Anesth Analg 2003;97:80-84
© 2003 International Anesthesia Research Society
ANESTHETIC PHARMACOLOGY
The Relationship of Posttetanic Count and Train-of-Four Responses During Recovery from Intense Cisatracurium-Induced Neuromuscular Blockade
Mohammad I. El-Orbany, MD*,
Ninos J. Joseph, BS*, and
M. Ramez Salem, MD*,
Department of Anesthesiology, *Advocate Illinois Masonic Medical Center, and
University of Illinois College of Medicine, Chicago, Illinois
Address correspondence and reprint requests to Mohammad I. El-Orbany, MD, Department of Anesthesiology, Advocate Illinois Masonic Medical Center, 836 W. Wellington Ave., Chicago, IL 60657. Address e-mail to mohammad.el-orbany-md{at}advocatehealth.com
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Abstract
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Posttetanic count (PTC) has been used to quantify intense degrees of nondepolarizing neuromuscular blockade. Our objective in the present investigation was to discern whether PTC correlates with recovery from intense cisatracurium-induced neuromuscular blockade under both inhaled and IV anesthesia. In 60 patients, anesthesia was induced with propofol 2 mg/kg and fentanyl 1.5 µg/kg IV. Recovery from intense neuromuscular blockade induced by cisatracurium (0.15 mg/kg) was studied in 2 groups. Group 1 (n = 30) had anesthesia maintained with propofol 100–200 µg · kg-1 · min-1 and 60% N2O in O2, whereas Group 2 (n = 30) had anesthesia maintained with isoflurane (end-tidal concentration 0.8%) and 60% N2O in O2. Neuromuscular functions were monitored using acceleromyography. Cycles of posttetanic stimulation were repeated every 6 min with train-of-four (TOF) stimulation in between. Measurement included times to posttetanic responses and to the first response to TOF stimulation (T1), as well as the correlation between PTC and T1. In Group 1, the mean times to PTC1 and T1 were 35.6 ± 7.5 and 46.9 ± 6.5 min, respectively. Corresponding times in Group 2 were 39.5 ± 6.8 and 56.7 ± 5.4 min, respectively. There was a good time correlation, r = 0.919 for propofol (Group 1) and r = 0.779 for isoflurane (Group 2), between PTC and T1 recovery in both groups. The PTC when T1 appeared ranged between 8 and 9 in Group 1 and 8 and 14 in Group 2. Conforming to original observations with other neuromuscular blocking drugs, there is a correlation between PTC and TOF recovery from intense cisatracurium-induced neuromuscular blockade allowing better monitoring of this intense degree of blockade during both IV (propofol) and isoflurane anesthesia.
IMPLICATIONS: Monitoring posttetanic count during intense neuromuscular blockade allows the clinician to estimate the intensity of the blockade and estimate recovery time. The relationship between posttetanic count and train-of-four recovery from intense cisatracurium-induced neuromuscular blockade was documented under both IV and inhaled anesthesia.
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Introduction
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Posttetanic count (PTC) is a well established method of evaluating neuromuscular recovery during intense neuromuscular blockade (1). It can be used when there is no response to single twitch, tetanic, or train-of-four (TOF) stimulation to assess the intensity of neuromuscular blockade and to estimate the duration after which the first twitch in the TOF (T1) is likely to reappear. A close correlation has been found between PTC and TOF recovery from intense pancuronium- (2), vecuronium- (3), atracurium- (4), and rocuronium-induced (5) neuromuscular blockade. Cisatracurium is a nondepolarizing neuromuscular blocking drug that has an intermediate duration of action (6) comparable to that produced after vecuronium, atracurium, or rocuronium. Although it is likely that a similar PTC/T1 relationship would apply during recovery from cisatracurium block, knowing the specific relationship may allow more precise neuromuscular monitoring during recovery from intense cisatracurium-induced blockade.
The objective of this study was to establish the relationship between PTC and TOF recovery from intense neuromuscular blockade induced by cisatracurium under both IV and inhaled anesthesia.
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Materials and Methods
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After IRB approval and obtaining written informed consents, 60 ASA physical status I and II adult patients who were scheduled for elective surgery requiring muscle relaxation and tracheal intubation were enrolled in the study. Patients with a history of neuromuscular disease or drug intake that could affect neuromuscular function were excluded from the study.
Anesthesia was induced with propofol 2 mg/kg and fentanyl 1.5 µg/kg IV and acceleromyographic neuromuscular monitoring was started using the TOF-Watch. Evoked response data were continuously displayed and simultaneously downloaded to disk for later analysis. Supramaximal stimulus and stabilization of response were sought after 50-Hz tetanic stimulation for 5 s. After calibration, cisatracurium 0.15 mg/kg (3 x 95% effective dose) was administered IV over 5 s. Responses to TOF stimulation applied to the ulnar nerve at the wrist every 15 s were recorded. Tracheal intubation was performed when the response was completely ablated. Posttetanic stimulation was applied according to the preprogrammed sequence (15 pretetanic 1-Hz single twitches followed by 50-Hz tetanic stimulation for 5 s followed by a 3-s pause after which 15 posttetanic 1-Hz stimuli were applied). This cycle was repeated every 6 min with TOF stimulation restarted 15 s after the last posttetanic stimulation and continued monitoring in between the 6-min cycles. Patients were randomly allocated to either of two groups according to the technique used for anesthesia maintenance. Group 1 (n = 30 patients) had their anesthesia maintained with an IV infusion of propofol 100–200 µg · kg-1 · min-1 and 60% N2O in O2, whereas Group 2 (n = 30 patients) had isoflurane (end-tidal concentration 0.8%) and 60% N2O in O2 for maintenance. Temperature was monitored by esophageal and skin probes in all patients. Warm forced air devices were used to maintain the upper body and extremities above 36°C.
Time from cisatracurium administration until the appearance of posttetanic responses was recorded, as well as the time to reappearance of the first twitch in the TOF. The correlation between the number of posttetanic responses elicited and the time interval until T1 appeared was evaluated.
All statistical analyses were performed using SPSS® software version 11.0.1 (SPSS, Chicago, IL). Statistical significance was accepted at P < 0.05. The nonlinear regression plots were created using Sigmaplot 2001 software version 7.0.1 (SPSS). The Student’s t-test and the Mann-Whitney U-test were used to identify significant differences in demographics between the two groups. The Student’s t-test was also used to compare the ranked times from cisatracurium administration to PTC1–10, as well as times to T1 between the two groups.
A nonlinear relationship between time to reappearance of T1 and number of PTC has been established for pancuronium, vecuronium, atracurium, and rocuronium (2–5). Time to T1 has been described by a near-linear decrease with the square root of PTC. This can be expressed as: t = a + b
PTC, where t = the interval between a given PTC and the first detectable response to TOF stimulation, a = a constant (intercept), and b = the regression coefficient (slope) of this near-linear relationship. The validity of this equation was tested for cisatracurium, in the dose given. The pooled data for each group were plotted separately and the nonlinear least squares regression lines were drawn with 95% confidence intervals. Pearson correlation coefficients were calculated for each group.
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Results
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There were no significant differences between the two groups in age, sex distribution, height, weight, and ASA physical status. The time needed for calibration and initial stabilization of response before cisatracurium administration was not different between the two groups (120 s in Group 1 and 130 s in Group 2) (Table 1).
Because posttetanic stimulation was applied at 6-min intervals, the time from cisatracurium administration to a single response to posttetanic stimulation (PTC1) was calculated only in those patients in whom a single response was recorded. These data were obtained in 21 patients in Group 1 and 24 patients in Group 2.
In Group 1, the time from cisatracurium injection to a single response could be elicited during posttetanic stimulation was 35.6 ± 7.8 min (Table 2). The time from cisatracurium injection to first detection of T1 was 46.9 ± 6.5 min. The mean time interval between PTC1 and reappearance of the first twitch in the TOF (T1) was 11.3 ± 1.9 min with a range of 10–18 min and a median of 10 min. Eight to nine responses to posttetanic stimulation could be elicited at the time T1 reappeared. In no patient did T1 appear within 10 min of the appearance of PTC1.
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Table 2. Comparison of Neuromuscular Effects of Cisatracurium 0.15 mg/kg During Isoflurane (Group 1) and Propofol (Group 2) Anesthesia
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In Group 2, the mean time to PTC1 was 39.5 ± 6.8 min. This time was not significantly different from that seen in propofol-maintained patients (Group 1). The time to reappearance of T1 in Group 2 (56.7 ± 5.4 min) was significantly longer (P < 0.0001) than that seen in Group 1. The mean time from PTC1 to reappearance of T1 was 16.5 ± 4.4 min (median 16 min) and the range was 12–30 min. Eight to 14 responses to posttetanic stimulation could be elicited at the time T1 reappeared. Table 2 shows the different mean (±SD) times to T1 and PTC1 and the PTC at which T1 appeared.
There was a good correlation between PTC and T1 recovery in both groups (Table 3) The relationship of PTC and time to T1 recovery after cisatracurium 0.15 mg/kg fitted the previously published model in both groups—r = 0.92 and r = 0.78, for Groups 1 and 2, respectively (Table 3 and Figs. 1 and 2).
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Figure 1. Relationship between the posttetanic count and time to onset of train-of-four (T1) response during neuromuscular blockade caused by cisatracurium during IV anesthesia with propofol (Group 1). The predicted mean curve (solid line) and 95% confidence limits (dashed lines) are shown. Where multiple overlapping data points cannot be identified, the cluster is representative and the total number of overlapping data points is provided in parentheses.
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Figure 2. Relationship between the posttetanic count and time to onset of train-of-four (T1) response during neuromuscular blockade caused by cisatracurium during inhaled anesthesia with isoflurane (Group 2). The predicted mean curve (solid line) and 95% confidence limits (dashed lines) are shown. Note that the outliers at the top of the graph represent two patients. Note also that overlap may obscure some data points.
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Discussion
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The results of this study establish the relationship between the number of responses to posttetanic stimulation and the time interval until the first response to TOF stimulation could be elicited during recovery from intense cisatracurium-induced neuromuscular blockade. The PTC/T1 time relationship has been demonstrated with other nondepolarizing neuromuscular blocking drugs and is specific for each drug (2–5). Figure 3 illustrates the relationship between the PTC and time when T1 is likely to be elicited for the various studied neuromuscular blocking drugs. The cisatracurium regression line lies within a close range to the other intermediate-duration neuromuscular blocking drugs.
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Figure 3. The relationship between the posttetanic count and time when onset of train-of-four (T1) is likely to be elicited for the various studied neuromuscular blocking drugs. Historical data from a, Howardy-Hansen et al. (2); b, Muchhal et al. (3); c, Bonsu et al. (4); and d, Schultz et al. (5).
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The time from cisatracurium administration until PTC1 was elicited was not affected by the technique used for anesthesia. Similar findings have been reported with other neuromuscular blocking drugs (7). A possible explanation for this finding is that posttetanic facilitation is a presynaptic phenomenon that occurs in the motor nerve endings, which are not blocked by inhaled anesthetics (8). The time interval from cisatracurium administration to T1, however, was prolonged with the use of isoflurane with respect to propofol, which extended the time interval between PTC1 and T1 in these patients (Group 2). Inhaled anesthetics potentiate neuromuscular blockade mainly through a postsynaptic effect, which also affects twitch recovery after TOF stimulation (9). An inhaled anesthetic prolongation of PTC1/T1 interval has been previously described (10).
In our study, neuromuscular monitoring was performed using acceleromyography. Previous studies may have used techniques other than acceleromyography to monitor neuromuscular function. More accurate and objective monitoring may have been obtained by using mechanomyography. However, the equipment needed for mechanomyography is rather bulky and difficult to fit in a busy operating room, requires elaborate setup procedures, and the need for arm stabilization. Comparisons between the present findings and those of past studies should recognize potential differences attributable to the choice of monitoring technique. However, studies have demonstrated good correlation between acceleromyography and those measured with a force-displacement transducer (11) or with electromyography (12).
One disadvantage of the equipment we used is the tendency for subsequent twitches to read larger than the control twitch. To avoid that, a 5-second 50-Hz tetanic stimulus was applied before the initial stabilization of response, as recommended by Kopman et al. (13). Another drawback lies in the way PTC should be applied. Tetanic stimulation should not be reapplied more often than six minutes. Otherwise, the local physiological changes at the myoneural junction can reflect false information about the status of neuromuscular transmission (2). Because there is no continuous monitoring of PTC, and because a stimulation sequence must be used before the count is elicited, the response may have synchronously happened at the time of stimulation or one minute before the stimulation, and the true value was overlooked. These limitations might have affected the precision of our results to ±1 minute.
The PTC method is the only method of nerve stimulation that allows the clinician to evaluate, in a quantitative manner, intense neuromuscular blockade. The advantage of this monitoring technique is obvious when it is crucial to avoid sudden movements of the respiratory muscles. After tracheal intubation facilitated by cisatracurium, monitoring PTC allows earlier prediction of when the response to TOF stimulation will reappear. No response to posttetanic stimulation (PTC0) indicates that the neuromuscular blockade is still intense and it will take at least 10 minutes before a response to TOF stimulation will appear. Conversely, a PTC of 8 indicates that a response to TOF is imminent.
Hiccups, bucking, and coughing can occur during surgical procedures despite total abolition of TOF responses at the wrist (14). When avoidance of such movements during anesthesia is necessary, the PTC can be used to quantify the more intense blockade necessary to ensure total diaphragmatic paralysis. It portends the onset of neuromuscular recovery and offers the opportunity to maintain adequate muscle relaxation by administering a maintenance dose.
In another clinical application, the PTC/T1 relationship can be used toward the end of surgery if there is no response to TOF stimulation. The PTC indicates how long it will take before reversal can be initiated (one or two responses to TOF stimulation at least). At this time, the anesthesiologist, guided by the posttetanic response, can make an informed decision regarding whether to administer a maintenance dose of neuromuscular blocking drug based on the expected end of surgery.
In conclusion, we studied the relationship between PTC and T1 reappearance during recovery from intense cisatracurium-induced neuromuscular blockade in 60 patients who received both propofol and isoflurane anesthesia. In agreement with earlier observations with other nondepolarizing neuromuscular blocking drugs, a close correlation was found between PTC and the time to T1. Monitoring PTC during intense cisatracurium-induced neuromuscular blockade allows the clinician to accurately assess the intensity of the blockade and estimate the recovery time to T1.
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Acknowledgments
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Funding for this project was provided by the Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL.
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References
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Accepted for publication February 5, 2003.
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Abstract
Introduction
