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ORIGINAL ARTICLE
Year : 2023 | Volume
: 24
| Issue : 1 | Page : 72-77
To study the effect of three different doses of dexmedetomidine as premedication on the incidence and severity of etomidate-induced myoclonus
Ketki Kaushal, Anita Kumari, Pooja Abbi, Ruchi Gupta
Department of Anesthesia, Sri Guru Ram Das University of Health Sciences, Amritsar, Punjab, India
Correspondence Address:
Dr. Ketki Kaushal
Department of Anesthesia, Sri Guru Ram Das University of Health Sciences, Amritsar, Punjab
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/TheIAForum.TheIAForum_3_23
Background and Aims: Etomidate, a carboxylated imidazole is a rapid-acting nonbarbiturate, nonopioid hypnotic agent that has unique hemodynamic stability, favorable toxic profile, and rapid recovery after a single dose. Myoclonus may occur when etomidate is used for induction of general anesthesia. We tested the hypothesis that premedication with different doses of dexmedetomidine reduces the incidence and severity of myoclonus as well as the side effects induced by etomidate.
Materials and Methods: This prospective, randomized, double-blinded study was done on ninety patients undergoing elective surgical procedures who were randomly allocated into three groups for intravenous administration of premedication of 0.3 μg/kg (Group DL), 0.5 μg/kg (Group DM), and 1.0 μg/kg (Group DH) dexmedetomidine in 100 mL normal saline 10 min before induction of general anesthesia with 0.3 mg/kg etomidate. The primary outcome was to evaluate the incidence of etomidate-induced myoclonus, while the severity of etomidate-induced myoclonus and the incidence of adverse effects were taken as secondary outcomes.
Results: The incidence of etomidate-induced myoclonus was reduced by 13.3% in Group DL, 36.7% in Group DM, and 56.7% in Group DH. The severity of myoclonus was significantly reduced in Group DH as compared to Group DL and DM (P = 0.001). Side effects such as bradycardia, hypotension, and nausea and vomiting were comparable among the three groups.
Conclusion: Premedication with dexmedetomidine 1 μg/kg before induction of general anesthesia not only resulted in a 56.7% reduction in the incidence of etomidate-induced myoclonus but also reduced the severity of myoclonus, without inducing any significant adverse effects, as compared to other two doses.
Keywords: Adverse effects, dexmedetomidine, etomidate, general anesthesia, myoclonus
An ideal induction agent for general anesthesia should have a rapid-onset, smooth induction, good hemodynamic stability, rapid clearance, and recovery with minimal residual sedation and above all minimal side effects. The most common drug used for intravenous induction is propofol. However, in patients with respiratory and airway disease, intracranial hypertension, or patients with shock, etomidate has been the drug of choice for induction. It is a rapidly acting nonbarbiturate nonopioid hypnotic agent containing, unique properties of hemodynamic stability favorable toxic profile, and rapid recovery after a single dose.[1] The side effects associated with the use of etomidate include reduced cortisol synthesis on prolonged use, pain on injection, thrombophlebitis, and myoclonus.[2],[3]
Myoclonus caused by etomidate is sudden in onset with brief involuntary muscle jerks which are either irregular or rhythmic, the incidence being 85% in nonpremedicated patients. Myoclonus can cause myalgias as well as an increased risk of aspiration in nonfasting patients. The mechanism of myoclonus is not clear. Earlier, it was believed to be some form of seizure activity but recently considered to be due to the disinhibition mechanism, where a large dose of etomidate depresses cortical activity before it diminishes subcortical activity.[4]
Many drugs have been used to prevent etomidate-induced myoclonus, but the advantage of α-2 agonist is that it not only causes a reduction in myoclonus but also provides sedation and analgesia. Since there is a paucity of data regarding the ideal dose of dexmedetomidine that should be used as a premedication for the prevention of etomidate-induced myoclonus. Hence, the present study has been designed to compare the effectiveness of three different doses of dexmedetomidine in reducing the severity of etomidate-induced myoclonus by giving it 10 min before induction of anesthesia.
The primary outcome was to evaluate the incidence of myoclonus (involuntary, jerky irregular, or rhythmic muscle movements of short duration) during the first 2 min resulting from injection of etomidate. The secondary outcome was as follows: the severity of etomidate-induced myoclonus and the incidence of adverse effects from the onset of action of dexmedetomidine to the end of the surgery, such as injection site pain, hypotension, bradycardia, nausea and vomiting, dry mouth, and myalgia.
Materials and MethodsA prospective, randomized, and double-blind comparative study was carried out on 90 patients posted for elective surgeries. After obtaining approval from the ethics committee on June 26, 2021, prior written informed consent was taken from all patients. The study protocol was registered with the Clinical Trial Registry of India (CTRI/2022/07/043998) on July 13, 2022. The study included patients of either sex between the age group of 18 and 65 years belonging to Class I and II of the American Society of Anesthesiologists (ASAs).
Patients with allergy to dexmedetomidine or etomidate, adrenal cortex dysfunction, neurologic diseases such as epilepsy, psychiatric disorders, history of uncontrolled hypertension, bradycardia, heart blocks, heart failure, pregnancy, hepatic failure, sepsis or systemic infections, morbid obesity, and anticipated difficult airway were excluded from the study. One hundred patients were assessed for eligibility out of which 8 patients did not meet the inclusion criteria and 2 patients declined to participate, rest 90 patients were subjected to random allocation in groups of 30 each had been done using computer-generated random number table [Figure 1]. Random allocation of patients in groups of 30 each had been done using computer-generated random number table. For further blinding, the slip was taken out by the consultant on duty not involved in the study and the drug was prepared according to the coded slip. Both patient and assessor were blinded.
Figure 1: CONSORT diagram. CONSORT: Consolidated Standards of Reporting TrialsStudy protocol
All patients included in the study were subjected to a detailed preanesthetic checkup and airway assessment 1 day before surgery. Patients were kept nil orally for 6 h preoperatively. On arrival into the operating room, baseline heart rate, respiratory rate, noninvasive blood pressure, electrocardiography, and peripheral capillary oxygen saturation were recorded and taken as baseline readings. Premedication was given slowly over 10 min using:
Group DL (n = 30): 0.3 μg/kg dexmedetomidine in 100 ml of normal salineGroup DM (n = 30): 0.5 μg/kg dexmedetomidine in 100 ml of normal salineGroup DH (n = 30): 1.0 μg/kg dexmedetomidine in 100 ml of normal saline.After preoxygenating all patients with 100% oxygen for 3 min, induction was done with 0.3 mg/kg etomidate injected over a period of 1 min and observed continuously for the occurrence of myoclonus till 2 min after etomidate injection. Loss of consciousness (LOC) was defined as the time from the beginning of the etomidate injection to the time when the patient was not responding to commands (such as “open your eyes”). The highest level of myoclonus was recorded for every patient. The time of onset, duration and intensity of myoclonus were recorded. Intensity of myoclonus was graded on a 4-point scale as validated by Holdcroft et al.[5],[6] 0 – No myoclonus; 1 – Mild myoclonus (involuntary movement at the small unit of muscle group); 2 – Moderate myoclonus (movement in large or two muscle groups or mild generalized response); and 3 – Severe myoclonus (generalized response or intense movement in two or more muscle groups).
After evaluation of myoclonus for 2 min, patients were further given an injection of butorphanol 1 mg and an injection of vecuronium 0.1 mg/kg to facilitate endotracheal intubation. Vitals were observed after the test solution, at induction, and after endotracheal intubation till the end of surgery. Maintenance of anesthesia was achieved with isoflurane in a mixture of 33% oxygen and 66% N2O along with vecuronium for muscle relaxation. Residual neuromuscular blockade was antagonized using an injection of neostigmine 0.05 mg/kg and an injection of glycopyrrolate 0.01 mg/kg after the completion of surgery. The endotracheal tube was removed when the patient started obeying commands and gained adequate motor tone. Side effects such as injection site pain, hypotension, bradycardia, nausea and vomiting, dry mouth, and myalgia were managed. The observations were carried out for at least 24 h postoperatively. Decoding of the drugs was done at the end of the study and the data were evaluated and statistically analyzed.
Sample size
The sample size calculation was performed using Epi Info 7.2.4.0. On the basis of incidence of etomidate-induced myoclonus in the results of previously done study.[7] Group size of the study was determined by considering power as 80% with an alpha error of 0.05%, and 10% dropout rate sample size had been calculated as 30 patients in each group.
Statistical analysis
Data from the present study were systematically collected, compiled in Microsoft Excel, and statistically analyzed using Statistical Package of Social Sciences (SPSS version 26, Chicago, SPSS Inc., USA) to draw relevant conclusions. The observations were tabulated in the form of mean ± standard deviation or numbers and percentages. Data were analyzed using ANOVA and post hoc Tukey test. Categorical data were analyzed using Chi-square test or Fischer's exact test as appropriate. Level of significance was determined as P ≤ 0.05 as significant and P ≤ 0.001 as highly significant.
ResultsThe demographic characteristics of the patients such as age, gender, weight, height, and ASA physical status were comparable among the three groups [Table 1].
Time of LOC was significantly reduced on comparing patients of Group DH with Group DL. Onset of myoclonus was significantly delayed and decreased in duration on comparing Group DH with Group DL [Table 2]. The onset, duration of myoclonus, and LOC were statistically significant among the three groups.
Similarly, the incidence varies as per the dose of dexmedetomidine used [Table 3].
However, on evaluating the grades of myoclonus, there was a highly significant reduction in the intensity of myoclonus in Group DH as compared to Group DL and DM (P = 0.001) [Table 4].
There was no statistically significant difference in baseline vitals among the three groups. There was no significant intergroup variation of heart rate, respiratory rate, oxygen saturation, systolic, diastolic, and mean arterial blood pressure among the three groups intraoperatively. Adverse effects such as injection site pain, myalgias, dry mouth, hypotension, bradycardia, and nausea and vomiting although present, were statistically insignificant when compared [Figure 2].
DiscussionEtomidate is a fast-acting intravenous anesthetic which has a low risk of hemodynamic damage with minimal blood pressure alteration, making it ideal as an induction agent in conditions such as shock, trauma, hypovolemia, or in patients with significant cardiovascular disease. However, its use is limited due to its adrenocortical depression, myoclonus, and injection site pain. Etomidate can induce myoclonus which may increase the risk of aspiration and decrease cardiac reserves and increases cardiac oxygen consumption.[8] Several studies have been conducted to find an appropriate drug to prevent or reduce the incidence and severity of etomidate-induced myoclonus such as midazolam,[9] dexmedetomidine,[10],[11] narcotics,[12] and propofol.[13]
Dexmedetomidine is a highly selective α2 agonist. Release of norepinephrine is inhibited by stimulation of synaptic α2 receptors in sympathetic nerve endings. It causes anxiolysis, analgesia, sympatholysis, and no respiratory depression. Myoclonus reducing effect of dexmedetomidine can be attributed to its anesthetic sparing and sedative effect.
On analyzing the results, the present study confirmed that premedication with different doses of dexmedetomidine reduced the incidence and severity of etomidate-induced myoclonus in a dose-dependent manner. Demographic values were comparable in both groups. The occurrence and severity of myoclonus in each group were observed. The time for LOC was significantly decreased among the three groups. Hence, etomidate dose reduction may be required during induction, after the use of premedication with dexmedetomidine. Malay et al.[10] concluded that premedication with 1 μg/kg dexmedetomidine significantly reduced the time of induction with etomidate as compared to midazolam.
The duration of myoclonus was significantly reduced on comparing the group receiving higher doses with the group getting lower doses (P = 0.0034). It was observed that myoclonus appeared significantly late in the group receiving higher doses with a shorter duration and lesser intensity. A study done by Fernandez and Neethu[14] observed the onset of myoclonus on etomidate injection after 52 s with a mean duration of myoclonus being 90 s in nonpremedicated patients induced with etomidate used for procedural sedation.
We observed myoclonus for 2 min following the etomidate injection. Mizrak et al.,[11] Doenicke et al.,[4] Singh et al.,[9] and Dey and Kumar[15] have not mentioned that for how long and when the myoclonus was observed after etomidate injection. The incidence of etomidate-induced myoclonus was significantly reduced in the group receiving higher doses than those receiving medium and lower doses (P = 0.002). Even the studies were done by Luan et al.[7] and Gunes et al.[16] found a greater reduction in myoclonus on premedication with 1.0 μg/kg as compared to 0.5 μg/kg dexmedetomidine.
There was a highly significant difference in the grade of myoclonus observed in all three groups (P = 0.001). Grade 3 myoclonus (severe form) was observed in a greater number of patients in the group receiving lower doses as compared to groups receiving medium and higher doses of dexmedetomidine. Mizrak et al.[11] graded myoclonus as mild in 16.0%, moderate in 3.0%, and severe in 13.0% of patients in the 0.5 μg/kg dexmedetomidine premedicated group.
At the higher dose of dexmedetomidine, the incidence of hypotension and sinus bradycardia was increased but was statistically insignificant. Myalgia, dry mouth, and injection site pain were found to be statistically insignificant. Miao et al.[17] found that there were no differences in the incidence of dizziness, respiratory depression, nausea vomiting, bradycardia, and hypotension among the control (Group S) and 0.5 μg/kg dexmedetomidine group (Group D). Pierre et al.[18] observed that on comparison of etomidate with propofol, the incidence of postoperative nausea and vomiting was 14.6% and 14.2% in male and 26.8% and 27.5% in female patients during the first two postoperative hours.
The limitation of the study is that there is no control group to compare the incidence and severity of myoclonus due to etomidate. The study assessed ASA I/II patients and does not reflect the optimum population for whom etomidate is the preferred induction drug such as patients in sepsis and cardiac pathology.
ConclusionWe conclude that dexmedetomidine 1.0 μg/kg is efficacious and the most favorable dose in suppressing etomidate-induced myoclonus by allowing a 56.7% reduction in the incidence as well as severity of myoclonus without inducing any significant adverse effects.
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Conflicts of interest
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