta Anaesthesiol Belg, 1997;48:35-44.

[52] 52. Sharpe MD - The use of muscle relaxants in the intensive care unit. Can J Anaesth, 1992;39:949-962.

[53] 53. Rossiter A, Souney PF, McGowan S et al - Pancuronium-induced prolonged neuromuscular blockade. Crit Care Med, 1991;19:1583-1587.

[54] 54. Head-Rapson AG, Devlin JC, Parker CJ et al - Pharmacokinetics of the three isomers of mivacurium and pharmacodynamics of the chiral mixture in hepatic cirrhosis. Br J Anaesth, 1994;73:613-618.

[55] 55. Eriksson LI, Lennmarken C, Wyon N et al - Attenuated ventilatory response to hypoxaemia at vecuronium-induced partial neuromuscular block. Acta Anaesthesiol Scand, 1992;36:710-715

[56] 56. Pedersen T, Viby-Mogensen J, Ringsted C - Anaesthetic practice and postoperative pulmonary complications. Acta Anaesthesiol Scand, 1992;36:812-818.

[57] 57. Watkins J - Investigation of allergic and hypersensitivity reactions to anaesthetic agents. Br J Anaesth, 1987;59:104-111.

[58] 58. Watkins J, Wild G, Bex S et al - A case for co-ordinated investigation and reporting of hypersensitivity-type drug reactions in the UK. Anaesthesia, 2000;55:1127-1128.

[59] 59. Laxenaire MC - Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994-December 1996). Ann Fr Anesth Reanim, 1999;18:796-809.

[60] 60. Mertes PM, Laxenaire MC - Allergic reactions occurring during anaesthesia. Eur J Anaesthesiol, 2002;19:240-262.

[61] 61. Seed MJ, Ewan PW - Anaphylaxis caused by neostigmine. Anaesthesia, 2000;55:574-575.

[62] 62. McNicholas JJ, Harban FM - Anaphylaxis caused by neostigmine. Anaesthesia, 2000;55:1039.

[63] 63. Laake JH, Rottingen JA - Rocuronium and anaphylaxis - a statistical challenge. Acta Anaesthesiol Scand, 2001;45: 1196-1203.

[64] 64. Heier T, Guttormsen AB - Anaphylactic reactions during induction of anaesthesia using rocuronium for muscle relaxation: a report including 3 cases. Acta Anaesthesiol Scand, 2000;44: 775-781.

[65] 65. Barthelet Y, Ryckwaert Y, Plasse C et al - Severe anaphylactic reactions after administration of rocuronium. Ann Fr Anesth Reanim, 1999;18:896-900.

[66] 66. Moss J, Rosow CE - Histamine release by narcotics and muscle relaxants in humans. Anesthesiology, 1983;59:330-339.

[67] 67. Watkins J - Adverse reaction to neuromuscular blockers: frequency, investigation, and epidemiology. Acta Anaesthesiol Scand, 1994;102:(Suppl):6-10.

[68] 68. Escolano F, Sierra P - Allergic reactions during anesthesia. Rev Esp Anestesiol Reanim, 1996;43:17-26.

[69] 69. Naguib M, Magbou M - Adverse effects of neuromuscular blockers and their antagonists. M E J Anesth, 1998;14:341-373.

[70] 70. Bevan DR - Neuromuscular blockade. Inadvertent extubation of the partially paralyzed patient. Anesthesiol Clin North America, 2001;19:913-922.

[71] 71. Pleym H, Bathen J, Spigset O et al - Ventricular fibrillation related to reversal of the neuromuscular blockade in a patient with long QT syndrome. Acta Anaesthesiol Scand, 1999;43: 352-355.

[72] 72. Delphin E, Jackson D, Rothstein P - Use of succinylcholine during elective pediatric anesthesia should be reevaluated. Anesth Analg, 1987;66:1190-1192.

[73] 73. Bowman WC - Non-relaxant properties of neuromuscular blocking drugs. Br J Anaesth, 1982;54:147-160.

[74] 74. Naguib M, Samarkandi AH, Bakhamees HS et al - Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine. Br J Anaesth, 1995;75:588-592.

[75] 75. Durant NN, Marshall IG, Savage DS et al - The neuromuscular and autonomic blocking activities of pancuronium, Org NC 45, and other pancuronium analogues, in the cat. J Pharm Pharmacol, 1979;31:831-836.

[76] 76. Tassonyi E, Neidhart P, Pittet JF et al - Cardiovascular effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting. Anesthesiology, 1988;69:793-796.

[77] 77. Strazis KP, Fox AW - Malignant hyperthermia: a review of published cases. Anesth Analg, 1993;77:297-304.