Evaluation of intense neuromuscular blockade caused by rocuronium using posttetanic count in male and female patients

STUDY OBJECTIVE: To establish the relationship between train-of-four (TOF) nerve stimulation and the number of posttetanic twitches (posttetanic count [PTC]) during neuromuscular blockade caused by rocuronium in males and females. DESIGN: Prospective, observational, clinical comparison. SETTING: Operating room of a university hospital. PATIENTS: 60 ASA physical status I and II patients (30 women and 30 men), aged 18 to 60 years, who were scheduled for elective orthopedic surgery and ear, nose, throat surgery with a planned duration of 2 hours. INTERVENTIONS; During fentanyl, propofol, and nitrous oxide (N(2)O) anesthesia, neuromuscular blockade was evaluated with accelerometry of the thumb using TOF and posttetanic twitch stimulation (PTTS) of the ulnar nerve in patients who received rocuronium 1 mg.kg(-1). MEASUREMENTS AND MAIN RESULTS: The first responses to PTTS were seen at mean times of 34.9 and 37.7 minutes after rocuronium injection in male and female patients, respectively (NS). The average interval between the appearance of a posttetanic response and the first response to TOF stimulation (T1) was not significantly different between male and female patients (15.4 +/- 4.8 min (SD) vs. 15.9 +/- 4.9 min, respectively). There was a significant negative correlation between PTC and the time to first response to TOF nerve stimulation (r = -0.83; p = 0.0001). Gender did not have a statistically significant effect on this relation (F = 0.9; p = 0.34). The intervals from administration of rocuronium to the first appearances of T1 and T2 were not significantly different between the two groups, but the intervals to the first appearances of T3 and T4 were significantly longer in female patients. CONCLUSIONS: Even though the times from initial administration of rocuronium 1 mg.kg(-1) to the first appearances of T3 and T4 are significantly longer in female patients, the intervals to the first detectable responses to PTTS and TOF are not significantly different between females and males. Gender has no significant effect on the relation between PTC and the time to T1.     

Clinical significance of posttetanic count (PTC) during onset and spontaneous offset of neuromuscular blockade induced by vecuronium]

To compare the clinical difference of posttetanic count (PTC) during onset and spontaneous offset, the changes of PTC during an intense neuromuscular blockade induced by vecuronium (0.08 mg.kg-1, i.v.) were measured using a neuromuscular transmission analyzer in 64 adult patients anesthetized with nitrous oxide and halothane. Furthermore, intubation score was evaluated when zero PTC was obtained. The obvious movement of diaphragm associated with endotracheal intubation was observed in 9 out of 20 patients (45%) even when it was performed after obtaining zero PTC. The difference of PTC responses between the onset and the offset was found. The difference was that, during the onset, a tetanic response was observed obviously and the height of the posttetanic single twitch was low, and during offset, even when no response was observed, the height of a posttetanic single twitch response was high with the same PTC. These facts indicate that the same PTC has different clinical significance during onset and offset.     

The relationship of posttetanic count and train-of-four responses during recovery from intense cisatracurium-induced neuromuscular blockade

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 micro g/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 micro g x kg(-1) x min(-1) and 60% N(2)O in O(2), whereas Group 2 (n = 30) had anesthesia maintained with isoflurane (end-tidal concentration 0.8%) and 60% N(2)O in O(2). 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 (T(1)), as well as the correlation between PTC and T(1). In Group 1, the mean times to PTC(1) and T(1) 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 T(1) recovery in both groups. The PTC when T(1) 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.     

Relationship between posttetanic count and response to carinal stimulation during vecuronium-induced neuromuscular blockade

The correlation between degree of peripheral neuromuscular blockade and response to carinal stimulation was evaluated in two groups of 25 patients: one group was anaesthetized with thiopental, N2O and halothane, and the other group received thiopental, N2O and fentanyl. The degree of peripheral blockade was evaluated using train-of-four (TOF) and posttetanic twitch (PTC) stimulation of the ulnar nerve. The degree of diaphragmatic paralysis was evaluated indirectly by stimulating the carina and observing the corresponding muscular response, which was graded as severe, mild or absent. During halothane anaesthesia a PTC of 0 always indicated that no response to carinal stimulation could be elicited. On the appearance of the first response to posttetanic twitch stimulation (PTC = 1), 2% of the patients showed a mild response to carinal stimulation. At the first response to TOF stimulation, 48% of the patients reacted with a mild response. During thiopental, N2O, fentanyl anaesthesia one of 25 patients showed a mild response to carinal stimulation at a PTC of 0. When PTC was 1, 20% of the patients reacted mildly to the stimulation. At the first response to TOF stimulation, 92% showed a response to carinal stimulation; 24% of these responses were severe, necessitating intervention. It is concluded that the TOF response elicited peripherally is a late sign of neuromuscular recovery of the diaphragm, and that the method of counting posttetanic twitches is superior to the TOF response in evaluating early recovery of this muscle. Further, to ensure total diaphragmatic paralysis, the neuromuscular blockade of the peripheral muscles should be so intense that no response to posttetanic twitch stimulation (PTC = 0) can be elicited.     

Recovery of neuromuscular blockade caused by vecuronium is delayed in patients with hypertriglyceridemia

We investigated the effects of hypertriglyceridemia on the onset and recovery of neuromuscular blockade, induced by vecuronium, over the adductor pollicis muscle, electromyographically. Eighteen adult patients with hypertriglyceridemia (hypertriglyceridemia group) and 18 healthy patients with normal serum triglyceride (control group) were studied. The supramaximal stimulating current for train-of-four (TOF) in the hypertriglyceridemia group was significantly higher than that in the control group (45.7 ± 16.7 vs 31.5 ± 9.8 mA; mean ± SD; P = 0.004). The onset of vecuronium 0.1 mg·kg⁻¹-induced neuromuscular blockade in the hypertriglyceridemia group did not significantly differ from that in the control group (240 ± 60 vs 279 ± 88 s; P = 0.132). Times from vecuronium to the return of T1, T2, T3, and T4 in the hypertriglyceridemia group were significantly longer than those in the control group (31.4 ± 6.2 vs 25.5 ± 6.2 min for T1; P = 0.008). During recovery from neuromuscular blockade, T1/control did not differ between the two groups. However, the TOF ratios (T4/T1) in the hypertriglyceridemia group were significantly lower than those in the control group 80–120 min after vecuronium (P < 0.05). We conclude that, in patients with hypertriglycemidemia, a higher current is needed to elicit supramaximal response of the adductor pollicis muscle, and recovery from vecuronium-induced neuromuscular blockade is delayed.     

Potentiation of pancuronium and vecuronium neuromuscular blockade by intravenous salbutamol

Three doses of salbutamol 125 μg iv were given, over 3.5 hr, to a 28-yr-old healthy, previously non-asthmatic man during thiopentone-O₂/ N₂O-isoflurane anaesthesia for treatment and prophylaxis of bronchospasm. Force of contraction of the adductor pollicis was measured before and after the last two injections. Initially, the patient was given pancuronium, 5 mg. Salbutamol, 125 μg iv, was given when T₁ blockade was 45%. Blockade increased to 66% over five minutes and returned to 45% after 18 min. Vecuronium was subsequently used to maintain relaxation. At the end of surgery, salbutamol was followed by an increase in T₁ blockade, from 66% to 86%, over five minutes which returned to 66% after ten minutes. It is concluded that intravenous salbutamol potentiates the neuromuscular blocking effect of nondepolarizing muscle relaxants.     

Nicorandil accelerates recovery of neuromuscular block caused by vecuronium

PURPOSE: To examine the effect of nicorandil, a K ATP channel agonist, on neuromuscular block caused by vecuronium in patients anesthetized with nitrous oxide, oxygen, isoflurane, and fentanyl. METHODS: Sixty adult patients were allocated to four groups of 15: nicorandil-post-tetanic count (N-PTC), nicorandil-train-of-four (N-TOF), control-post-tetanic count (C-PTC) or control-train-of-four (C-TOF) group. In the N-PTC and N-TOF groups, 0.1 mg kg nicorandil was given as a bolus followed by an infusion at 1 microg x kg(-1) x min(-1). Two minutes after the bolus, 0.1 mg x kg(-1) vecuronium was administered. In the C-PTC or C-TOF group normal saline was given instead of nicorandil. PTC and TOF responses were measured mechanically using a force displacement transducer. RESULTS: Time from the administration of vecuronium to the onset of neuromuscular block in the N-PTC or N-TOF group did not differ from that in the C-PTC or C-TOF group (241 +/- 33 vs 225 +/- 32 sec, mean +/- SD). Times from vecuronium injection to the return of PTC in the N-PTC and C-PTC groups, and those of T1, T2, T3, and T4 (first, second, third, and fourth stimulation of TOF) in the N-TOF and C-TOF groups did not differ. Recoveries of PTC in the N-PTC and C-PTC groups followed similar time course. T1/control twitch height and TOF ratio (T4/T1) in the N-TOF group were higher than those in the C-TOF group 80-120 min and 100-120 min after administration of vecuronium, respectively. CONCLUSION: Nicorandil accelerates recovery of neuromuscular block caused by vecuronium.     

The ulinastatin-induced effect on neuromuscular block caused by vecuronium

We examined the effect of ulinastatin, a protease inhibitor purified from human urine, on neuromuscular block caused by vecuronium. Sixty adult patients were randomly divided into four groups of 15 patients each: ulinastatin-posttetanic count (U-PTC), ulinastatin-train-of-four (U-TOF), control-posttetanic count (C-PTC) or control-train-of-four (C-TOF) group. In the U-PTC and U-TOF groups, a bolus dose of ulinastatin 5000 U/kg was administered 2 min before the injection of vecuronium 0.1 mg/kg. In the C-PTC and C-TOF groups, normal saline was administered instead of ulinastatin. The onset of neuromuscular block in the U-PTC and U-TOF groups was significantly slower than in the C-PTC and C-TOF groups (250+/-49 vs 214+/-35 s, mean +/- SD, P < 0.05). The time from the vecuronium injection to the return of PTC in the U-PTC group was significantly shorter than in the C-PTC group (11.0+/-2.8 vs 17.6+/-6.8 min, P < 0.05). Similarly, times to the returns of T1, T2, T3, and T4 (first, second, third, and fourth stimulation of TOF) in the U-TOF group were significantly shorter than in the C-TOF group (18.5+/-5.0 vs 28.0+/-9.1 min for T1, P < 0.05). PTC in the U-PTC group was significantly higher than in the C-PTC Group 10-30 min after the administration of vecuronium (P < 0.05). T1/control twitch height and TOF ratios in the U-TOF group were significantly higher than those in the C-TOF Group 30-70 min and 40-70 min after the administration of vecuronium, respectively (P < 0.05). Ulinastatin delays the onset of neuromuscular block and hastens its recovery caused by vecuronium. IMPLICATIONS: Ulinastatin delays the onset of neuromuscular block and hastens its recovery caused by vecuronium. This is because ulinastatin may release acetylcholine at the neuromuscular junction and increase hepatic and/or renal clearance of vecuronium.     

Double burst stimulation for monitoring profound neuromuscular blockade: a comparison with posttetanic count and train of four.

Double burst stimulation (DBS) is a new nerve stimulation pattern introduced to facilitate tactile evaluation of recovery from neuromuscular blockade. DBS consists of two bursts of high frequency stimulations separated by a short time interval. The relationships between DBS, post-tetanic count (PTC) and train-of-four (TOF) on the evoked twitch response was investigated in 16 surgical patients and 7 intensive care patients given atracurium for muscle relaxation. A significant correlation between the twitch height of the first response to DBS and the number of post-tetanic responses was demonstrated when PTC was more than five (r = 0.47, p < 0.0003). When the first twitch of TOF was still not measurable, the first twitch of DBS ranged from 0 to 20% of the TOF-control twitch height. Furthermore the DBS ratio was significantly correlated to the TOF ratio (r = 0.92-0.96, p < 0.0002). It is concluded that DBS not only can be used for monitoring of recovery from neuromuscular blockade, but also for monitoring of intense degrees of neuromuscular blockade.     

Onset and duration of neuromuscular blockade following high-dose vecuronium administration

To determine the onset time and duration of high doses of vecuronium, 40 ASA Physical Status 1 and 2 patients were randomly assigned to receive either 100, 200, 300, or 400 micrograms/kg of vecuronium bromide for muscle relaxation during elective general surgery. Neuromuscular blockade was continuously quantitated by recording the electromyographic response to stimulation of the ulnar nerve train-of-four. The rate of onset of neuromuscular blockade, endotracheal intubating conditions, duration of neuromuscular blockade, and hemodynamic effects of vecuronium at each dose were evaluated and compared. The time from vecuronium administration to complete abolition of twitch tension (T1 = 0%) decreased from 208 +/- 41 to 106 +/- 35 s as the vecuronium dose was increased from 100 to 400 micrograms/kg (P less than 0.01). Corresponding times to endotracheal intubation (T1 less than 20%) also decreased from 183 +/- 24 to 96 +/- 31 s with increasing doses (P less than 0.01). Recovery time (T1 = 25%) increased from 37 +/- 13 to 138 +/- 24 min with increasing doses (P less than 0.01). No significant hemodynamic differences between the four groups were observed. Endotracheal intubating conditions were good or excellent in all patients. High doses of vecuronium may, therefore, be a useful alternative to succinylcholine when a rapid onset of neuromuscular blockade is required.     

Localized hypothermia influences assessment of recovery from vecuronium neuromuscular blockade

The purpose of this study was to determine the extent to which localized hypothermia of a monitored extremity alters the assessment of recovery from vecuronium- induced neuromuscular blockade. Bilateral integrated evoked electromyographic (IEMG) responses were measured in the ulnar distribution of 14 anaesthetized patients who had differing upper extremity temperatures as measured at the adductor pollicis to determine whether localized hypothermia alters the clinical assessment of spontaneous recovery from vecuronium- induced neuromuscular blockade. All patients received general anaesthesia with thiopentone, N₂O/ O₂ and opioid; 11/14 patients received isoflurane for blood pressure control. Bilateral adductor pollicis, oesophageal and ambient temperatures, and IEMG evoked response (t₁) expressed as percent unparalyzed control were recorded during the anaesthetic. The difference in evoked response between the warmer and the colder upper extremity was calculated at 25%, 50% and 75% spontaneous recovery from neuromuscular blockade in the warm extremity. Differences in temperature between extremities ranged from 0.2–11° C. The difference in IEMG- evoked response between extremities was proportional to the difference in temperature, and there was a direct correlation (r = 0.78) between IEMG response and extremity temperature; IEMG response was absent when extremity temperature was less than 25° C. We concluded that localized hypothermia in the monitored extremity decreases the IEMG- evoked response to vecuronium neuromuscular blockade; the greater the temperature decrease, the less the evoked response. Thus, the administration of nondepolarizing relaxants may be inappropriately influenced by monitoring neuromuscular blockade in a cold extremity, especially if its temperature is <25° C.     

Reversal of intense neuromuscular blockade following infusion of atracurium

In order to evaluate reversal time from very intense neuromuscular blockade caused by a continuous infusion of atracurium, the time course of neostigmine induced reversal from different levels of neuromuscular blockade was evaluated using the post-tetanic count (PTC) and the train-of-four (TOF) in 30 patients anesthetized with nitrous oxide, fentanyl, and thiopental. Reversal time (time from administration of neostigmine at different PTC levels to a TOF ratio of 0.7) was found to depend upon the degree of blockade at the time of reversal. Median reversal time from a PTC of 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, and greater than 13 (but less than 10% twitch height) to a TOF ratio of 0.7 was 31, 23, 19, 18, 14, and 13 min, respectively. Spontaneous recovery from PTC level of 1-2, when atracurium infusion was stopped, to a PTC level at which antagonism was induced and reversal time were both correlated to the square root of the PTC. Total recovery time (spontaneous recovery plus reversal time) was not shortened by an early injection of neostigmine. It is concluded that neostigmine administration during intense neuromuscular blockade following atracurium infusion does not shorten total recovery time and offers no clinical advantages.     

Effects of age on neuromuscular blockade by vecuronium as measured by accelography under sevoflurane anesthesia

We evaluated possible differential effects of age on a single bolus intravenous injection of vecuronium using accelography under sevoflurane anesthesia. Thirty anesthetized patients were divided into three groups of 10 patients as follows: group 1=age 1–5 years; group 2=age 20–40 years, and group 3=age >70 years. Vecuronium 0.1 mg·kg⁻¹ was given to facilitate tracheal intubation. Onset time, i.e., the time from the start of injection of the first dose of vecuronium to development of maximal twitch depression in group 1 was significantly shorter than those in groups 2 and 3 (103.5±30.4s, 166.5±32.7s, and 202.5±56.7s; mean±SD;P<0.01). Clinical duration, i.e., the time from completion of maximal block to 25% recovery of train-of-four (TOF) ratio in group 1 was significantly shorter than that in group 3 (43.6±12.0 min and 67.3±15.6 min;P<0.01). The reversal time from 25% to 75% of the TOF ratio after the administration of neostigmine in group 1 was not significantly different from those in groups 2 and 3 (172.5±73.9s, 219.0±59.7s, and 222.0±155.7s). The authors conclude that the time to maximal twitch depression after the administration of vecuronium is significantly shorter in children than that in adults, and that the fastest recovery from vecuronium is also observed in children.