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Succinylcholine is highly water soluble and rapidly redistributes into the extracellular fluid volume. For this reason the dose required for intravenous administration in infants (2.0 mg/kg) is approximately twice that for older patients (1.0 mg/kg). Succinylcholine is the only short-acting relaxant that is effective when given intramuscularly. Reliable muscle relaxation occurs within 3 to 4 minutes after 5 mg/kg in infants and 4 mg/kg (intramuscularly) in children older than 6 months. [212] The skeletal muscle relaxation produced by intramuscular administration may last up to 20 minutes; more rapid onset is not achieved by splitting the dose into two injections or by changing the concentration. In an emergency situation, succinylcholine may be administered intralingually, which will further speed the onset of relaxation because the drug is more rapidly absorbed from the tongue than from peripheral skeletal muscle.[213]
Cardiac arrhythmias frequently follow intravenous administration, especially during halothane anesthesia. Intravenous administration of atropine (but not intramuscular administration of atropine as a premedication) reduces the incidence of arrhythmias. Cardiac sinus arrest may follow the first dose of succinylcholine but is more common after repeated bolus administration; such arrest may occur in patients of any age. Although the incidence of bradycardia is low in older patients, I have observed one 13-year-old patient in whom asystole developed for approximately 30 to 45 seconds after a single dose of succinylcholine administered with thiopental but not atropine; the asystole occurred before intubation and with 100% oxygen saturation. Therefore, atropine should probably be given intravenously just before the first dose of succinylcholine in all children, including teenagers.
Succinylcholine has received much attention because of the severity of its possible complications. The potential for rhabdomyolysis, hyperkalemia, masseter spasm, and malignant hyperthermia suggests that succinylcholine should not be used routinely. Two studies, flawed because
With the foregoing cautions in mind, one should not yet completely abandon succinylcholine because it is the only commercially available ultrashort-acting muscle relaxant that provides a dependable, rapid onset of action. The intravenous use of this drug should be limited to patients who have a full stomach or to treat laryngospasm; intramuscular or submental (intralingual) administration is indicated for patients with difficult intravenous access when control of the airway is deemed essential. Until an ultrashort-acting nondepolarizing relaxant becomes available, succinylcholine remains the drug of choice when rapid onset of muscle relaxation is needed. High-dose rocuronium may be a suitable alternative (see the next section). [217]
A comparison of infants with older children or adults regarding their response to nondepolarizing muscle relaxants shows that infants are generally more sensitive to these drugs and that their response varies to a greater degree. [218] Although the initial dose per kilogram needed for neuromuscular blockade is often similar for patients of all ages, the greater volume of distribution and the reduced renal or hepatic function of neonates result in a slower rate of excretion and hence a prolongation of the effect. Neuromuscular blockade occurs at a lower blood concentration.[219] Another observation is that the onset of and recovery from neuromuscular blockade may be slightly shorter in children with right-to-left intracardiac shunts.[220]
The choice of nondepolarizing muscle relaxant depends on the side effects and the duration of muscle relaxation required.[218] If tachycardia is desired (e.g., with fentanyl anesthesia), pancuronium would be the choice. Vecuronium, atracurium, and cisatracurium are useful for shorter procedures in infants and children; they may also be administered as a constant infusion.[221] [222] [223] The method of excretion of atracurium and cisatracurium (Hofmann elimination and ester hydrolysis) makes these relaxants particularly useful in newborns and patients with liver or renal disease.[218] [224] [225] [226] Vecuronium is valuable because no histamine is released; however, the duration of action is prolonged in newborns, which makes it similar to pancuronium.[227]
Mivacurium is a short-acting nondepolarizing relaxant that is hydrolyzed by plasma cholinesterase.[228] It offers the advantage of providing satisfactory conditions for endotracheal intubation for brief surgical procedures. A disadvantage is prolonged neuromuscular blockade in the occasional patient with unrecognized cholinesterase deficiency.[229] A dose of 0.2 to 0.3 mg/kg provides adequate relaxation within 2 minutes; spontaneous 95% twitch recovery occurs within 20 minutes.[230] This drug is ideal for administration by constant infusion because there does not appear to be any drug accumulation. Pipecuronium and doxacurium are long-acting, nondepolarizing relaxants; their role has yet to be defined for children, but in general, their duration of action is shorter than in adults.[231] [232]
Rocuronium has a clinical profile similar to that of vecuronium, cisatracurium, and atracurium but offers the advantage that it can be administered intramuscularly.[218] [233] [234] One study observed that acceptable conditions for intubation are produced by rocuronium within 3 to 4 minutes after a 1-mg/kg intramuscular dose in infants and a 1.8-mg/kg intramuscular dose in children older than 1 year; these effects were more dependable with deltoid than with quadriceps muscle injection. [235] This onset time is similar to that produced with intramuscular succinylcholine; however, the duration of action is approximately 1 hour, which could be a distinct disadvantage for a brief procedure. The onset of neuromuscular blockade with intravenous rocuronium (1.2 mg/kg) is also nearly the same as and intubation conditions are identical to those produced with succinylcholine (1.5 mg/kg).[217] I have used this dose with thiopental (5 to 6 mg/kg) for rapid-sequence induction after preoxygenation in patients in whom succinylcholine might present an added risk. Even better intubating conditions are achieved with the administration of lidocaine (1 mg/kg) and propofol (3.0 mg/kg) just before the rocuronium (1.2 mg/kg). Most patients can be intubated at 45 seconds. The disadvantage is that the duration of action is 60 to 90 minutes, thus limiting its usefulness to long cases or accepting the fact that prolonged neuromuscular blockade is more desirable than the potential risk from the shorter duration of succinylcholine. Conversely, at low doses of rocuronium (0.3 mg/kg), satisfactory conditions for intubation are achieved within 3 minutes when combined with an inhaled drug, but successful reversal can usually be achieved within 15 minutes. In addition, this low dose is not associated with any difference in response in children with renal failure.[236]
Table 60-4 provides commonly recommended guidelines for dosages. Because of the extreme variability in response, the doses of long-acting muscle relaxants used for infants should be titrated carefully, starting with a third to half the usual dose administered to older patients. I recommend antagonism of neuromuscular blockade in all neonates and small infants, even if they have recovered clinically, because any increase in the work of breathing may cause fatigue and respiratory failure. Useful signs of reversal are the ability of the infant to lift the legs and arms and recovery of the train-of-four response to peripheral nerve stimulation.[237]
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