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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 12  |  Issue : 2  |  Page : 99-109

A comparison between intrathecal dexmedetomidine with hyperbaric bupivacaine and intrathecal fentanyl with hyperbaric bupivacaine in lower abdominal surgeries: A prospective double-blinded study


Department of Anesthesiology, Jawaharlal Nehru Medical College, DMIMS (DU), Wardha, Maharashtra, India

Date of Web Publication8-Sep-2017

Correspondence Address:
Karuna Taksande
Department of Anesthesiology, Jawaharlal Nehru Medical College, DMIMS (DU), Sawangi (Meghe), Wardha, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdmimsu.jdmimsu_55_17

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  Abstract 

Background: The aim of this study is to compare the efficacy and safety of injection dexmedetomidine 5 μg and injection fentanyl when given intrathecally as adjuvant to injection bupivacaine in patients undergoing total abdominal hysterectomy in terms of the following parameters: (1) Characteristics of onset of sensory and motor block. (2) Characteristics of regression of sensory and motor block. (3) Level of sedation (4) Hemodynamic stability as assessed by pulse rate, systolic, and diastolic blood pressure (BP) and requirements of vasopressors. (5) Quality of postoperative analgesia as assessed by visual analog scale. (6) Evaluation of complications associated with injection dexmedetomidine and injection fentanyl when used as an adjuvant to injection bupivacaine. Materials and Methods: Ninety patients of the American Society of Anesthesiologists Class I and II posted for lower abdominal surgeries were allocated randomly into three groups of thirty patients each. C group: (n = 30) received 0.5 mL normal saline with hyperbaric bupivacaine 17.5 mg in 3.5 mL to make 4 mL. D group: (n = 30) received dexmedetomidine 5 μg with hyperbaric bupivacaine 17.5 mg in 3.5 mL diluted with 0.4 mL normal saline to make it 4 mL. F group: (n = 30) received fentanyl 25 μg with hyperbaric bupivacaine 17.5 mg in 3.5 mL to make 4 mL. Results and Conclusion: We observed that the groups were comparable with respect to demographic data (age, weight, height and duration of surgery) and onset time of sensory and motor blockade. The onset of sensory and motor block was slightly delayed in both groups. Two segment regression time of sensory blockade and time to reach Bromage scale 0 was greatly significant in dexmedetomidine and fentanyl. However, in comparison of the two, dexmedetomidine was clearly superior. The groups were comparable in terms of hemodynamic parameters, oxygen saturation, and respiratory rate, though there had been a statistically significant fall in BP and heart rate when compared to baseline. Sedation scores were found to be statistically significantly higher in group dexmedetomidine as compared to Fentanyl. The results showed statistically significant increase in the duration of postoperative analgesia in group using dexmedetomidine as compared to group fentanyl. The requirement of first rescue analgesic was greatly significant. The group using fentanyl had an postoperative pain free period of unto 4 h and dexmedetomidine had analgesia period unto 7 h. We found some adverse effects such as hypotension, bradycardia, nausea and vomiting with dexmedetomidine and fentanyl; however, the results were statistically insignificant. To conclude, the addition of dexmedetomidine prolonged the sensory and motor block significantly when used with hyperbaric bupivacaine intrathecally, to a much greater extent to the addition of fentanyl without increasing the incidence of significant adverse effects.

Keywords: Hyperbaric bupivacaine, intrathecal dexmedetomidine, intrathecal fentanyl


How to cite this article:
Varghese LA, Taksande K. A comparison between intrathecal dexmedetomidine with hyperbaric bupivacaine and intrathecal fentanyl with hyperbaric bupivacaine in lower abdominal surgeries: A prospective double-blinded study. J Datta Meghe Inst Med Sci Univ 2017;12:99-109

How to cite this URL:
Varghese LA, Taksande K. A comparison between intrathecal dexmedetomidine with hyperbaric bupivacaine and intrathecal fentanyl with hyperbaric bupivacaine in lower abdominal surgeries: A prospective double-blinded study. J Datta Meghe Inst Med Sci Univ [serial online] 2017 [cited 2017 Sep 26];12:99-109. Available from: http://www.journaldmims.com/text.asp?2017/12/2/99/214192


  Introduction Top


Spinal anesthesia has the potential of being uniquely safe anesthetic technique till when the physiological trips are within certain limits beyond which, complications of the procedure starts appearing. The complications of spinal anesthesia, namely, hypotension, bradycardia, postspinal headache, nausea, vomiting and occasional neurological complications have damaged its reputation. Despite the waxing and waning of its popularity, spinal anesthesia remains one of the basic techniques in the arsenal of modern anesthesiologists. The reason for its renewed popularity in recent years has been the realization that spinal anesthesia can combine a low degree of physiological trespass on the one hand and profound degree of sensory denervation and muscle relaxation on the other hand.[1]

The utility of spinal anesthesia has its limitations for prolonged surgeries because of short duration of action of local anesthetics. Hence, it became necessary to look for ways to prolong the duration of spinal anesthesia. Various drugs such as morphine, pethidine, phenylephrine, neostigmine, ketamine, and alpha 2 (α2) agonists have been used intrathecally for this purpose.[2] The addition of adjuvants such as clonidine and opioids intrathecally to local anesthetics have gained widespread popularity due to belief that they provide longer duration of postoperative analgesia and allows the reduction of the amount of local anesthetic, thus decreasing the incidence of side effects. The discovery of opioid receptors and endorphins in spinal and supra spinal regions soon led to use of use of spinal opioids.[3] Opioids produce intense, prolonged analgesic action without gross autonomic changes, loss of motor power or impairment sensation other than pain when injected intrathecally or epidurally.[4]


  Materials and Methods Top


The present study had been carried out in the Department of Anesthesiology, Jawaharlal Nehru Medical College at the Acharya Vinobha Bhave Rural Hospital, Sawangi, during the period of August 2013–October 2015. This study was a prospective, double-blinded study where ninety patients posted for lower abdominal surgery under spinal anesthesia were studied, to compare intrathecal dexmedetomidine with hyperbaric bupivacaine and intrathecal fentanyl with hyperbaric bupivacaine in lower abdominal surgeries.

Ninety patients of the American Society of Anesthesiologists (ASA) Class I and II posted for lower abdominal surgeries were allocated randomly into three groups of thirty patients each. Three groups were divided as C group: (n = 30) will receive 0.5 mL normal saline with hyperbaric bupivacaine 17.5 mg in 3.5 mL to make 4 mL. D group: (n = 30) will receive dexmedetomidine 5 μg with hyperbaric bupivacaine 17.5 mg in 3.5 mL diluted with 0.4 mL normal saline to make it 4 mL. F group: (n = 30) will receive fentanyl 25 μg with hyperbaric bupivacaine 17.5 mg in 3.5 mL to make 4 mL.

Inclusion criteria were ASA Grade I and II patients, age group 25–65 years and patients undergoing lower abdominal surgery. The exclusion criteria were unwillingness of the patient, local sepsis at the site of proposed puncture, weight >90 kg, height <145 cm or more than 175 cm, patients with history of hypertension, and electrocardiogram (ECG). Changes, for example, sinus bradycardia and heart blocks, spinal deformity or tuberculosis spine, patients being treated with anticoagulants, central nervous system (CNS) active drugs, patients suffering from bleeding diathesis or coagulation disorders, patients on alpha adrenergic receptor (AR) blockers, increased intracranial pressure, patients with history suggestive of psychiatric disorder, and patients with neurological disease with either motor or sensory deficit.

Preoperative assessment was done for each patient and informed written consent was taken 1 day before surgery. At the preanesthetic interview, patients were familiarized with intraoperative and postoperative questionnaires. Preoperatively, patients were given tablet alprazolam 0.25 mg and tablet ranitidine 150 mg at night before surgery and at 6 am on the day of surgery. No premedication was given just before surgery. Patients were kept fasting as per the standard guidelines. All patients underwent standard monitoring including an ECG (12 lead), noninvasive blood pressure (BP), and pulse oximetry. Baseline vital parameters were recorded. An intravenous (IV) line was obtained with 18 gauge cannula. Preloading with ringer lactate was started at 10 mL/kg which was completed before giving anesthesia. The anesthesiologist in charge of the surgery prepared drug of his own choice and labeled it as study drug and handed it over to the anesthesiologist who was part of the anesthesia team after putting code number on the pro forma. Hemodynamic monitoring was done by the team of anesthesiologists; data and pro formas were collected and handed over to an investigator, who was not a part of the anesthesia team. Decoding of the patients was done at the end of the study. Spinal anesthesia was performed under all aseptic precautions. Patients back was painted, prepared, and draped. The subarachnoid block was instituted with a 25 gauge quincke needle in the left lateral position by midline approach through L3-L4 interspace. All patients were given supine posture immediately. All patients received oxygen by nasal cannula at 3 L/min. Time of induction of anesthesia was noted.

The parameters noted were onset of sensory blockade and motor blockade, maximum level of sensory blockade attained and time taken for the same was noted, maximum level of motor blockade attained and time taken for the same was noted, two segment regression time of sensory blockade, total duration of motor blockade, level of sedation, total duration of surgery, assessment of postoperative pain using verbal analog scale (VAS), time to first rescue analgesic, adverse effects, and administration of drugs in case of adverse effects.

Sensory blockade was tested using pinprick method with a blunt-tipped needle at every 2 min for the first 10 min and every 15 min until regression to two segments below the maximum level was achieved. The quality of motor blockade was assessed by modified Bromage scale. Hemodynamic monitoring was done during the block every 2 min for the first 10 min and after that, every 15 min till the end of surgery. Postoperatively, for the first 2 h, the patient was monitored every 15 min, after which, vitals were recorded every 2 h. This was continued up to 12 h postoperatively.

Statistical analysis

The statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 17.0, (SPSS Inc, Chicago, IL) statistical analysis software. The values were represented in number (%) and mean ± standard deviation (SD). The data on demographic parameters such as age and gender were obtained for patients from three groups and expressed in terms of frequency distributions. In addition, the mean and SD of age was obtained for the three groups. The distribution of patients in each group according to ASA was obtained. The mean and SD of the baseline characteristics of patients in three groups were obtained and compared for statistical significance using one-way analysis of variance (ANOVA). The dermatomal sensory levels across three groups were compared using Pearson's Chi-square test. The mean time for regression of sensory block by two segments and the mean duration of onset of motor blockade across three groups was compared using one-way ANOVA. Moreover, the intraoperative and postoperative mean pulse rate, systolic, diastolic BP (DBP), respiratory rates, and sedation scores across three groups at different time points were compared for statistical significance using one-way ANOVA.

All the analyses were performed in R-3.0.0 programming language using validated scripts, and the statistical significance was evaluated at 5% level.


  Results Top


In dexmedetomidine group, the mean age of patients was 43.57 ± 8.75 years while in fentanyl group, the mean age was 38.83 ± 11.24 years. In control group, the mean age of patients was 44 ± 4.88 years. The mean age of fentanyl group seems to be slightly lower than the other two groups. This finding has no specific contribution to our study. In dexmedetomidine group, there were 19 (63%) patients in ASA 1 criterion, followed by 11 (37%) patients in ASA 2 criterion. In fentanyl group, there were 17 (57%) patients in ASA criterion 1, and 13 (43%) patients in ASA criterion 2. In control group, there were 21 (70%) patients in ASA criterion 1, and 9 (30%) patients in ASA criterion 2. There is no significant difference in the comparison between the three groups. The mean body mass index (BMI), in dexmedetomidine group was 19.94 ± 4.7 kg/m 2 while in fentanyl group, the mean BMI was 22.34 ± 3.31 kg/m 2. In control group, the mean BMI was 21.79 ± 2.59 kg/m 2. There is no significant difference in this comparison. In dexmedetomidine group, the mean onset of sensory block was 6.70 ± 0.79 min while in fentanyl group, it was 8.03 ± 1.22 min. In control group, the mean onset of sensory block was 5.87 ± 1.38 min. The difference in the means across groups was statistically significant with P < 0.0001 using one-way ANOVA. Post hoc analysis revealed a significant difference between fentanyl and dexmedetomidine groups and also between fentanyl and control groups. Onset was delayed with the addition of fentanyl by almost a minute, when compared to the dexmedetomidine group, on comparison with the control group; onset was delayed by almost 2 min.

In dexmedetomidine and fentanyl group, there were 21 (70%) patients with T5 level while 9 (30%) patients achieved T4 level in each of the groups. In control group, there were 15 (50%) patients with T6 level, followed by 6 (20%) patients with T4 level, and 4 (13.3%) patients with T5 level. 5 (16.6%) patients achieved T8 level in this group. The number of patients in T4 and T5 levels in two test groups were significantly higher than that of control group as indicated by P < 0.0001, signifying that maximum level achieved, i.e. T4 was achieved by both.

In dexmedetomidine group, it was 162 ± 26.83 min while in fentanyl group, the mean time was 122.73 ± 15.31 min. In control group, the mean time was 65.70 ± 12.21 min. The difference in the mean times was highly significant across groups as indicated by P < 0.0001 using one-way ANOVA. Tukey's post hoc analysis revealed a significant difference of mean time between all the three groups. The dexmedetomidine group took maximum time for regression of sensory block by two segments. This clearly states that both fentanyl and dexmedetomidine is far superior to plain bupivacaine in this regard. While comparing between the study groups, dexmedetomidine is appreciably remarkable.

In dexmedetomidine group, the mean time of onset was 11.03 ± 0.93 min while in fentanyl group, the mean duration was 11.03 ± 0.93 min. In control group, the mean duration was 7.27 ± 1.26 min. The difference of values was highly significant across study groups as indicated by P < 0.0001. The post hoc analysis revealed that both treatment groups significantly differed from control group. The control group had a faster onset of motor blockade, i.e., almost 7 min, and the study group had a delay of 3 min.

In dexmedetomidine group, the mean duration of motor blockade was 330.27 ± 37.26 min while in fentanyl group, the mean duration was 264.28 ± 28.26 min. In control group, the mean duration of motor blockade was 161.67 ± 36.30 min.

At 0th min, i.e., just postinduction, in dexmedetomidine group, the mean pulse rate was 92.33 ± 16.86/min, while in fentanyl group, the mean pulse rate was 94.20 ± 12.58/min. In control group, the mean pulse rate was 78.03 ± 12.16/min. The difference in the mean intraoperative pulse rate was highly significant across groups as obtained using one-way ANOVA and indicated by P < 0.0001. Paired analysis using Tukey's post hoc test suggested that mean pulse rate of patients in dexmedetomidine and fentanyl groups was significantly higher than that of control group. It is evident that at all the points, the difference was statistically significant (P< 0.05). The post hoc analysis reveals the significance for pair-wise comparison of mean pulse rate between groups. Groups with similar superscripts indicate insignificant difference while different subscripts imply a significant difference. Initially, up to 2 min, the mean pulse rate in dexmedetomidine group was significantly higher than the other two groups while from 4 min onward, the mean in this group was significantly lower as compared to other two groups. Dexmedetomidine group exhibits a distinctly balanced control of hemodynamics after the 4th min of induction.

Immediately after surgery, the mean pulse rate of patients in dexmedetomidine group was 75.43 ± 13.36 per min while in fentanyl group was 68.23 ± 6.67/min. In control group, it was 83.60 ± 6.09/min. The difference in the means was statistically significant with P < 0.0001 using one-way ANOVA. The post hoc analysis revealed a significant difference between all pairs of groups as indicated by the superscripts in the table.

Likewise, the difference in the mean postoperative pulse rate across groups was evaluated for significance up to 720 min using one-way ANOVA. Table shows that at each point, the difference was statistically significant with P < 0.05. It is evident from the graph that up to 75 min, the mean rate in fentanyl group was smallest while beyond this time point, the mean pulse rate in dexmedetomidine group was least which continued till 720 min.

Dexmedetomidine group had a lasting consequence on the hemodynamics. This group remained stable through H and E postoperative period.

The graph above shows the mean intraoperative systolic BP (SBP) at different time points in three groups. It reveals that the difference in the mean intraoperative SBP was statistically significant across groups at 0, 2, 4, 6, 8, 10, 30, 75, and 90 min time points using one-way ANOVA as indicated by P < 0.05. The superscripts indicate the statistical significance through paired comparisons using post hoc test. For the remaining time points, the means differ insignificantly across groups as indicated by P > 0.05.

The difference in the mean was statistically significant across groups at all the time points except points 30 min, 105 min, and 360 min. Up to almost 90 min, the mean postoperative SBP in treatment groups was significantly higher than control group except at time point 30 min. Beyond 90 min, the mean SBP in fentanyl group was significantly lower as compared to other two groups, except at time points 105 min and 360 min (P > 0.05).

It shows that the mean DBP was significantly different across groups at all time points except 15 min, 75 min and 105 min as indicated by P < 0.05 using one-way ANOVA. The post hoc analysis reveals that up to nearly 7 min, the mean DBP in dexmedetomidine group was significantly higher than other two groups as indicated by superscripts. Beyond 10 min, the mean DBP in this group was significantly on a lower side compared to fentanyl group; and at few points nearly same as that of control group. It is evident from the table that the difference in the means at different time points up to 720 min was statistically significant with P < 0.05 using oneway ANOVA, except at time point 120 min. The post hoc analysis revealed significantly lower mean DBP in control group at most of the points while the difference between two treatment groups was almost insignificant. Graph 18 shows the mean postoperative DBP at different time points in three groups.

[Table 1] shows the mean verbal analog score at different time points postoperatively in three groups. The difference in the mean postoperative verbal analog score was statistically significant across groups at 60, 90, 240, 360, 480, and 720 min as obtained using one-way ANOVA, indicated by P < 0.05. The score was significantly low in dexmedetomidine group up to 360 min, while beyond this point, the score was lower in fentanyl group.
Table 1: Comparison of duration of Analgesia

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In dexmedetomidine group, the mean duration of analgesia was 584 ± 120.96 min while in fentanyl group, the mean duration was 287.73 ± 181.52 min. In control group, the mean duration of analgesia was 208.5 ± 162.05 min.

It is evident from this table that the difference in the mean sedation scores was statistically significant across groups at time points 45, 60, and 75 min as obtained using one-way ANOVA, indicated by P < 0.05. The mean scores in dexmedetomidine group were significantly higher than that of other two groups at all the time points.

In dexmedetomidine group, 10 (33.3%) patients had hypotension for which injection mephentermine 6 mg was given, around 2 patients had bradycardia which was treated with injection atropine 0.6 mg. Seven (24%) patients had episodes of nausea and 2 (6%) had vomiting. No other adverse effects such as respiratory depression, urinary retention, and pruritus were noted in this group of patients. Our patients were catheterized before surgery, hence, the incident of urinary retention could not be found. In fentanyl group, around 13 (43%) patients had episodes of hypotension and 9 (30%) patients had episodes of bradycardia. Nine (30%) patients had episodes of nausea and of the 6 (20%) had vomiting. Totally 2 (6%) patients had a single episode of respiratory depression, i.e. respiratory rate <10 breaths/min. One (3%) patient had pruritus postoperatively. Urinary retention could not be quantified as patients were catheterized. No other adverse effects could be found. In the control group, 20 (66%) patients had hypotension and 8 (26%) patients had bradycardia. 10 (33%) patients had nausea out of which 4 (13%) patients has vomiting. No incidences of respiratory depression, urinary retention, pruritus, could be found. All episodes of bradycardia across all groups was treated with injection atropine 0.6 mg and injection mephentermine 6 mg. Dexmedetomidine clearly is superior, as the incidences of adverse effects are reduced.

The palliation from the misery of pain has been the sizable goal of anesthesia. With the knowledge of anatomy, physiology, pharmacology, and technical skill, the anesthesiologists are the foremost physicians to treat pain. The preference of anesthesia rests on several factors including the desire of patients, comfort of surgeons, indication of surgery, control of analgesia intra operative and postoperative, early recovery, and requirement of monitoring. Regional anesthesia has been proved to blunt the stress response to surgery, to discount the intra operative blood loss and to ebb the incidence of postoperative thromboembolic events. In addition, it is found to decline the morbidity and mortality in high-risk surgical patients. Spinal anesthesia results from injecting local anesthetic directly into the intrathecal space. To improve the spinal anesthetic efficacy, adjuvants from different pharmacological classes of drugs are used to enhance and prolong analgesia, to lower dose requirements, and to reduce dose-dependent side effects. Postoperative analgesia has always been an area of concern for surgeons as well as anesthesiologist, as an uneventful and pleasant postoperative period plays a vital role in surgical outcome and patient welfare.

Bupivacaine is a well-established long-acting regional anesthetic agent and remains the most widely used drug as spinal anesthetic but with limited postoperative analgesia duration when used alone.[5] Hence, various adjuvants have been confederated with local anesthetic agents for increasing the duration of analgesia. To maintain the advantage of low-dose bupivacaine while improving intraoperative quality of anesthesia, different agents such as epinephrine, phenylephrine, adenosine, magnesium sulfate, benzodiazepines, ketamine, neostigmine, and opioids have been used as adjuvants for prolonging the duration of spinal anesthesia.[6] The use of neuraxial opioids is associated with many side effects, so various options including α2 agonists have been extensively used as an alternative to eliminate the opioid-related side effects such as respiratory depression, nausea, urinary retention, and pruritus. The pharmacological properties of α2 - agonists have been extensively studied and employed clinically to achieve the desired effects in regional anesthesia.[7] The use of intrathecal clonidine for postoperative analgesia alone or coadministered with local anesthetics or opioids has been previously described, but the literature on intrathecal dexmedetomidine is scarce. The α2 agonists act by binding to presynaptic C-fibers and postsynaptic dorsal horn neurons. Their analgesic action is a result of depression of release of C-fiber transmitters and hyperpolarization of postsynaptic dorsal horn neurons. Intrathecal α2 agonists have been found to have antinociceptive action for both somatic and visceral pain.[8]

Following the successful use of intrathecal dexmedetomidine in animal studies in a dose range of 2.5–100 μg,[9] its use in human studies has also shown promising results in terms of early sensory and motor blocks and enhanced postoperative analgesic effect.[10] The largest dose of intrathecal dexmedetomidine, 100 μg has been used in a sheep model where a 7-day follow-up showed no neurological deficits in the studied animals.[9] On the other hand, fentanyl, a lipophilic μ-receptor agonist opioid, is being used as an adjuvant for a long time with no major complications besides some side effects. It has been proved beyond doubt in various studies that dexmedetomidine enhances the duration and efficacy of analgesia and has sedative and hypnotic effects [10] when used in the subarachnoid space along with bupivacaine, a potent local analgesic. In the present study, an attempt was made to compare the analgesic effects and side-effects of dexmedetomidine and fentanyl when used as an adjuvant with bupivacaine in patients undergoing lower abdominal surgeries. For this, a comparative study was carried out in which a total of ninety patients undergoing abdominal surgeries under spinal anesthesia using bupivacaine were enrolled. Of these ninety patients, 30 each were randomly allocated to three study groups – Group C was used as control, in Group D, patients managed with spinal bupivacaine with dexmedetomidine as adjuvant, and Group F, patients were given bupivacaine and fentanyl as adjuvant. The patients have been randomized into the mentioned groups and were compared in terms of onset and duration of sensory and motor blockade, regression of sensory and motor blockade, sedation score, postoperative analgesia using VAS, time to requirement of first rescue analgesia, and the adverse effects. Heart rate, BP, respiratory rate, and sedation scores have also been recorded at various time intervals intraoperatively and postoperatively up to 12 h. Rescue analgesia has been given using injection diclofenac 75 mg intramuscularly. Various side effects such as hypotension, bradycardia, sedation, nausea, vomiting, respiratory depression, pruritus, and urinary retention have been also been looked for, evaluated and treated when found necessary [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11].
Figure 1: Dexmedetomidine and Fentanyl group, 21 patients with T5 level, while 9 patients achieved T4 level in each of the groups

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Figure 2: Fentanyl and Dexmedetomidine groups

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Figure 3: Post-hoc analysis revealed that both treatment groups significantly differed from Control group

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Figure 4: Comparison between three groups at study group against mean onset of motor blockade

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Figure 5: Comparison between three groups at study group against mean

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Figure 6: The graph shows the mean post-operative pulse rate at different time points in three groups

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Figure 7: The graph shows the mean intra-operative systolic blood pressure at different time points in three groups

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Figure 8: The graph shows the mean post-operative systolic blood pressure at different time points in three groups

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Figure 9: The graph shows the mean post-operative verbal analogue score at different time points in three groups

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Figure 10: The graph shows the mean intra operative sedation score at different time points in three groups

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Figure 11: The graph shows various adverse effects noted during surgery

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Demographic data

The three groups were comparable with respect to their age. The mean age was 43.57 years for dexmedetomidine and 38.83 years for fentanyl and 44 years for control group. The distribution of the patients according to their age was statistically insignificant (P > 0.05).

Three groups which were divided according to the ASA criteria. Dexmedetomidine group had 63% patients in ASA criteria 1 and 37% in ASA criteria 2. Fentanyl group had 17% in ASA criteria 1 and 43% subjects in ASA criterion 2. However, once again, this parameter seems to be insignificant. We had excluded ASA criteria 3 and 4 in this study. The mean BMI for dexmedetomidine group was 19.94 ± 4.7 kg/m 2, and that was fentanyl group was 22.34 ± 3.31 kg/m 2. For control group, the mean BMI was 21.79 ± 2.59 kg/m 2. Patients with higher BMI were excluded for the study. Hence, this parameter also holds insignificant.

Sensory blockade

Onset of sensory block

The time taken from the completion of injection of study drug till the patient does not feel pinprick at T10 was considered as time of onset of sensory block. In our study, we established that the mean onset of sensory block in dexmedetomidine group was 6.70 ± 0.79 min while in fentanyl group, it was 8.03 ± 1.22 min. In control group, it was 5.87 ± 1.38 min. The difference in the means across groups was statistically significant with P < 0.0001 using one-way ANOVA. Post hoc analysis revealed a significant difference between fentanyl and dexmedetomidine groups and also between fentanyl and control groups. Onset was delayed with the addition of fentanyl by almost a minute when compared to the dexmedetomidine group and on comparing to the control, the onset was delayed by almost 2 min. Kanazi et al.[11] stated that a small intrathecal dose of dexmedetomidine (3 μg), used in combination with bupivacaine in human beings for spinal anesthesia, has been shown to produce a shorter onset of motor block and a prolongation in the duration of motor and sensory block with hemodynamic stability and lack of sedation. Our study differs from their observations to this effect, and we noted that the onset with the addition of dexmedetomidine delayed onset by almost a minute, whereas addition of an opioid, i.e. fentanyl delayed the onset by 2.2 min. Jamliya et al.[12] in 2013 conducted a study to compare the effect of adding dexmedetomidine in intrathecal bupivacaine versus intrathecal bupivacaine alone. Here, they wrapped up that the onset of action was delayed in the study group with dexmedetomidine. This of course was in agreement to our result. Joshi et al.[13] conducted a study in 2013 on the effect of intrathecal dexmedetomidine bupivacaine combination on duration of subarachnoid block and postoperative analgesia. They concluded that the group using dexmedetomidine had a longer onset of action, but prolonged analgesia. Our study confirms this finding.

Maximum dermatomal sensory level achieved

Maximal level achieved in our study was in dexmedetomidine and fentanyl group, there were 21 (70%) patients with T5 level while 9 (30%) patients achieved T4 level in each group. In control group, there were 15 (50%) patients with T6 level, followed by 12 (40%) patients with T4 level, and 2 (6.67%) patients with T8 level. Only 1 (3.33%) patient achieved T5 level in this group. The number of patients in T4 and T5 levels in two test groups were significantly higher than that of control group as indicated by P < 0.0001, signifying that maximum level achieved, i.e. T4 was achieved by both fentanyl and dexmedetomidine groups. In October 1989, Hunt et al.[14] had published their study on the use of subarachaniod fentanyl in cesarean delivery, and they concluded that all patients had achieved T4 level and complete motor block within 10 min of induction. This is comparable with our study. It was clearly better than plain bupivacaine as proved before. With use of bupivacaine alone, only 80% of the patients had achieved the T4–T5 level. Eid et al.[15] found that median and range of peak sensory level reached was T5 (T3–T9) for group receiving 10 μg dexmedetomidine and T7 (T4–T9) for group receiving 15 μg dexmedetomidine (P = 0.08).

Two segment regression in sensory block

In dexmedetomidine group, the mean time was 162 ± 26.83 min, while in fentanyl group, the mean time was 122.73 ± 15.31 min. In control group, the mean time was 65.70 ± 12.21 min. The difference in the mean times was highly significant across groups as indicated by P < 0.0001 using one-way ANOVA. Tukey's post hoc analysis revealed significant difference of mean time between all the three groups. These observations have been consistent with Al-Mustafa et al.,[10] Eid et al.,[15] who found statistically significant difference in two-segment regression time. They also found the time to two-segment sensory regression to be 103 ± 28.7 min with 10 μg dexmedetomidine while it was 200.6 ± 30.9 min in group of patients receiving 15 μg dexmedetomidine. It has been postulated that dexmedetomidine stimulate α2 receptors directly in the spinal cord, thus inhibiting the firing of nociceptive neurons. The local anesthetics act by blocking sodium channels whereas the α2 adrenoceptor agonist acts by binding to presynaptic C-fibers and postsynaptic dorsal horn neurons. The effect of dexmedetomidine is additive or synergistic effect secondary to the action of local anesthetics. Hence, the prolonged action of dexmedetomidine was noted.

The dexmedetomidine group took maximum time for regression of sensory block by two segments. This clearly states that both fentanyl and dexmedetomidine is far superior to plain bupivacaine. While comparing between the studies groups, dexmedetomidine is appreciably remarkable, with extended time for the same effect.

Motor blockade

Onset of motor block

The motor blockade has been assessed using modified Bromage scale. This is a simple tool to apply in clinical settings. Bromage scale is a qualitative measure of intensity of block that analyses movements in various muscle groups. It has been previously explained in the chapter containing the materials and methods. In dexmedetomidine group, the mean onset time for motor blockade was 11.03 ± 0.93 min, while in fentanyl group; it was 11.03 ± 0.93 min. In control group, the mean onset time was 7.27 ± 1.26 min. The difference of means was highly significant across study groups as indicated by P < 0.0001. The post hoc analysis revealed that both treatment groups significantly differed from control group in respect of onset of motor block. The control group had a faster onset of motor blockade, i.e. almost 7 min, and the study groups had a delay of 3 min to achieve the target. Our study indicated that there was a quicker onset of motor block in the control group, but there was delay in the onset of motor block in both dexmedetomidine and fentanyl groups. Since the studies we referred to did not use a control group, we could not compare our results with the existing studies. In a study done by Gupta et al.,[16] in 2011, there was no difference in the onset time to Bromage 3 motor block 11.6 ± 1.8 min in group dexmedetomidine and 11.2 ± 1.3 min in group fentanyl. They did not use a control group. Our results derived are comparable to their findings, the difference being negligible.

Duration of motor block

In dexmedetomidine group, the mean duration of motor blockade was 330.27 ± 37.26 min while in fentanyl group, the mean duration was 264.28 ± 28.26 min. In control group, the mean duration of motor blockade was 161.67 ± 36.3 min. Our results have been consistent with those of Eid et al.,[15] Al-Mustafa et al.,[10] Sunil et al.,[17] who compared different doses of dexmedetomidine intrathecally and found significant prolongation of motor block with higher doses. Al-Mustafa et al.[10] found that the regression to Bromage grade 0 was 302 ± 36.7 min in patients receiving 10 μg dexmedetomidine while it was 246 ± 25.7 min in patients receiving 5 μg dexmedetomidine. Similar results were observed by Eid et al.,[15] who found time of regression to bromage grade 0 was 336 ± 58 min with 15 μg of dexmedetomidine and 280 ± 46 min with 10 μg dexmedetomidine. The increase in duration of motor effect might be caused by direct impairment of excitatory amino acid release from spinal interneurons. Al-Ghanem et al.[18] in 2009, inferred that the regression time to reach modified Bromage 0 in Group D (240 ± 364 min) was significantly longer than that for group F (155 ± 46 min), P < 0.001. The time reach S1-segment was significantly longer in Group D (274.8 ± 73.4 min.) than in Group F (179.5 ± 47.4 min.) (P< 0.001). Our findings are in consistence with the above results. Clearly, dexmedetomidine is superior to fentanyl, especially in prolonged surgeries, providing sustained blockade.

Hemodynamics

One of the main disadvantages of spinal anesthesia is adverse changes in hemodynamic parameters. In our study, bradycardia was defined as a decrease in pulse rate to <50 beats/min. Two patients in the dexmedetomidine group had episodes of bradycardia, whereas nine patients in fentanyl group and 8 in the control group had the same. This was treated with injection Atropine 0.6 mg IV single dose. On intragroup analysis, there was a significant drop in heart rate in the dexmedetomidine group after the 4th min of induction and continued to be stable throughout the intraoperative and into the postoperative period. Mohamed et al.[19] in 2012 studied that the addition of 5 μg dexmedetomidine to 10 mg bupivacaine or 5 μg dexmedetomidine to 10 mg bupivacaine and 25 μg fentanyl intrathecally before the induction of general anesthesia in major abdominal cancer surgery induced a significant reduction in the intraoperative pulse rate and BP. This was in agreement with Al-Ghanem et al.,[18] where the use of dexmedetomidine was found to be associated with a decrease in heart rate and BP. Bindra et al.[20] had published a case report of sinus arrest with use of intrathecal dexmedetomidine. Hence, we have executed at most caution for the all the patients.

Hypotension was defined when mean arterial pressure ≤60 mmHg. There has been statistically significant fall in systolic and DBP from baseline in each group of patients (intragroup analysis). In our study, we found that there was decrease in BP starting from 6 to 8 min after administration of subarachnoid block up to 75 min in group dexmedetomidine and 105 min in group fentanyl in postoperative period in a dose dependent manner. However, on the intergroup comparison, results have been statistically insignificant both intraoperatively and postoperatively (P > 0.05).

Dexmedetomidine evokes a biphasic BP response: a short hypertensive phase and subsequent hypotension. The two phases are considered to be mediated by two different α2-AR subtype; the α2B receptor is responsible for initial hypertensive phase whereas hypotension is mediated by α2A receptor. α2 receptors are located in blood vessels where they mediate vasoconstriction and on sympathetic terminals, they inhibit norepinephrine release. The responses of activation of α2 receptors cause contraction of vascular smooth muscles leading to hypertension. The initial response lasts for 4–5 min and is followed by decrease in BP of 10%–20% below baseline and also stabilization of the heart rate below the baseline values. Both these effects are caused by the inhibition of central sympathetic outflow overriding the direct stimulating effect.[19] Hence, this could be the plausible cause in our case. The postoperative pain relief and hemodynamics were better with the addition of fentanyl. Bradycardia was found in 10%–15% of the cases which was not statistically significant. In our study, the baseline (preoperative) SBP in dexmedetomidine group was 129.97 ± 11.81 mmHg and DBP was 81.10 ± 7.84 mmHg. During the surgery, highest SBP was seen at 4th min (143.53 ± 14.83 mmHg) immediately after giving subarachnoid block, and a minimum of at 20th min (104.93 ± 11.12 mmHg) and the lowest diastole recorded was at 25th min at (59.10 ± 5.29 mmHg). During the postoperative period, these patients had a stable hemodynamic state, owing to probably to good analgesia period. The baseline (preoperative) SBP in fentanyl group was 120.33 ± 11.95 mmHg which was incidentally also the highest noted. During the surgery, lowest recorded at 6th min (99.40 ± 7.17 mmhg). In our study, the dose of bupivacaine used was 15 mg in all groups which is likely to produce dense axonal blockade as discussed above and hence could mask the hypotensive effect of dexmedetomidine even in higher doses. Around ten patients in the dexmedetomidine group experienced hypotension, whereas 13 patients in the fentanyl group and almost 20 subjects in the control group. Each instance of hypotension was treated with pushing crystalloid and injection mephentermine 6 mg. Besides routine parameters indicating hemodynamic changes discussed above other indicators such as SpO2 and Respiratory rate (postoperative period) were found to have no significant difference between the three study groups.

Postoperative pain and analgesia

Control of acute postoperative pain may improve long-term recovery and quality of life. The intensity of pain was assessed using a VAS. In the study previously discussed, carried out by Mohamed et al.,[19] the time of the first rescue analgesic requirement was significantly prolonged in the dexmedetomidine group (3.30 h) and the dexmedetomidine + fentanyl group (5.41 h) compared to the control group (0.233 ± 0.11 h). Gupta et al.[16] compared the role of intrathecal dexmedetomidine and fentanyl as adjuvants to bupivacaine. They concluded that intrathecal dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability, and reduced demand for rescue analgesics in 24 h as compared to fentanyl. In another study, Gupta et al.[21] found that the addition of 5 μg of dexmedetomidine to 3 mL 0.75% isobaric ropivacaine intrathecally produced a prolongation in the duration of the motor and sensory block in lower limb surgeries. This can probably be explained as administration of α2 adrenergic agonist through intrathecal and epidural route provides an analgesic effect in postoperative period. At spinal cord level, activation of both α2-C and α2-ARs in the neurons of superficial dorsal horn, especially lamina II directly reduces pain transmission by suppressing the release of pro-nociceptive transmitter, substance P and glutamate from primary afferent terminals, and by hyper polarizing spinal interneurons through Gprotein-mediated activation of potassium channels. The mean duration of analgesia noted in the dexmedetomidine group was about 584 ± 120.96 min, and the fentanyl group recorded a period of 287.73 ± 181.52 min. From this study, we can infer that dexmedetomidine almost doubles the time of analgesia as compared to fentanyl and plain bupivacaine. The rescue analgesia has been given for pain score of >4 in the form of intramuscular injection diclofenac 75 mg.

Sedation

The mean score in dexmedetomidine group till 120 min was significantly lower than that of other two groups while beyond this time point, the mean score in fentanyl group was significantly higher than dexmedetomidine group. The control group barely had any sedation. On comparing the sedation scores in three groups, the sedation score has been found to be lower in group dexmedetomidine as compared to group fentanyl. Our results have been consistent with Eid et al.[15] who found statistically significant decrease in sedation score with increasing dose of dexmedetomidine. The hypnotic and supra spinal analgesic effects of dexmedetomidine are mediated by the hyper polarization of nor adrenergic neurons, which suppresses neuronal firing in the locus ceruleus along with the inhibition of norepinephrine release and activity in the descending medullospinal noradrenergic pathway, secondary to the activation of central α2 adrenoceptors. Dexmedetomidine-induced sedation qualitatively resembles normal sleep. Mohamed et al.,[19] stated there were no significant differences in sedation scores among groups. Intrathecally administered α2-agonists have a dose-dependent sedative effect. Our study is in contradiction to this, as dexmedetomidine group had significant sedation.

Side effects

Respiratory depression is defined as a respiratory rate of <10 breaths/min, and this was not observed in any patient in the control and dexmedetomidine group. Euphoria and dysphoria was not observed in any patient. Two patients in the fentanyl group was noted to have mild respiratory depression, which did not require to be managed. In dexmedetomidine group, 10 (33.3%) patients had hypotension for with injection mephentermine IV 6 mg was given, around two patients had bradycardia which was treated with injection Atropine IV 0.6 mg. Where as in fentanyl group, around 13 (43%) patients had episodes of hypotension and 9 (30%) patients had episodes of bradycardia. Dexmedetomidine is an α2-adrenergic agonist which acts peripherally and centrally. Cardiovascular depression from α2 adrenergic agonists can occur at both brain and spinal cord sites. Postsynaptic activation of α2 adrenoreceptors in the CNS inhibits sympathetic activity and thus can decrease BP and also heart rate.[16] Gupta et al.[16] observed that intraoperative ephedrine requirement to be more in dexmedetomidine group, but it has been statistically insignificant. The incidence of bradycardia and thus use of atropine has been higher in dexmedetomidine group than in placebo group, but the difference is statistically insignificant. There were no differences in incidence of chest tightness, somnolence, or shivering using the unpaired student test. Nausea with or without vomiting was associated with the hypotensive episodes. This may be explained by the fact that increased vagal activity after sympathetic block causes increased peristalsis of the gastrointestinal tract, which leads to nausea. Episodes of nausea and vomiting were treated with injection ondensteron 8 mg was given to treat nine patients in dexmedetomidine group and 15 patients in fentanyl group. The incidence of pruritus was negligible. This is comparable with the results of the study by Gupta et al.[21] Although urinary retention has been reported with intrathecal opioids, we were unable to evaluate this because all our patients routinely had a Foley's catheter for 24 h.


  Summary and Conclusion Top


α2-AR agonists have been the focus of interest for their sedative, analgesic, perioperative sympatholytic, and hemodynamic-stabilizing properties. They reduce the need for higher dosages of anesthetics.

We observed that the groups were comparable with respect to demographic data (age, weight, height, and duration of surgery) and onset time of sensory and motor blockade. The onset of sensory and motor block was slightly delayed in both study groups than the control group. Two segment regression time of sensory blockade and time to reach Bromage scale 0 was greatly significant in dexmedetomidine and fentanyl, but in comparison of the two, dexmedetomidine was clearly superior.

The groups were comparable in terms of hemodynamic parameters, oxygen saturation, and respiratory rate though there had been a statistically significant fall in BP and heart rate when compared to baseline in the dexmedetomidine group. Sedation scores were found to be statistically significantly higher in group dexmedetomidine as compared to fentanyl intraoperatively and postoperatively.

The results showed statistically significant increase in the duration of postoperative analgesia in group using dexmedetomidine as compared to group fentanyl. The requirement of first rescue analgesic was greatly significant. The group using fentanyl had an postoperative pain free period of unto 4 h, and dexmdetomidine had analgesia period unto 7 h.

We found some adverse effects such as hypotension, bradycardia, nausea and vomiting with dexmedetomidine and fentanyl, but the results were statistically insignificant.

To conclude, the addition of dexmedetomidine prolonged the sensory and motor block significantly when used with hyperbaric bupivcaine intrathecally, to a much greater extent to the addition of fentanyl without increasing the incidence of significant adverse effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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