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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094On-line version ISSN 1806-907X

Rev. Bras. Anestesiol. vol.54 no.4 Campinas July/Aug. 2004 



Rapid sequence induction of anesthesia*


Inducción anestésica con la técnica de secuencia rápida



Eduardo Toshiyuki Moro, TSA, M.D.I; Norma Sueli Pinheiro Módolo, TSA, M.D.II

IAnestesiologista dos Hospitais da UNIMED e Santa Lucinda, da Cidade de Sorocaba, SP; Instrutor do CET do Conjunto Hospitalar de Sorocaba, PUC/SP e Aluno do Programa de Pós-Graduação em Anestesiologia da FMB - UNESP, nível de Mestrado
IIProfessora Adjunta Livre-Docente do Departamento de Anestesiologia da FMB - UNESP





BACKGROUND AND OBJECTIVES: Rapid sequence induction anesthesia is primarily used to protect airways when there is gastric content aspiration risk. This study aimed at reviewing the technique and different protocols looking for the rational use of available drugs, in the search for ideal tracheal intubation conditions without increasing the risk of gastric content aspiration or other complications.
CONTENTS: A technical review of rapid sequence induction of anesthesia is presented, emphasizing the rational use of hypnotics, opioids and neuromuscular blockers (NMB) to shorten the period between loss of consciousness and correct tracheal tube positioning, that is, shorten the period of highest risk for aspiration while maintaining excellent intubation conditions.
CONCLUSIONS: Tracheal intubation after rapid sequence induction of anesthesia is indicated for patients at risk for gastric content aspiration without suspicion of difficult intubation. The adequate indication of the technique, its judicious application and the rational use of available drugs may promote excellent intubation conditions, with fast onset, early return to consciousness and spontaneous breathing in case of tracheal intubation failure.



JUSTIFICATIVA Y OBJETIVOS: La inducción de la anestesia por medio de la técnica de secuencia rápida es utilizada, principalmente, para proteger las vías aéreas, cuando hay riesgo de aspiración del contenido gástrico. El objetivo de este artículo es revisar a técnica y los diferentes protocolos que buscan del uso racional de los fármacos disponibles, visando condiciones ideales de intubación traqueal, sin aumentar el riesgo de aspiración del contenido gástrico o de otras complicaciones.
CONTENIDO: Presenta una revisión de la técnica de la inducción con secuencia rápida, enfatizando el uso racional de los hipnóticos, opioides y bloqueadores neuromusculares (BNM), para reducir el período entre la pérdida de la consciencia y el correcto posicionamiento del tubo traqueal, o sea, diminuir el período de mayor riesgo para aspiración y aún mantener excelentes condiciones de intubación traqueal.
CONCLUSIONES: La intubación traqueal después de inducción anestésica por medio de la técnica de secuencia rápida está indicada en aquellos pacientes, con riesgo de aspiración gástrica, en que no hay sospecha de intubación traqueal difícil. La indicación correcta de la técnica, su aplicación criteriosa y la utilización racional de las drogas disponibles pueden promover condiciones excelentes de intubación, con corto período de latencia, rápido retorno de la consciencia y de la respiración espontánea, caso haya falla en la intubación traqueal.




In 1946, Mendelson1 has related food intake to aspiration during labor with general anesthesia under mask.

Rapid sequence induction anesthesia to protect airways from gastric content aspiration in risk patients has evolved since the introduction of succinylcholine 50 years ago and the first description by Sellick2, in 1961, of cricoid cartilage pressure to prevent regurgitation.

This technique has been widely used in emergency procedures and obstetric anesthesia when there is indication for general anesthesia. It has also been used in situations in which, although there is no emergency, there is gastric content aspiration risk, such as in cases of obesity, gastroesophageal reflux or diabetes mellitus. The technique involves previous oxygenation, analgesia, muscle relaxation and cricoid cartilage pressure. Positive pressure ventilation should be avoided until the correct positioning of tracheal tube and cuff in the trachea. So, the interval between consciousness loss and tracheal intubation is the period of highest risk for gastric content aspiration. A major challenge for rapid sequence induction protocols is shortening this risk period while maintaining excellent tracheal intubation conditions3.



Material to be used should be previously checked and tested, including two aspirators, two laryngoscopes, tracheal tubes of different sizes, material for potential difficult intubation, etc.4. At this moment and if available, laryngeal mask or Fast Track may be very useful.

Patients positioning should also be taken into consideration. Patients at risk for pulmonary aspiration should be placed in the horizontal position with the dorsum elevated approximately 30º as compared to the remaining body. If there is vomiting or regurgitation, table position should be promptly changed to a reverse position, with the head below the trunk to prevent vomiting aspiration4.

It is important to remind that preoperative evaluation for difficult airway identification is mandatory. It may be achieved by Mallampati classification5 or parameters proposed by Benumof (Table I)6.

Once difficult intubation is identified, preconized management is oral or nasotracheal tube introduction with the patient awaken, preceded by adequate preparation (conscious sedation, antiansialogogue, topic anesthesia or upper laryngeal and glossopharyngeal lingual branch nerves blockade)7. According to difficult airway algorhythm developed by the American Society of Anesthesiologists, when airway difficulty is only noticed after general anesthetic induction and ventilation under mask is not possible, laryngeal mask or Combitube® should be promptly placed, transtracheal jet ventilation should be started or emergency cricothyroidotomy should be performed. After eliminating the risk for hypoxia, it is possible to awaken the patient, perform tracheostomy or use non conventional intubation techniques, such as fibroscopy through laryngeal mask7.

Sellick in his original work2, recommends that nasogastric tube should be removed before anesthetic induction because it decreases pressure on lower esophageal sphincter. However, two studies in cadavers have shown that the tube acts as a safe path for gastric content when an effective cricoid cartilage pressure is applied8,9. Based on these data, Smith10 has suggested that the tube should be left in situ during rapid sequence induction, provided it is associated to a well-applied Sellick's maneuver.



Cricoid cartilage pressure (Sellick's maneuver)2 for allowing esophageal compression against the vertebral column has become universal practice during anesthetic induction in patients with potentially full stomach11. When adequately performed, this maneuver prevents gastric inflation in children12 and adults13,14, in addition to increasing upper esophageal sphincter tone15. Lower esophageal sphincter tone decreases with such compression16, suggesting the presence of mechanoreceptors in the pharynx which would promote the reflex relaxation of this sphincter. This effect, however, does not seem to trigger gastroesophageal reflux17.

Inadequate Sellick's maneuver may deform cricoid cartilage, close vocal cords and impair ventilation, especially in females18. Strength applied to airway should be enough to prevent aspiration but not so strong to obstruct it or allow for esophageal rupture in case of vomiting. Cephalad and backwards orientation of the applied strength seems to improve structures visualization through laryngoscopy19.

A major scenario to be considered is tracheal intubation failure in patients with full stomach under cricoid cartilage compression. In this case, laryngeal mask may help ventilation and oxygenation; further studies, however, have shown that Sellick's maneuver prevented its adequate positioning20,21. So, to help ventilation, oxygenation or even tracheal intubation via laryngeal mask, it may be necessary to interrupt Sellick's maneuver. This interruption is a reasonable option since cricoid cartilage compression may become ineffective few minutes after its application22.



Ideal tracheal intubation conditions after rapid sequence induction of anesthesia include hypnosis, muscle relaxation and blockade of autonomic response to laryngoscopy, with fast installation and short duration. Bronchospasm, laryngospasm and hemodynamic instability should be avoided3.

Thiopental without opioid or neuromuscular blocker (NMB) was introduced in 1948 as an agent promoting adequate tracheal intubation conditions23. Propofol also suppresses reflex pharyngeal and laryngeal responses, being more effective than thiopental when used for this aim24. However, these techniques (hypnosis without muscle relaxation or autonomic response blockade) may be associated to non-ideal tracheal intubation conditions and undesirable hemodynamic responses in some patients.

A study carried out in the UK in 200025 has shown that almost half the anesthesiologists had experienced at least one tracheal intubation failure after rapid sequence induction and more than ¼ had seen regurgitation. The extent to which the induction technique has contributed to tracheal intubation failure or to protect patients should be better explained by further studies25.

The search for better tracheal intubation conditions after rapid sequence induction has led to the administration of fast onset and short duration opioids, such as alfentanil. In the dose of 30 µ associated to propofol (2.5 it has allowed for better tracheal intubation conditions and cardiovascular response suppression even without neuromuscular blocker26. Preanesthetic medication with benzodiazepine or lidocaine (1 2 minutes before alfentanil and propofol administration has improved tracheal intubation conditions especially due to cough reflex suppression27. Other studies, however, have shown that thiopental associated to alfentanil promotes better intubation conditions as compared to propofol associated to the same drug28.

When succinylcholine (1 was administered associated to alfentanil (10 µ and propofol (2.5, tracheal intubation conditions were almost ideal29.

A limiting factor for propofol, especially in hypovolemic, elderly or with cardiovascular disease patients is the possibility of hypotension30,31. This can also be observed with propofol, however not so intense28. So, some alternatives have been proposed to decrease propofol-induced hemodynamic effects. Vuyk et al. have shown decreased propofol dose when alfentanil was associated in progressive doses32. However, 50 µ or more of this opioid associated to propofol (2 has resulted in 30% blood pressure decrease33.

Synergism with midazolam has also been proposed34, which would allow for decreased propofol doses thus attenuating hemodynamic effects. In the dose of 0.05, midazolam prolongs recovery time35, which however seems not to be true after 0.03 36.

Gamlin et al. have shown that 15 to 20 mg ephedrine for every 200 mg propofol during anesthetic induction would effectively attenuate blood pressure changes without hypertension or tachycardia37.

Etomidate (0.3 associated to alfentanil (40 µ provides tracheal intubation conditions similar to propofol but with less blood pressure changes. Tracheal intubation however may only be performed 90 seconds after etomidate injection, which is a period too long for rapid sequence induction as compared to thiopental or propofol3.

Agents such as midazolam are not a good choice as single hypnotic for rapid sequence induction since their onset is too long38. Conversely, 1.5 ketamine seems to be a good alternative39 mainly in patients with hemodynamic instability and without intracranial hypertension, although undesirable effects such as illusions, sleep disorders and delirium are not uncommon40.

Remifentanil has allowed for major advances in rapid sequence induction protocols. This is a new opioid with fast onset, ultra-short half life and, as opposed to alfentanil, its duration is poorly affected by the dose. Remifentanil injection, for its unique pharmacokinetic properties, may promote deep analgesia without prolonged respiratory depression or loss of consciousness. Maximum peak in the action site may be reached in 1 to 2 minutes after bolus administration41,42. The metabolic process through blood and tissue esterases allows for its fast excretion and return to spontaneous ventilation43.

Potential side effects associated to remifentanil include chest stiffness, respiratory depression or loss of consciousness44. Jhaveri et al.45 have studied the effects of different remifentanil doses in loss of consciousness and chest stiffness and have not found loss of consciousness with doses below 5 µ No patient has developed severe chest stiffness but mild to moderate chest stiffness has been frequent. However, Streisand et al.46 have shown in volunteers that after chest stiffness developed by high fentanyl doses, there has been no need for neuromuscular blockers to adequately ventilate patients.

In a comparative study between remifentanil (3 to 4 µ and alfentanil (30 µ associated to propofol (2.5 without neuromuscular blockers, the frequency of excellent tracheal intubation conditions was significantly higher in patients receiving remifentanil, although in this group many patients had some type of movement47.

Tracheal intubation without neuromuscular blocker is possible, especially with the association of remifentanil to propofol48,49 or thiopental50. However, Dumus et al.49, in 2003, have found acceptable intubation conditions after propofol (2 and remifentanil (0.5 µ in just 20% of patients. When remifentanil dose was increased to 2.5 µ there has been acceptable conditions in 75% of patients. Increasing opioid dose to 3 to 4 µ has provided better intubation conditions, but has also increased the incidence of undesirable hemodynamic changes such as hypotension and bradycardia49. So, rapid sequence induction without neuromuscular blocker should be indicated for those cases where succinylcholine or non-depolarizing neuromuscular blockers are counterindicated50. It is important to stress that inadequate intubation conditions predispose to airway trauma, intubation failure and difficult ventilation48.



In 2001, Morris et al.25 have carried out a survey among UK anesthesiologists and have observed that 99% of them used succinylcholine for rapid sequence induction. In 66% of cases, this was used as single neuromuscular blocker and in 30% it was associated to rocuronium.

Succinylcholine was introduced in the clinical practice in 1951 and is still being used, in spite of its several side effects51. Its popularity comes from its fast onset around 30 and 60 seconds and its ultra-short duration (less than 10 minutes)52. The incidence of severe complications, such as malignant hyperthermia, fatal hyperkalemia, bradyarrhythmias, and increased intragastric and intraocular pressure has led to the search for non depolarizing agents without such undesirable effects but with similar onset and duration.

Two neuromuscular blockers were then introduced in the market - rapacuronium and rocuronium. The former is an aminosteroid non depolarizing neuromuscular blocker (not introduced in Brazil), with fast onset and short duration53,54. Unfortunately, the high incidence of severe complications, such as bronchospasm55,56 and the presence of active metabolites during continuous infusion54, has led the manufacturer to interrupt its commercialization.

Rocuronium, an aminosteroid neuromuscular blocker of intermediary action is becoming popular for patients with full stomach due to fast vocal cords blockade and relative cardiovascular stability51,57,58. When fast onset and tracheal intubation conditions similar to those obtained with succinylcholine are desired, 1 mg rocuronium or more should be used59-63. However, these doses imply longer duration, thus being not recommended for short procedures63 or imposing higher risk for patients with potential difficult intubation in cases of tracheal intubation failure57.

Succinylcholine (1 or rocuronium in doses above 0.6 allow for lower opioid dose during rapid sequence induction3,64. So, patients under induction, without neuromuscular blocker would receive 30 to 40 µ alfentanil or 4 µ remifentanil. With the use of the above-mentioned neuromuscular blockers, doses would be decreased to 10 to 20 µ and 1 µ, respectively3.



Alternative techniques have been used aiming at accelerating non depolarizing neuromuscular blockers onset. Among them, there is the administration of fractional doses of such drugs, that is, a low neuromuscular blocker dose some minutes before its or other neuromuscular blocker paralyzing dose65. This technique was called priming by Foldes66, and the semi-paralyzing dose was called priming dose. Although ineffective to induce neuromuscular block, this first dose would occupy a considerable number of postsynaptic receptors, allowing for the faster onset of the second neuromuscular blocker dose. This technique, however, is not risk-free and has as undesirable effects muscle weakness (ptosis, diplopia, swallowing difficulty), hypoventilation, decreased coughing capacity, decreased pulmonary volume and potential for oxygenation deterioration, among others. There may be pharyngeal muscles relaxation, thus a higher risk for gastric regurgitation67-73. There is no consensus to date about the amount of the priming dose. While some authors65,74,75 recommend 20% to 30% DE95, others76,77 emphasize that it should not go beyond 10% DE95. In addition, the interval between priming and intubation dose varies among different neuromuscular blockers76,78. For cisatracurium and rocuronium, intervals proposed by Kopman et al.76 are 6 and 3 minutes, respectively. Although Naguib79 has observed 20% decrease in rocuronium's onset time with priming dose (20% of DE95), as compared to bolus injection, other authors65,80-84 have not observed this same decrease. The difference of results in these studies could be attributed to methodological differences involving priming doses, the interval between them and the second drug dose65. So, priming dose is not recommended for rocuronium since the risks involved with its use during rapid sequence induction overcome the advantages57.

Tan et al.85 have studied tracheal intubation conditions after the association of propofol (2.5 and ephedrine (15 mg) as compared to propofol (2.5 without ephedrine, followed by rocuronium (0.6 Tracheal intubation was performed 1 minute after and they have observed a significant higher number of excellent tracheal intubation conditions in the propofol-ephedrine group (84%) as compared to the propofol group (32%). In addition, blood pressure was maintained close to pre-induction values in the ephedrine group. According to the author, this association allows for fast onset without high rocuronium doses (0.9 to 1.2

A study by Naguib86 has shown synergism in the association of rocuronium and mivacurium. The group receiving 0.3 mg (1 x DE95) rocuronium and 0.075 mg (1 x DE95) mivacurium had a faster onset as compared to the group receiving a single rocuronium dose (0.6 In fact, according to Fletcher87, this synergism reaches its peak with the use of 1 x DE95 of each drug. So, the association of these two neuromuscular blockers seems to be an alternative for the use of high rocuronium doses during rapid sequence induction when fast onset and short duration is desired. The mechanism involved in this result would be an initial pre-synaptic action especially involving rocuronium, resulting in the synergism between it and mivacurium88-90. However, according to Lien91, in spite of studies carried out to characterize the exact nature of such interactions, other factors make duration of action after the association of neuromuscular blockers unpredictable.

New drugs are being studied, still in phase II, that is animal research. They seem to be promising in terms of replacing succinylcholine and to fast antagonize neuromuscular block with high rocuronium doses51,92. TAAC 3 is an esther di-propinyl derived, made up of 3 isomers, which, in lab animals, has shown similar onset and shorter recovery time as compared to succinylcholine93. Org 25.969 is a cyclodextrine and, in Rhesus monkeys, has promoted immediate motor block reversion by a mechanism implying the formation of molecular complexes with steroid neuromuscular blockers. So, it may be administered for deep muscle relaxation with fast recovery, to prevent residual curarization or muscarinic or nicotinic effects secondary to atropine or neostigmine administration, in addition to provide good hemodynamic stability94,96.



Tracheal intubation after rapid sequence induction of anesthesia is indicated for patients at risk for gastric aspiration without suspicion of difficult intubations.

Preparing the material in advance, positioning the patient and adequately applying Sellick's maneuver are part of the technique.

Rational use of available drugs should provide excellent tracheal intubation conditions, promote fast onset and return to consciousness and spontaneous ventilation in case of intubation failure. The choice of the hypnotic should be based on its pharmacokinetic profile, on patient's physical status, on the possibility of promoting hemodynamic instability or other side effects. The previous use of benzodiazepines and intravenous lidocaine may be useful as coadjuvants.

Remifentanil, an ultra-short duration opioid, has become an excellent option for the blockade of autonomic responses associated to intubation and may be very useful in this situation.

In the market for more than 50 years, succinylcholine is still the neuromuscular blocker of choice, although its side effects have encouraged the search for an alternative that would maintain its properties of fast onset and ultra-short duration. So, rocuronium has been shown to be a good alternative to replace succinylcholine although high doses are needed to promoted desirable actions, which increases its duration.

New techniques have been proposed as alternatives to succinylcholine or to higher rocuronium doses. Experimentally, new drugs have been tested with promising results.



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Correspondence to
Dr. Eduardo Toshiyuki Moro
Address: Av. Araçoiaba 85, SR 02, Condomínio Fazenda Lago Azul
ZIP: 18190-000 City: Araçoiaba da Serra, Brazil

Submitted for publication August em 20 de agosto de 2003
Accepted publication November 14, 2003



* Received from CET/SBA da Faculdade de Medicina de Botucatu da Universidade do Estado de São Paulo (FMB - UNESP), Botucatu, SP

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