|Year : 2017 | Volume
| Issue : 2 | Page : 51-55
Evaluation of the effect of transdermal nitroglycerine patch on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy
Rama Chatterji, Anupama Gupta, Vinay Kumar Sharma, Chandra Shekhar Chatterji
Department of Anaesthesiology, SMS Medical College, Jaipur, Rajasthan, India
|Date of Submission||11-Oct-2017|
|Date of Acceptance||01-Nov-2017|
|Date of Web Publication||12-Dec-2017|
Dr. Anupama Gupta
Flat No. 5, Rajkiya Bahumanjila Pratham Shreni Aawas, Near Mahila Thana, Gandhinagar, Jaipur - 302 015, Rajasthan
Source of Support: None, Conflict of Interest: None
Aim: The aim of this study is to evaluate the effect of transdermal nitroglycerin on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy.
Materials and Methods: Totally 140 patients of the American Society of Anesthesiologists Grade I or II, posted for abdominal hysterectomy under spinal anesthesia, were randomized to four groups using computer-generated random number list. Group B received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml normal saline and placebo patch, Group BN received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml NS and transdermal nitroglycerin (t-NTG), Group BD received 3 ml of 0.5% hyperbaric bupivacaine with 5 mcg (0.5 ml) dexmedetomidine and placebo patch and Group BDN received 3 ml of 0.5% hyperbaric bupivacaine with 5 μg (0.5 ml) dexmedetomidine and t-NTG patch. Outcomes measured include the total duration of analgesia, onset, and duration of sensory and motor block and any adverse effects.
Results: The total duration of analgesia was longest in Group BDN (349.9 ± 40.6 min). It was significantly longer than Group BD (252.3 ± 34.0 min) and Group B and BN (130.5 ± 18.8, 138.3 ± 19.2 min). Time taken for two segment regression was comparable in Group B (79.9 ± 14.4 min) and Group BN (87.1 ± 22.6 min), but it was significantly longer in Group BD (122.5 ± 17.2 min) and Group BDN (136.4 ± 25.5 min). There was no significant difference in other variables between the groups.
Conclusion: Transdermal nitroglycerine itself does not exhibit any analgesic potential of its own but, it enhances the analgesic potential of intrathecal dexmedetomidine.
Keywords: Analgesia, dexmedetomidine, spinal anesthesia, transdermal nitroglycerin patch
|How to cite this article:|
Chatterji R, Gupta A, Sharma VK, Chatterji CS. Evaluation of the effect of transdermal nitroglycerine patch on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy. Indian Anaesth Forum 2017;18:51-5
|How to cite this URL:|
Chatterji R, Gupta A, Sharma VK, Chatterji CS. Evaluation of the effect of transdermal nitroglycerine patch on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy. Indian Anaesth Forum [serial online] 2017 [cited 2019 Aug 25];18:51-5. Available from: http://www.theiaforum.org/text.asp?2017/18/2/51/220560
| Introduction|| |
Pain is an unpleasant sensation that originates from ongoing and impending tissue damage. Subarachnoid block is safe and effective means of providing surgical anesthesia and postoperative analgesia for lower abdominal surgeries, but even with long-acting local anesthetic (LA) such as bupivacaine, the duration of postoperative analgesia is often inadequate. To improve the quality and duration of analgesia, various adjutants are being used with LAs.
Dexmedetomidine is being used widely as adjuvant to LA's nowadays, as it enhances analgesia when used with bupivacaine due to synergistic action., Studies demonstrated that nitric oxide (NO) interact synergistically with dexmedetomidine after intravenous (IV)/spinal administration through the activation of L-arginine/NO/cGMP pathway , which plays an important role in spinal nociceptive process. Hence, NO generator nitroglycerin patch may also potentiate dexmedetomidine's analgesic effects.
We hypothesized that using a transdermal nitroglycerin (t-NTG) patch will enhance the analgesic efficacy of intrathecal dexmedetomidine and bupivacaine without any side effects and hemodynamic variations in patients undergoing abdominal hysterectomy.
| Materials and Methods|| |
This randomized, double-blind hospital-based comparative study was conducted after obtaining approval from our Institution's Ethics Committee (ref no. 2247/MC/EC/2016) and written informed consent from the patients. Totally 140 female patients, 35–65 years of age, American Society of Anesthesiologists (ASA) physical Status of I or II, posted for abdominal hysterectomy under spinal anesthesia were considered for enrollment into four groups.
A sample size of 32 patients in each group was calculated to have at least 80% power and an alpha error of 0.05 to detect the expected differences between the groups with respect to the primary goal of total duration of analgesia. Patients with history of hypertension, cardiorespiratory disease, diabetes mellitus, chronic headache, spinal deformity, and history of allergy to any of the study drugs were excluded from the study. One hundred and forty patients were randomized into four groups of thirty-five patients using computer-generated random number list and the allocated group number of each patient was kept in a sealed opaque envelope.
After confirming overnight fasting, patients were taken into operation theater. All patients were monitored for heart rate (HR), electrocardiogram, noninvasive blood pressure, peripheral oxygen saturation (SpO2), and respiratory rate. Baseline parameters were noted, 18G IV cannula was inserted, and lactated Ringer's solution was infused at 10 ml/kg. Subarachnoid block was performed in sitting position, at L3–L4 interspace using 25G Quincke needle under aseptic conditions. Patients received medications by spinal route depending on the group allocated by randomization.
- Group B: Bupivacaine 0.5% (3 ml) +0.5 ml normal saline + Placebo patch
- Group BD: Bupivacaine 0.5% (3 ml) +5 μg (0.5 ml) dexmedetomidine + Placebo patch
- Group BN: Bupivacaine 0.5% (3 ml) +0.5 ml normal saline + transdermal nitroglycerin patch
- Group BDN: Bupivacaine 0.5% (3 ml) +5 μg (0.5 ml) dexmedetomidine + transdermal nitroglycerin patch.
The patient and the anesthetist involved in drug preparation, block administration, and the one who recorded the data were blinded to the study drugs.
The sensory block was assessed by pinprick test using 25G hypodermic needle along anterior axillary line on both sides until the level had stabilized for 4 consecutive tests. Onset of sensory blockade was defined as the time from the subarachnoid injection to the time when sensory block occurred at L2 level. Grading of sensory blockade was done using a 3 point pinprick test scale: 0-sharp pain, 1-touch sensation only, and 2-loss of touch sensation. Duration of sensory block was defined as time taken by it to regress two segments from the highest achieved level.
Motor blockade was assessed using Bromage Scale:
- No motor block, full movement
- Inability to raise extended leg; can bend knee
- Inability to bend knee; can flex ankle
- Complete motor block, no movement.
Assessment of motor block was done every 5 min. Till the Bromage 3 score was achieved. Onset of motor block was defined as the time taken for motor block to reach Bromage 3 and duration of motor block was defined as the time elapsed from the Bromage score 3–0.
Perioperative monitoring of HR and noninvasive blood pressure was done every 5 min for first 30 min, thereafter every 10 min and any changes >20% from the baseline value were treated. Hypotension was defined as mean arterial pressure (MAP) >20% decrease in baseline values, treated with injection ephedrine in incremental doses. Bradycardia was defined as HR <60/min, treated with injection atropine 0.4–0.6 mg IV in incremental doses.
Postoperative pain was evaluated on 100 points visual analogue scale  (0 = no pain to 100 = worst possible pain). Duration of analgesia was taken as the time taken from the subarachnoid injection to the first dose of rescue analgesic demanded by the patient. Injection diclofenac sodium (75 mg) intramuscular (IM) was given as rescue analgesic when the patient complained of pain, and the number of rescue analgesic doses given in 24 h was recorded.
Any side effects including hypotension, bradycardia, nausea and vomiting, headache, sedation, and respiratory depression were recorded. Nausea and vomiting were treated with injection ondansetron 6 mg. Sedation was graded by four-point score  (0-alert and wide awake, 1-arousable to verbal command, 2-arousable with shaking, and 3-unarousable.)
Quantitative data were represented as mean ± standard deviation; number and percentage were used for qualitative data. Statistical analysis was done for comparing observed data by using Student's t-test and analysis of variance. P < 0.05 was considered statistically significant.
| Results|| |
All four groups were comparable with respect to patient's age, weight, height, ASA physical status, duration of surgery, and baseline hemodynamic parameters [Table 1].
The onset of sensory block, assessed by pinprick was 6.8 ± 1.0, 6.6 ± 1.0, and 6.5 ± 1.2 and 6.5 ± 1.5 min in Group B, BN, BD, and BDN, respectively [Table 2]. Time of onset of motor blockade was 8.8 ± 1.2, 8.7 ± 1.1, and 8.2 ± 1.5 and 8.3 ± 1.1 min in Group B, BN, BD, and BDN, respectively [Table 2]. No statistically significant difference was found between the four groups (P > 0.05).
The mean duration of analgesia was comparable between the Group B and BN (130.5 ± 18.8, 138.3 ± 19.2 min), but it was significantly shorter than group BD (252.3 ± 34.0 min). Longest duration of analgesia was observed in group BDN (349.9 ± 40.6 min). It was highly significant statistically when compared to Group BD, BN, and Group B (P = 0.000 for BDN vs BD/BN/B) [Table 2].
Time taken for two segment regression was 79.9 ± 14.4, 87.1 ± 22.6, 122.5 ± 17.2, and 136.4 ± 25.5 min in Group B, BN, BD, and BDN group, respectively. Statistically, Group B and BN were comparable. Statistically, significant difference was found between Group BD and B/BN (P< 0.000). Time taken for two segment regression was found to be longest in the Group BDN in comparison to Group B/BN/BD (P = BDN vs. BD 0.009, BDN vs. B/BN 0.000) [Table 2].
The average VAS pain score at 2 h was 0.0 ± 0.0 (no pain) in Group BD and BDN, 15.4 ± 4.4 in Group BN and 29.6 ± 6.7 in group. Statistically highly significant reduction in VAS scores was observed in Group BDN and BD in comparison to Group BN and B.
Total number of IM diclofenac injection given in 24 h, were significantly less in Group BD (1.57 ± 0.50) and BDN (1.34 ± 0.48) in comparison to Group B (3.0 ± 0.61) and BN (2.9 ± 0.56), (P< 0.001) while no significant difference was observed between Group B and BN (P = 1.00) [Table 2].
All the patients in four groups remained hemodynamically stable during the intraoperative and postoperative period; the mean values of HR and mean arterial pressure were comparable between all the groups [Figure 1] and [Figure 2]. There were no significant differences found regarding the incidences of adverse effects such as nausea, vomiting, headache, hypotension, bradycardia, sedation, and respiratory depression in patients of either group [Figure 3].
|Figure 1: Distribution of mean arterial blood pressure at different time intervals|
Click here to view
| Discussion|| |
Effective control of postoperative pain remains a major concern; various adjutants have been used in addition to the intrathecal LAs for supplementation of intraoperative anesthesia and postoperative analgesia. These adjutants not only reduce the dose of LAs but also provide prolonged postoperative analgesia with reduced incidence of side effects such as central nervous system depression, motor effects, or hypotension. Time of onset of sensory and motor block were comparable among all four groups. These observations were similar to the study conducted by Al Ghanem et al., who observed no difference in the onset time in patients receiving dexmedetomidine (7.5 ± 7.4 min) and fentanyl (7.4 ± 3.3 min) as adjutants to isobaric bupivacaine (P = 0.95).
We observed that mean time for two segment regression of sensory blockade was significantly prolonged in Group BD (122.5 ± 17.2 min) and Group BDN (136.4 ± 25.5 min) as compared to group 79.9 ± 14.8 min in Group B and 87.1 ± 22.6 min in Group BN.(P = 0.000). These findings are in accordance with other similar studies in which significant prolongation in mean duration of sensory blockade in dexmedetomidine group was observed.,
Total duration of motor blockade was comparable in all the four groups; it was around 120 min in contrast to other studies,,, which showed significantly prolonged duration of motor block when dexmedetomidine was given intrathecally with bupivacaine.
The results of our study demonstrated a significant increase in the duration of postoperative analgesia when dexmedetomidine 5 μg was added to intrathecal bupivacaine in patients undergoing total abdominal hysterectomy. Analgesic efficacy of dexmedetomidine, when used along with intrathecal bupivacaine, has been established in several studies.,,,
The mechanism of action by which intrathecal α2-adrenoceptor agonists prolong the motor and sensory block of LAs is not well known. The LAs act by blocking sodium channels while the clinical effects of dexmedetomidine are attributed to the activation of presynaptic alpha-2 receptors in the locus coeruleus region of the brainstem. Activation of these receptors causes hyperpolarization of noradrenergic neurons thus inhibiting noradrenalin release and inhibiting activity in descending medullospinal noradrenergic pathways. This antinociceptive effect may explain the prolongation of the sensory block when added to spinal anesthetics.
We observed that the total duration of postoperative analgesia was further increased with the use of transdermal NTG patch along with intrathecal dexmedetomidine and bupivacaine. Use of transdermal NTG patch provided almost 7 h long pain-free period in comparison to 4.5 h in intrathecal dexmedetomidine and bupivacaine group. No increase in the incidence of adverse effects was noted on addition of t-NTG. Our results are in accordance with studies ,,, they also observed enhanced duration of postoperative analgesia without significant change in hemodynamic variables and untoward side effects such as nausea, vomiting, sedation and respiratory depression, when t-NTG was used along with intrathecal clonidine, fentanyl, neostigmine, and bupivacaine, respectively.
The exact mechanism of NO-induced augmentation of dexmedetomidine analgesia is unknown. As NO was shown to be a central neurotransmitter,, it is postulated that NO may occupy a key position in the antinociceptive and in the endogenous mediation of pain. Acetylcholine and dexmedetomidine induce analgesia through the activation of the arginine-NO-cGMP pathway. Guanylate cyclase activity in the brain is markedly stimulated by NO, generated from L-arginine or provided through an exogenous source, as in the present study through transdermal nitroglycerine. Evidence suggest that NO modulates the synaptic transfer of signals in both the central and the peripheral nervous system.
| Conclusion|| |
Our results showed that transdermal nitroglycerine itself does not exhibit any analgesic potential of its own, but it enhances the analgesic potential of intrathecal dexmedetomidine. However, the exact underlying mechanism of it needs to be evaluated further.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]