Effect of adding clonidine to intrathecal bupivacaine on the quality of subarachnoid block: A prospective randomized double-blind study.

CONTEXT: The purpose of adding an adjuvant to local anesthetic in a central neuraxial blockade is to augment the desirable pharmacological actions of the agent and/or to minimize its undesirable pharmacological effects. Clonidine is an alfa-2 receptor agonist which has gained popularity in recent times as an adjuvant in spinal anesthesia. AIMS: To evaluate the influence of clonidine on the hemodynamic stability and the duration of anesthesia when added to intrathecal hyperbaric bupivacaine. SETTINGS AND
DESIGN: Prospective randomized double blind study. SUBJECTS AND METHODS: Fifty patients scheduled for spinal anesthesia were randomized into two Groups A and B with 25 in each. Group A patients received 3 ml 0.5% heavy bupivacaine + 30 μg (0.2 ml) clonidine and Group B patients received 3 ml 0.5% heavy bupivacaine + 0.2 ml normal saline in the subarachnoid space. The blood pressure and heart rate were closely monitored. The time for attaining peak sensory block, time for two segment regression, decrease in the heart rate, total requirement of mephentermine to counter the hypotension, and the number of patients requiring mephentermine in each group was tabulated and analyzed. STATISTICAL ANALYSIS USED: Descriptive and inferential statistical methods were used to analyse the data. The power of the study was calculated using online power calculator for two independent sample study.
RESULTS: The time for attaining peak sensory block was similar in both the groups. The time for two segment regression in Group A was 62.6 min and in Group B was 38.08 min. Twelve percent of patients in Group A and 52% of patients in Group B required mephentermine with the mean consumption being 0.72 mg in Group A and 5.65 mg in Group B.
CONCLUSIONS: Addition of low-dose clonidine to intrathecal bupivacaine not only prolonged the duration of spinal anesthesia but also provided a stable intraoperative hemodynamic profile.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

The purpose of adding an adjuvant to local anesthetic in a central neuraxial blockade is to augment the desirable pharmacological actions of the agent and/or to minimize its undesirable pharmacological effects. It is the duty of the anesthesiologist to understand and safeguard the subtle balance between the desirable and undesirable effects of the adjuvant, which is mainly influenced by the dose of the drug and the clinical condition of the patient. An adjuvant can be safely used only when the benefit of using it clearly outweighs the possible risks. Many agents viz., midazolam,[1] opioids,[2] ketamine,[3] dexamethasone,[4] neostigmine,[5] etc., were studied as adjuvants in spinal anesthesia. Effect on the duration of spinal anesthesia has been the primary end point in almost all the studies and hypotension, bradycardia, nausea, and vomiting being the most common adverse effects observed. Clonidine is an alfa-2 receptor agonist which has gained popularity in recent times as an adjuvant in spinal anesthesia. Thus in this study, we sought to evaluate the influence of clonidine on the hemodynamic stability and the duration of anesthesia when added to intrathecal hyperbaric bupivacaine.

SUBJECTS AND METHODS

Objectives

To evaluate the efficacy of clonidine as an adjuvant to intrathecal hyperbaric bupivacaine in terms of:

Time for attaining peak sensory block

Time for two segment regression from peak sensory level

Requirement of mephentermine to counter hypotension

Percentage of individuals requiring mephentermine.

Methodology

Approval from the Institutional Ethics Committee was obtained before starting the study. Written informed consent was obtained from all the patients who were enrolled in the study. In this randomized, double-blinded prospective study, all adult patients belonging to the American Society of Anesthesiologists status 1 and 2 scheduled for elective surgeries under spinal anesthesia from January 2008 to June 2008 were included. Patients with a gross spinal abnormality, localized skin infection, neural disease, severe valvular heart disease, shock, hypertension, diabetes mellitus, pulmonary/hepatic/renal diseases, peripheral neuropathy, psychiatric disorders, coagulation abnormalities, dysrhythmias, and patients on beta blockers were excluded from the study. Patients were randomly allocated into two Groups A and B using a computer-generated randomization program. In the operating room, after connecting standard monitors and securing intravenous access, baseline blood pressure and heart rate were recorded, and preloading was done with 500 ml crystalloid solution. Subarachnoid space was engaged in lateral decubitus position in L4-5/L3-4 intervertebral space with 23-gauge Quincke needle under strict aseptic precautions. After confirming a clear and free flow of cerebrospinal fluid, patients in Group A received 3 ml of 0.5% hyperbaric bupivacaine + 30 µg (0.2 ml) of clonidine and patients in Group B received 3 ml of 0.5% hyperbaric bupivacaine + 0.2 ml normal saline. The study medication of 3.2 ml was prepared by an anesthetist who was blinded to the study, in a 5 ml syringe, coded and handed over to another anesthetist who was blinded to the drug for administering and further monitoring. The peak sensory level attained was recorded with a pinprick, and the time was documented. The time for two segment regression from the peak sensory block was also recorded. Vitals were closely monitored in the intraoperative and postoperative period. Injection mephentermine was administered as 6 mg boluses as and when the systolic blood pressure dropped below 90 mmHg. All the observations were tabulated and analyzed statistically.

Statistical analysis

Descriptive and inferential statistical methods were used to analyse the data. In descriptive statistics, calculation of means, standard deviation were done with the help of Microsoft Excel. In inferential statistics, Student's t-test of difference between two means was used to test the difference in the quantitative parameters viz., age, time for attaining peak sensory block, time for two segment regression, decrease in the heart rate, and requirement of mephentermine. Chi-square test was used to test the difference between the gender distributions and the percentage of individuals required mephentermine in both the groups. The power of the study was calculated using online power calculator for two independent sample study.

RESULTS

A total of 50 patients were enrolled in the study during the said period of 6 months with 25 in each group. The sample size was adequate as the power of the study calculated on the basis of time for two segment regression as well as mephentermine consumption was 100%. As represented in Table 1, no significant difference was observed between the two groups in the demographic profile. Mean time required for attaining peak sensory block was slightly more in the clonidine group (16.16 min) than in the control (15.6 min). However, the difference was not statistically significant. However, the time for two segment regression was very much prolonged in Group A (62.6 min) as compared to Group B (38.08 min), and the difference was highly significant. In the hemodynamic domain, the fall in heart rate was more in Group A (27.04 beats/min) than in Group B (20.08 beats/min). However, the stability of blood pressure was observed to be more in the clonidine group. The percentage of patients who required mephentermine to counter hypotension was significantly more in the control group (52%) than in the clonidine group (12%). Similarly, the average consumption of mephentermine was also more in the control group (5.65 mg) than in the clonidine group (0.72 mg), and the difference was statistically highly significant.

Table 1

Clonidine vs control

DISCUSSION

A good volume of literature is available on the role of clonidine as adjuvant in the central neuraxial blockade. Most of the studies[678910] have shown that the duration of anesthesia was prolonged by adding clonidine to intrathecal bupivacaine. The primary outcome of our study is in agreement with the conclusions of those studies. The mean time for two segment regression of the sensory block from the peak sensory level was observed to be significantly more in the clonidine group (62.6 min) than in control group (38.08 min) [Figure 1]. The time for attaining peak sensory level was however comparable between the groups suggesting that the onset of sensory block is not much influenced by adding clonidine in spinal anesthesia [Figure 2]. However, previous studies have shown that clonidine hastened the onset of action in epidural anesthesia.[1112] Regarding the hemodynamics, we observed that the mean falls in the heart rate was more in the clonidine group as compared to the control [Figure 3]. Niemi[13] added 3 µg/kg of clonidine to the local anesthetic in spinal anesthesia and observed that it caused a more fall in the blood pressure. Similar results were observed with the doses of 75 µg[14] and also 30 µg when administered along with sufentanil for labor analgesia.[15] However, in our study, the fall in the blood pressure was significantly less in the clonidine group than in the control group, which was reflected in the mean consumption of mephentermine compared in both the groups [Figure 4] and the also in the percentage of individuals required mephentermine compared in both the groups [Figure 5]. Thus, it was observed in our study that clonidine conferred a better hemodynamic stability when added in low-dose (30 µg).

Figure 1

Time for peak sensory level (original)

Figure 2

Time for two segment regression (original)

Figure 3

Decrease in heart rate (original)

Figure 4

Percentage of patients required mephentermine (original)

Figure 5

Mephentermine consumption (original)

CONCLUSIONS

The addition of clonidine in low-dose (30 µg), as an adjuvant to intrathecal bupivacaine, not only prolonged the duration of spinal anesthesia but also provided a stable intraoperative hemodynamic profile.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.