Intraoperative hemodynamics with vecuronium bromide and rocuronium for maintenance under general anesthesia

Abstract

Aims:

The present study is undertaken to compare the hemodynamic effects using vecuronium versus rocuronium for maintenance in patients undergoing general surgical procedures.

Settings and Design:

It is a prospective, randomized, and cohort study.

Subjects and Methods:

100 patients were randomly divided into two groups. All patients were induced with 5 mg/kg of thiopentone sodium, and intubation conditions were achieved with 1.5 mg/kg of suxamethonium, using a well-lubricated cuffed endotracheal tube of appropriate size. When the patient started to breathe spontaneously, they were administered either 0.6 mg/kg of rocuronium (Group A) or 0.1 mg/kg of vecuronium (Group B). Hemodynamic parameters (heart rate and mean arterial pressure [MAP]) were monitored before administering the drug; at 1, 5, 10, 15, and 20 min after the drug and at the end of the surgery.

Statistical Analysis Used:

Data were compiled, analyzed and presented as frequency, proportions, mean, standard deviation, percentages, and t-test using SPSS (version 16). A P < 0.05 was considered as significant.

Results:

The heart rate increased significantly at 1-min and 5-min after administration of rocuronium (83.76 ± 10.37 and 86.8 ± 9.98), unlike vecuronium. However, it gradually declined towards normal, and change in heart rate with either drug was not significant beyond 10 min. The MAP decreased significantly at 1-min after administration of rocuronium (96.68 ± 7.57) which later showed a gradual increasing trend when compared to vecuronium which had no statistically significant change at any time.

Conclusions:

For short surgical procedures rocuronium is a good alternative to vecuronium, as the drug is reasonably cardio stable, produces excellent intubation conditions, has a shorter duration of action, and shows minimal cumulative effect.

INTRODUCTION

Rapid and safe endotracheal intubation is of utmost importance in the practice of general anesthesia. The role of muscle relaxation is used to serve two prime purposes, to facilitate endotracheal intubation and the other, to provide surgical relaxation.[1,2,3] The ease of performing endotracheal intubation depends upon the degree of muscle relaxation, depth of anesthesia, and skill of anesthesiologist.[2] The onset time, duration of a muscle relaxation and type of surgery are critical factors in choosing the appropriate muscle relaxant to achieve rapid, successful tracheal intubation.[4]

An ideal neuromuscular blocking agent for intubation should have a rapid onset, brief duration of action, provide excellent intubation conditions, and should be free from side-effects. For several decades, suxamethonium was the gold standard relaxant for rapid sequence intubation. However, the unintended side-effects such as muscle fasciculation, hyperkalemia, the rise in intracranial and intraocular pressures led to the search of newer relaxants.[5]

Among the nondepolarizing muscle relaxants, vecuronium and atracurium were presented as an attractive alternative to succinylcholine. However, neither of these agents had the onset time as short as needed for endotracheal intubation.[2] The various methods such as using higher bolus dose, priming principle, timing principle were used to reduce their onset time, but at the cost of a prolonged duration of action or hazardous side-effects.[6] Therefore, the quest for an ideal nondepolarizing agent continued for rapid and safe endotracheal intubation until rocuronium was introduced into clinical practice.

Suxamethonium is the most commonly and widely used for more than 40 years as a muscle relaxant in patients with full stomach or the patients requiring emergent intubation. In addition to fasciculation, suxamethonium has got many side-effects such as bradycardia, and other dysrhythmias, rise in serum potassium, postoperative myalgia, incidence of prolonged recovery in patients with pseudocholinesterase deficiency and triggering of malignant hyperthermia. Rocuronium fills the gap for an agent with rapid onset while it lacks the adverse effects associated with suxamethonium and retains medium duration of action.[7]

Different techniques that have been used to decrease the effective onset time of nondepolarizing muscle relaxants include priming and the administration of large doses.[8,9] A technique that uses the “timing principle” has been applied to rapidly produce good intubating conditions. When this technique is used, a single bolus dose of a muscle relaxant is administered, and anesthesia is induced at the onset of clinical weakness.[10] In this way, the time from the induction of anesthesia to complete muscle relaxation is reduced, and the peak effect of the muscle relaxant and intravenous (IV) induction drug may more closely coincide.[11]

The major advantage of rocuronium is its rapid onset of action, which is useful for facilitating tracheal intubation. In adults, satisfactory intubating conditions developed between 60 and 90 s after injection of twice the 95% effective dose of rocuronium, but there are few data about onset of neuromuscular blockade and tracheal intubation conditions after rocuronium in young children.[12,13,14] Clinically acceptable intubating conditions are produced more rapidly and are of better quality, after rocuronium compared with both vecuronium and atracurium. Good-to-excellent intubating conditions after rocuronium 0.6 mg/kg can be obtained within 30–60 s in young children.[15]

In India, rheumatic heart disease is still common and in these patients, multiple valvular lesions are encountered. It is conceivable that rocuronium (an analogue of vecuronium) with mild vagolytic action leading to small increase in heart rate, similar duration of action to vecuronium, a favorable recovery pattern, and noncumulative property may be beneficial in most cardiac lesions. However, these hemodynamic effects have mostly been described in patients undergoing coronary artery bypass graft surgery, and there is limited literature regarding its use in patients undergoing valve surgery in conjunction with morphine as the opioid.[16] Vecuronium and rocuronium decrease the heart rate and should be preferred in patient with faster baseline heart rate. In terms of intubating conditions rocuronium and vecuronium provide best conditions, but onset is faster with rocuronium.

The purpose of this study is to compare the hemodynamic effects using vecuronium versus rocuronium in patients undergoing general surgical procedures.

SUBJECTS AND METHODS

After obtaining Institutional Ethical Committee clearance and written informed consent for surgery and general anesthesia, this prospective, randomized study was done with 100 hemodynamically stable patients, belonging to American Society of Anesthesiologists physical status Grades I and II, aged between 20 and 60 years, undergoing various surgical procedures were randomly selected over a period of 3 months. All patients had undergone thorough preanaesthetic evaluation on the previous day of surgery.

Patients with known allergy to the pretreatment or study drugs, with anticipated difficult airway intubation and with known systemic disorders such as cardiovascular, pulmonary, hepatorenal, or metabolic diseases were excluded from the study. The method of randomization applied was in the pattern “A,” “A,” “B,” “B,” “A,” “A,” and so on. Basic lab investigations such as hemoglobin, fasting or random blood sugar, blood urea, serum creatinine, electrocardiography, and chest X-ray was carried out routinely in all patients. The entire procedure and purpose was explained to the patient in his/her language.

Each patient was premedicated with injection glycopyrrolate (0.005 mg/kg), injection midazolam (1 mg), injection ondansetron (4 mg), injection ranitidine (50 mg) administered intravenously before shifting to the operating room. Atropine and promethazine were deliberately avoided since they alter the hemodynamics. All these patients were kept nil per oral from midnight. Pulse rate and blood pressure were recorded prior to and after the administration of premedication.

An IV line was secured using 18-gauge IV cannula, and routine monitors (electrocardiogram, noninvasive blood pressure, pulse oximetry) were applied in the operating room. The small silver electrodes of the peripheral nerve stimulator were placed so as to stimulate the ulnar nerve and to monitor the effect of neuromuscular blocking agents. Baseline readings were recorded. All patients were given 5 ml/kg/h of lactated Ringer's solution during the study period. Drug and equipment necessary for resuscitation were kept ready. All patients were induced with 5 mg/kg of injection thiopentone sodium, until the loss of eyelash reflex and intubation was achieved with 1.5 mg/kg of suxamethonium, using a well-lubricated cuffed endotracheal tube of appropriate size. When the patient started to breathe spontaneously, 0.6 mg/kg of rocuronium was administered to the patients belonging to the study group and 0.1 mg/kg of vecuronium was administered to the patients belonging to the control group.

All patients were ventilated with nitrous oxide-oxygen using Bain's circuit in the ratio of 66:33%. Isoflurane in appropriate concentrations (1–2%) was used whenever required to maintain deeper planes of anesthesia. Halothane was deliberately avoided since it interferes with cardiovascular stability. Pulse rate and blood pressure were recorded 1-min after administration of the drug and every 5 min until 20 min and at the end of the surgery. To obtain mean arterial pressure (MAP) we used the formula, diastolic blood pressure +1/3 pulse pressure. Repeat doses of 1/5^th the original dose were given in both groups with respect to the T2 response in train-of-four sequence. T1-90% blockade; T2-85% blockade; T3-80% blockade, and T4-75% blockade.

Residual paralysis at the end of surgery was reversed with 0.05 mg/kg of neostigmine and 0.02 mg/kg of glycopyrrolate given intravenously. After thorough oral suctioning, extubation was done at the onset of regular, spontaneous respiration, confirming spontaneous eye opening, intact deglutinating reflexes, and good limb movements. The patient was then shifted to postoperative recovery ward, and any adverse reactions noted.

The following observations were recorded during the procedure, that is, heart rate recorded either by electrocardiogram or pulse oximetry at regular intervals until the end of surgery and blood pressure was recorded at regular intervals using a sphygmomanometer. The primary outcome measure of the study was to assess the hemodynamic changes with respect to heart rate and MAP. The secondary outcome measures were to look for any complications such as arrhythmias, ischemic changes, or hypotension.

Statistical analysis

The analysis of the data and application of various statistical tests were carried out with help of statistical package for social science (SPSS) version 16 for Microsoft Windows and the sample size was calculated for 5% level of significance and power of the study was 95%. Data were compiled, analyzed and presented as frequency, proportions, mean, standard deviation, percentages, and t-test. A P < 0.05 was considered as significant. Finally, the results in the two groups were compared to draw the conclusion.

RESULTS

The study was conducted in our institution and involved 100 patients undergoing elective surgery under general anesthesia. The patients selected were randomly divided into two groups. One group of 50 patients had received rocuronium 0.6 mg/kg (Group A), and the other group of 50 patients had received vecuronium 0.1 mg/kg (Group B). The hemodynamic changes were observed in administering the drug and every 5 min until 20 min and at the end of surgery.

Demographically both groups were similar in respect to age and sex [Table 1].

Table 1.

Demographics

Heart rate

In the study group, a significant increase in pulse rate was observed at 1-min (P < 0.05) and 5 min after the administration of the drug (P < 0.001) compared with preoperative values. The maximum increase was observed at 5 min after the administration of the drug. Pulse rate then showed a decreasing trend after 5 min of administration of rocuronium and was found to be statistically insignificant (P > 0.05).

Whereas, in the control group, pulse rate showed a mild increase at 1-min after injection of the drug. Then the pulse rate showed a decreasing trend and no significant change in pulse rate was observed at 5 min, 10 min, 15 min, and 20 min or at the end of the surgery when compared to preoperative values. The change in pulse rate after the administration of vecuronium was found to be statistically insignificant (P > 0.05). The relevant statistical data of pulse rate changes with rocuronium and vecuronium are summarized in Table 2 and Figure 1. The degree of freedom used in the calculation was 98 with a 95% confidence interval.

Table 2.

Mean heart rate (beats/min)

Figure 1.

Comparison of mean pulse rate. A = Rocuronium, B = Vecuronium

Mean arterial pressure

In the study group, MAP showed a significant decrease 1-min after injection of the drug (P < 0.05). Then the MAP showed a gradual increasing trend. These changes in MAP showed not much difference with the preoperative value and were found to be statistically insignificant (P > 0.05).

In the control group with vecuronium, the MAP showed a gradual decreasing trend after the administration of the drug. These changes in MAP showed not much difference with the preoperative values and were statistically insignificant (P > 0.05). The relevant statistical data of pulse rate changes with rocuronium and vecuronium are summarized in Table 3 and Figure 2. The degree of freedom used in the calculation was 98 with a 95% confidence interval.

Table 3.

Mean blood pressure (mmHg)

Figure 2.

Comparison of mean arterial pressure. A = Rocuronium, B = Vecuronium

DISCUSSION

Dale discovered the role of acetylcholine in neuromuscular transmission and gave new insights in the structure activity relationship of muscle relaxants and the basic differentiation of two classes of muscle relaxants-the depolarizers and nondepolarizers. Succinylcholine reliably produces muscle relaxation within 60 s of its administration. The introduction of rocuronium bromide, ORG-9426, a nondepolarizing agent with a quick onset and intermediate duration of action, has one-sixth of potency of vecuronium and is extremely cardio stable and has a rapid onset of action, which would render it the muscle relaxant of choice for facilitation of both routine and crash intubation.[1]

Taking these aspects into consideration, the present study was undertaken to evaluate and compare the hemodynamic changes between vecuronium and rocuronium. In this study conducted, patients were given rocuronium 0.6 mg/kg in Group A and vecuronium bromide 0.1 mg/kg intravenously in Group B. There were no statistically significant differences in patient's age or sex. (P > 0.05) [Table 1].

The cardiovascular effects were studied by observing the changes in pulse rate and MAP. The changes were observed in the preoperative period, 1-min after injection of the drug and thereafter every 5 min interval until 20 min and at the end of the surgery.

In our study, in the rocuronium group, we could notice a significant increase in pulse rate (P < 0.05) at 1-min and 5 min after the administration of the drug. The maximum increase in pulse rate was observed at 5 min after the administration of the drug. Pulse rate then showed a decreasing trend and the change in pulse rate was found to be statistically insignificant (P > 0.05) compared to preoperative values. 1-min after administration of the drug, pulse rate increased by 10% compared to the preoperative value. 5 min after administration of the drug pulse rate increased by 14.8% compared to the preoperative value.

In case of MAP, in the study group with rocuronium, we could observe a statistically significant decrease (P < 0.05) in MAP at 1-min after the administration of the drug. Then the MAP showed a gradual increasing trend. These changes in MAP showed not much difference with the preoperative value and were found to be statistically insignificant (P > 0.05).

One minute after administration of the drug MAP decreased by 7.1% compared to preoperative value.

In the control group with vecuronium no statistically significant (P > 0.05) change in pulse rate and MAP were observed at 1-min, 5 min, 10 min, 15 min, 20 min, and at the end of surgery compared to preoperative values.

In the study group and control group, no other abnormalities such as ventricular ectopic beats, ischemic changes or rhythm disturbances were observed during our study. No episodes of hypotension were observed. There was no prolonged muscle weakness or residual paralysis in any of the cases studied.

Hemodynamic effects of vecuronium was studied by Wierda et al., in 1989 and reported that vecuronium did not influence the heart rate, or systolic, or diastolic arterial blood pressure.[17]

McCoy et al., compared the hemodynamic effects of rocuronium during fentanyl anesthesia with vecuronium. They concluded in their study that rocuronium caused a mild increase in heart rate while MAP was decreased though insignificantly.[18]

Clinical response to rocuronium during isoflurane anesthesia was studied by Quill et al., in 1991.[19] They reported in their study that rocuronium caused a mild increase in heart rate while the MAP decreased though the changes were statistically found to be insignificant.

Cardiovascular effects of an intubating dose of rocuronium was studied by Wierda et al., in 1997 and concluded that rocuronium caused a mild increase in heart rate without a change in MAP.[20]

In addition to this, studies conducted by Sacan et al., have clearly shown that Sugammadex administered at 4 mg/kg intravenously, more rapidly, and effectively reversed residual neuromuscular blockade with rocuronium when compared with neostigmine (70 mcg/kg) and edrophonium (1 mg/kg).[21] Sorgenfrei et al., have also done studies proving that at doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner.[22]

In our study too, we found that rocuronium caused mild increase in heart rate while the MAP decreased after the administration of the drug. The results of the present study also showed that vecuronium is associated with good hemodynamic stability and do not cause any significant change in pulse rate or MAP. Therefore, in addition to rocuronium providing good intubation conditions, it exhibits good hemodynamic stability, and has a rapid onset of action with much lesser side-effects when compared to other nondepolarizing muscle relaxants. Moreover, with the availability of the first selective relaxant binding agent, sugammadex which is specific for reversal of neuromuscular blockade by rocuronium, makes it a useful addition to the reversal agents commonly employed in anesthetic practice. Hence, rocuronium can prove to have a greater role with respect to general anesthesia in the years ahead. Apart from this it is also possible to use the evidence from this study in noncardiac surgeries using these agents when suxamethonium has to be eliminated for its adverse effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest