Anesth Analg 2001;93:345-347
© 2001 International Anesthesia Research Society
PEDIATRIC ANESTHESIA
Unmasked Residual Neuromuscular Block After Administration of Vecuronium for Days
Gavin F. Fine, MB BCh*,
Barbara W. Brandom, MD*, and
Robert F. Yellon, MD
Departments of *Anesthesiology and Otolaryngology, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Address correspondence to Gavin Fine, MD, Department of Anesthesiology, Children’s Hospital of Pittsburgh, One Children’s Place, Pittsburgh, PA 15213-2583. Address e-mail to finegf{at}anes .upmc.edu.
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Abstract
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IMPLICATIONS: Significant neuromuscular block may be present in patients who have received vecuronium for days.
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Introduction
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Children undergoing single-stage laryngotracheal reconstruction often receive neuromuscular blockers in the intensive care unit (ICU) to prevent dislodgment of the endotracheal tube and to facilitate healing of the graft (1). After several days, if direct visualization of the surgical site reveals acceptable anatomy, the trachea can be extubated as soon as the patient is awake and strong. Thus, it is appropriate to titrate sedatives and neuromuscular blockers so that their effects are minimal at that time.
We present the case of a 3-yr-old who received vecuronium for 4 days after laryngotracheal reconstruction. Significant unexpected neuromuscular block was documented during direct laryngoscopy and tracheoscopy without further administration of a neuromuscular blocker.
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Case Report
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A 3-yr-old, 10.3-kg male child underwent repair of subglottic stenosis by single-stage laryngotracheal reconstruction. His medical history included birth at 34 wk gestation, reactive airway disease, gastroesophageal reflux, complete repair of Tetralogy of Fallot, and DiGeorge syndrome (abnormal development of the fourth branchial arch and derivatives of the third and fourth pharyngeal pouches resulting in abnormalities of the thymus, parathyroid, and great vessels). Physical examination revealed slight stridor and sternotomy scar. There was no hepatic or renal impairment.
Postoperatively he received infusions of fentanyl 20 µg/hr, and vecuronium 2.43 µg · kg-1 · min-1 with intermittent boluses of fentanyl, midazolam, and clindamycin. On the second and third days in the ICU, the vecuronium infusion was stopped temporarily. Spontaneous movement was noted within 2 h. Vecuronium was then continued at the same rate to prevent spontaneous movement. At this rate of infusion of blocker, there were less than 5 responses to 1 Hz stimulation after 5 s of 50 Hz stimulation. After 4 days of vecuronium infusion, the drug was discontinued. Propofol was given while the ulnar nerve was stimulated at 2 Hz for 2 s at 60-s intervals and the train-of-four ratio (T4/T1, ratio of the amplitude of the fourth to the first response of the evoked electromyogram of the adductor pollicis) was recorded with a Neuromuscular Transmission Monitor (Datex, Helsinki, Finland). Until 10 h after termination of vecuronium T4/T1 was <0.4. The interval in which the T4/T1 was between 0.4 and 0.7 was 10 h. The interval in which the T4/T1 was between 0.7 and 0.9 was 4 h. Twenty-eight hours after discontinuation of the infusion of vecuronium, T4/T1 was 1.0, and the patient was then taken to the operating room. This was on the seventh day after beginning vecuronium infusion.
The child received sevoflurane and nitrous oxide for bronchoscopy before attempted extubation. The larynx and trachea were sprayed with 3 mL of 1% lidocaine. After 20 min of 2.0% to 2.5% sevoflurane, sevoflurane was increased to 3% for 5 min. At that time the initial response to the train-of-four stimuli had decreased to 75% of what it had been on entry to the operating room and T4/T1 was 0.33 (Fig. 1). This nadir of neuromuscular function occurred 25 min after beginning sevoflurane. After conclusion of endoscopy, an orotracheal tube was placed. Fifteen minutes after stopping sevoflurane administration the T4/T1 was more than 0.7. The patient returned to the ICU. Tracheal extubation was successful 3 h later when the ICU physicians judged he was ready (2).
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Figure 1. Time is increasing from left to right on the x-axis. Minutes since beginning the record are noted on the top of the graph. Neuromuscular function (as % of baseline) is increasing with elevation of the y-axis. When the first response is equal to the fourth response to a train-of-four stimulation, a solid black mark is displayed. As the fourth response decreases, the first response is seen as the thin black line above the solid black area that indicates the fourth response.
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Plasma was obtained for measurement of vecuronium and 3-OH-vecuronium (3). The concentrations of 3-OH-vecuronium/vecuronium were 45/450 ng/mL on the second day, 96/529 ng/mL on the fourth day of infusion of vecuronium, and 13/27 ng/mL 24 h after termination of the infusion. Clearance of vecuronium, estimated by dividing infusion rate, 2.43 µg · kg-1 · min-1, by the measured plasma concentrations, was 5.4 mL · kg-1 · min-1 and 4.6 mL · kg-1 · min-1.
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Discussion
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This case emphasizes that the patient who has received vecuronium and antibiotics for days in the ICU may be particularly sensitive to the neuromuscular effects of drugs administered during anesthesia. The anesthetic course of this patient suggests that quantitative monitoring of neuromuscular function is prudent in such situations. If the neuromuscular block present at the end of the diagnostic procedure had been unrecognized in this case and the endotracheal tube had been removed, it is likely that airway function would have been compromised.
Previous observations without quantitative monitoring (4) have suggested that recovery from block would be faster in this case, yet some residual neuromuscular block could still be present. For example, without quantitative monitoring, a T4/T1 between 0.4 (5) and 0.9 cannot be detected. Recovery of evoked neuromuscular function of the adductor pollicis to a T4/T1 of >0.7 has been considered synonymous with recovery of upper airway and respiratory function (6). However, weakness of the masseter, orbicularis oris, speech, and grip strength persist until the T4/T1 reaches 0.9 (7). Therefore the patient may experience upper airway dysfunction (8) as a result of residual block when block is difficult to detect. After infusion of vecuronium for days, neuromuscular function had recovered to the most stringent criteria when our patient entered the operating room for bronchoscopy. Nevertheless, the drugs he received for anesthesia produced a clinically significant, but manually undetectable, degree of block.
There could be several reasons why recovery was so slow. When accelerometry was used to titrate vecuronium infusion to maintain one response to train-of-four stimuli, the infusion rate was 50% less than was given to this child and spontaneous recovery occurred more quickly (9). This child received a higher infusion rate. Clearance of vecuronium in this patient was not significantly different from that measured during general anesthesia after a short infusion of vecuronium at the same rate given to this patient (10). This suggests that the volume of distribution of vecuronium increased with continued exposure to the drug. However, in six adult ICU patients, steady-state volume of distribution of vecuronium did not change significantly over 3–6 days (11).
Clindamycin may potentiate block (12,13) and has been associated with slower spontaneous recovery from doxacurium in similar patients (14). Sevoflurane (15) and lidocaine (16) can augment block. The plasma concentration of lidocaine after tracheal spray could be 2.5 to 3.0 µg/mL (17). Whichever drugs significantly enhanced the block, it is not surprising that a significant increase in depth of block was noted in this case, given the slow spontaneous recovery from vecuronium. The presence of T4/T1 of 1.0 does not preclude the presence of residual block at higher stimulation frequency (18).
Another reason for slow recovery is that the metabolite of vecuronium, 3-OH-vecuronium, probably contributed to the block after the end of the infusion. The C50 of vecuronium and 3-OH-vecuronium is 102 ng/mL and 123 ng/mL respectively (19). Thus 3-OH-vecuronium has 80% of the potency of its parent compound, vecuronium. Furthermore, the kinetics of these two compounds differ. The plasma clearance of 3-OH vecuronium is less than that of vecuronium, and its steady-state volume of distribution is larger, resulting in a longer terminal half-life and mean residence time (19). Although persistence of 3-OH-vecuronium has been noted in two patients with decreased creatinine clearance (20,21), this has not been observed previously in a patient with normal renal function.
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Accepted for publication April 10, 2001.
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Abstract
Introduction
