Rapid sequence intubation : a practical approach for the pediatrician in the emergency room

Intubation is one of the key procedures in emergency situations in Pediatrics. Rapid sequence intubation, which comprises the simultaneous or sequential administration of inducing agents (sedatives and analgesics) and neuromuscular relaxants, is not a common practice among pediatricians, despite many studies showing that it greatly improves intubating conditions and even reduces complications in the procedure. This article presents an update of the main available drugs as well as the indicated uses in airway management in the ICC.


INTRODUCTION
Airway maintenance is a priority in patient care at the emergency sector.The objective is to ensure that ventilation and oxygenation are in accordance with patients' demand.Tracheal intubation (TI) is often the definitive procedure to reach that purpose.
2][3] It is precisely indicated in "full stomach" situations 4 .However, given the need to facilitate TI conditions and produce better visualization, RSI has been indicated as a standard procedure for TI in emergency settings. 3deal conditions for intubation are defined as complete mandible relaxation, open and immobile vocal cords, absence of coughing, resistance or of diaphragm movement in response to intubation. 2,3To reach these ideal conditions, four objectives must be achieved with this technique: analgesia, amnesia or unconsciousness, muscle relaxa-Sequência rápida de intubação: uma abordagem prática para o pediatra em situações de urgência Karina Camargos Martins 1 , Adrianne Mary Leão Sette e Oliveira 2 , Alexandre Rodrigues Ferreira 3 1 Horizontal Care Physician at the Pediatrics ICU at the University Hospital of the Federal University of Minas Gerais (UFMG).Belo Horizonte, MG -Brazil. 2 Physician.Coordinator of the Pediatrics ICU at the University Hospital of the Federal University of Minas Gerais.
Belo Horizonte, MG -Brazil. 3Physician.Associate Professor of the Department of Pediatrics at the Federal University of Minas Gerais School of Medicine.Medical Coordinator of the Functional Pediatrics Unit of the University Hospital of the Federal University of Minas Gerais.Belo Horizonte, MG -Brazil.
Rapid sequence intubation: a practical approach for the pediatrician in the emergency room DOI: 10.5935/ 2238-3182.20130033Rapid sequence intubation: a practical approach for the pediatrician in the emergency room signs and symptoms, allergies, medications, past medical history, last oral intake, and events leading up to the need for intubation. 5efore the TI procedure a clinical examination must always be conducted in order to estimate the potential risk of difficult intubation.Whenever possible, laryngeal masks or other supraglottic devices must be available for the cases when the procedure is not successful and ventilation is difficult. 3,6,7

Preparation and monitoring
Preparation must always be initiated by checking and defining the necessary material for a successful procedure: operational O 2 source with humidifier, oxygen supply system (preferably high-flow with nonrebreather mask) for prior patient hyperoxygenation, vacuum source with suction probe connection, tested ventilation unit adequately sized for the child (producing adequate pressure and with a non defective reservoir), mask appropriate for the age group connected to the ventilation unit, appropriate and tested laryngoscope, tracheal tube (TT) in three sizes (one adequate for the age group, one smaller, and one larger), tube guide, and previously planned and prescribed medication.In addition, one must not forget two reliable calibrous access ways, cardiorespiratory monitoring, and a team prepared for the procedure. 3everal formulas may be employed to calculate the correct size of the tracheal tube for a given pediatric age group.For children over two years of age, the size (internal diameter in milliliters) may be calculated using the formula: uncuffed TT (tracheal tube) size (ID in mm) = (age in years/4) + 4, infants up to 1 year of age: 3.5, toddlers between 1 and 2 years: 4. TT (tracheal tube) cuffed size (ID in mm) = age (years)/4 + 3.5, infants up to 1 year of age: 3, toddlers between 1 and 2 years: 3.5 tube.Physicians should be aware that in case the cuffed tube is used, inflation pressure in the cuff must be between 20 and 25 cm H 2 O. Formulae may also be used for estimating the depth of tube insertion.This insertion distance (depth) in centimeters (from the distal end of the tube to the alveolar ridge) for children over two years of age may be approximated by adding 12 to half the patient's age: insertion depth (cm) = age (years)/2 + 12.Alternatively, the insertion distance (in centimeters) from the distal end of the tube to the lip may be estimated by multiplying the internal diameter of the selected tube by three. 5on, and reduction of autonomic reflexes generated by a nociceptive stimulus.Relative or absolute contraindications to RSI include lack of experience or training on the technique, and anticipation of a difficult airway.In those cases, there are safe alternatives to RSI and to unforeseen difficult intubation, such as the use of topic anesthesia and conscious sedation preserving spontaneous ventilation and the protective reflexes of the airway, or the use of supraglottic devices.
This article proposes to discuss mainly the medication used in RSI and its prescription according to clinical situation, with a focus on the emergency setting: intubation at emergency rooms and intensive care units.We will not focus on the elective situations of operating rooms and the neonatal period.This research attempts to approach the pediatric population, despite the several limitations this implies given the lack of studies on this age group.Therefore, many studies on adults will be quoted and used as references.

INDICATION AND PREPARATION FOR TRACHEAL INTUBATION (TI)
The main indications for TI in pediatric emergency settings are: treatment of shock and/or respiratory failure, and situations that lead to altered consciousness.The most common etiologies of respiratory failure may be didactically divided into: upper airway obstruction, lower airway obstruction, parenchymal diseases and breathing control (neurological issues that do not guarantee either airway protection or ventilation itself). 5

RAPID SEQUENCE INTUBATION
A safe and effective RSI requires compliance to a specific sequence of steps that starts with a review of the patient's history and is followed by an adequate preparation of the equipment, personnel and medication.[3]

Brief anamnesis and physical examination
To obtain the necessary information for a safe procedure, the SAMPLE history mnemonic can be used: Rapid sequence intubation: a practical approach for the pediatrician in the emergency room In cases considered reflexive, such as hypoxia, and in laryngoscopy, what can be seen is that there is peripheral vasoconstriction simultaneous to bradycardia, and the effects are compensated in the systemic pressure.However, in the cases of vagomimetic bradycardia such as those induced by drugs, this vasopressor response generally does not happen, with devastating effects.As an example, succinylcholine can induce severe bradycardia and asystole regardless of the disease or concomitant use of other medication. 8iven all that has been discussed up to this point, use atropine is always recommended as pre-medication for children under the age of one year, from 1-5 years when using succinylcholine, and above that age if a second dose of succinylcholine is used. 2,3,5,8The use of atropine as pre-medication has also been currently recommended for septic shock, considering the potentially devastating effects bradycardia could have in such conditions, especially if followed by vasoplegia. 8,9The recommended dose is 0.02 mg/kg, bearing in mind that the minimum dose is 0.1 mg, and that the maximum dose is 0.5 mg.Doses lower than the minimum may induce paradoxical bradycardia.
Lidocaine may also be used in this phase and is mainly prescribed in cases of head trauma or when intracranial hypertension is suspected.Its exact mechanism of action is not yet clear, but it is probably related to the suppression of coughing, depression of brain metabolism, and membrane stabilization. 1,10,11pioids have traditionally been excluded from RSI, which included the use of only one sedative (Thiopental, at the time) and a muscle relaxant (succinylcholine). 12,13However, in recent years, opioids have been added to the arsenal of drugs used in rapid sequence intubation.The most frequently used and most easily available at emergency centers is fentanyl, a powerful analgesic with mild sedative effects.It also decreases the hypertensive response to intubation, a reaction more significant in adults. 1,14t may cause chest tightness, which seems to occur more commonly with high doses and fast injection.
All patients must be continuously monitored before, during, and after the RSI, with constant assessment of oxygenation (O 2 saturation), ventilation (capnography, if available), circulation (heart rate and ECG), and temperature.However, the most important aspect is the continuous supervision of the clinical aspects during every step of the RSI.

Preoxygenation
The first step -preoxygenation -may be completed with the use of oxygen at 100% from a mask with a nonrebreathing reservoir for 3-5 min. 2,3The objective is to denitrogenate the patient, allowing for more time without desaturation so that the physician may perform the procedure without the risk of hypoxia.Children often tolerate less time until desaturation than adults, both due to the lower reserves and to the increased use of oxygen per kilogram.

Pre-medication
Part of the current RSI medication is made up of agents used to attenuate the adverse respiratory, cerebral, cardiovascular, and intraocular effects of laryngoscopy procedures.They are known as pre-medication, and the main ones are atropine, lidocaine, and opioids 1,2,3 .The choice depends on each child's clinical condition.
TI is a noxious stimulus and laryngoscopy induces several physiological changes in children, the most frequent being marked vagal response and bradycardia with repercussions.Before birth and during the first 3-6 months of life, an autonomic imbalance can be observed due to dense vagal innervation of the sinoatrial node and poor sympathetic innervation of the ventricles and conduction system 8 .The vagal response may happen both by hypoxia and by laryngoscopy, in addition to certain medications that induce bradycardia.Rapid sequence intubation: a practical approach for the pediatrician in the emergency room ve described in this article with analgesic properties), sedation and amnesia, while it maintains cardiovascular stability and preserves spontaneous respiration and the protective reflexes of the airways, as well as having bronchodilator properties. 2,3,5,17ifferently from most agents, it is not titratable, with dissociative effects shown with 1.5-2 mg/kg venous (IV) and 3 or 4 mg/kg intramuscular (IM) doses. 17Once the dissociative effects are reached, administration of additional doses does not improve or deepen sedation, as is the case with opioids, sedatives, and inhalational agents, but it increases the action time.In addition, it has been described that the amount of ketamine does not have relevant effects on the integrity of the airway and respiration, and the highest risk of respiratory depression is associated to the rapid infusion of the medication in a time bracket that must be between 30-60 seconds. 17espite a laryngospasm-inducing effect that has been described in several conditions, including asthma, there are no contraindications in this clinical setting for intubation with this agent provided that a neuromuscular blocker is used. 17][3] There are many questions about the possibility of increased intracranial pressure with the use of ketamine. 18The practical guideline for the use of ketamine in the emergency department 17 has removed Traumatic Brain Injury from the list of relative contraindications.However, it has maintained masses, CNS abnormalities and hydrocephaly as diagnoses that require careful use (relative contraindications).In regard to the use of alternative agents, it would be prudent to use the latter if the patient conditions so allow, especially if the patient shows barriers to the flow of cerebrospinal fluid. 17In case of ICH and hemodynamic instability, one must weigh the risks versus the benefits of the use of ketamine.Hypersalivation and dysphoric and psychometric effects are not usual during RSI.
Still according to the guideline, 17 other relative contraindications of ketamine are porphyria, glaucoma, ocular injury, and known or suspected cardiovascular disease (angina pectoris, heart failure, hypertension or risk factors for coronary heart disease).It should be used with caution in cases of ongoing pulmonary disease or other situations that may induce laryngospasms (keeping in mind that the contraindication ceases to exist with the use of muscle relaxants).The guideline mentions as absolute contraindications to the use of Extra care must be taken when drugs are used in hemodynamically unstable conditions, since there are negative hypotensive and inotropic effects, mainly when associated to benzodiazepines; lower doses must be considered in these cases. 3,15

Induction agents: sedatives
The choice of induction agent must be made according to the clinical setting.There is no ideal medication for all circumstances, but preference must be given to those with most benefits and minimal side effects.The ideal medication must have a rapid and predictable onset of action to produce loss of consciousness and improve intubation conditions in cases of inadequate paralysis. 12The main properties of each agent must therefore be well known.

Etomidate
Etiomidate is an induction agent rarely used in Pediatrics.It is a hypnotic barbituric that has a fast onset of action (30-60 seconds), peak action within a minute, and short half-life (10-15 minutes), with an induction dose of 0.2 to 0.4 mg/kg. 3,5It practically has no effect on blood pressure, and was considered ideal until very recently for situations with risk of hypotension. 1 Etomidate has a brain protection effect because it reduces blood flow brain and brain use of O 2 and is recommended as the sedative of choice in situations of traumatic brain injury (TBI), particularly in hypotension. 2,3It has no analgesic effects and may reduce the seizure threshold in patients with the risk of convulsive seizures, such as epileptic patients. 1,2everal current studies have shown that single doses of this medication can interfere in the production of cortisol and have, for this reason, been contraindicated for sepsis and septic shock. 9,16tamine Ketamine is a dissociative agent whose pharmacology is different from other analgesics and sedatives. 17It causes dose-dependent depression of the CNS characterized by deep amnesia and analgesia associated to slow nystagmus, eye movement, and electroencephalographic dissociation between the corticothalamic and limbic systems.[3]

Neuromuscular blocking
It is common to avoid the use of neuromuscular blocking in the pediatric practice of intubation. 19Nevertheless, to reach acceptable conditions for intubation, many times high doses of opioids and sedatives are used and present a high risk of hypotension and bradycardia.0][21][22][23][24][25] Neuromuscular blocking must always be used as a part of RSI, except under conditions that predict difficult airways or when there are no alternative conditions to approach the "no intubation, no ventilation" situation.
In addition to reducing laryngeal trauma, optimal intubation conditions may reduce morbidity for patients during the procedure (deoxygenation and its consequences) by facilitating it.
Neuromuscular blocking drugs are divided into two classes based on their mechanism of action at the neuromuscular junction: a) depolarizing agents, and b) nondepolarising agents.Both induce motor paralysis by preventing acetylcholine stimulus on the nicotinic receptors, thereby interrupting neuromuscular transmission.Succinylcholine and rocuronium are the most appropriate NMBs for RSI.

Depolarizing: succinylcholine
Depolarizing neuromuscular blockers, whose only representative for clinical use is succinylcholine, operate as acetylcholine receptor agonists in a biphasic manner: first it opens the sodium channels of the cellular membrane, resulting in a brief depolarization which can be clinically observed, such as muscle fasciculation.It then prevents the binding of acetylcholine to its receptors, where it binds and promotes a complete block. 1,3uccinylcholine has a fast onset of action (one minute) and short duration time (5-15 minutes) and ventilation may return in 9-10 minutes. 1 Dosing is controversial, with references mentioning mainly the faster metabolism of children under three years of age ketamine age below three months and psychiatric disorders, bearing in mind that this guideline is intended to be the rule not only for TI, but for sedation in general.It is therefore considered that, in the case of age, the concern is airway obstruction, laryngospasm and apnea, which can be precipitated by ketamine.In RSI and with the use of muscle relaxants such effects would seem less important.Ketamine has also been advocated for due to its minimal cardiovascular effects and the potential of adrenal suppression of other agents with blood pressure preservation effects (etomidate) as the drug of choice in pediatric septic shock. 9

Midazolam
Despite its very frequent use, midazolam is considered a suboptimal agent for intubation, both for not producing proper sedation and for producing non-ideal sedation conditions. 2 It has sedative, hypnotic, amnesiac, anxiolytic, muscle relaxant and anticonvulsant effects.
It must be used with caution in conditions of hemodynamic instability due to its negative and vasodilator inotropic effects, especially if associated with opioids. 3iopental This is a thiobarbituric with fast onset of action (30 seconds) and short half-life.It reduces O 2 consumption, cerebral blood flow and intracranial pressure. 1,3However, it is associated with hypotension due to effects in myocardial contractility, vascular resistance and venous return. 1,3Therefore, it must not be used in patients with hemodynamic instability 1,3 .Thiopental may cause laryngospasm, hypersalivation, and bronchospasm. 1[3]

Propofol
Propofol is a liposoluble agent that induces hypnosis in the arm-brain circulation time. 1 It has a short half-life and duration of action, anticonvulsant and antiemetic properties, and provides the best conditions for intubation without the use of muscle relaxants. 1,2,12Propofol also reduces intracranial pressure and brain metabolism.It has a tendency to lower Rapid sequence intubation: a practical approach for the pediatrician in the emergency room the drug of choice when succinylcholine is contraindicated.In 0.6 mg/kg doses it has an onset of action of about 90 seconds and duration of 45 minutes in infants and 27 minutes in children; in higher doses, such as 1.2 mg/kg, the onset of action is 30 seconds and average duration is 53 minutes. 1 Intubation conditions are described as the same as with acetylcholine in some of the literature 24 , but a review by Cochrane in 2008 25 comparing intubation conditions ranks succinylcholine as superior if lower doses are used, but shows no difference when 1.2 mg/kg doses of rocuronium are used, bearing in mind that with that dose the duration time increases.
Since neuromuscular junctions in young patients are insufficient, steroidal relaxants have a longer time of action with higher doses, 20 which extends even more the blocking time when they are used.In cases of presumed difficult airways, they must be avoided.Neuromuscular blocking induced by rocuronium may be completely antagonized by acetylcholinesterase inhibitors such as neostigmine.

CONCLUSION
Rapid sequence intubation must always be the method of choice for intubation in emergency situations.The steps must be remembered for a safe procedure and materials must always be checked before initiating the RSI.It is important that emergency room pediatricians know the drugs available to them as well as their indications and contraindications so that they are able to choose the best option according to the clinical scenario of each child.The use of muscle relaxants should not be disregarded, especially because they facilitate TI conditions and also cause less airway lesions and other complications.and advocating higher doses for this age group. 3,20he dose is 3 mg/kg for infants under one year of age and 2 mg/kg for the other age groups.
Despite the emergence of new agents and given all of the above mentioned properties, succinylcholine remains the relaxant of choice in most intubation procedures in emergency settings. 1,2,20uccinylcholine must be avoided after the first 24 hours in patients with burns and after 72 hours in patients with acute denervation syndromes or polytrauma.2][3] It causes an increase in serum potassium of up to 0.5 mEq/L. 3Succinylcholine causes masseter muscle rigidity in 0.3 to 1% of pediatric patients.Such condition, if severe, can be an early sign of malignant hyperthermia.
Another relative contraindication includes patients with intracranial or intraocular pressure; there is much controversy on the matter. 1,2The risks versus benefits of its use must always be measured, considering that there is no conclusive evidence for this contraindication.
Succinylcholine may induce arrhythmias, the most frequent of them being bradyarrhythmias, which justifies the use of atropine as pre-medication in children. 2,3,5ndepolarising Nondepolarizing neuromuscular blocks are competitive antagonists of acetylcholine receptors and are an alternative to succinylcholine.They are also called steroidal relaxants.
Rocuronium is one of the most used in the clinical practice.It derives from vecuronium and is the nondepolarizing neuromuscular relaxant with the fastest onset of action.It blocks the binding of acetylcholine to the nicotinic receptor.Rocuronium is

Steps Actions
Check materials Check necessary equipment and connections; Calculate the doses for pre-medication, sedatives, and neuromuscular relaxants available at the facility; Arrange for cardiac arrest sheet to be filled out.

Monitor
Wrist oximetry and ECG.

Maintain Airways
Open airways and position head; Suction secretion; If possible pre-oxygenate with non-rebreather mask or other high flow device (ex.HOOD for infants); Ventilate with mask and ventilation unit connected to the oxygen source if necessary (ex.apnea before administering all medication); Check for chest expansion, auscultation, and saturation measures.
To be continued…

Table 1 -
Materials for intubation