Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 2  |  Page : 190-194  

Evaluation of analgesic effect of nitroglycerine added to lignocaine in intravenous regional anesthesia


1 Department of Emergency Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
2 Department of Anesthesiology, Karpaga Vinayaga Institute of Medical Sciences, Kanchipuram, Tamil Nadu, India

Date of Web Publication1-Mar-2016

Correspondence Address:
Shalini Kishor Thombre
A2/103 Bhagyashree Society, Sinhagad Road Parvatti S. No. 133, Pune 4110301, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-2870.177657

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  Abstract 

Background: In this study, we used nitroglycerine (NTG) as an adjuvant to lignocaine in intravenous regional anesthesia (IVRA) to enhance the analgesic property of lignocaine. Aim: To evaluate the effect of addition of NTG to lignocaine in IVRA. Objective: To find out the onset, duration, and requirement of postoperative analgesics with the addition of NTG. Materials and Methods: This was a randomized (block randomization), double-blinded, placebo-controlled study of 60 patients of the American Society of Anesthesiologists Class I and II, undergoing hand and forearm surgeries. Patients received IVRA with 3 mg/kg 2% lignocaine diluted to a total volume of 40 ml to which either 150 μg NTG or equal volume of saline was added. Intraoperatively and postoperatively, pain score was evaluated using visual analog scale. The sensory and motor block onset and recovery time and the subsequent analgesic requirement in first 24 h were recorded. Results: Motor and sensory block onset time were significantly shorter (P < 0.001), and motor and sensory block recovery time were prolonged (P < 0.001) in NTG group compared to plain lignocaine group. Intra-operatively fentanyl requirement was significantly lower and quality of sensory and motor blockade was better in study group than control group (P < 0.001). In addition, patients in NTG group required significantly less number of analgesics in the first 24 h as compared to the other group. Nitrates are potent relaxers of vascular smooth muscles and act by dilating veins, arteries, and arterioles. In IVRA, most of the anesthetic agent is absorbed into the limb tissue. Thus, the local anesthetic agent reaches to the nerves and nerve endings quickly. Thus shortens the onset time and also prolongs sensory and motor blockade and reduces total analgesic consumption in first 24 h without significant side effects. Conclusion: NTG as an adjuvant to lignocaine for IVRA reduces the total analgesic consumption in first 24 h and improves sensory and motor block without side effects.

Keywords: Intravenous regional anesthesia, lignocaine, nitroglycerine


How to cite this article:
Thombre SK, Vishwasrao SS, Dole A. Evaluation of analgesic effect of nitroglycerine added to lignocaine in intravenous regional anesthesia. Med J DY Patil Univ 2016;9:190-4

How to cite this URL:
Thombre SK, Vishwasrao SS, Dole A. Evaluation of analgesic effect of nitroglycerine added to lignocaine in intravenous regional anesthesia. Med J DY Patil Univ [serial online] 2016 [cited 2024 Mar 28];9:190-4. Available from: https://journals.lww.com/mjdy/pages/default.aspx/text.asp?2016/9/2/190/177657


  Introduction Top


Intravenous regional anesthesia (IVRA) is reliable and cost effective. It reduces the nursing time demand in Postanesthesia Care Unit and helps in early hospital discharge. However, its limitations are prolonged onset time, tourniquet pain, and immediate recovery after tourniquet release thereby immediate requirement of postoperative analgesic drugs. Various studies have been conducted using adjuvants such as morphine, fentanyl, sufentanil, and tramadol and nonsteroidal antiinflammatory drugs such as lornoxicam, tenoxicam, and ketorolac. [1] This study was undertaken to evaluate the effect of addition of nitroglycerine to lignocaine during IVRA to enhance the effect of anesthesia. Our aim in this study was to highlight the importance of nitroglycerine (NTG) as an adjuvant to lignocaine in IVRA (Bier's block) to enhance the analgesic property of lignocaine. [2] NTG, first synthesized in 1846 by Sobrero, it was used for relief of anginal pain. NTG is metabolized to produce nitric oxide (NO), which causes an increase in the intracellular concentration of cyclic guanosine monophosphate, which produces pain modulation in the central and peripheral nervous system. [3]


  Materials and Methods Top


This study was approved by the Hospitals' Ethics Committee, and informed consent was obtained. This randomized, double-blinded, placebo-controlled study was done on 60 patients of the American Society of Anesthesiologists (ASA) Grades I and II. Those patients scheduled for hand and forearm surgery of <1 h duration were included in the study. Patients with hypersensitivity to local anesthetics, patients with skeletal muscle disorders, sickle cell anemia, history of giddiness, and vertigo were excluded from the study. The protocol for the study and the use of visual analog scale (VAS) were explained to all patients in the preoperative visit.

Patients were randomized by block randomization. We wrote AB on one piece of paper and BA on another paper. Both were folded and randomly chosen by either Group 1 or Group 2 after the detailed examination and informed written consent. Patients were not aware to which group they belonged to. Anesthesia residents involved in the study were blinded to the syringes used for IVRA. All medications were prepared by residents not participating in the study. The volume to be injected in IVRA was prepared in syringes with labels indicating only the serial number of the patient. Patients were to receive one of the two assigned study medications, Group 1 and Group 2.

Group 1: 3 mg/kg 2% lignocaine to a total volume of 40 ml (in normal saline) +placebo (equal volume of normal saline as that of NTG).

Group 2: 3 mg/kg 2% lignocaine to a total volume of 40 ml (in normal saline) + NTG (150 mcg) (in insulin syringe).

Patients were taken up for surgery after confirming basic investigations and adequate starvation. Routine monitoring consisted of pulse rate, noninvasive blood pressure (NIBP), oxygen saturation, and electrocardiogram (ECG).

An IV cannula was secured in the nonoperative upper extremity for the administration of fluids and drugs. All the patients were premeditated with injection midazolam 0.05 mg/kg IV and injection ondansetron 8 mg IV. Twenty-four gauge IV cannula was placed in the upper extremity to be blocked, as distally as possible. A double tourniquet was placed on the operative side. Exsanguination of the arm was done by elevating the arm for 3 min. After exsanguination of the arm, the proximal cuff was inflated to approximately 250 mmHg. Circulatory isolation of the arm was verified by inspection, absence of radial pulse, and loss of pulse oximetry tracing in the ipsilateral index finger. IVRA was established by double tourniquet technique, and injecting any one of the two drug groups by an anesthesiologist blinded to the group study. Pulse, blood pressure, ECG, and oxygen saturation were monitored during injection and every 3 min after injection till 30 min. Patients were watched for perioral numbness, twitching, bradycardia, and hypotension.

Sensory block was assessed by pinprick method performed with 22-gauge short-beveled needle. Sensory block onset time was noted as the time elapsed from injection of drug to sensory block achieved in all dermatomes. Motor function was assessed by asking the patient to flex and extend the wrist and fingers, and the time of complete motor block was noted when no voluntary movement was possible. Motor block onset time was the time elapsed from injection of drug to complete motor block. The distal tourniquet was inflated to 250 mmHg, and the proximal tourniquet was released. Pulse rate, oxygen saturation, NIBP, and VAS scores (0 = No pain and 10 = Worst pain imaginable) were monitored at 5, 10, 20, and 30 min after injection of anesthetics.

When pain due to tourniquet was more than 3 on VAS, injection fentanyl 0.5-1 mcg/kg was given. The total fentanyl requirement dose and time were noted. The tourniquet was not deflated before 30 min and was not inflated for more than 1 h. Tourniquet was deflated for 10 s and reinflated for 5 s, and this was done for 3 times before final deflation. After releasing the tourniquet, blood pressure was measured at an interval of 15 and 30 min. Sensory and motor block recovery time were noted. Sensory block recovery time was the time elapsed after tourniquet deflation up to recovery of all the sensations in all dermatomes. Motor block recovery time was noted as the time elapsed after tourniquet deflation up to the movement of fingers and wrist. Patients were observed for any side effects such as headache, nausea, vomiting, gastric discomfort, skin rash, and tinnitus after the release of tourniquet. Postoperatively, diclofenac sodium was the rescue drug used, when VAS >3. Patients were monitored for the time to first analgesic and the total number of analgesics required in the first 24 h.

The sample size was calculated taking the power of test equal to 95%. Statistical comparisons were made for blood pressure and heart rate in intraoperative and postoperative period, sensory and motor block onset and recovery time, fentanyl requirement for tourniquet pain and postoperative analgesic requirement, in both the groups. Statistical analysis was done with unpaired "t"-test (intraoperative and postoperative blood pressure and heart rate, fentanyl requirement for tourniquet pain, first postoperative analgesic requirement, and total analgesic requirement in 24 h, sensory and motor block onset and recovery time comparison in both the groups), and "Chi-square" t-test (intraoperative assessment of tourniquet pain by VAS score, postoperative pain assessment in first 4 h by VAS score, comparison in both the groups).


  Results Top


Demographic data of the groups were comparable for mean age sex ratio weight and duration of surgery [Table 1]. There was no significant difference in types of surgical procedure, duration of surgery, and tourniquet time. There was no exclusion from the study because of technical failure. [Table 1]: Values are shown as mean and standard deviation. No significant differences were found between the groups.
Table 1: The two groups showing age, sex ratio, weight, and duration of surgery

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There was also no statistical difference between groups when compared for mean arterial blood pressure, and heart rate at any intraoperative and postoperative period (P > 0.05) [Figure 1] and [Figure 2].
Figure 1: Mean arterial blood pressure in Groups 1 and 2

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Figure 2: Mean heart rate in Groups 1 and 2

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Sensory and motor block onset times were statistically shorter while recovery times were statistically prolonged in Group 2 (NTG group) compared with Group 1 (P < 0.001) [Table 2].
Table 2: Sensory and motor block onset and recovery time

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Supplemental fentanyl for intraoperative tourniquet pain was given in patients with a VAS score of more than 3. Twenty-one patients in Group 1 and 4 patients in Group 2 (NTG group) required supplemental fentanyl (P < 0.001).

The first fentanyl requirement time for tourniquet pain was statistically prolonged in Group 2 (30 ± 8 min) compared to Group 1 (19.2 ± 6 min) (P < 0.001) [Table 3]a
Table 3:

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Intraoperative fentanyl requirement was less in Group 2 (26 ± 10 mcg) compared to Group 1 (53 ± 10 mcg) (P < 0.001) [Table 3]b.

Postoperative VAS scores are shown in [Table 4].
Table 4: Postoperative assessment of pain in first 24 h

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The time to first postoperative analgesic requirement was statistically prolonged (240 ± 60 min) in Group 2 compared to Group 1 (40 ± 20 min) (P < 0.001) [Table 5].
Table 5: Time required for fi rst postoperative analgesic and number of patients in each group

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Total diclofenac consumption was statistically lower in Group 2 (40 mg ± 20 mg intramuscular [IM], 50 mg ± 20 mg oral) compared to Group 1 (100 mg ± 30 mg IM,75 mg ± 25 mg oral) (P < 0.05) [Table 6].
Table 6: Total diclofenac requirement in 24 h

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No patient developed an intraoperative headache, bleeding, gastric discomfort, or nausea as side effects.


  Discussion Top


About 60 adult patients of ASA Grades I and II scheduled for hand and forearm surgery of <1 h duration were included in the study. The main result of our study was that addition of NTG to lignocaine for IVRA decreased tourniquet pain, improved the speed of onset, prolonged the recovery time thus decreased intraoperative and postoperative analgesic requirement, without causing any side effects.

NTG is metabolized to NO in the cell. NO causes an increase in intracellular concentration of cyclic guanosine monophosphate, which produces pain modulation in the central and peripheral nervous system. [3] In addition, the direct stimulation of peripheral fibers mimicking the action of locally applied acetylcholine. These mechanisms might contribute to the analgesic effects of NTG added to lignocaine in IVRA. In addition, the beneficial effects of NTG might depend on the strong vasodilatory effect that promotes better distribution of lignocaine to nerves which explains the rapid onset of sensory and motor block. [3],[4]

As in this study, very small dose of NTG (150 mcg) was added to lignocaine, for an analgesic effect, we did not notice any case of hypotension due to NTG. From the previous studies, data in humans suggest large doses of transdermal NTG, as 30 mg daily, are hyperalgesic and doses <6 mg are analgesic. [5],[6]

Mechanism of action of local anesthetic in Biers' block: Local anesthetic diffuses into the small veins surrounding the nerves and then into the vasa nervorum and capillary plexus of the nerves, leading to centrifugal conduction block in the nerves involved. Local anesthetic then diffuses into the small nerves in the skin, blocking their conduction.

Abbasivash et al. studied the effect of addition of 200 μg of NTG to lignocaine in IVRA. They observed that onset time for sensory and motor block was shortened in the study group (2.61 vs. 5.09 and 4.22 vs. 7.04 min, respectively), P < 0.05. The recovery time of sensory and motor block and the onset of tourniquet pain were also prolonged (7.26 vs. 3.43, 9.70 vs. 3.74, and 25 vs. 16.45 min, respectively). In our study, we had similar results. [7]

Honarmand et al. compared the analgesic effect of three different doses of NTG when added to lignocaine in IVRA - The doses were 200, 300, and 400 μg, respectively (control group was LA solution 0.5% 40 ml) (LN1, LN2, and LN3). They concluded that there was shortening of onset time for both sensory and motor block in LN3 (NTG 400 μg) group as compared to all the other groups (Group LN1, LN2). The quality of anesthesia and perioperative analgesia was better in LN3 group than the other three groups.

Ours was the first experience of addition of NTG in IVRA. Hence, we used a lower dose with encouraging results. However, in future, we will be undertaking comparison of addition of higher doses of NTG to LA in IVRA. [8]

Asadi and Mehri D studied the effect of addition of NTG 200 μg to lignocaine in IVRA for elective forearm and hand surgery. The sensory blockade time was longer, and onset was shorter in NTG + LA group. Opioid injections frequency was lower in NTG + LA group. Our observations are similar to this study. [9]


  Conclusion Top


NTG added to lignocaine during IVRA causes shortened sensory and motor block onset time, reduced tourniquet pain, prolonged sensory and motor block recovery time, prolonged first analgesic requirement in both intraoperative and postoperative period, and decreasing total amount of analgesic in first 24 h with no side effects.

Acknowledgment

Work done at MIMER Medical College, Talegaon, Pune, Maharashtra, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Choyce A, Peng P. A systematic review of adjuncts for intravenous regional anesthesia for surgical procedures. Can J Anaesth 2002;49:32-45.  Back to cited text no. 1
    
2.
Sen S, Ugur B, Aydin ON, Ogurlu M, Gursoy F, Savk O. The analgesic effect of nitroglycerin added to lidocaine on intravenous regional anesthesia. Anesth Analg 2006;102:916-20.  Back to cited text no. 2
    
3.
Durate ID, Lorenzetti BB, Ferreira SH. Peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway. Eur J Pharmacol 1990;186:289-93.  Back to cited text no. 3
    
4.
Fleming SA, Veiga-Pires JA, McCutcheon RM, Emanuel CI. A demonstration of the site of action of intravenous lignocaine. Can Anaesth Soc J 1966;13:21-7.  Back to cited text no. 4
    
5.
Berrazueta JR, Poveda JJ, Ochoteco J, Amado JA, Puebla F, Salas E, et al. The anti-inflammatory and analgesic action of transdermal glyceryltrinitrate in the treatment of infusion-related thrombophlebitis. Postgrad Med J 1993;69:37-40.  Back to cited text no. 5
    
6.
Lauretti GR, Oliveira AP, Julião MC, Reis MP, Pereira NL. Transdermal nitroglycerine enhances spinal neostigmine postoperative analgesia following gynecological surgery. Anesthesiology 2000;93:943-6.  Back to cited text no. 6
    
7.
Abbasivash R, Hassani E, Aghdashi MM, Shirvani M. The effect of nitroglycerin as an adjuvant to lidocaine in intravenous regional anesthesia. Middle East J Anaesthesiol 2009;20:265-9.  Back to cited text no. 7
    
8.
Honarmand A, Safavi M, Fatemy A. The analgesic effect of three different doses of nitroglycerine when added to lidocaine for intravenous regional anesthesia in trauma patients. Ulus Travma Acil Cerrahi Derg 2011;17:497-503.  Back to cited text no. 8
    
9.
Asadi HK, Mehri D. The analgesic effect of nitroglycerin added to lidocaine on quality of intravenous regional anesthesia in patients undergoing elective forearm and hand surgery. Acta Cir Bras 2013;28:19-25.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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