Rev Bras Anestesiol 2012; 62: 3: 439-450 SPECIAL ARTICLE

SPECIAL ARTICLE

Postoperative Residual Paralysis

Ligia Andrade da Silva Telles Mathias 1, Ricardo Caio Gracco de Bernardis 2

Summary: Mathias LAST, Bernardis RCG Postoperative Residual Paralysis.

2012 Elsevier Editora Ltda. All rights reserved.

DESCRIPTION OF THE EVIDENCE COLLECTION METHOD Multiple searches were carried out in the PubMed database to identify articles with better methodological design, followed by critical evaluation of their contents and classification according to the strength of evidence. According to the recommendations of the Oxford Centre for Evidence Based Medicine, literature systematic reviews and randomized clinical trials were preferred. Searches were carried out between January 2009 and July 2010. For the search in PubMed, different keywords combinations were used (random*; neuromuscular; postanesthesia; care; residual; paralysis; complications; blockade; curarization) as well as controlled vocabulary terms (Anesthesia, Perioperative Complications [MeSH]; Residual Neuromuscular Blockade [MeSH]; Postanesthesia Care Unit [MeSH]; Monitoring Neuromuscular blockade [MeSH]; and Randomized Controlled Trial, Guidelines, Task force [Publication Type]). Were selected studies that evaluated the incidence, diagnostic tests, complications and prevention of postoperative residual paralysis in animals, conscious volunteers and patients submitted to surgical procedures, without distinction.

D: Opinion without critical evaluation, based on consensuses, physiological studies or animal models.

OBJECTIVE To evaluate incidence, diagnostic tests, complications and prevention of postoperative residual paralysis (PORP).

INTRODUCTION Definition Postoperative residual paralysis (PORP), also known as residual postoperative neuromuscular blockade, is defined as postoperative paralysis or muscle weakness due to incomplete or absent antagonism of nondepolarizing neuromuscular blockers (NMB) 1(D). The T4/T1 ratio of 0.9 was assessed using the train-of-four stimuli (TOF). It is currently considered the gold standard of complete reversal of neuromuscular blockade 1(D).

Incidence RECOMMENDANTIO DEGREE AND STRENGTH OF EVIDENCE A: Experimental or observational studies of best consistency. B: Experimental or observational studies of least consistency. C: Case Reports (non-controlled studies). PORP after the end of anesthesia has been reported in several studies, with an incidence ranging from 5% to 88%, considering PORP as T4/T1 ratio < 0.9 2(B), 3(A), 4(B), 5(A).

What are the factors that alter the incidence of postoperative residual paralysis?
Received from the Brazilian Society of Anesthesiology, Brazil. 1. PhD, Faculdade de Medicina da Universidade de So Paulo (FM-USP); Adjunct Professor, Head of the Discipline of Anesthesiology, Faculdade Cincias Mdicas da Santa Casa de So Paulo (FCMSCSP) 2. PhD, Surgery, FCMSCSP; Medical Director, Surgical Center, Irmandade da Santa Casa de Misericrdia de So Paulo Correspondence to: Sociedade Brasileira de Anestesiologia Rua Professor Alfredo Gomes, 36 Botafogo 22251080 Rio de Janeiro, RJ, Brazil E-mail: rba@sba.com.br

The great variability is due to different methods: use of T4/T1 ratio of 0.7, 0.8 or 0.9 as PORP criterion 6,7(B); use of different NMB of short, intermediate and long-term duration 3(A), 6,7(B); use of single or repeated doses, or continuous infusion of NMB 3(A), 6,7,8(B); assessment method of the residual NMB 1(D), 9(A); with or without reversal of neuromuscular blockade at the end of anesthesia with anticholinesterase drugs, with dose and interval between the anticholinesterase
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drugs and degree assessment of neuromuscular blockade 3(A), 4,6-8(B); age 10(B); presence of kidney, cardiac or neuromuscular dysfunction 11(D); drug use that can alter the pharmacodynamics and/or pharmacokinetics of NMB (calcium channel blockers, magnesium, lithium, antibiotics, local anesthetics, inhaled anesthetics, opioids, benzodiazepines) 11(D); and electrolyte abnormalities, metabolic or respiratory acidosis and hypothermia 1,11,12(D). The comparison of the PORP incidence and duration after multiple doses of cisatracurium and rocuronium showed that, at the end of surgery, the PORP incidence is significantly lower with rocuronium (44%) than with cisatracurium (57%). However, the time to achieve a T4/T1 ratio < 0.9 after the last dose of NMB is significantly higher with rocuronium 2(B). The T4/T1 ratio measured 5 minutes after the end of the surgical procedure is significantly higher in the rocuronium group in comparison to cisatracurium, but at the end of 10 minutes there is no further significant difference between the T4/T1 ratio values for the two NMBs 5(A). When long-term NMB is used, the PORP incidence is significantly lower in patients being monitored, while there is no significant difference for those using short and mid-term NMB 13(A). The incidence of PORP upon entering the post-anesthetic care unit (PACU) also shows great variability 4,14-16(B). The relationship between PORP and time in the PACU using mid-term NMB shows that age and T4/T1 ratio < 0.9 are independent variables associated to the length of stay in the PACU, but not to the type of NMB (vecuronium and cisatracurium) 15(B). Recommendation: As PORP can occur after any general anesthesia that used NMB, neuromuscular blockade monitoring is recommended during and after general anesthesia and throughout post-anesthesia recovery.

strength (measured with a dynamometer); maximal inspiratory pressure > 25 cm H2O, and vital capacity > 15 mL.kg-1 - all of them in conscious and cooperative patients 2,6,8(B), 17(D).

Qualitative or subjective tests They consist in visual and/or tactile observation of the response evoked by electrical stimulation of the peripheral motor nerve. The number of responses and fatigue are assessed after TOF, or double burst stimulation (DB) of the ulnar nerve adductor pollicis muscle, or the presence of fatigue after tetanic stimulation (TS) at 50 Hz or 100 Hz, or post-tetanic count (PTC) that consists in the use of a continuous standard single stimulation 1 to 3 seconds after tetanic stimulation, counting the number of muscle contractions 17-19(D).

Quantitative or objective tests These are tests in which a quantitative evaluation of TOF (T4/ T1 ratio) is carried out using as standard the assessment of the ulnar nerve adductor pollicis muscle through acceleromyography, electromyography, kinemyography, phonomyography and mechanomyography. The TOF and PTC monitoring allows the classification of neuromuscular blockade according to its depth: intense blockade is the period with no response of PTC (PTC = 0) and T4/T1 (0); deep blockade is the period with PTC 1 and no response of the T4/T1 ratio (0); and moderate blockade occurs when the T4/T1 ratio is between T1 and T3. From T4 return to the normal pattern of T4/T1 ratio (> 0.9), the period is called recovery (Chart 1) 20(D). Recommendation: Quantitative analysis is always better than the qualitative one for the PORP diagnosis.

What is the validity and correlation between the different PORP diagnostic tests? Diagnostic tests What are the diagnostic tests of Postoperative Residual Paralysis? The diagnostic tests are clinical, qualitative and quantitative. Clinical tests have shown the following values of sensitivity, specificity, positive and negative predictive values 19(D):

Capacity to keep the head up for 5 seconds: 0.19;

0.88; 0.51; 0.64;

Clinical tests Several clinical tests have been recommended to assess the reversal of neuromuscular blockade, such as: capacity to hold up the head for 5 seconds or to elevate an arm or a leg; eye opening when requested; protrusion or capacity to remove the tongue when held manually; maintenance of hand grip
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Capacity to hold up the arm or the leg for 5 seconds: 0.25; 0.84; 0.50; 0.64; Protrusion or capacity to remove the tongue: 0.22;
0.88; 0.52; 0.64; Maintenance of hand grip strength: 0.18; 0.89; 0.51; 0.63.

None of the available clinical trials showed a positive correlation with the T4/T1 0.9, or ruled out the possibility of PORP 7,8,19(B) 21(C).
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Chart 1 Levels of Neuromuscular Blockade After Administration of Non-Depolarizing NMB at a Single Intubation Dose 20(D).
NMB: neuromuscular blockade, TOF: T4/T1 ratio; PTC: post-tetanic counting

NMB injection

Neuromuscular blockade Start

Intense Blockade TOF = 0; PTC = 0

Deep Blockade TOF = 0; PTC 1

Moderate blockade TOF = T1 to T3

T4 Onset Recovery

Qualitative tests were not superior to clinical trials 19(D), and the use of DB did not eliminate the possibility of PC 19(D), 23(B). There is no significant correlation between subjective and objective evaluation of the evoked response, considering T4/ T1 0.9 as the standard for PORP absence 24(B), 25(C). There is no consensus that quantitative tests of neuromuscular function are superior to qualitative ones. Regarding neuromuscular monitoring and PORP, there is also no consensus that the use of quantitative tests of neuromuscular function promote a reduction in PORP incidence 9,13(A), 17(D). Regarding the clinical and scientific use of acceleromyography compared to signals and/or symptoms of PORP and to pulmonary function, clinical or qualitative tests of neuromuscular function, one can concluded that accelerometry is the best test to diagnose PORP (Table I) 26(B) and intraoperative monitoring with acceleromyography improves PORP detection, being as sensitive as mechanomyography. There is not sufficient evidence that when accelerometry is used uncorrected (without normalization), the value of the T4/T1 ratio should be increased above 0.9 to exclude clinically significant PORP 9(A).
22(A)

PORP Complications PORP can lead to several complications. There is association between T4/T1 ratio < 0.9 and the following complications: Impaired coordination between the lower pharyngeal constrictor muscle contraction and relaxation of the upper esophageal sphincter; difficulty in swallowing and delay on the start of swallowing reflex 27,28(B); decreased tonus of the upper esophageal sphincter 27,28(B); and increased risk of passive regurgitation 27,29(B); Decreased volume of the upper airways; muscle dilating function impairment of the upper airways; decreased retropalatal and retroglossal inspiratory volume of upper airways; attenuation of the normal increase of posterior airway diameter during forced inspiration; and decreased activity of the genioglossus muscle during maximum voluntary tongue protrusion 30(B); Decreased ventilator response to hypoxia in hypocapnia 31-33(B); Decrease in forced inspiratory volume in one second and of the inspiratory flow, upper airway obstruction, and incapacity to keep the patent airways 28(B); muscle weakness symptoms such as diplopia, difficulty to speak and drink, facial muscle weakness, incapacity to hold up the head for 5 seconds and generalized weakness 2(B); At the end of the anesthesia, either at the PACU or the Intensive Care Unit (ICU), it is known that: There is increased risk of postoperative hypoxemia 3(A), 34(B); There is an incidence increase of upper airway obstruction during transportation to PACU 35(B); There are symptoms and signs of deep muscle weakness 3(A); There is an incidence increase of critical respiratory events in the PACU 34,35(B);
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Recommendation: Acceleromyography is recommended for monitoring the NMB degree in intraoperative and post-anesthetic periods.

Table I Comparison of Sensitivity, Specificity, Positive and Negative Predictive Value of Tests with Double Burst Stimulation of the Adductor Pollicis Muscle of the Ulnar Nerve, Tetanic stimulation at 100 Hz and Acceleromyography to Detect Postoperative Residual Paralysis 26(B) DB Sensitivity Specificity NPV PPV 29 (13-45) 100 (100-100) 29 (13-45) 100 (100-100) Acceleromyography TS 70 (54-86) 88 (67-100) 47 (23-71) 95 (86-100) 74 (59-89) 54 (23-88) 38 (12- 64) 85 (72-99)

Values shown in percentage and 95% confidence interval. DB: double burst stimulation; TS: tetanic stimulation with 100 Hz; NPV: Negative Predictive Value; PPV: Positive Predictive Value.

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There is delay in PACU discharge 3(B); There is an increase in ventilator weaning and intubation time in patients undergoing cardiac surgical procedures 36 (A); There is an increased incidence of postoperative pulmonary complications (atelectasis and pneumonia) 10(B).

PORP prevention How can PORP be prevented? The prevention of PORP is based on the complete reversal of the nondepolarizing NMB effects. It can be attained by waiting for the spontaneous termination of NMB effect, which is not predictable 6(B) or by pharmacological reversal, ensuring the safety of the effect end 11,37(D). The quantitative monitoring of neuromuscular blockade is the only sure way to evaluate its complete reversal 28,38,39(B). Reversal may be accomplished through the use of anticholinesterase agents (ACAs), or a specific reversal agent for vecuronium and rocuronium 11,37(D). The ACAs used in anesthesia are neostigmine and edrophonium, administered intravenously at doses of 0.04 mg.kg-1 and 1.0 mg.kg-1, with peak action occurring at 7-11 minutes and 1-2 minutes, respectively 11,37(D). Both have very variable latency to complete reversal of neuromuscular blockade 11,37(D), reaching up to 80 minutes 37(D), depending on the blockade degree. ACAs have several limitations: they depend on the degree of neuromuscular blockade 40(B); they have adverse effects on different organs and systems due to the antimuscarinic action; they have a ceiling effect 41(D); they can lead to unpredictable reversal of neuromuscular blockade when used in patients with other comorbidities, or in situations such as hypothermia, or when using certain drugs such as calcium-channel blockers, aminoglycosides and magnesium sulphate 37(D); and they can promote blockade by desensitization, with increased muscle weakness when used at high doses, or when used after complete recovery of neuromuscular blockade or without previous use of NMB 43(C), 42,44(D). They can also decrease the activity of the upper airway dilating muscles, if used after recovery of neuromuscular blockade induced by rocuronium 45(B). When administered, ACAs should be associated with anticholinergic agents to reduce secondary muscarinic effects, with atropine being the most frequently used 37(D), 40(B). The uncertainty regarding anticholinesterase drugs effectiveness in the neuromuscular blockade reversal, in addition to the incidence of their adverse effects has resulted in the use of sugammadex 37(D). Due to its selectivity, sugammadex reverses the neuromuscular block induced by vecuronium and rocuronium and does not inhibit the effects of NMB belonging to the class of benzylisoquinoline alkaloids 46(A), 47,48(B), 49(A). The sugammadex-rocuronium complex is eliminated by the kidney 50(B). However, the comparative use between patients with chronic renal failure and with normal renal function,
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associated with rocuronium, shows that the time to reach T4/ T1 of 0.9 is similar in both groups and there is absence of recurarization or of adverse effects 50(B). Sugammadex has a higher reversal rate of rocuroniuminduced neuromuscular blockade when compared with neostigmine in situations of moderate or deep blockade 51-54,56(A) 55(B). The same situation occurs in the reversal of neuromuscular blockade induced by vecuronium 57(A). After rocuronium or vecuronium use, sugammadex at a dose of 2 mg.kg-1 completely reverses (T4/T1 ratio 0.9) the moderate neuromuscular blockade and at a dose of 4 mg.kg-1 it reverses deep neuromuscular blockade 58(A), 59,60(B). The use of sugammadex at doses < 2 mg.kg-1 is related to transient return of the neuromuscular blockade 61(D). In no ventilation, no intubation situations, which often occur shortly after anesthetic induction and failed tracheal intubation attempt, sugammadex at a dose of 16 mg.kg-1 promotes immediate reversal of the neuromuscular blockade induced by rocuronium at a dose 1.0 to 1.2 mg.kg-1 58(A), 60(B). In this situation, the reversal time of neuromuscular blockade with the association rocuronium 1.2 mg.kg-1 and sugammadex 16 mg.kg-1 (3 minutes after the NMB) is lower than of succinylcholine 1 mg.kg-1 62(A). Sugammadex was successfully used in children between 2 and 11 years old at a dose of 2 mg.kg-1, without adverse events 63(A), as well as in patients with heart disease (coronary ischemic disease, arrhythmia and congestive heart failure) to be submitted to noncardiac procedures 64(A), in patients with history of pulmonary disease 11,37(D), in pregnant women who underwent a C-section 65(C), and in obese patients with body mass index (BMI) > 30 kg.m-2 37(D). In elderly patients (age > 64 years), the use of sugammadex at a dose of 2 mg.kg-1 results in reversion of the neuromuscular blockade within a shorter time than in young adult individuals (difference of 42 seconds) 66,67(B). The sugammadex interaction has been experimentally demonstrated with flucoxacillin, fusidic acid and toremifene, with a delay in the reversal time of neuromuscular blockade. However, the interaction with flucoxacillin has not been proven clinically and no drug has been shown to promote recurarization or reversal of neuromuscular blockade 68(C). Adverse events due to sugammadex use are rare, including nausea, vomiting, headache, neck pain, back pain, coughing, dysgeusia, constipation, and pyrexia, most likely related to drugs used during anesthesia 46 (A). Movements can also be observed before the end of the anesthesia, due to superficial anesthesia 11(D), 49(A). The onset of spontaneous evolution of allergic reaction following the use of sugammadex has been reported in only six patients 37,11(D), 46(A). Recommendation: PORP prevention after nondepolarizing NMB can be attained by using anticholinesterase agents associated with anticholinergics, or sugammadex if vecuronium or rocuronium are administered. Sugammadex is recommended whenever rocuronium or vecuronium is used, as it is the only specific reverser.
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FINAL RECOMMENDATIONS The PORP shows high incidence and may lead to adverse events with increased postoperative morbidity and mortality. Monitoring of the neuromuscular blockade is recommended

by quantitative tests such as acceleromyography. The use of cholinesterase inhibitors for pharmacological reversal of neuromuscular blockade is not free of adverse effects. Therefore, we recommend the use of sugammadex for reversal of neuromuscular blockade induced by rocuronium or vecuronium.

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Rev Bras Anestesiol 2012; 62: 3: 439-450 ARTIGO ESPECIAL

ARTIGO ESPECIAL

Paralisia Residual Ps-Operatria

Ligia Andrade da Silva Telles Mathias 1, Ricardo Caio Gracco de Bernardis 2

Resumo: Mathias LAST, Bernardis RCG Paralisia Residual Ps-Operatria.

2012 Elsevier Editora Ltda. Todos os direitos reservados.

DESCRIO DO MTODO DE COLETA DE EVIDNCIA Foram realizadas mltiplas buscas na base de dados PubMed para identificao de artigos com melhor desenho metodolgico, seguida de avaliao crtica de seu contedo e classificao de acordo com a fora da evidncia. De acordo com as normas do Oxford Centre for Evidence Based Medicine, deu-se preferncia s revises sistemticas da literatura e aos ensaios clnicos randomizados. As buscas foram realizadas entre janeiro de 2009 e julho de 2010. Para as buscas no PubMed, foram utilizadas diferentes combinaes de termos abertos (random*; neuromuscular; postanesthesia; care; residual; paralysis; complications; blockade; curarization) e termos do vocabulrio controlado (Anesthesia, Perioperative Complications [MeSH]; Residual Neuromuscular Blockade [MeSH]; Postanesthesia Care Unit [MeSH]; Monitoring Neuromuscular blockade [MeSH]; e Randomized Controlled Trial, Guidelines, Task force [Publication Type]). Foram selecionados os estudos que avaliaram incidncia, testes diagnsticos, complicaes e preveno da paralisia residual ps-operatria em animais, voluntrios conscientes e pacientes submetidos a procedimentos cirrgicos, sem distino.

OBJETIVO Avaliar incidncia, testes diagnsticos, complicaes e preveno da paralisia residual ps-operatria (PRPO).

INTRODUO Definio Paralisia residual ps-operatria, tambm conhecida como bloqueio neuromuscular residual ps-operatrio, definida como paralisia ou fraqueza muscular ps-operatria decorrente de antagonismo incompleto ou ausente dos bloqueadores neuromusculares (BNM) adespolarizantes 1(D). A relao de T4/T1 de 0,9 foi avaliada pela sequncia de quatro estmulos (SQE) e considerada atualmente padro-ouro de reverso completa do bloqueio neuromuscular 1(D).

Incidncia A PRPO aps o final da anestesia tem sido relatada em vrios estudos, com incidncia variando de 5% a 88%, considerando-se PRPO como a relao T4/T1 < 0,9 2(B), 3(A), 4(B), 5(A).

GRAU DE RECOMENDAO E FORA DE EVIDNCIA A: Estudos experimentais ou observacionais de melhor consistncia; B: Estudos experimentais ou observacionais de menor consistncia; C: Relatos de casos (estudos no controlados); D: Opinio desprovida de avaliao crtica, com base em consensos, estudos fisiolgicos ou modelos animais.

Quais so os fatores que alteram a incidncia de paralisia residual ps-operatria? A grande variabilidade deve-se aos diferentes mtodos utilizados, tais como: utilizao de valor da relao T4/T1 de 0,7; 0,8 ou 0,9 como critrio de PRPO 6,7(B); uso de diferentes BNM de curta, intermediria e longa durao 3(A), 6,7(B); uso de doses nicas, doses repetidas ou infuso contnua de BNM 3(A),6,7,8(B); mtodo de avaliao do BNM residual 1(D), 9(A); reverso ou no do bloqueio neuromuscular ao final da anestesia com anticolinestersicos, com dose e intervalo entre o uso de anticolinestersicos e a avaliao do grau do bloqueio neuromuscular 3(A),4,6-8(B); idade 10(B); presena de disfuno renal, heptica, cardaca ou neuromuscular 11(D); utilizao de frmacos que podem alterar a farmacodinmiRevista Brasileira de Anestesiologia Vol. 62, No 3, Maio-Junho, 2012

Recebido da Sociedade Brasileira de Anestesiologia, Brasil. 1. Doutora, Faculdade de Medicina da Universidade de So Paulo (FM-USP); Professora Adjunta, Responsvel, Disciplina de Anestesia, Faculdade Cincias Mdicas da Santa Casa de So Paulo (FCMSCSP) 2. Doutor, Cirurgia, FCMSCSP; Diretor Mdico, Centro Cirrgico, Irmandade da Santa Casa de Misericrdia de So Paulo Correspondncia para: Sociedade Brasileira de Anestesiologia Rua Professor Alfredo Gomes, 36 Botafogo 22251080 Rio de Janeiro, RJ, Brasil E-mail: rba@sba.com.br

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ca e/ou farmacocintica dos BNM (bloqueadores de canal de clcio, magnsio, ltio, antibiticos, anestsicos locais, anestsicos inalatrios, opioides, benzodiazepnicos) 11(D); e alteraes eletrolticas, acidose metablica ou respiratria e hipotermia 1,11,12(D). A comparao de incidncia e durao da PRPO aps administrao de doses mltiplas de cisatracrio e rocurnio constatou que ao final do procedimento cirrgico, a incidncia de PRPO significativamente menor com rocurnio (44%) do que com cisatracrio (57%), mas o tempo para atingir relao T4/T1 < 0,9 aps a ltima dose do BNM significativamente maior para o rocurnio 2(B). A relao T4/T1 avaliada 5 minutos aps o final do procedimento cirrgico significativamente maior no grupo rocurnio comparado ao grupo cisatracrio, mas ao final de 10 minutos j no h mais diferena significativa entre os valores de relao T4/T1 para os dois BNM 5(A). Quando utilizados os BNM de longa durao, a incidncia de PRPO significativamente menor em pacientes sob monitorao, enquanto entre os BNM de durao curta e intermediria no h diferena significativa 13(A). A incidncia de PRPO na entrada da sala de recuperao ps-anestsica (SRPA) apresenta tambm grande variabilidade 4,14-16(B). A relao entre PRPO e o tempo de permanncia na SRPA, utilizando BNM de durao intermediria evidencia que idade e relao T4/T1 < 0,9 so variveis independentes associadas ao tempo de permanncia na SRPA, e no ao tipo de BNM (vecurnio e cisatracrio) 15(B). Recomendao: Como a PRPO pode ocorrer aps qualquer anestesia geral em que foi utilizado BNM, recomenda-se a monitorao do bloqueio neuromuscular durante e aps toda anestesia geral e na recuperao ps-anestsica.

Testes qualitativos ou subjetivos Constituem na observao visual e/ou ttil da resposta evocada estimulao eltrica do nervo motor perifrico. So avaliados o nmero de respostas e fadiga aps SQE, ou estimulao com double burst (DB) do msculo adductor pollicis do nervo ulnar, ou presena de fadiga aps estimulao tetnica (ET) com 50 Hz ou 100 Hz, ou contagem ps-tetnica (CPT) que consiste na aplicao de estmulo simples padronizado contnuo, 1 a 3 segundos aps a estimulao tetnica, contando-se o nmero de contraes musculares 17-19(D).

Testes quantitativos ou objetivos So testes em que se realiza avaliao quantitativa da SQE (relao T4/T1), utilizando-se como padro a avaliao do msculo adductor pollicis do nervo ulnar, por meio da aceleromiografia, eletromiografia, cinemiografia, fonomiografia e mecanomiografia. A monitorao com a SQE e a CPT permite a classificao do bloqueio neuromuscular de acordo com a sua profundidade: bloqueio intenso o perodo em que no h resposta da CPT (CPT = 0) e da relao T4/T1(0); bloqueio profundo o perodo em que a resposta da CPT maior ou igual a 1 (CPT 1) e no h resposta da relao T4/T1(0); e bloqueio moderado ocorre quando a relao T4/T1 situa-se entre T1 e T3. A partir da volta de T4 at o padro normal da relao T4/T1 (> 0,9), o perodo denominado de recuperao (Quadro 1) 20(D). Recomendao: A avaliao quantitativa sempre superior qualitativa para o diagnstico de PRPO.

Testes diagnsticos Quais so os testes diagnsticos de Paralisia Residual Ps-Operatria? Os testes diagnsticos so os clnicos, qualitativos e quantitativos.

Qual a validade e a correlao entre si dos diferentes testes diagnsticos de PRPO? Os testes clnicos mostraram os seguintes valores de sensibilidade, especificidade, e valores preditivos positivo e negativo 19(D): Capacidade de manter a cabea erguida por 5 segundos: 0,19; 0,88; 0,51; 0,64; Capacidade de manter o brao ou a perna elevados por 5 segundos: 0,25; 0,84; 0,50; 0,64; Protruso ou capacidade de retirar a lngua: 0,22; 0,88; 0,52; 0,64; Manuteno da contrao muscular da mo: 0,18; 0,89; 0,51; 0,63.

Testes clnicos Vrios testes clnicos foram preconizados para avaliar a reverso do bloqueio neuromuscular todos em pacientes conscientes e cooperativos 2,6,8(B), 17(D) , tais como: capacidade de manter por 5 segundos a cabea erguida, um brao ou uma perna elevados; abertura dos olhos sob comando; protruso ou capacidade de retirar a lngua quando aprendida manualmente; manuteno da contrao muscular da mo (aferida com dinammetro); presso inspiratria mxima maior que 25 cm H2O; e capacidade vital maior que 15 mL.kg-1.
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Nenhum dos testes clnicos disponveis apresentam correlao positiva com a relao T4/T1 0,9, ou exclui a possibilidade de PRPO 7,8,19(B), 21(C). Os testes qualitativos no se mostraram superiores aos testes clnicos 19(D),22(A) e o uso do DB no eliminou a possibilidade de PC 19(D), 23(B).
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Quadro I Nveis de Bloqueio Neuromuscular aps Administrao de BNM. No Despolarizante em Dose nica de Intubao20(D). BNM: bloqueio neuromuscular, SQE: relao T4/T1; CPT: contagem ps-tetnica.

Injeo do BNM

Incio do bloqueio Neuromuscular

Bloqueio Intenso SQE = 0; CPT = 0

Bloqueio Profundo SQE = 0; CPT 1

Bloqueio moderado SQE = T1 a T3

Recuperao aparecimento de T4

No h correlao significativa entre avaliao subjetiva e objetiva da resposta evocada, considerando a relao T4/ T1 0,9 como padro de ausncia de PRPO 24(B),25(C). No h consenso de que os testes quantitativos da funo neuromuscular sejam superiores aos testes qualitativos. Sobre monitorao neuromuscular e PRPO, tambm no h consenso de que o uso de testes quantitativos da funo neuromuscular promovam reduo da incidncia de PRPO 9,13(A), 17(D). Sobre uso clnico e cientfico da aceleromiografia, comparado a sinais e/ou sintomas de PRPO e aos testes de funo pulmonar, clnicos ou qualitativos da funo neuromuscular, conclui-se que a aceleromiografia o melhor teste para o diagnstico de PRPO (Tabela I) 26(B) e que a monitorao intraoperatria com a aceleromiografia aumenta a deteco de PRPO, sendo to sensvel quanto a mecanomiografia nesse sentido. No existem evidncias suficientes de que quando utilizada aceleromiografia no corrigida (sem normalizao), o valor da relao T4/T1 deva ser aumentado acima de 0,9 para excluso de PRPO clinicamente significante 9(A). Recomendao: Recomenda-se a utilizao da aceleromiografia para monitorao do grau de bloqueio neuromuscular nos perodos intraoperatrio e ps-anestsico.

Tabela I Comparao de Sensibilidade, Especificidade, Valor Preditivo Positivo e Negativo dos Testes de Estimulao com Double Burst do Msculo Adductor Pollicis do Nervo Ulnar, Estimulao Tetnica com 100 Hz e Aceleromiografia para Detectar Paralisia Residual PO 26(B) DB Sensibilidade Especificidade VPN VPP 29 (13-45) 100 (100-100) 29 (13-45) 100 (100-100) Aceleromiografia ET 70 (54-86) 88 (67-100) 47 (23-71) 95 (86-100) 74 (59-89) 54 (23-88) 38 (12- 64) 85 (72-99)

Valores apresentados em porcentagem e intervalo de confiana de 95%. DB: estimulao com double burst; ET: estimulao tetnica com 100 Hz; VPN: Valor Preditivo Negativo; VPP: Valor Preditivo Positivo.

Complicaes da PRPO A PRPO pode levar a diferentes complicaes. H associao entre a relao T4/T1 < 0,9 e as seguintes complicaes: Prejuzo da coordenao entre a contrao do msculo constritor farngeo inferior e o relaxamento do esfncter esofgico superior; dificuldade de deglutio e retardo do incio do reflexo de deglutio 27,28(B); reduo do tnus do esfncter esofgico superior 27,28(B); e risco aumentado de regurgitao passiva 27,29(B); Reduo dos volumes das vias areas superiores; prejuzo da funo dilatadora muscular das vias a

reas superiores; diminuio do volume inspiratrio retropalatal e retroglossal das vias areas superiores; atenuao do aumento normal do dimetro das vias areas posteriores durante a inspirao forada; e reduo da atividade do msculo genioglosso durante protruso mxima voluntria da lngua 30(B); Reduo da resposta ventilatria hipoxia em hipocapnia 31-33(B); Diminuio do volume inspiratrio forado em 1 segundo, diminuio do fluxo inspiratrio, obstruo das vias areas superiores e inabilidade de manter as vias areas patentes 28(B); Sintomas de fraqueza muscular como diplopia, dificuldade de falar e beber, fraqueza muscular facial, incapacidade de manter por 5 segundos a cabea erguida e fraqueza generalizada 2(B);

Ao final da anestesia, seja na SRPA ou na unidade de terapia intensiva (UTI), sabe-se que: H risco aumentado de hipoxemia ps-operatria 3(A),34(B); H aumento da incidncia de obstruo das vias areas superiores durante o transporte para SRPA 35(B);
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H sintomas e sinais de fraqueza muscular profunda 3(A); H aumento da incidncia de eventos respiratrios crticos na SRPA 34,35(B); H retardo na alta da sala SRPA 3(B); H aumento do tempo de desmame do ventilador e do tempo de intubao em pacientes submetidos a procedimentos cirrgicos cardacos 36(A); H aumento da incidncia de complicaes pulmonares ps-operatrias (atelectasia e pneumonia) 10(B).

Preveno da PRPO Como pode ser realizada a preveno da PRPO? A preveno da PRPO tem como base a completa reverso dos efeitos dos BNM adespolarizantes. Isto pode ser alcanado aguardando o trmino espontneo do efeito do BNM, que no previsvel 6(B) ou por meio da reverso farmacolgica dos mesmos, garantindo a segurana do trmino da ao 11,37(D). A monitorao quantitativa do bloqueio neuromuscular o nico meio seguro de avaliar a reverso completa do mesmo 28,38,39(B). A reverso pode ser obtida por meio do uso de agentes anticolinestersicos (ACE), ou de agente reversor especfico do rocurnio e vecurnio 11,37(D). Em anestesia, os ACE utilizados so a neostigmina e o edrofnio, administrados por via venosa, nas doses de 0,04 mg.kg-1 e 1,0 mg.kg-1, com pico de ao de 7 a 11 minutos e de 1 a 2 minutos respectivamente 11,37(D). Ambos apresentam latncia para reverso completa do bloqueio neuromuscular muito varivel 11,37(D), podendo chegar a 80 minutos 37(D), dependendo do grau de bloqueio. Os ACE possuem vrias limitaes: dependem do grau de bloqueio neuromuscular 40(B); tm efeitos adversos em diferentes sistemas e rgos devido ao antimuscarnica; apresentam efeito teto 41(D); podem levar reverso no previsvel do bloqueio neuromuscular quando utilizados em pacientes com outras comorbidades ou em situaes como hipotermia, ou ainda em uso de determinados frmacos como bloqueadores do canal de clcio, aminoglicosdeos e sulfato de magnsio 37(D); e podem promover bloqueio por dessensibilizao, com aumento da fraqueza muscular quando empregados em altas doses, ou quando usados aps recuperao completa do bloqueio neuromuscular ou sem uso prvio de BNM 43(C),42,44(D). Podem tambm diminuir a atividade da musculatura dilatadora das vias areas superiores, se utilizados aps recuperao do bloqueio neuromuscular induzido pelo rocurnio 45(B). Em sua administrao, os ACE devem ser associados a anticolinrgicos para reduzir os efeitos secundrios muscarnicos, sendo a atropina o mais frequentemente utilizado 37(D),40(B). A insegurana quanto eficcia dos anticolinestersicos na reverso do bloqueio neuromuscular, aliada incidncia de efeitos adversos com o uso dos mesmos, tem levado ao uso do sugamadex 37(D). Devido sua seletividade, o sugamadex reverte o bloqueio neuromuscular induzido pelo roRevista Brasileira de Anestesiologia Vol. 62, No 3, Maio-Junho, 2012

curnio e vecurnio e no inibe os efeitos dos BNM da classe dos benzilisoquinolenicos 46(A),47,48(B),49(A). O complexo sugamadex-rocurnio eliminado por via renal 50(B), no entanto, o uso comparativo entre pacientes com insuficincia renal crnica e com funo renal normal, associado ao rocurnio, demonstra que o tempo para atingir relao T4/T1 de 0,9 similar em ambos os grupos e h ausncia de recurarizao ou de efeitos adversos 50(B). O sugamadex apresenta maior velocidade de reverso do bloqueio neuromuscular induzido pelo rocurnio quando comparado com a neostigmina em situaes de bloqueio moderado ou profundo 51-54,56(A) 55(B). A mesma situao ocorre na reverso do bloqueio neuromuscular induzido pelo vecurnio 57(A). Aps uso de rocurnio ou vecurnio, o sugamadex na dose de 2 mg.kg-1 reverte completamente (relao T4/T1 0,9) o bloqueio neuromuscular moderado e na dose de 4 mg.kg-1 reverte o bloqueio neuromuscular profundo 58(A), 59,60(B). O uso de sugamadex em doses menores que 2 mg.kg-1 est relacionado com retorno transitrio do bloqueio neuromuscular 61(D). Na situao denominada no ventilo, no intubo, que ocorre muitas vezes logo aps a induo anestsica e tentativa frustrada de intubao traqueal, o sugamadex, na dose de 16 mg.kg-1 promove reverso imediata do bloqueio neuromuscular induzido por rocurnio na dose de 1,0 a 1,2 mg.kg-1 58(A), 60(B). Nessa situao, o tempo de reverso do bloqueio neuromuscular da associao rocurnio 1,2 mg.kg-1 e sugamadex 16 mg.kg-1 (3 minutos aps o BNM) menor do que o da succinilcolina 1 mg.kg-1 62(A). O sugamadex foi usado com sucesso em crianas entre 2 e 11 anos na dose de 2 mg.kg-1, sem eventos adversos 63(A), assim como em pacientes portadores de doenas cardacas (doena isqumica coronariana, arritmia e insuficincia cardaca congestiva) a serem submetidos a procedimentos no cardacos 64(A), em pacientes com histria de doena pulmonar 11,37(D), em gestantes submetidas a cesrea 65(C), e em obesos com ndice de massa corporal (IMC) > 30 kg.m-2 37(D). Em pacientes idosos (idade > 64 anos), o uso de sugamadex na dose de 2 mg.kg-1 produz reverso do bloqueio neuromuscular em um tempo maior do que em adultos jovens (diferena de 42 segundos) 66,67(B). A interao do sugamadex foi demonstrada experimentalmente com flucoxacilina, cido fusdico e toremifeno, com retardo do tempo de reverso do bloqueio neuromuscular. No entanto, a interao com flucoxacilina no foi comprovada clinicamente e no foi evidenciado nenhum frmaco que promova recurarizao ou volta do bloqueio neuromuscular 68(C). Os eventos adversos por uso de sugamadex so raros, entre eles, nuseas, vmitos, cefaleia, dor de garganta, dor nas costas, tosse, disgeusia, constipao e pirexia, mais provavelmente relacionados aos frmacos utilizados durante o ato anestsico 46(A). Podem tambm ser observados movimentos antes do final da anestesia, devidos anestesia superficial 11(D), 49(A). O aparecimento de reao alrgica de evoluo espontnea, aps o uso de sugamadex foi relatado em apenas seis pacientes 37,11(D),46(A).
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Recomendao: A preveno da PRPO aps uso de BNM adespolarizantes pode ser feita com o uso de anticolinestersicos associados aos anticolinrgicos ou, no caso do uso do rocurnio ou vecurnio, utilizando-se o sugamadex. Recomenda-se o uso do sugamadex sempre que o BNM for o rocurnio ou vecurnio, por ser o nico reversor especfico.

RECOMENDAES FINAIS A PRPO apresenta incidncia elevada e pode levar a eventos adversos, com aumento da morbimortalidade ps-operatria. Recomenda-se a monitorao do bloqueio neuromuscular por meio de testes quantitativos como aceleromiografia. O uso de anticolinestersicos para reverso farmacolgica do bloqueio neuromuscular no isento de efeitos adversos. Sendo assim, recomenda-se o uso do sugamadex na reverso do bloqueio neuromuscular induzido pelo rocurnio ou vecurnio.

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Resumen: Mathias LAST, Bernardis RCG Parlisis Residual Postoperatoria.

DESCRIPCIN DEL MTODO DE RECOLECCIN DE LA EVIDENCIA Se realizaron mltiples bsquedas en el banco de datos PubMed para la identificacin de los artculos con un mejor formato metodolgico, seguidas de una evaluacin crtica de su contenido y clasificacin de acuerdo con la fuerza de la evidencia. De acuerdo con las normas del Oxford Centre for
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MATHIAS, BERNARDIS

Evidence Based Medicine, se le dio preferencia a las revisiones sistemticas de la literatura y a los ensayos clnicos randomizados. Las bsquedas se hicieron entre enero de 2009 y julio de 2010. Para las bsquedas en el PubMed, se usaron diferentes combinaciones de trminos abiertos (random*; neuromuscular; postanesthesia; care; residual; paralysis; complications; blockade; curarization) y de trminos del vocabulario controlado (Anesthesia, Perioperative Complications [MeSH]; Residual Neuromuscular Blockade [MeSH]; Postanesthesia Care Unit [MeSH]; Monitoring Neuromuscular blockade [MeSH]; y Randomized Controlled Trial, Guidelines, Task force [Publication Type]). Se seleccionaron los estudios que evaluaron la incidencia, los test de diagnstico, las complicaciones y la prevencin de la parlisis residual postoperatoria en animales, en voluntarios conscientes y en los pacientes sometidos a procedimientos quirrgicos, sin distincin.

GRADO DE RECOMENDACIN Y FUERZA DE LA EVIDENCIA A: Estudios experimentales u observacionales de mejor consistencia; B: Estudios experimentales u observacionales de menor consistencia; C: Relatos de casos (estudios no controlados); D: Opinin que no tiene evaluacin crtica, con base en los consensos, en los estudios fisiolgicos o en los modelos animales.

OBJETIVO Evaluar la incidencia, los test de diagnstico, las complicaciones y la prevencin de la parlisis residual postoperatoria (PRPO).

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Revista Brasileira de Anestesiologia Vol. 62, No 3, Maio-Junho, 2012