Comparison of Dexmedetomidine and Magnesium Sulfate as Adjuvants with Ropivacaine for Spinal Anesthesia in Infraumbilical Surgeries and Postoperative Analgesia.

INTRODUCTION: Postoperative pain is a major cause of fear and anxiety in hospitalized patients and so if patients remain pain-free during this period, they can cooperate with the circumstances well, leading to early recovery. Over the last two decades, there has been considerable revival of interest in the use of regional anesthesia techniques for surgery and pain management. As very few studies have been conducted using ropivacaine with dexmedetomidine and magnesium sulfate (MgSO4) as adjuvants, the present study was undertaken with primary aims to compare the hemodynamic stability, onset and duration of sensory and motor block and with secondary aims of the postoperative analgesic effect of dexmedetomidine and MgSO4 along with ropivacaine.
MATERIALS AND METHODS: After getting the Institutional Ethics Committee approval, this study was conducted on fifty patients of the American Society of Anesthesiologists physical Status I and II aged between 20 and 65 years of either sex and scheduled to undergo infraumbilical surgeries under spinal anesthesia. They were divided into two groups of 25 each. Group D patients received 3 ml of 0.75% isobaric ropivacaine hydrochloride with 10 μg of dexmedetomidine whereas Group M patients received 75 mg of MgSO4 in the place of dexmedetomidine. The quality of surgical analgesia and quality of intraoperative muscle relaxation were assessed and graded.
RESULTS: We found out that onset of sensory and motor block was earlier in Group D in comparison to Group M. There was a significant reduction in the time to the first rescue analgesia in group receiving intrathecal dexmedetomidine.
CONCLUSION: It is concluded from our study that ropivacaine plus dexmedetomidine group are better than ropivacaine plus MgSO4 in providing early onset of sensory and motor block as well as in providing postoperative analgesia.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.[1] It is the duty of anesthesiologist to provide the essential four A's of rapid outpatient recovery – alertness, analgesia, alimentation, and ambulation.[2] The most terrible period as far as pain is concerned is the first 24 h, when the severity of pain and vital signs are fluctuating. Postoperative pain is a major cause of fear and anxiety in hospitalized patients. On the other hand, if patients remain pain-free during this period, they can cooperate with the circumstances well, leading to early recovery.[3] Relief of pain is not only a humanitarian consideration but also an important means for reduction of morbidity and mortality. Over the last two decades, there has been considerable revival of interest in the use of regional anesthesia techniques for surgery and pain management. Ropivacaine was approved for the intrathecal route by the European Union in February 2004 and has consistently demonstrated an improved safety profile over bupivacaine with a reduced central nervous system (CNS) and cardiotoxic potential,[4] together with a wide clinical utility at different doses and for a wide range of indications.[56]

Subarachnoid block with local anesthetics such as bupivacaine and ropivacaine is a commonly used anesthetic technique in elective infraumbilical surgeries. It not only provides adequate intraoperative anesthesia but also effective pain relief in the initial postoperative period; however when its effect wears off, patient starts experiencing pain. The local anesthetics act by blocking sodium channels to relieve pain. Nowadays, use of intrathecal adjuvants have gained popularity for prolonging the duration and quality of block. Spinal anesthesia's quality has been reported to be improved by adding opioids (such as morphine, fentanyl, and sufentanil) and other drugs (such as dexmedetomidine, clonidine, magnesium sulfate [MgSO4], neostigmine, ketamine, and midazolam), but no drug to inhibit nociception is without associated adverse effects. Magnesium[6] blocks calcium influx and noncompetitively antagonizes N-methyl-D-aspartate receptor channels leading to analgesia and can cause side effects of nausea, vomiting, and hypotension at higher doses. Dexmedetomidine[78] acts as an agonist on α2 receptor found in the peripheral and CNSs. Stimulation of the receptors in the brain and spinal cord inhibits neuronal firing, causing hypotension, bradycardia, sedation, and analgesia whereas the analgesic action of intrathecal α2-adrenoceptor agonist is by depressing the release of C-fiber transmitters and by hyperpolarization of postsynaptic dorsal horn neurons. This antinociceptive effect may explain the prolongation of sensory block when added to spinal anesthetics. The prolongation of the motor block of spinal anesthetics may result from the binding of α2 adrenoceptor agonists to motor neurons in the dorsal horn.

As very few studies have been conducted using cardio stable drug ropivacaine with dexmedetomidine and MgSO4 as adjuvant, the present study was undertaken with primary aims to compare the hemodynamic stability, onset and duration of sensory and motor block and with secondary aims of postoperative analgesic effect of dexmedetomidine (10 µg) and 75 mg of MgSO4 given intrathecally along with 0.75% ropivacaine.

MATERIALS AND METHODS

After getting Institutional Ethics Committee approval, this prospective randomized, double-blind study was conducted on fifty patients of the American Society of Anesthesiologists physical Status I and II aged between 20 and 65 years of either sex admitted in Guru Nanak Dev Hospital, Amritsar scheduled to undergo infraumbilical surgeries under spinal anesthesia. Patient's unwillingness, coagulation disorders, neurological disorders, morbid obesity, any life-threatening disease, signs of sepsis, previous injury, deformity or previous surgery of spine, anticipated difficulty in regional anesthesia, allergy to study drug, pregnancy, and lactation were taken as exclusion criteria. Thorough preanesthetic checkup of all patients including all routine investigations was done. The procedure was explained to the patient and written informed consent was taken. Pain visual analog scale (VAS) scores were explained to all patients. Premedication was given as tablet alprazolam 0.25 mg a night before surgery, injection glycopyrrolate 0.2 mg, and injection midazolam 0.04 mg/kg body weight by intravenous route just before the procedure in all the groups.

Preoperatively, pulse rate and noninvasive systolic and diastolic blood pressure of the patients were recorded. In operation theater, intravenous line was secured with 18-gauge intricate, and all the patients were preloaded with 10 ml/kg body weight of Ringer lactate solution over 15–20 min. Multipara monitors were applied, and baseline pulse rate, noninvasive systolic and diastolic blood pressure, oxygen saturation (SpO2), and electrocardiogram (ECG) were recorded. Patients were put in the lateral decubitus position. After scrubbing, washing and wearing sterile gown and gloves, back of the patient's was cleaned with povidone-iodine scrub and then painted with povidone-iodine solution. The area was draped with sterile sheet. L3 and L4 space was located (in case of difficulty L2 and L3 space). Skin wheal was raised with 2% lignocaine and then with midline approach a 23-gauge spinal needle was inserted in the space. After the free flow of cerebrospinal fluid, drug was injected in the space.

Group D: 25 patients received 3 ml of 0.75% isobaric ropivacaine hydrochloride with 10 µg of dexmedetomidine

Group M: 25 patients received 3 ml of 0.75% isobaric ropivacaine hydrochloride with 75 mg of MgSO4.

Sensory block was assessed by the loss of sensation to pinprick in the midline using a 22-gauge blunt hypodermic needle every 3 min interval till no change in level occurred. The degree of motor block was assessed every 3 min for first 30 min by the modified Bromage scale. 0 = No motor blockade, 1 = Inability to raise extended leg but can flex knee, 2 = Inability to flex knee, can flex ankle, and 3 = No movement, unable to flex ankle joint. Motor blockade and sensory blockade were assessed at the end of surgery also. Oxygen was routinely administered through oxygen mask at the rate of 5 L/min.

Bradycardia (defined as heart rate <60 beats/min) was treated with intravenous atropine 0.5 mg. Hypotension (defined as systolic blood pressure <20% of baseline value) was treated with intravenous ephedrine as per required and additional Ringer's lactate solution. Operation was started when full surgical anesthesia had developed. In case of failed neuraxial block and total spinal, patient was given general anesthesia and the case was excluded from the study. Continuous multipara meter monitoring (pulse rate, respiratory rate, noninvasive systolic and diastolic blood pressure, SpO2, and ECG) was done for hemodynamic response. Readings were recorded preoperatively, intra-operatively every 3 min for the first 30 min, and thereafter every 15 min till the end of surgery in both the groups.

The quality of surgical analgesia, quality of intra-operative muscle relaxation (as per operating surgeon) were assessed and graded. After completion of surgery, patient were monitored postoperatively for sensory block, motor block and analgesia (according to VAS) every 30 min for 1 h and then hourly till first rescue analgesia was given in the form of nonsteroidal anti-inflammatory drug (injection diclofenac 75 mg intramuscularly) or opioid (injection tramadol 50–100 mg intravenously) when VAS >3. Any side effect or complication was noted and managed postoperatively.

RESULTS

There was no difference in age, height, body weight, and body mass index between the group. Systolic, diastolic arterial blood pressures, heart rate, and SpO2 remained stable, and there was no significant difference between the groups.

The onset of Bromage 3 motor block and time to reach T10 sensory dermatome level was statistically significant between Group D and Group M. Onset time for sensory and motor block was significantly earlier in Group D but delayed in Group M. The time for regression of sensory block to L1 dermatome and Bromage 0 motor block was significantly prolonged in Group D compared to Group M. The time of total analgesia and mean total doses required during postoperative period for additional analgesics were also significantly different in the two groups with Group D having longer duration of analgesia and less requirements of analgesics [Tables 1–3 and Graph 1].

Table 1

Sensory block characteristics

Table 3

Postoperative parameters

Graph 1

Sensory and motor characteristics in the two groups.

The total amount of fluid administered following spinal anesthesia, the duration of surgery, amount of ephedrine or atropine, bradycardia and hypotension, need of additive analgesia intraoperatively, blood transfusion, shivering, and nausea or vomiting in the intraoperative or in postanaesthesia care unit was comparable in the two groups (P > 0.05). Hemodynamic parameters were too comparable in both the groups intraoperatively as well as postoperatively.

Similarly, the quality of surgical anesthesia and muscle relaxation was excellent and satisfactory as per surgeons opinion in both the groups and comparable.

In Group D, VAS started increasing at 4 h, but patient demanded the first dose of rescue analgesia at 7th h postoperatively. Then, VAS score started increasing again and second dose of rescue analgesia was given at 15th h. Then, the third dose of rescue analgesia was given at 24th h [Graph 2].

Graph 2

The visual analog scale score in the two groups.

In Group M, VAS started increasing at 4 h, but patient demanded the first dose of rescue analgesia at 5th h postoperatively. Then, VAS score started increasing again and second dose of recue analgesia was given at 10th h. VAS started increasing again and the third dose of rescue analgesia was given at 18th h. Then, the fourth dose of rescue analgesia was given at 24th h.

The total duration of analgesia was measured from the time of point zero till the patient demanded first rescue analgesic when VAS >3. Rescue analgesia needed was more in Group M as compared to Group D which was statistically significant.

DISCUSSION

Spinal anesthesia is simple to perform, uses small dose of drugs, offers rapid onset of action, reliable surgical anesthesia, and good muscle relaxation. These advantages are sometimes offset by a relatively short duration of action and complaints of postoperative pain when effect wears off. Spinal anesthesia with ropivacaine hydrochloride is increasingly being used these days owing to its lack of cardiotoxicity and neurotoxicity. The efficacy of local anesthetics can be enhanced using adjuvants such as opioids, α2 agonists, magnesium, neostigmine, ketamine.[910] Prolongation of the duration of spinal block is desirable both for long procedures and for postoperative pain relief. In our study, we compared the addition of intrathecal magnesium and dexmedetomidine to ropivacaine in terms of onset and regression of sensory and motor block and its hemodynamic profile as well as the side effects. Jabalameli and Pakzadmoghadam[11] compared the effects of adding different doses of intrathecal MgSO4 for spinal anesthesia in the cesarean section and showed that all doses studied provide safe and effective anesthesia, but 75 mg of this drug increases duration of postoperative analgesia and prolong than sensory and motor block without significant increase in side effects, so we choose 75 mg of magnesium as our test drug. Largest dose of dexmedetomidine used intrathecally in humans was 10 µg. The previous studies revealed hemodynamic stability with 5 and 10 µg of dexmedetomidine as intrathecal adjuvant which was suitable for spinal anesthesia for lower abdominal gynecological surgery. Various studies have reported that 10 µg intrathecal dexmedetomidine is safe and devoid of any neurotoxic side effect; hence, we used 10 µg dexmedetomidine[11] along with 22.5 mg isobaric ropivacaine (0.75%).

In our study, we found out that onset of sensory block was earlier in Group D in comparison to Group M which was statistically significant. This was supported by a study conducted by Shukla et al.[12] and Naithani et al.,[13] who found rapid onset of surgical anesthesia in dexmedetomidine group (2.27 ± 1.09 min) when compared to intrathecal magnesium (6.46 ± 1.33 min). Our results were different because we used safer ropivacaine instead of bupivacaine. Dexmedetomidine as such does not speed up the onset of action but in comparison to magnesium is faster, which actually slows the speed of onset. Ozalevli et al.[14] observed a similar delay in onset of spinal anesthesia when adding intrathecal magnesium to fentanyl and isobaric bupivacaine.

In our study, Group D achieved faster motor block which was again statistically significant when compared to Group M. Similar results have been found by Shukla et al.[12] where dexmedetomidine group took (3.96 ± 0.92 min), whereas magnesium group took (7.18 ± 1.38 min) with bupivacaine to achieve the desired motor block.

Sunil et al.[15] with the usage of 10 µg of intrathecal dexmedetomidine with hyperbaric bupivacaine found that there is a quicker onset of sensory and motor block when compared to magnesium. Similar results were given by Al-ghanem[16] and Malleeswaran et al.[17] Reason for this delayed onset of action in magnesium group may be due to change in pH and baricity of bupivacaine due to addition of MgSO4.

In our study, it was observed that addition of dexmedetomidine and magnesium both prolonged the duration of sensory as well as motor block when added to ropivacaine (intrathecally), but prolongation was more in dexmedetomidine group as compared to magnesium group which was statistically significant. This result showed a similar trend as observed by Shukla et al.,[12] which showed the regression time of block, both sensory up to T10 dermatome and motor to Bromage 3, was prolonged in Group D (352 ± 45 min and 331 ± 35 min) and in Group M (265 ± 65 min and 251 ± 51 min) which was statistically significant. In addition, Sunil et al.[15] showed similar results that the time for regression of sensory block to L1 dermatome and Bromage 0 motor block was significantly prolonged in Group D compared to Group M.

There was a significant delay in the time to the first rescue analgesia in group receiving intrathecal dexmedetomidine when compared to magnesium and also the mean total dose and times of use of analgesics were also reduced in both group with reduction in dexmedetomidine group significantly more than magnesium group. Similar findings are observed by Mahendru et al.,[18] Gupta et al.,[19] and Al-Mustafa et al.[20] The quality of surgical anesthesia was excellent in both groups in the intraoperative period. We also did not observe any significant hemodynamic side effect or any other complications such as nausea, vomiting, pruritus, urinary retention, shivering, in our study in both groups.

CONCLUSION

Thus, it is concluded from our study that ropivacaine when combined with dexmedetomidine provided adequate subarachnoid block for lower abdominal surgeries. Both groups were effective in providing adequate surgical anesthesia and hemodynamic stability, but ropivacaine plus dexmedetomidine group is better than ropivacaine plus MgSO4 group as regards:

Earlier onset of sensory and motor block

Prolonged duration of sensory and motor block

Longer duration of postoperative analgesia

Lesser number of doses of rescue analgesia required.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Table 2

Motor block characteristics