improve local aesthetic effects in Bier's Block? a double blind placebo controlled study".

Transcription

1 Title of the article: Does the use of nitro-glycerine patch improve local aesthetic effects in Bier's Block? a double blind placebo controlled study". Type of article: Original Ahmed Said Elgebaly, MD. Assistant professor Department of Anesthesia and Postsurgical Intensive Care, Faculty of Medicine, Tanta University, Egypt. Address of corresponding author: Dr. Ahmed Said Elgebaly Department of Anesthesia and Postsurgical Intensive Care, 19 Elfaloga Street, Elgharbia, Tanta, Egypt Tel: elgebaly_13@hotmail.com Funding: Author received no funding for this study. Conflict of Interest: No Conflict of Interest

2 Does the use of nitro-glycerin patch improve local anaesthetic effects in Bier's Block? a double blind placebo controlled study Abstract: Background: Bier's block is a costeffective, simple, and reliable technique of regional anaesthesia. It provides rapid onset, easy application and effective anaesthesia with safe termination and turning away of adverse effects that are inherent to general anesthesia. Local anaesthetics have been used with numerous additives to cut back bandage pain, length post deflation analgesia and improve block quality. Aim: Assess the nitroglycerin patch as anew additive to Bier's block and its impacts on the dose and effects of local anaesthetic. Design: A prospective, randomized, double-blinded placebo controlled study. Methods: Forty patients of each sexes belonging to ASA I or II undergoing elective tendon repair surgeries of the forearm and hand. Patients were divided into two equal groups as follows: Group C received only lidocaine (1.5 mg/kg 0.25%), and Group N received lidocaine (1.5 mg/kg 0.25%) + five mg transcutaneous nitroglycerin patch. Onset and recovery times for sensory and motor block, (VAS) Visual analogue score scores for bandage pain, postoperative VAS score, analgesic requirements; patient satisfaction and surgeon opinion were recorded. Results: Sensory block onset time was shorter in Group N (3.80±1.0) than C (5.72±1.46) and motor block onset time was shorter in Group N (10.72±1.93) than C (13.56±1.26). Sensory block recovery time was prolonged in Group N (10.56±1.12) than C (6.88±1.45), and motor block recovery time was prolonged in Group N (13.04±1.57) than C (11.96±1.72). Bandage pain had lower VAS scores in Group N. Post operative VAS scores showed significant differences between both groups at the following points of measurement 30 minutes, 1 hour and 4 hours after bandage deflation. Post operative analgesic effect was the longest in Group N (187.20±60.79 min) than C (51.60±25.28 min). Patients' satisfaction and surgeons' opinion were better in Group N than C. Conclusion: Transcutaneous nitroglycerin patch as a supplementation to Bier's block reduced the dose of lidocaine used, the sensory and motor block onset times, VAS scores, analgesic consumption intra- and post-operatively. Length the sensory and motor block recovery times, duration of post-operative analgesic effect and delayed the first time to analgesic requirement with better patient satisfaction and surgeon opinion and no adverse effects. Key words: Bier's block, nitroglycerin patch and local anesthetics.

3 Introduction: Providing satisfactory and prolonged analgesia is an important goal within the management of postoperative pain. Bier's block is a technique that is mostly used for providing anaesthesia and analgesia during the operation. Using additives with lidocaine may prolong the duration of postoperative analgesia (3). Intravenous regional anesthesia (IVRA) which was firstly described by August Bier in 1902 (1) is used successfully as a sole technique for upper limb surgeries. (2) It is a reliable, simple, cost-effective and widely accepted technique of regional anesthesia. (3) Disadvantages of Bier's block are including the potential for local anaesthetic toxicity, emergence of pain following removal of the bandage (within three five minutes), and lack of postoperative analgesia. (4)(5) Several adjuncts have been used including narcotics, non steroidal anti-inflammatory drugs (NSAIDS), muscle relaxants, α 2 agonists and neostigmine. (6) Nitroglycerine (NTG) and nitric oxide generator contained in transcutaneous nitroglycerine, help in distribution of local anaesthetic agents to neuron trunks by vasodilatation (7) (8). Aim of this study is to assess if the supplementation of five mg nitroglycerin patch to low dose lidocaine whether or not will improve the overall Bier's block effect either intra- or post operatively as primary outcomes and also, analgesic requirements, patient satisfaction and surgeon opinion as secondary outcomes. Materials and methods: After obtaining the approval from the native Ethics and Research Committee and written informed consent from all the study participants. A double-blind prospective randomized study enrolled forty ASA physical status I or II patients of each sexes, aged 18 years and undergoing elective tendon repair surgeries of the forearm.patient refusal, Reynauld s disease, Sickle cell disease, crush injuries, swelling or skin infection at the site of injection, patients with history of allergy to nitroglycerin or lidocaine and surgeries > 60 minutes or < 30 minutes were excluded from the study. After history taking, complete clinical examination and laboratory investigations, monitoring of the patient with non invasive blood pressure (NIBP), ECG and peripheral oxygen saturation was performed. ; A 20 Gauge intravenous cannula was inserted in the contra lateral hand for crystalloid infusion.randomization by use of sealed envelopes and allocation of patients to two equal groups were done as follows:

4 Group C ( Control group ): 40 cc of 1.5 mg/kg of 0.25 % lidocaine diluted in normal saline (0.9 % NaCl) was used for administering Bier's block. Empty Nitroglycerin patch was applied on the ventral aspect of proximal forearm of the operative arm 2 hours preoperatively. Group N ( Lidocaine and transdermal Nitroglycerin patch group): 40 cc of 1.5 mg/kg of 0.25% lidocaine diluted in normal saline (0.9 % NaCl) with application of 5 mg of transcutaneous Nitroglycerin patch was used for administering Bier's block. Nitroglycerin patch was applied on the ventral aspect of proximal forearm of the operative arm 2 hours preoperatively. Another 22 Gauge intravenous cannula was inserted in the dorsum of operative hand (as distal as possible) for injection of the study drugs. A double pneumatic bandage was placed on the upper arm with generous layers of cotton padding on operative side ensuring that no wrinkles are formed and the bandage edges do not touch the skin and then it was exanguated by 2 min. elevation and wrapping with an Esmarch bandage. Before lidocaine was injected, circulatory isolation of the arm was verified by inspection, absence of radial pulse and loss of pulse oximetry tracing in the ipsilateral index finger, then the lidocaine solution was injected by inflation to a minimum of 250 mmhg for bandage lying at proximal site. Block onset was estimated after ten minutes of local anaesthetic administration. Distal bandage was inflated up to 250 mmhg after fifteen minutes and the proximal bandage was deflated after taking out transdermal nitroglycerin patch. If no block occurs up to 15 minutes the patient was excluded and replaced with another matched one. Deflation of cuff not done until thirty minutes after lidocaine injection passed because systemic toxicity of lidocaine may occur and was not inflated for more than one and half hours. Assessment of demographic data, duration of surgery, sensory and motor block onset and recovery times, onset time of bandage pain and number of patients complaining from it, intra-operative and 24 hours postoperative analgesic requirements. Postoperative VAS score and first time of analgesic requirement were recorded. Also, patient satisfaction, by asking the patient to rate the operative conditions according to the following numerical scale: 0= Unsuccessful. 1= Poor. 2= Moderate (pain required supplemental analgesia).3= Good (Minor pain with no need of supplemental analgesia). 4= Excellent (No pain), surgeon opinion as surgeon was blind to patient randomization and asked to rate the score of the operative conditions such as movement of limb or bleeding and the score was according to the following numerical scale: 4 = Excellent.3 = Good. 2= Acceptable.1= Poor.0= Unsuccessful.

5 Complications as [CNS (circum oral numbness, headache, convulsions or coma) or CVS ( bradycardia, arrhythmia or hypotension)] were recorded. Statistical analysis Data were fed to the computer and analyzed using IBM SPSS software package version Qualitative data were described using number and percent. Quantitative data were described using mean and standard deviation. Comparison between different groups regarding categorical variables was tested using Chisquared test (χ2). The distributions of quantitative variables were tested for normality using Kolmogorov-Smirnov test, Shapiro-Wilk test and D'Agstino test. If it reveals normal data distribution, parametric tests was applied. If the data were abnormally distributed, non-parametric tests were used. For normally distributed data, comparison between more than two population were analyzed F-test (ANOVA) to be used. For abnormally distributed data, Kruskal Wallis test was used to compare between different groups and pair wise comparison was assessed using Mann- Whitney test. P-value of (> 0.05) was considered not statistically significant, P-value of ( 0.05) was considered statistically significant and P-value of ( 0.001) was considered statistically highly significant. Results: Demographic data were comparable with insignificant difference in age, sex, weight, ASA physical status, duration and type of surgery. [Table 1] Sensory block onset time was shorter in Group N (3.80±1.0) than Group C (5.72±1.46) and motor block onset time was shorter in Group N (10.72±1.93) than Group C (13.56±1.26). Sensory block recovery time was prolonged in Group N (10.56±1.12) than Group C (6.88±1.45), and motor block recovery time was prolonged in Group N (13.04±1.57) than Group C (11.96±1.72). [Table 2] VAS scores for bandage pain showed significant differences between the two groups at the following points of measurement 10, 15, 20 and 30 minutes after tourniquet inflation. Also, there was a significant difference in number of patients complained of bandage pain between the two groups whereas in Group C 52% of patients complained of bandage pain and in Group N 24% of patients complained of bandage pain. Onset time of bandage pain was longer in Group N (29.17±2.04 min) than Group C (21.54±3.15 min) [Table 3]. Post operative VAS scores showed significant differences between the two groups at the following points of measurement 30 minutes, 1 hour and 4 hours after bandage deflation with lower VAS scores in Group N (1.36 ±0.81, 1.92 ±0.40) [Table 4]. Post

6 operative analgesic effect was longer in Group N (187.20±60.79 min) than Group C (51.60±25.28 min). Post operative analgesic requirement was the lowest in Group N (33.60±9.95 mg) [Table 5] [Figure1]. In the present study, the patients' satisfaction about the operation and surgeons' opinion of the operative conditions were better in Group N than Group C. No adverse effects or complications were seen in this study. No evidence of central nervous system complications (as circum oral numbness, headache, convulsions or coma) or cardiac complications (as arrhythmias, hypotension or bradycardia) were seen after lidocaine administration, before and during surgery and after release of the bandage. Discussion: Our study results showed that the addition of 5 mg transcutaneous nitroglycerin patch as adjuvant to the lidocaine during Bier's block, reduced the dose of lidocaine to 1.5 mg/kg lidocaine 0.25%, shortened the sensory and motor block onset times, prolonged the sensory and motor block recovery times, decreased VAS scores and analgesic consumption, prolonged the duration of post-operative analgesic effect of Bier's block and delayed the first time to analgesic requirement and improved the quality of Bier's block with no adverse effects. The beneficial effects of NTG seem to be influenced by a direct potent vasodilatory effect that promotes distribution of lidocaine to nerves that is mainly dose dependant. (9) The details of the pain relieving mechanism of NTG have been well understood by several studies (10, 11). NTG exerts its analgesic effect as it is metabolized to nitric oxide (NO) in the cell. NO causes an increase in the intracellular concentration of cyclic guanosine monophosphate, which produces pain modulation in the central and peripheral nervous systems. NO generators also induce antiinflammatory effects and analgesia by blocking hyperalgesia and the neurogenic component of inflammatory edema by topical application. (12) The first study on adding nitroglycerin to lidocaine for Bier's block for hand and forearm surgery was performed by Sen S et al; (13) who studied the effect of adding nitoglycerin to lidocaine for Bier's block on 30 patients undergoing hand surgery in two groups. The control group (group C, n = 15) received a total dose of 40 ml with 3 mg/kg of lidocaine diluted with saline, and the NTG group (group NTG, n = 15) received an additional 200 μg NTG, In agreement with our results Sen S et al; (13) proved that there was hemodynamic stability in the perioperative period, shortened the onset time of sensory block with prolonged sensory block recovery time, shortened the onset time of motor block with prolonged recovery time, shortened VAS scores of bandage pain, and improved quality of anaesthesia in group NTG, VAS scores were lower in group NTG

7 after bandage release and in the postoperative period. First analgesic requirement time was longer in group NTG than in group C. Postoperative analgesic requirements were significantly smaller in group NTG. Similar results were obtained by various other authors a Cakmak BM et al; (5) who studied 60 patients undergoing elective hand, wrist, and forearm surgery procedures distributed into three groups, lidocaine group (group L) which received 3mg/kg lidocaine 2% diluted with saline to a total volume of 40mL, lidocaine and lornoxicam group (group LL) which received 3mg/kg lidocaine 2% was diluted with saline to a total volume of 40mL and also 8mg lornoxicam was added to the solution, and lidocaine with lornoxicam and transdermal nitroglycerin group (group LL-N) which received 3mg/kg lidocaine 2% was diluted with saline to a total volume of 40mL and also 8mg lornoxicam was added to the solution and nitroglycerin patch 5 mg was applied to the surgical site, they found that shortened sensory and motor block onset times and prolonged sensory and motor block recovery times in group LL-N and LL groups compared with L group. Previous researches did not study the patients' satisfaction, surgeons' opinion and adverse effects or complications.in the present study we focused on these parameters and found that the patients' satisfaction about the operation and surgeons' opinion of the operative conditions were better in Group N than Group C with no adverse effects or complications were seen in this study. Contrary to Cakmak BM et al; (5) and although we used the transcutaneous nitroglycerin as they did but in our study we got the same results with low lidocaine concentration (40 cc of 1.5 mg/kg of 0.25 % lidocaine diluted in normal saline (0.9 % NaCl) was used for administering Bier's block). Low lidocaine concentration was the primary and effective cause for decreasing the resulted adverse effects and complications intra and postoperative and increase patients' satisfaction, surgeons' opinion in our study. Also, Asadi HK et al; (14) studied the analgesic effect of nitroglycerin when added to lidocaine for Bier's block on 40 patients scheduled for elective forearm and hand surgery and agreed our results by reporting shorter sensory block onset time and delay in sensory block recovery time after bandage release in the nitroglycerin group with shorter motor block onset time and delay in recovery time after bandage release in the first group, the frequency of opioid injections was significantly lower in those who administered lidocaine and nitroglycerin. Elmetwaly et al; (6) studied the effect of adding ketamine or nitroglycerin to lidocaine for Bier's block on Seventy-five patients undergoing hand surgery and found that postoperative VAS scores were higher for the first 4 h in control group compared with the other study groups. Also, Cakmak BM et al; (5) noted and agreed these results by approving that postoperative VAS scores were higher for the first 4 hours in group C compared with the other study group.

8 Study limitations and recommendations: The major limitation of present study was the current small sample size since we were able to enroll only 40 patients. More studies with high and sufficient sample sizes are required to confirm these results. We recommend further larger studies to determine the effect of different doses of lidocaine and nitroglycerin and other additives that can affect Bier's block conditions Conclusion: From the present study results we conclude that, the addition of five mg transcutaneous nitroglycerin patch as supplementation to 1.5 mg/kg lidocaine 0.25% for Bier's block reduced the dose of lidocaine, sensory and motor block onset times, VAS scores and analgesic consumption. Length the sensory and motor block recovery times, the duration of post-operative analgesic effect, the first time to analgesic requirement, improved the quality of Bier's block with better patients' satisfaction and surgeons' opinion and no side effects. References: 1. Gupta B, Verma RK, Kumar S, et al. Comparison of analgesic efficacy of dexmedetomidine and midazolam as adjuncts to lignocaine for intravenous regional anesthesia. Anesth Essays Res. 2017; 11: Verma RN, Hasnain S, Sreevastava DK, et al. Anesthetic management of forearm fractures using a combination of haematoma block and intravenous regional anesthesia. Med J Armed Forces India. 2016; 72(3): Marashi S, Yazdanifard A, Shoeibi G. The Analgesic Effect of Intravenous Neostigmine and Transdermal Nitroglycerin Added to Lidocaine on Intravenous Regional Anesthesia (Bier's Block): A Randomized, Controlled Study in Hand Surgery. Inter J of Pharmacol. 2008; 4(3): Jafarian AA, Imani F, Salehi R, et al. Simple arm tourniquet as an adjunct to double-cuff tourniquet in intravenous regional anesthesia. Anesth Pain Med. 2016; 6(3): e Cakmak BM, Cakmak G, Akpek E, Arslan G, Sahin MS. Peri- and postanalgesic properties of lidokain, lornoxicam, and nitroglycerine combination at intravenous regional anesthesia. Biomed Res Int. 2014; 2014: Elmetwaly KF, Hegazy NA, Aboelseoud AA, Alshaer AA. Does the use of ketamine or nitroglycerin as an adjuvant to lidocaine improve the quality of intravenous regional anesthesia? Saudi J Anesth. 2010; 4(2): Glantz L, Godovic G, Lekar M, Kramer M, Eidelman LA. Efficacy of transdermal nitroglycerin combined with etodolac for the treatment of chronic post-thoracotomy pain: an open-label prospective clinical trial. J Pain

9 Symptom Manage 2004; 27(3): Lauretti GR, Perez MV, ReIs MP, PereIra NL. Double- blind evaluation of transdermal nitroglycerine as adjuvant to oral morphine for cancer pain management. J Clin Anesth; 2002; 14(2): Jorge LL, Feres CC, Teles VE. Topical preparations for pain relief: efficacy and patient adherence. J Pain Res. 2010; 4: Lauretti GR, Lima IC, Reis MP, et al. Oral ketamine and transdermal nitroglycerin as analgesic adjuncts to oral morphine therapy for cancer pain management. Anesthesiol. 1999; 90(6): Hashimoto S, Kobayashi A. Clinical pharmacokinetics and pharmacodynamics of glyceryl trinitrate and its metabolites. Clin Pharmacokinet 2003; 42(3): Butterworth JF, Mackey DC, Wasnick JD. Hypotensive agents. Butterworth JF, Mackey DC, Wasnick JD. (eds) Morgan & Mikhail's Clinical Anesthesiology. 5 th ed. New York. McGraw-Hill. 2013; 15: 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(3): 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(1):

10 Table (1): Demographic data: Group C Group N P value (n=20) (n=20) Age (yr) ±9.91 ±9.31 Sex (%) M F Weight (kg) ±12.53 ±9.97 ASA (%) I II Duration of surgery (min) ± ± Data are represented as mean ±SD, yr: year, kg: kilogram, min: minute M: male, F: f Table (2): Sensory and motor block onset and recovery times: Group C Group N (n=20) (n=20) P value Sensory block 5.72 ± ±1.0 <0.001 * onset time (min) Motor block ± ±1.93 <0.001 * onset time (min) Sensory block recovery time (min) 6.88 ± ±1.12 <0.001 * Motor block ± ±1.57 <0.001 * recovery time (min) Data are represented as mean ±SD * statistically significant at p <0.05

11 Table (3): VAS scores for tourniquet pain: Group C Group N (n=20) (n=20) P value 5 Min ± ± Min ± ±0.63 <0.001 * 15 Min ± ±0.35 <0.001 * 20 Min ± ±0.58 <0.001 * 25 Min ± ±0.78 <0.001 * 30 Min ± ± * End of surgery 2.24 ± ± Data are represented as mean ±SD * statistically significant at p <0.05 min: minute Table (4): Post operative VAS score: Group C Group N (n=20) (n=20) P value 30 min ± ±0.81 <0.001 * 1 hr 2.96 ± ±0.40 <0.001 * 2 hrs 2.08 ± ± hrs 2.16 ± ±1.05 <0.001 * 6 hrs 2.0 ± ± hrs 2.08 ± ± hrs 1.68 ± ± hrs 1.44 ± ± hrs 0.76 ± ± hrs 0.44 ± ± Data are represented as mean ±SD * statistically significant at p <0.05 hr: hour Table (5): Analgesic requirements: Intraoperative (Pethidine 0.5 mg/kg) Postoperative (Ketorolac 30 Group C (n=20) ± ±14.70 mg) mg: milligram kg: kilogram Data are represented as mean ±SD Group N (n=20) ± ±9.95 P value * * * statistically significant at p <0.05