Effect of intravenous dexmedetomidine on spinal anaesthesia with 0.5% hyperbaric bupivacaine in lower abdominal surgeries: A prospective randomized control study.

BACKGROUND: Regional anesthesia is the preferred technique for most of lower abdominal and lower limb surgeries. For decades, lignocaine had been the local anesthetic of choice for spinal anesthesia. Recent studies show that intravenous clonidine and dexmedetomidine can prolong the duration of the spinal anesthesia. Dexmedetomidine is a more suitable adjuvant compared to clonidine due to its more selective α2A receptor agonist activity. AIM: The study was undertaken to evaluate the effects of intravenous administration of dexmedetomidine on spinal anesthesia with 0.5% hyperbaric bupivacaine in lower abdominal surgeries. STUDY
DESIGN: Prospective randomized, double-blind control study.
MATERIALS AND METHODS: Sixty patients of American Society of Anaesthesiologists Grades I and II, 20-60 years age, undergoing lower abdominal surgeries under spinal anesthesia were randomized into two groups by computer-generated table. Group 1: Bupivacaine and dexmedetomidine group; and Group 2: Bupivacaine and saline group. Spinal anesthesia was given with 15 mg of 0.5% bupivacaine. Patients in Group 1 received dexmedetomidine 1 μg/kg over 20 min followed by 0.5 μg/kg/h, intravenously till the end of surgery. Patients in Group 2 received normal saline. Observations were analyzed using Student's unpaired t-test.
RESULTS: The mean duration of analgesia in group 1 was 219.7 ± 2.55 minutes and in group 2 was 150.2 ± 5.7 minutes. The prolongation in duration of analgesia in dexmedetomidine group was statistically significant. The mean durations of motor blockade in Group 1 and Group 2 were 189.6 ± 2.14 and 158.2 ± 5.31 min, respectively.
CONCLUSION: Intravenous dexmedetomidine is useful to maintain hemodynamic stability and prolong spinal analgesia.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Regional anesthesia is the preferred technique for most of abdominal and lower limb surgeries. To prolong the duration of action of bupivacaine, many adjuvants such as epinephrine, phenylephrine, magnesium sulfate, neostigmine, opioids, clonidine have been used through intrathecal route.[12] Recent studies have shown that intravenous clonidine and dexmedetomidine prolong the duration of spinal anesthesia.[2345] Dexmedetomidine possesses anxiolytic, sedative, analgesic, and sympatholytic properties. Sedation and anxiolysis are produced by binding to α2 receptors in the locus coeruleus.[67] Systemic and intrathecal injection of dexmedetomidine produces analgesia by acting at spinal level, laminae VII and VIII of the ventral horns of the spinal cord.[8] Our study was designed to evaluate the effects of intravenous dexmedetomidine on spinal anesthesia with 0.5% hyperbaric bupivacaine.

Aim

The objective of this study is to evaluate the effect of intravenous administration of dexmedetomidine on spinal anesthesia with 0.5% hyperbaric bupivacaine in lower abdominal surgeries.

Objectives of the study

To evaluate:

The onset and duration of sensory blockade and analgesia

The onset and duration of motor blockade

Hemodynamic stability and sedation.

The present study was a prospective randomized, double-blind control study done on 60 patients undergoing elective lower abdominal surgeries. All cases of (American Society of Anaesthesiologists) Grades I and II with age between 20 and 50 years of either gender were included in the study.

Exclusion criteria

Patients using α2 adrenergic receptor antagonists, calcium channel blockers, angiotensin-converting enzyme inhibitor, patient with neurological disorders, allergy to study drug, coagulation disorders, spine deformities, and pregnancy were excluded from the study.

MATERIALS AND METHODS

After obtaining an approval of the Institutional Ethical Committee, the present study was conducted over a period of 1 year from November 2012 to December 2013. All the patients were randomly allocated into two groups of 30 each using computer-generated random number. An informed, valid, written consent was obtained for conduct of the study. All patients were kept nil by mouth from midnight before surgery and tablet alprazolam (0.01 mg/kg) was administered at bedtime the day before surgery. Intravenous access was established with an 18-gauge cannula and preloading was done with 15 ml/kg lactated Ringer's solution, 30 min before the procedure. A pulse oximeter, noninvasive blood pressure (BP), and electrocardiogram monitor were applied to each patient on arrival to the operating room and baseline parameters were recorded. All the patients were randomly allocated into two groups of 30 each by computer-generated number. The patient and the anesthesiologist were blinded to the treatment group, and all recordings were performed by an anesthesiologist, who was blinded to randomization schedule. An anesthesiologist, who was blinded to the study drug used, documented all the parameters. Group 1 (dexmedetomidine) was Bupivacaine and dexmedetomidine group and Group 2 (control) was Bupivacaine and saline group.

Under strict aseptic conditions, subarachnoid block was performed at L3–L4 intervertebral space through midline approach using a 25-gauge Quincke spinal needle. After ensuring free flow of cerebrospinal fluid 0.5% heavy bupivacaine, 15 mg was administered intrathecally. Group 1: Intravenous dexmedetomidine at a rate of 1 µg/kg as a loading dose in first 10 min was immediately administered after spinal anesthesia, later at the rate of 0.5 µg/kg/h as maintenance dose. Group 2: Intravenous 0.9% saline in equal amounts was administered. Hemodynamic parameters of the patient were recorded.

Following parameters were recorded:

Onset of analgesia was assessed by loss of sensation to pinprick every 30 s till the level of T10 dermatome was achieved. The highest level of analgesia after 10 min was assessed. Intensity of motor blockade was assessed by modified Bromage scale every 2 min for first 10 min. Duration of sensory blockade was assessed by two segments regression and analgesia was assessed from the onset of subarachnoid block to the time of administration of rescue analgesia. Duration of motor blockade was noted. Vital parameters were monitored. Modified Bromage scale was used to assess the motor blockade as shown in Table 1. Side effects if any such as bradycardia, hypotension, and nausea were recorded during the study period. Duration of analgesia was defined as the time from subarachnoid block to visual analog scale >2, at that point rescue analgesia was given as shown in Figure 1.

Table 1

Modified bromage scale

Figure 1

Visual analog scale

Ramsay level of sedation score was used to assess the level of sedation as shown in Table 2.

Table 2

Ramsey level of sedation score

Statistical analysis

Statistical analysis was done using Student's t-test and P < 0.05 was considered statistically significant.

OBSERVATIONS AND RESULTS

In this study, sample was taken at random from a population when each member of the population has an equal chance of being chosen. The purpose is to produce groups that are as nearly similar as possible before the experimental procedure. We used Student's unpaired t-test for statistical analysis. It was used because two sets of population were compared which were independent and identically distributed. The statistical software used was SPSS version 16 (SPSS for Windows, SPSS Inc., Released 2007, Chicago, IL, USA) for analysis. For the operational feasibility in the time-bound period, we decided a sample size of 60 patients. However, for the extrapolation of the results to general population, a larger sample size would be mandatory.

Following were the observations and results of the present study. Comparison of time of onset of analgesia in Group 1 was 2.25 ± 0.18 min and Group 2 was 2.5 ± 0.19 min as shown in Table 3, with P < 0.0001. Comparison of time of onset of motor blockade in both groups was as shown in Table 4. Onset of motor block in Group 1 was 8.51 ± 0.175 min and Group 2 was 9.32 ± 0.14 with P < 0.0001. Comparison of time of two segment regression in both groups is depicted in Table 5. Two-segment regression was prolonged in Group 1 which was 142.5 ± 2.32 and in Group 2 was 93 ± 1.8, which was statistically significant. Comparison of duration of motor blockade in both groups as shown in Table 6 reveals the duration in Group 1 as 189.6 ± 2.14 and Group 2 as 158.2 ± 5.31 with P < 0.0001.

Table 3

Comparison of time of onset of analgesia

Table 4

Comparison of time of onset of motor blockade

Table 5

Comparison of time of two segment regression

Table 6

Comparison of duration of motor blockade

Comparison of duration of analgesia is shown in Table 7. Duration of analgesia in Group 1 was 219.7 ± 2.55 and that of Group 2 was 150.2 ± 5. P value was considered statistically significant.

Table 7

Comparison of duration of analgesia

DISCUSSION

The intrathecal 0.5% hyperbaric bupivacaine is the drug of choice for surgeries lasting for about 120 min. To prolong the duration of spinal anesthesia, various drugs such as magnesium sulfate, neostigmine, midazolam, fentanyl, and clonidine have been used through intrathecal route as adjuvant to local anesthetic. Opioids have attained an integral role as a spinal anesthetic adjuvant, but its addition to local anesthetic solution may lead to pruritus and respiratory depression.[7]

Clonidine, an α2 agonist, is widely used by oral, intrathecal, and intravenous routes as an adjuvant to prolong the duration of spinal anesthesia.[2] Recent studies have shown that giving dexmedetomidine intravenously can also prolong the duration of spinal anesthesia with better hemodynamic stability and minimal side effects.[12] Dexmedetomidine is a new α2 agonist, approved by the Food and Drug Administration in 1999 for use as an analgesic and sedative in the intensive care units.[36] α-adrenoceptor agonists have different α1:α2 selectivity. Clonidine, the first developed and the most known α2 agonist, is considered as a partial α2 agonist, since its α1:α2 selectivity is 200 while α1:α2 selectivity of dexmedetomidine is 1620 and hence has 8 times more affinity for α2 receptors than that of clonidine.[910] Intravenous dexmedetomidine has been used as an adjuvant agent with spinal anesthesia as it prolongs motor and sensory blockade[11] with early onset and prolonged duration of action.[1] Dexmedetomidine differs from clonidine as it possess most selective α2 adrenoceptor agonist activity especially for the 2A subtype of this receptor, which makes it a more sedative and analgesic agent than clonidine. Due to this greater selectivity, dexmedetomidine is more suitable adjuvant to spinal anesthesia compared to clonidine.[3] Despite sound levels of sedation, there is limited respiratory depression, providing wide safety margins.[12] Dexmedetomidine is thus used as an adjuvant in epidural,[13] spinal,[14] and intravenous regional anesthesia. A biphasic cardiovascular response has been described after the administration of dexmedetomidine. The administration of a bolus of 1 µg/kg dexmedetomidine initially results in a transient increase of the BP and a reflex decrease in heart rate. The initial increase in BP is probably due to the stimulation of peripheral α2 β receptors. The initial response lasts for 5–10 min and is followed by a decrease in BP below baseline, and a stabilization of the heart rate, both of these effects are caused by the inhibition of the central sympathetic outflow overriding the direct stimulating effects.[15]

In our study, the demographic profile (age-, gender-, weight-, and height-wise distributions) was comparable in both the groups. The mean of maximum height of sensory blockade in dexmedetomidine group was (T4–T6) compared to (T6–T8) level in control group. The maximum height of sensory blockade of the present study was in accordance with study of Kaya et al.[16] in both the groups. Mean durations of two segment regression in dexmedetomidine and control groups were 142.5 ± 2.32 and 93 ± 1.8 min, respectively, and were in accordance with study of Kaya et al.[16] (145 ± 26 and 97 ± 27 min in dexmedetomidine and control groups, respectively). This was comparable with the study done by Gupta,[7] time required for two segment regression was significantly prolonged in Group 1 (124.35 ± 30.7) when compared with Group 2 (98.54 ± 23.2), P < 0.05. The mean duration of motor blockade in present study was in accordance with study of Al-Mustafa et al.[2] The mean duration of analgesia in the present study was comparable with Whizar et al.[3] (208 ± 43.5 and 137 ± 121.9), Abdelkarim et al.[8] (2011) (209.6 ± 25.9 and 149.4 ± 14.6 min in dexmedetomidine and control group, respectively) and Gupta[7] in Group 1 (259.70 ± 46.87 min vs. 216.40 ± 31.43 min in Group 2, P < 0.001).

Administration of dexmedetomidine intravenously produces supraspinal action, which reduces the release of norepinephrine and inhibits sympathetic activity, thus resulting in decreasing heart rate and BP.[2] Heart rate was significantly decreased in dexmedetomidine group, whereas systolic, diastolic BP, and mean arterial pressure were comparable in both the groups. The sedation score (Ramsay) was higher in Group 1 (dexmedetomidine) as compared to Group 2 (control). Side effects: Bradycardia was observed in 7 (23.33%) patients, hypotension in 2 (6.66%) patients and nausea in 1 (3.33%) patient in dexmedetomidine group, whereas in control group 2 (6.66%) patients had bradycardia, 3 (10%) patients had hypotension and 1 (3.33%) patient had nausea.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.