Introduction
Regional anesthesia techniques are preferred for mostof the abdominal and lower limb surgeries. Among them, subarachnoid block (SAB) is a widely used regional anesthetic technique, particularly advantageous for gynecological, lower abdominal, pelvic andlower limb surgeries as it allows the patient to remain awake, minimize or completely avoid problems associated with airway management.

Hyperbaric Bupivacaine 0.5% is extensively used for spinal anaesthesia. Alpha 2 adrenoceptor agonists like clonidine and dexmedetomidine have been studied for prolongation of spinal anaesthesia with promising results. 1-4
Alpha 2 receptor agonists act on adrenoreceptors in spinal cord and block the conduction of C and A delta fibres, increasing potassium conductance and intensifies conductance block of local anaesthetic.
Dexmedetomidine, a new ? 2 adrenoreceptor agonist is highly specific for ?2 adrenoreceptor, possesses anxiolytic, sedative, analgesic, anaesthetic sparing effects and sympatholytic properties. Sedation and anxiolysis are produced by binding to ?2 receptors in the locus coeruleus. Because it affects the locus ceruleus area which is associated with modulation of sleep and respiration, it has a sedative effect with minimal respiratory depression. Systemic and intrathecal injection of dexmedetomidineproduces analgesia by acting at spinal level, laminae VII and VIII of theventral horns of the spinal cord. Dexmedetomidine is currently approved by the FDA for administration by the intravenous route but approval for intrathecal route is still awaited. Commonly used intravenous methods of dexmedetomidine include a bolus intravenous administration before or after spinal anaesthesia and a loading dose followed by continuous infusion. However a loading dose followed by continuous infusion has been reported to increase the incidence of hypotension and bradycardia.

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

The optimal dose ormethod of administration of intravenous dexmedetomidine under spinal anaesthesiahas not been defined yet. Current literature suggests that a ceiling effect was seen on prolongingpost-spinal analgesia after 0.5mcg/kg boluses. With increasing the dose beyond0.5 mcg/kg resulted in unwanted side effects notably bradycardia and excessivesedationSo, the present study was conducted to evaluate which bolus dose of intravenous dexmedetomidineout of 0.5mcg/kg and 1.0 mcg/kg was more effective in prolongation of duration of spinal anaesthesia with 0.5% hyperbaric bupivacaine with minimal side-effectsin abdominal surgeries.

Aims and objectives
PRIMARY OBJECTIVE:
To find out which bolus dose of intravenous dexmedetomidine out of 0.5mcg/kg and 1.0 mcg/kg is more effective in prolongation of duration of spinal anaesthesia with 0.5% hyperbaric bupivacaine with minimal side-effects.

SECONDARY OBJECTIVES
To observe the differences between group of patients receiving low bolus dose of intravenous dexmedetomidine and group of patients receiving higher bolus dose of intravenous dexmedetomidine before intrathecal injection of hyperbaric bupivacaine.

To compare the incidence of side effects and adverse effects between the group of patients receiving low bolus dose of intravenous dexmedetomidine and group of patients receiving higher bolus dose before intrathecal injection of hyperbaric bupivacaine.

Material and methods
STUDY DESIGN: The study was a hospital based prospective,observational study.

STUDY SITE: The study was conducted in BharatiVidyapeeth Deemed University Medical College and Hospital, SangliSTUDY DURATION: The study duration was of 18 months.

STUDY POPULATION: All patients admitted in the hospital for undergoing abdominal surgeries under spinal anesthesia SAduring the study period January 2018 to December 2018 were included in the study.

STUDY SUBJECTS:
Inclusion criteria: All patients undergoing major abdominal surgeries under SA with hyperbaric Bupivacaine were included in the study as per the consultant anesthesiologist’s discretion.

Exclusion criteria:Patients using ?2 adrenergic receptor antagonists,calcium channel blockers, angiotensin?converting enzymeinhibitor, patient with neurological disorders, allergy tostudy drug, coagulation disorders, spine deformities, pregnancy and patients unwilling to participate in the studywere excluded from the study.

Patients meeting the inclusion criteria were divided into 2 groups, Group A and Group B. The allotment of the patients in either group A or group B was decided by the consultant anesthesiologist.

Group A:A total of 83 patients received bolus of 0.5 mcg/kg body weight of intravenous Inj. Dexmedetomidine over 10 min followed by 5 min later Inj. Bupivacaine 0.5% heavy intrathecally.

Group B:A total of 83 patients received bolus of 1.0 mcg/kg body weight of intravenous Inj. Dexmedetomidineover 10 min followed by 5 min later Inj. Bupivacaine 0.5% heavy intrathecally.

ETHICS:
Institutional ethical committee approval was obtained prior to the initiation of the study. Written informed consent was obtained from all the study participants before inclusion into the study. No identifiable data was collected and all the collected data was confidential. Although the results of the trial will be published or presented, the identity of the patients will remain confidential.
SAMPLE SIZE:
A sample size of 76 patients in each group was estimated for a study power of 90% and two tailed alpha of 0.05, expected difference between both the groups was 61.5 and standard deviation was taken as 37. Considering 10% dropout rate, total 83 patients in each groupundergoing abdominal surgeries under spinal anesthesia with intrathecal hyperbaric 0.5% bupivacaine fulfilling the inclusion criteria were enrolled in the study.

STUDY CONDUCT:
After receiving the study subject in pre anesthesia room, the baseline parameters were noted. All patients were kept nil by mouth from midnight before surgery. Intravenous access was established with an 18?gauge cannula. All the patients were premedicated with injection ondansetron 4 mgiv. All emergency drugs were kept ready. Standard monitoring of vitals was done using non-invasive arterial blood pressure (BP), ECG, heart rate (HR) and pulse oximetry. The arterial blood pressure (BP), baseline mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2) was recorded. Preloading was done with 15 ml/kg lactated Ringer’s solution, after which the study drug was administered over a 10 min period. Five min after end of study drug infusion, the patient was placed in sitting position. Under all safety aseptic precautions, lumbar puncture was performed through a midline approach using a 25-gauge Quincke spinal needle. Upon confirmation of the intrathecal position of the needle by back flow and slight aspiration of cerebrospinal fluid, the intrathecallly hyperbaric bupivacaine 0.5% was injected. The amount of hyperbaric bupivacaine 0.5% was determined empirically by the anesthesiologist according to the height, weight and age of the patient and in consideration of the target sensory level of anesthesia. After administration of the intrathecal anesthetic, the patient’s position was immediately changed to supine and the patient was given 4L of O2 by simple face mask. Intra-operatively, heart rate, SpO2, mean arterial blood pressure, systolic and diastolic blood pressures were recorded continuously. The sensory block level was assessed by the loss of pinprick sensation with a 24-gauge hypodermic needle along the mid-clavicular line bilaterally. The motor block level was assessed by the modified Bromage scale. Appendix 1The onset of sensory and motor blockade was noted. The level of sedation was evaluated throughout the study period using Ramsay Sedation Score (RSS). Appendix 1
Preparation of Dexmedetomidine infusion: Two ml of Inj. Dexmedetomidine (one ampoule contain 2 ml, 100 microgram per ml) was withdrawn in 50 ml syringe and diluted with 38 ml of normal saline. Total 40 ml volume was prepared (5 microgram per ml). Syringe was loaded on syringe infusion pump and connected to patient through IV extension set.
Intra-operative and post-operative complications if any were observed and managed according to standard procedures and directions. Hypotension defined as ; 20% decrease in systolic blood pressure compared with baseline pressure was treated with 50-100 ml of intravenous crystalloid fluid replacement and a 6 mg ephedrine bolus. Bradycardia defined as a heart rate of less than 50 bpm was treated with 0.6 mg of intravenous atropine. Shivering was treated with warm drapes and warm IV fluids. Time taken for first demand of rescue analgesia was noted and analgesia was provided in the form of injection Tramadol 50 mg slowly intravenously if VAS score is ; 3/4. Time for two segment regression of sensory blockade was assessed. All the patients were observed in post?anesthesia recovery room and later in high dependency ward as per institutional protocol. A questionnaire prepared was filled up as per response of patients and charts were maintained.

OUTCOMES MEASURED:
The primary outcomes measured were
Onset and duration of sensory block
Onset and duration of motor block
Visual analogue score (VAS) for pain
Ramsay Sedation Score
Modified Bromage scale
The secondary outcomes measured were
Postoperative hemodynamic variations
Postoperative temperature variations
Postoperative respiratory depression
Postoperative complications
STATISTICAL ANALYSIS:
Normality of data was assessedusing the Kolmogorov–Smirnov test. Qualitative data was expressed using descriptive statistics.Quantitative data were expressed as median andrange. Between group differences were assessed using unpaired t test. All analyses were done at 5%significance using IBM SPSS Statistics for Windows, Version 20.0. Armonk,NY and Microsoft Excel 2013.

Observations and Results
In the present study all patients meeting the inclusion criteria during the study period January 2 018 to December 2018 were enrolled in the study. Total 83 patients were enrolled in each group. There were no deviations from the study protocol.
a.Baseline demographic and clinical parameters were comparable in both groups. Table 1 and Table 2
Table 1: Demographic characteristics
Group A Group B
Age (Medrange) 45yrs 38 to 59yrs 45yrs 35 to 60 yrs
Gender
Males n (%) 13 (15.66%) 12 (14.46%)
Females n (%) 70 (84.34%) 71 (85.54%)
Table 2: Clinical characteristics
Group A Group B
Diagnosis
Bilateral inguinal hernia 13 (15.66%) 12 (14.46%)
Uterine fibroid 70 (84.34%) 71 (85.54%)
Surgery performed
Abdominal hysterectomy 70 (84.34%) 71 (85.54%)
Bilateral hernioplasty 13 (15.66%) 12 (14.46%)
b. Sensorimotor block:
There was a statistically significant difference in the duration of both sensory and motor blockade between both the groups. Group B patients showed a faster onset of sensory block whereas onset of motor block was the same in both groups. Sensorimotor block was prolonged significantly in patients belonging to Group B. Table 3 and 4
Values are expressed as Median Range Table 4: Motor block characteristics
Group A Group B P value
Time of onset of motor block Time in seconds 208 135-286 208 126-284 0.0864
Duration of motor block time
Table 3: Sensory block characteristics
Group A Group B P value
Time of onset of sensory block Time in seconds 8664-118 8363-108 ;0.05
Duration of sensory block
Time in minutes 227 202-245 238 217-253 ;0.0001
Values are expressed as Median Range Table 4: Motor block characteristics
Group A Group B P value
Time of onset of motor block Time in seconds 208 135-286 208 126-284 0.0864
Duration of motor block time in minutes 200 178-216 208 192- 235 ;0.0001
Table 3: Sensory block characteristics
Group A Group B P value
Time of onset of sensory block Time in seconds 8664-118 8363-108 ;0.05
Duration of sensory block
Time in minutes 227 202-245 238 217-253 ;0.0001
g. Complications/ADRs:
The patients in Group B had comparatively greater adverse events of hypotension, bradycardia and nausea as compared to Group A. Table 5: Complications
Group A Group B
Hypotension 13 (15.66%) 16 (19.28%)
Bradycardia 17 (20.48%) 20 (24.096%)
Nausea 3 (3.61 %) 5 (6.02%)
Discussion
The intrathecal 0.5% hyperbaric bupivacaine is the drug ofchoice 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
Intravenous ?2 agonists prolong the duration of subarachnoid block by their supra-spinal action at locus ceruleus and dorsal raphe nucleus. Activation of ?2-A receptors, located presynaptically at locus ceruleus decrease the release of norepinephrine and leads to sedation and hypnosis, while those in the descending medullo-spinal noradrenergic pathway terminate the propogation of pain signals to provide analgesia. ?2-A receptors at substantia gelatinosa in the spinal cord exhibit their analgesic action by inhibition of nociceptive neurons and hence preventing substance P release. Hypotension and bradycardia are attributed to post-synaptic ?2-A receptor activation in CNS which in turn decreases sympathetic outflow. Thus ?2 agonists effectively modulate pain at various levels of the pain pathway, through supraspinal, spinal and peripheral mechanisms. IJCA_4
Dexmedetomidine is a new ?2agonist, approved by the Food and Drug Administrationin 1999 for use as an analgesic and sedative in theintensive care units.3,6 ??adrenoceptor agonists havedifferent ?1:?2 selectivity. Clonidine, the first developedand the most known ?2 agonist, is considered asa partial ?2 agonist, since its ?1:?2 selectivity is200 while ?1:?2 selectivity of dexmedetomidine is1620 and hence has 8 times more affinity for ?2receptors than that of clonidine.9,10 Intravenousdexmedetomidine has been used as an adjuvantagent with spinal anesthesia as it prolongs motor andsensory blockade11 with early onset and prolongedduration of action.1Despite sound levelsof sedation, there is limited respiratory depression,providing wide safety margins.12 Dexmedetomidineis thus used as an adjuvant in epidural,13 spinal,14and intravenous regional anesthesia. Anaesthesia Essays 103497
Several clinical studies have investigated the effects of intravenous dexmedetomidine on spinal anesthesia. Previous studies used various doses and types of local anesthetics for spinal anesthesia as well as various doses and infusion methods of intravenous dexmedetomidine, so it is not easy to reliable translation into clinical practice. Mostly, dexmedetomidine was administered at an initial loading dose from 0.25 to 1 ug/kg, and/or a maintenance infusion with rates between 0.2 and 0.5 ug/kg/h throughout the duration of surgery 5-10. According to the results of previous clinical studies, intravenous dexmedetomidine can prolong the duration of sensory blockade and, to a lesser extent, prolong the motor blockade duration 13. However, few studies have directly compared different amounts of dexmedetomidine. In particular, 0.5 ug/kg and 1 ug/kg are commonly used doses in clinical practice.kjae-67-different doses of dexmedThe present study was conducted to find out which bolus dose of intravenous dexmedetomidine out of 0.5mcg/kg and 1.0mcg/kg is more effective in prolongation of duration of spinal anaesthesia with 0.5% hyperbaric bupivacaine with minimal side-effects.

According to the results of previous clinical studies, intravenous dexmedetomidine can prolong the duration of sensory blockade and, to a lesser extent, prolong the motor blockade duration 13..kjae-67-different doses of dexmedIn the present study, faster onset and significantly prolonged duration of sensory block was seen in patients receiving 1ug/kg dexmedetomidine Group B as compared to those receiving 0.5ug/kg dexmedetomidine Group A. The onset of motor block was the same in both groups with a significantly prolonged duration of motor block in Group B compared to A. Dexmedetomidine produces a greater degree of differential blockade by preferentially blocking the myelinated A ?-fibers involved in sensory conduction over the unmyelinated C fibers involved in motor conduction 13.

The administration of intravenous dexmedetomidine in spinal anesthesia may actually have a dual effect by both enhancing the local anesthetic action and providing sedation. Dexmedetomidine affects the locus ceruleus area of the brain, which induces sedation resembling natural sleep by means of sleep modulation and respiration control 3,16. It is correlated with cooperative sedation, which is different from the clouding of consciousness that occurs with drugs that act on GABA receptors, such as propofol or midazolam 17. In the present study, intraoperative sedation was comparable in both groups (mean RSS Group A 3.11 vs mean RSS Group B 3.22) however postoperative sedation was deeper in Group B (mean RSS Group A 0.9985 vs mean RSS Group B 1.16). Studies show that the extent of sedation deepens on increasing the dosage of dexmedetomidine as seen in our study 13. But unlike other sedatives, patients can be easily aroused 14.Previous studies have evaluated the sedation effect of dexmedetomidine by injecting it until patients reached 3 or 4 point on Ramsay sedation score and with confirming the patient’s comfortableness and the satisfaction of the operating surgeon. kjae-66-371_0.5 vs 1 ugDexmed. Previous studies show that oxygen saturation is better maintained by dexmedetomidine than midazolam 18. In the present study, dexmedetomidine provided sufficient oxygen saturationin both groups (99.9247% in Group A vs 100% in Group B).

Almost all patients showed a 0-1 degree of pain using the Visual Analogue Scale (VAS) 2,3,4,5,6 and 8 hours postoperatively, which means there was almost no pain. This was in line with the findings of other similar studies. kjae-66
A biphasic cardiovascular response was seen after the administration of dexmedetomidine. The administration of a bolus of 1 ?g/kg dexmedetomidine initially resulted 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 ?2 ? 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 Anaesthesia Essays 103497
Summary
A total of 166 patients undergoing major abdominal surgeries under SA with hyperbaric Bupivacaine were included in the study.
Patients were equally divided into two groups of n=83 in each. Group A received bolus of 0.5 mcg/kg body weight of intravenous Inj. Dexmedetomidine over 10 min and Group B received bolus of 1.0 mcg/kg body weight of intravenous Inj. Dexmedetomidine, both followed by 5 min later Inj. Bupivacaine 0.5% heavy intrathecally.

Faster onset and significantly prolonged duration of sensory block was seen in patients receiving 1ug/kg dexmedetomidine Group B as compared to those receiving 0.5ug/kg dexmedetomidine Group A.

The onset of motor block was the same in both groups with a significantly prolonged duration of motor block in Group B compared to A.

Intraoperative sedation was comparable in both groups (mean RSS Group A 3.11 vs mean RSS Group B 3.22) however postoperative sedation was deeper in Group B (mean RSS Group A 0.9985 vs mean RSS Group B 1.16).

Dexmedetomidine provided sufficient oxygen saturation in both groups (99.9247% in Group A vs 100% in Group B).

Majority patients in both groups showed VAS value of one postoperatively.

Hemodynamic parameters
The patients in Group B had comparatively greater adverse events of hypotension (19.28% Group B vs 15.66% Group A), bradycardia(24.096 % Group B vs 20.48% Group A) and nausea(6.02%Group B vs 3.61 % Group A) as compared to Group A.
Conclusions
Dexmedetomidine given as bolus dose of1.0 mcg/kg intravenously with 0.5% hyperbaric bupivacainewas found to be more effective than bolus dose of 0.5 mcg/kg in prolongation of duration of spinal anaesthesia, however with greater side-effects.

Appendix
Ramsay Sedation Score
Grade 1: patient anxious, agitated, or restless;
Grade 2: patient cooperative, oriented, and tranquil alert;
Grade 3: patient responds to commands;
Grade 4: asleep, but with brisk response to light glabellar tap or loud auditory stimulus;
Grade 5: asleep, sluggish response to light glabellar tap or loud auditory stimulus; and
Grade 6:asleep, no response.

Visual Analogue Scale
TIME OF ONSET OF PAIN BY VISUAL ANALOGUE SCALE-
1 2 3 4 5 6 7 8 9 10
No pain Moderate pain Worst pain imaginable
0 – No pain
2 – Mild annoying pain
4 – Nagging, uncomfortable pain
6 – Distressing, miserable pain
8 – Intense dreadful, horrible pain
10 – Worst possible, unbearable excruciating pain

x

Hi!
I'm Piter!

Would you like to get a custom essay? How about receiving a customized one?

Check it out