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Get Permission Bharathi B M, Tulsi T, and Bagliker: A study to evaluate the efficacy of intrathecal dexmeditomedine in patients undergoing laparoscopic surgeries under conventional general anaesthesia


Introduction

Alpha (α)2- adrenoreceptor agonists have been used as adjuvant to anaesthetic agents in peri-operative period for its several beneficial actions.1 Dexmedetomidine, a new α2 agonist provides stable hemodynamic condition, good quality of intra operative analgesia and prolonged post-operative analgesia with minimal side effects.2 This effect is due to sparing supraspinal CNS sites from excessive drug exposure, resulting in robust analgesia without heavy sedation. It produces dose dependent sedation, anxiolysis, and analgesia without respiratory depression.3

The analgesic effect of Dexmedetomidine is qualitatively different as compared to opioids in general anaesthesia.1 The adverse effect of dexmedetomidine include hypotension, nausea, bradycardia, atrial fibrillation and hypoxia.3

The development of minimally invasive surgery in the modern era has not only revolutionized surgery but this process has also influenced the practice of anaesthesiology. Laparoscopic procedure is one among those which has the advantage of less pain, less trauma and shorter hospital stay in a cost-effective manner. However, laparoscopic surgeries are usually performed by insufflation of gases like carbon dioxide into the abdominal cavity.4 The creation of pneumoperitoneum along with change in patient positions result in marked pathophysiological alterations.5 The pneumoperitoneum causes stress hormone response leading to hemodynamicinstability.

To overcome these alterations, spinal anaesthesia has been tried for laparoscopic as the sympathectomy would counteract for the hemodynamic changes. But the pneumoperitoneum for a longer duration in an awake patient with compromised position resulted in discomfort.

Regional anesthesia in combination with general anesthesia can reduce the surgical stress response, hemodynamic changes and the need for sedatives and analgesics with quicker recovery.6 Dexmeditomedine is new highly selective alpha 2 receptor agonist.7 It decreases the sympathetic outflow from CNS thereby reducing hemodynamic stress from the central nervous system thereby reducing the hemodynamic stress response and anaesthetic requirements in a laparoscopic surgery. It prolongs the duration of analgesia when given intrathecally.8, 9 There is less literature with intrathecal dexmeditomidine in laparoscopic surgeries under general anaesthesia. Hence, we hereby make an attempt in this study presuming that the stress attenuating properties of dexmeditomedine would counter the hemodynamic instability created in a laparoscopic surgery.

Materials and Methods

Following approval of the Institutional Ethics Committee, the study was conducted in 90 patients over a period of 4 months. The patients were selected and divided into two groups of 45 each by using computer generated randomization table.

Group ‘D’: Intrathecal Dexmeditomedine 5µg (0.05ml) diluted to 0.5ml with cerebrospinal fluid followed by conventional general anaesthesia: 45

Group ‘E’: Conventional general anaesthesia alone: 45

Pre-anaesthetic examination including detailed history and systemic examination as well as airway examination was conducted prior to enrolment of the patient for the study. Informed written consent was obtained from the patients after explanation of the anaesthesia technique. All patients received premedication with Tablet Ranitidine 150mg and Tablet Anxit 0.5mgthe night before surgery. The selected patients was kept fasting overnight for a period of 8hours.

Anaesthetic procedure

On shifting the patient to the operation theatre, an 18 gauge intravenous line was secured on to either of the upper limbs. Monitors including electrocardiogram, non-invasive blood pressure monitor and pulse oximeter was connected to the patient. Baseline hemodynamic parameters were measured.

Under aseptic precautions, a lumbar puncture was performed in the patients allotted to group D, in the left lateral position using 25 gauge Quincke type spinal needle at the L3-L4 inter vertebral space by midline approach to get a free flowing, clear cerebrospinal fluid.

Injection Dexmeditomedine 5µg (0.05ml) was diluted in 0.5ml of cerebrospinal fluid to total volume of 1ml and injected intrathecally. The patients were made supine immediately. At 5 minutes interval was given for recording of post injection hemodynamic parameters prior to general anaesthesia. Patients were premedicated with Injection glycopyrrolate 0.04 mg/kg, Injection midazolam 0.02 mg/kg and Injection Fentanyl 2µg/kg intravenously. After adequate preoxygenation, conventional general anaesthesia was given to the patients. Whereas the patients allotted to group C received conventional general anesthesia alone after adequate premedication and preoxygenation. The volatile inhalational agent was used in lowest possible concentration necessary to keep the mean arterial pressure and heart rate within 20 percentage of baseline and at the same time maintaining bispectral index between 40 and 60. At the end of the procedure, residual neuromuscular blockade was adequately reversed and extubated after adequate recovery.

Duration of surgery and quantity of volatile inhalational agent consumed was recorded at the end of surgery. Patients were shifted to post-operative ward and monitored for heart rate, blood pressure and oxygen saturation. Level of pain and sedation was assessed using VisualAnalogue scale and Ramsay sedation scores respectively. Time to the first rescue analgesic was noted and rescue analgesia was given with Injection Paracetamol 1gram intravenous infusion over 15 minutes. Post-operative nausea and vomiting was treated using Injection Ondansetron 0.08mg/kg intravenously.

Statistical analysis

Data was entered in Microsoft Excel and was exported into SPSS version 24.0. Data was analyzed by descriptive statistics, Student’s t test was used to compare the significant difference between two means. Chi - square or Fisher’s exact probability test was used for association of qualitative variables. p< 0.05 is considered statistically significant.

Results

Table 1
Variable Group D (Intrathecal Dexmeditomedine 5μg given)(n=37) Mean(SD) Control(n=37) Mean (SD)
Age(in years) 39(10.44) 40.27(10.07)
Weight(in kgs) 60.86(6.98) 63.57(6.24)
Height(in kgs) 154.54(3.66) 156.03(3.97)
Male/Female 9/28 16/21
ASA I/II 27/10 27/10
Duration of surgery(hour) 0.71(0.38) 0.57(0.21)

There were no significant differences among groups in demographic data, clinical characteristics and duration of surgery (P > 0.05) (Table 1).

Table 2

Heart rate (Induction)

Heart rate Group D (Intrathecal Dexmeditomedine 5μg Given)(N=37) Mean(SD) Control(n=37) Mean(SD) t-value p-value
5 minutes 87.51(16.11) 80.32(9.39) 2.345 0.022*
10 minutes 88.08(14.05) 85.59(9.0) 0.907 0.368
15 minutes 89.78(12.94) 94.92(10.96) -1.842 0.070
20 minutes 95.73(13.44) 105.62(13.98) -3.09 0.003**
25 minutes 90.84(8.89) 112.27(12.26) -8.61 0.001**
30 minutes 86.97(15.44) 116.81(13.87) -8.74 0.001**
35 minutes 91.70(13.57) 120.08(14.29) -8.76 0.001**
40 minutes 91.29(12.86) 119.65(13.54) -9.10 0.001**

[i] *significant

[ii] **highly significant

Table 3

Heart rate (Insufflation time)

Heart rate Group D (Intrathecal Dexmeditomedine 5μg Given)(n=37) Mean(SD) Control(n=37) Mean(SD) t-value p-value
1 minute 91.49(16.64) 93.84(10.19) -7.33 0.466
2 minutes 92.43(15.62) 103.19(12.78) -3.241 0.002**
3 minutes 93.76(18.56) 112.68(12.91) -5.091 0.001**
4 minutes 94.19(19.38) 119.27(9.97) -7.00 0.001**
5 minutes 95.49(17.38) 112.16(9.47) -8.199 0.001**
10 minutes 94.68(16.44) 123.03(11.87) -8.505 0.001**
15 minutes 93.95(12.94) 120.27(13.08) -8.704 0.001**
20 minutes 89.49(10.28) 113.46(11.73) -9.348 0.001**

[i] *significant

[ii] **highly significant

Table 4

SBP (Induction)

SBP Group D (Intrathecal Dexmeditomedine 5μg given)(n=37) Mean(SD) Control(n=3) Mean(SD) t-value p-value
5 minute 111.70(12.94) 124.08(17.70) -3.41 0.001**
10 minutes 113.32(12.42) 128.30(11.91) -5.29 0.001**
15minutes 115.35(19.210) 140.43(8.04) -7.32 0.001**
20 minutes 121.05(16.29) 146.0(9.74) -7.99 0.001**
25 minutes 122.81(12.62) 157.86(12.99) -11.77 0.001**
30 minutes 130.43(15.59) 163.65(12.66) -10.06 0.001**
35 minutes 129.84(10.75) 168.0(13.57) -13.41 0.001**
40 minutes 131.29(11.53) 168.11(17.77) -10.36 0.001**

[i] **highly significant

Table 5

SBP (Insufflation time)

SBP Group D (Intrathecal Dexmeditomedine 5μg Given) (n=37) Mean(SD) Control(n=37) Mean(SD) t-value
1 minute 124.08(19.52) 143.97(16.16) -4.77 0.001**
2 minutes 130.35(24.04) 150.43(17.86) -4.08 0.001**
3 minutes 132.89(22.42) 158.14(14.86) -5.71 0.001**
4 minutes 132(19.37) 164.03(12.04) -8.54 0.001**
5 minutes 133.08(17.18) 168.76(12.85) -10.11 0.001**
10 minutes 120.73(11.67) 171.84(14.90) -13.86 0.001**
15 minutes 126.76(10.81) 165.35(15.59) -12.37 0.001**
20 minutes 125.78(11.51) 153.38(13.44) -9.49 0.001**

[i] **highly significant

Table 6

DBP (Induction)

DBP Group D (Intrathecal Dexmeditomedine 5μg given)(n=37) Mean(SD) Control(n=37) Mean(SD) t-value p-value
5 minute 73.59(8.69) 77.57(8.97) -1.93 0.057
10 minutes 71.05(9.35) 76.92(7.25) -3.02 0.004**
15 minutes 74.62(14.67) 82.86(2.84) -3.35 0.001**
20 minutes 82.03(13.15) 84.7(3.31) -1.20 0.234
25 minutes 81.24(8.36) 89.92(10.09) -4.03 0.001**
30 minutes 82.27(8.39) 90.11(7.91) -4.13 0.001**
35 minutes 84.38(7.51) 89.95(5.34) -3.68 0.001**
40 minutes 84.66(7.004) 89.46(4.72) -3.43 0.001**

[i] **highly significant

Table 7

DBP (Insufflation time)

DBP Group D (Intrathecal Dexmeditomedine 5μg Given)(n=37) Mean(SD) Control(n=37) Mean(SD) t-value
1 minute 82.73(11.99) 84.86(11.24) -0.79 0.432
2 minutes 87.73(15.82) 86.05(8.55) -0.57 0.573
3 minutes 87.89(12.61) 88.05(8.18) -0.07 0.948
4 minutes 86.59(10.74) 89.08(8.16) -1.121 0.266
5 minutes 85.76(9.46) 90.92(7.66) -2.58 0.012*
10 minutes 85.22(6.19) 90.62(3.53) -4.61 0.001**
15 minutes 81.62(5.49) 89.03(2.89) -7.26 0.001**
20 minutes 81.19(5.36) 86.08(2.38) -5.07 0.001**

[i] *significant

[ii] **highly significant

Table 8

Mean Arterial Pressure (Induction)

Mean Arterial Pressure Group D (Intrathecal Dexmeditomedine 5μg Given)(n=37) Mean(SD) Control(n=37) Mean(SD) t-value p-value
5 minute 85.97(9.92) 90.49(5.63) -2.35 0.022
10 minutes 84.69(10.62) 94.57(9.45) -4.19 0.001**
15minutes 88.19(16.56) 102.08(3.77) -4.97 0.001**
20 minutes 95.06(14.04) 105.03(4.64) -4.09 0.001
25 minutes 94.22(9.74) 112.62(10.49) -7.76 0.001**
30 minutes 97.72(10.19) 114.54(8.33) -7.73 0.001**
35 minutes 99.58(9.11) 116.08(7.39) -8.51 0.001**
40 minutes 100(8.80) 115.32(7.82) -7.77 0.001**
45 minutes 96.18(9.54) 98.57(35.19) -0.35 0.73

[i] **highly significant

Table 9

Mean Arterial Pressure (Insufflation time)

Mean Arterial Pressure Group D (Intrathecal Dexmeditomedine 5μg given)(n=37) Mean(SD) Control(n=37) Mean(SD) t-value
1 minute 94.81(11.87) 105.29(12.61) -3.01 0.001
2 minutes 98.83(14.96) 102.38(27.37) -0.68 0.496
3 minutes 101.33(13.44) 111.86(10.88) -3.62 0.001
4 minutes 99.72(11.47) 114.66(8.08) -6.33 0.001
5 minutes 100.97(10.60) 110.68(27.85) -1.96 0.054
10 minutes 100.28(7.86) 117.46(4.15) -11.47 0.001**
15 minutes 95.89(5.73) 115.17(5.12) -14.94 0.001**
20 minutes 96.11(5.88) 102.97(25.43) -1.58 0.119

[i] *significant

[ii] **highly significant

Regarding hemodynamic variables measured during the intraoperative period, there was a significant reduction in pulse rate during induction starting at 20 minutes until 40 minutes in the group D [Table 2] and there was significant reduction in pulse rate during insuffulation time starting at 2 mins to 20 mins in group D in comparison to the control group (P <0.05)[Table 3]. Systolic blood pressure showed a significant reduction during induction starting at 5 minutes until 40 minutes in group in comparison to the control group (P < 0.05)[Table 4]. Systolic blood pressure showed a significant reduction during insufflation starting at 5 minutes until 40 minutes in group in comparison to the control group(P < 0.05)[Table 5]. There was a significant reduction in diastolic blood pressure during induction starting at 5 minutes until 20 minutes in group D in comparison to the control group (P< 0.05) [Table 6]. There was a significant reduction in diastolic blood pressure during insufflation starting at 10 minutes until 40 minutes in group D in comparison to the control group (P < 0.05)[Table 7]. Mean arterial pressure showed a significant reduction during induction starting at 10 minutes until 40 minutes in group in comparison to the control group (P < 0.05)[Table 8]. Mean arterial pressure showed a significant reduction during insufflation starting at 10 minutes until 20 minutes in group in comparison to the control group(P < 0.05)[Table 9]. There was decrease in consumption of inhaltional agents in dexmedetomidine group. There were no significant differences between groups in hemodynamic variables measured during the postoperative period.

Discussion

In a study conducted by Vinith K Srivastava et al, in 2015, a total of 60 patients were included. The patients were divided into three groups of 30 each. Group D received intravenous dexmedetomidine, group E received intravenous esmolol, group C received normal saline. They observed that in group D, there was no significant increase in HR and BP after pneumoperitoneum at any time intervals. Hence, Dexmedetomidine is more effective than esmolol for attenuating hemodynamic response to pneumoperitoneum in laparoscopic surgeries. 10

In a Randomised, double blinded study conducted by Ashraf Amin Mohammed et al in 2012, 90 patients were randomly assigned to receive intrathecally either 0.5% bupivacaine with 5µg dexmedetomidine alone or dexmedetomidine with fentanyl along with bupivacaine. They found that dexmedetomidine given intrathecally improves the quality and the duration of post-operative analgesia and also provides analgesic sparing effect in patients undergoing major surgeries. 3

In a study done by Rajini Gupta et al in 2011, 60 patients classified in American Society of Anaesthesiologists classes I and II scheduled for lower abdominal surgeries were studied. Patients were randomly allocated to receive Bupivacaine plus dexmedetomidine and bupivacaine plus fentanyl. They observed that Patients in dexmedetomidine. Group had a significantly longer sensory motor block than fentanyl group. Hence dexmedetomidine maintains hemodynamic stability, and reduced demand for rescue analgesics.11

In our study, we have compared between 2 groups, one group received 5 micrograms of intrathecal dexmeditomedine in addition to general anaesthesia in patients undergoing laparoscopic surgeries and the other group received only conventional general anaesthesia. We found that the hemodynamic variables like heart rate, SBP, DBP and MAP were more stable in group D compared to group E during induction, intubation and creation of pneumoperitonium as well as decreases the requirement of rescue analgesics. Hence we can conclude that use of intrathecal dexmeditomedine will decrease the hemodynamic response to intubation, insufflation. It will also decrease the requirement of intra operative opioid consumption and post-operative rescue analgesia

Conclusion

Dexmedetomidine 5 µg given intrathecally improves the hemodynamic stability, decreased intraoperative requirement of fentanyl, inhalational agents and the duration of postoperative analgesia and also provides an analgesic sparing effect in patients undergoing laparoscopic abdominal surgeries.

Source of Funding

None.

Conflict of Interest

None.

References

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