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Does Patient-Controlled Infraclavicular Perineural Dexmedetomidine Increase the Duration of Postoperative Analgesia?/Hasta Kontrollu Infraklavikular Perinoral Dexmedetomidin Postoperatif Analjezi Suresini Uzatiyor Mu?

INTRODUCTION

Regional anesthesia techniques have important advantages compared to general and systemic analgesia, including excellent pain control, reduced adverse effects and less length of stay in the post-anesthesia care unit (1-3). Peripheral nerve blocks don't only reduce the need for intraoperative analgesia, but they also provide effective analgesia in the postoperative period without significant systemic side effects (4).

With the use of perineural catheters, early discharge is provided with postoperative analgesia (5). With the continuous infusion of local anesthetic through the catheter, pain control is provided with less opioid consumption and healing process is accelerated with patient satisfaction (6,7).

Adjuvant agents are often used in combination with local anesthetics in order to increase the duration and quality of the block in peripheral nerve blocks (8). Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist. It has several effects such as reduced blood pressure, sedation, sleep, analgesia and reduction of the memory loss and in shivering. Its administration alone or in combination has been tested(9-11) and also there are studies demonstrating that perineural administration of dexmedetomidine in combination with local anesthetics prolongs the duration of nerve block(12,13). However, there was no data related to the perineural infusion of dexmedetomidine in the literature.

In this study, we aimed to investigate effect of perineural infusion of dexmedetomidine added to bupivacaine on the duration of postoperative analgesia, 24-hour needs for analgesia, side effects of dexmedetomidine, ramsay sedation scale and neurological follow-up examination.

SUBJECTS AND METHODS

After approval was obtained from the ethics committee of Erzincan University (Decision No. 08/06) and the patient's consent, a total of 60 ASA I-II patients aged between 18 and 65 years who were to undergo distal upper extremity surgery in our clinic between July 2015 and January 2016 were evaluated retrospectively. ASA I: A normal healthy patient(Healthy, non-smoking, no or minimal alcohol use). ASA II: A patient with mild systemic disease (Mild diseases only without substantive functional limitations. Examples include (but not limited to): current smoker, social alcohol drinker, pregnancy, obesity (30 < BMI < 40), well-controlled DM/HTN, mild lung disease). These operations included all of upper extremity surgery such as soft tissue operations, fracture of distal radius or carpal tunnel syndrome, etc. (ClinicalTrials.gov ID: NCT02550782)

Measurements

Patients were divided into two groups according to the analgesic protocol given in the postoperative period.

Group 1: n=30: infraclavicular patient-controlled perineural bupivacaine (0.5 % MARCAIN flacon, Astra Zeneca, Sweden) (0.1 % bupivacaine, bolus dose 5 ml, infusion rate 5 ml/h, lockout time 1 hour)(14).

Group 2: n=30: infraclavicular patient-controlled perineural bupivacaine + dexmedetomidine (PRECEDEX 200 mcg, Abbott, USA) (0.1 % bupivacaine + 200 mic/100 cc dexmedetomidine, bolus dose 5 ml, infusion rate 5 ml/h, lockout time 1 hour)(15).

Infusion dose of dexmedetomidine was adjusted so as not to exceed 1 mic/kg.

Patients in group 1 and group 2 were selected from patients operated on exactly the same anesthetic protocols. Patients who underwent infraclavicular nerve block and infraclavicular perineural catheter insertion prior to surgery and who were given analgesia by the patient-controlled method in the postoperative period were selected. Patients who received bupivacaine and bupivacain + dexmedetomidine infusion via the perineural catheter in the postoperative period were included in the study for the purpose of the study.

In our clinic; after the patients are brought to their services, patient-controlled analgesia was initiated by an anesthetist, when the patient's visual analogue scale [greater than or equal to] 4. Time of the first analgesic administered was taken as the Minute 0. All the patients were informed about the patient-controlled analgesia device and told to push button of the device if visual analogue scale [greater than or equal to] 4. Patients NIBP, heart rate (HR), SpO2, modified ramsay scale for the sedation (1-6: 1: agitated, restless; 2: oriented, cooperative; 3: responding to commands only; 4: brisk response to light glabellar tap; 5: sluggish response to light glabellar tap and 6: no response)(16), VAS, first analgesic administration time, amount of analgesic needed by the patients and nausea/vomiting were recorded at the minutes 0, 30, 60, 90 and 120, and then at the hours 4, 6, 8, 12 and 24.

If a patient used 10 ml of the analgesic and has still pain, applied intravenous 100 mg Tramadol HCl. If the patient has still pain after 100 mg of iv tramadol, diclofenac sodium administered intramuscularly.

Infraclavicular perineural catheter was removed by the anesthetist at the end of 24th hour and all the patients with infraclavicular perineural inserted underwent neurological examination of the forearm after 1 month.

Statistical analyses:

The study power was calculated based on the study by Esmaoglu et al.(13) in which dexmedetomidine prolonged the duration of analgesia from an average of 670 (70) to 880 (70) minutes. Considering perineural single dose administration, this SD of 70 minutes was taken as 100 minutes for the perineural infusion our study. Accordingly, study strength value of 85% was obtained at the significance level of p<0.0500 in the two group with sample size of 30 and 30.

One-Sample Kolmogorov-Smirnov Test was used to determine the normal distribution (Table 3). In the intergroup comparisons; Chisquare test was used for the categorical variables (Table 2), Student's t-test for normally distributed continuous variables (Table 1 and Table 3) and Mann-Whitney U-test variance analysis for the non-normally distributed continuous variables and ordered variables (Table 3). Statistical analysis was performed using SPSS 21.0 for Windows package software and p<0.05 values were considered as statistically significant.

RESULTS

The study included total 60 patients over 18 years old. Mean age of all patients was found as 44.57[+ or -]11.9 with 27 female and 33 male patients. No significant difference was found between the groups in terms of age and gender, (As shown in Table 1 and Table 2).

When systolic (SAP) and diastolic arterial pressures (DAP) monitored in our study were compared between the groups; SAP was found to be significantly higher in the Group 1 compared to the Group 2 at 6th hour (p: 0.007). SAP values measured at the hours 8 and 12 were higher in the Group 2, but the difference was not statistically significant (p: 0.920, p: 0.347). Diastolic arterial pressures were higher in the Group 1 in the first two hours and at the hours 24, but the differences were not statistically significant. Whereas, these values were significantly higher in the Group 1 and the 4th and 6th hours (p: 0.000, p: 0.003)(Table 3) (Figure 1).

When heart rates were compared between the groups; heart rates were higher in the Group 2 at all hours. However, these results were found to be statistically significant at the hours 8, 12 and 24 (p: 0.004, p: 0.002, p: 0.002) (Table 3) (Fig. 2).

In none of our patients SpO2 dropped under 95% and sedation was not observed in any patient in the dexmedetomide group.

When VAS values were compared between the groups in our study; patients in the Group 1 were found to significantly feel pain and require analgesics at the 4th and 6th hours (p: 0.002, p< 0.05). Whereas time of the first sensation of pain in the Group 2 was found as the 6th hour. There was pain sensation in both the groups at the hours 8, 12 and 24, but the difference were not statistically significant (p: 0.592, p: 0.136, p: 0.195; respectively) (Fig. 3).

When the number of patient initiated requests for analgesia was examined; the mean numbers of the need for analgesia was found as 5.8[+ or -]1.4 times in the Group 1 and 2.2[+ or -]0.4 times in the Group 2 (p< 0.05).

Nausea/vomiting occurred in 2 patients in the Group 1 and 3 patients in the Group 2. No any problem was found in neurological examinations of our patients, that were performed after 1 month.

DISCUSSION

We found that dexmedetomidine added to bupivacaine infused through an infraclavicular catheter prolonged the time until analgesia was requested, and decreased the need for 24-hour analgesia without significant systemic side effects (sedation, bradycardia and hypotension etc.) at these doses.

Dexmedetomidine is an alpha-2 agonist affecting the central nerve system. It has several effects such as decrease in blood pressure, sedation, sleep, analgesia and shivering. In our study, systolic and diastolic arterial pressures were lower in the group which received dexmedetomidine added to bupivacaine compared to the group administered bupivacaine alone. These lower values were attributed to the inhibition of sympathetic activity with the postsynaptic activation of alpha 2 adrenoceptor in central nervous system, resulting in decreased heart rate and blood pressure(17,18). In our study, contrary to expectations heart rate was in rise in the Group 2 than in the Group 1 over 24 hours. This condition monitored from the 0th minute was attributed to the personal characteristics of patients and dose of dexmedetomidine kept low. Both arterial pressures and heart rates increased at the 8th and 12nd hours were attributed to the again high VAS values at the same hours.

It has been demonstrated in many studies that, dexmedetomidine increases the duration of postoperative analgesia and prolongs time of the first need for analgesia (8,13,19-23). Similarly, in our study also dexmedetomidine was found to increase the duration of postoperative analgesia and prolong time of the first need for analgesia. Time for the first need for analgesia was found as the 4th hour in bupivacaine and 6th hour in dexmedetomidine group. Also total need for analgesics were significantly reduced in the Group 2. Masuki et al. reported that, dexmedetomidine causes reduction of local anesthetic absorption and thus prolongs its effect by inducing vasoconstriction around the injection (24). Likewise in a study by Memis(25) and Esmaoglu (13), the authors attributed this prolongation effect to reduction of the release of norepinephrine by peripheral alpha 2 agonists, resulting in a decrease in pain because of the independent inhibitor effects on action potential of the nerve fibers.

Swami et al. stated that administration of perineural dexmedetomidine has a sedative effect (15). Guo et al. noted that the the sedative effect results from the suppression of the release of substance P matter which plays a role in the pain conduction at the dorsal root level and the activation of alpha-2 in the locus cereleus(18). Differently in their study Bekker et al. concluded that perineural administration of dexmedetomidine may be helpful in the case of sedation(26). In parallel, in our study perineural infusion of dexmedetomidine did not cause sedation in any of our patients. This finding may be because the infusion of dexmedetomidine in this study results in a more peripheral than central alpha 2 effect (27).

None of or patients developed neurological deficits. This is parallel to the animal studies by Brummet in which dexmedetomidine did not caused axon or myelin damage even in high doses (25-40 mic/kg) (12).

Good postoperative analgesia helps patients to return their normal daily lives in a shorter time, increases patient satisfaction and reduced the length of stay in hospital and costs. Regional anesthesia techniques provide a excellent pain control, contributing to these processes. In recent years, peripheral nerve blocks and even peripheral nerve catheter insertion have been introduced in order to protect patients against the side effects of opioids used for postoperative purposes(28,29). However, peripheral nerve catheter is a procedure which takes longer time and is more expensive and painful for patients with a higher rate of complications and needs more postoperative care(28,29). Ultrasound guidance reduces the time necessary for catheter insertion, and may improve success rates(30). Patients who underwent ultrasonography were included in this study and the success rate of the blocks and the insertion of catheters are 100%. There are no technical failures of PCA devices.

Our study has some limitations. First, number of the intragroup patients are small. Further studies with larger number of cases are needed in order to obtaine stronger data. Second, plasma levels of dexmedetomidine that could support its peripheral rather than central effects were not studied. Third, because of feared perineural side effects of dexmedetomidine, lock-out time was defined as 1 hour. This condition may be caused by the ineffectiveness of bupivacaine alone. Fourth, VAS values was evaluated at rest, not at movement.

CONCLUSION

We found that dexmedetomidine added to bupivacaine infused through an infraclavicular catheter prolonged the time until analgesia was requested, and decreased the need for 24-hour analgesia without any side effect (sedation, bradycardia and hypotension etc.) at these doses. Patient-controlled administration of dexmedetomidine at low doses provides a comforTable and good postoperative analgesia, high patient satisfaction and low incidence of adverse effects.

REFERENCES

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[2] Liu SS. The effect of analgesic technique on postoperative patient-reported outcomes including analgesia: a systematic review. Anesth Analg 2007; 105: 789-808.

[3] McCartney CJ1, Brull R, Chan VW, Katz J, Abbas S, Graham B, et al. Early but no long-term benefit of regional compared with general anesthesia for ambulatory hand surgery. Anesthesiology 2004; 101: 461-7.

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[5] Williams BA, Spratt D, Kentor ML. Continuous nerve blocks for outpatient knee surgery. Tech Reg Anesth Pain Man 2004;8:76-84.

[6] White PF, Issioui T, Skrivanek GD, Early JS, Wakefield C. The use of a continuous popliteal sciatic nerve block after surgery involving the foot and ankle: does it improve the quality of recovery? Anesth Analg 2003;97:1303-9.

[7] di Benedetto P, Casati A, Bertini L, Fanelli G, Chelly JE. Postoperative analgesia with continuous sciatic nerve block after foot surgery: a prospective, randomized comparison between the popliteal and subgluteal approaches. Anesth Analg 2002;94:996-1000.

[8] F. W. Abdallah and R. Brull. Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systematic review and meta-analysis. British Journal of Anaesthesia 110 (6): 915-25 (2013).

[9] Elliott S, Eckersall S, Fliqelstone L. Does addition of clonidine affect duration of analgesia of Bupivacaine in inguinal hernia repair. Br J Anaesth 1997;79:446-9.

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[12] Brummett CM, Norat MA, Palmisano JM, Lydic R. Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat. Anesthesiology 2008; 109: 502-11.

[13] Esmaoglu A, Yegenoglu F, Akin A, Turk CY. Dexmedetomidine added to levobupivacaine prolongs axillary brachial plexus block. Anesth Analg 2010; 111: 1548-51.

[14] Svediene S, Andrijauskas A, Ivaskevicius J, Saikus A. The efficacy comparison of on-demand boluses with and without basal infusion of 0.1 % bupivacaine via perineural femoral catheter after arthroscopic ACL reconstruction. Knee Surg Sports Traumatol Arthrosc. 2013 Mar;21(3):641-5.

[15] Swami SS, Keniya VM, Ladi SD, Rao R. Comparison of dexmedetomidine and clonidine (alpha2 agonist drugs) as an adjuvant to local anaesthesia in supraclavicular brachial plexus block: A randomised double-blind prospective study. Indian J Anaesth. 2012; 56(3):243-9.

[16] Agarwal S, Aggarwal R, Gupta P. Dexmedetomidine prolongs the effect of bupivacaine in supraclavicular brachial plexus block. J Anaesthesiol Clin Pharmacol 2014;30:36-40.

[17] Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999;54:146-65.

[18] Guo TZ, Jiang JY, Buttermann AE, Maze M. Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology 1996;84:873-81.

[19] Brummett CM, Padda AK, Amodeo FS, Welch KB, Lydic R. Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase in the duration of thermal antinociception in sciatic nerve block in rat. Anesthesiology. 2009; 111:1111-9.

[20] Zhang Y, Wang CS, Shi JH, Sun B, Liu SJ, Li P, et al. Perineural administration of dexmedetomidine in combination with ropivacaine prolongs axillary brachial plexus block. Int J Clin Exp Med. 2014;7:680-5.

[21] Marhofer D, Kettner SC, Marhofer P, Pils S, Weber M, Zeitlinger M. Dexmedetomidine as an adjuvant to ropivacaine prolongs peripheral nerve block: A volunteer study. Br J Anaesth. 2013;110:438-42.

[22] Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand. 2006;50:222-7.

[23] Kenan Kaygusuz, Iclal Ozdemir Kol, Cevdet Duger, Sinan Gursoy, Hayati Ozturk, Ulku Kayacan, et al. Effects of Adding Dexmedetomidine to Levobupivacaine in Axillary Brachial Plexus Block. Current Therapeutic Research Volume 73, Number 3, June 2012.

[24] Masuki S, Dinenno FA, Joyner MJ, Eisenarch JH. Selective alpha2 -adrenergic properties of dexmedetomidine over clonidine in the human forearm. J Appl Physiol 2005;99:587-92.

[25] Memis D, Turan A, Karamanlioglu B, Pamukcu Z, Kurt I. Adding dexmedetomidine to lignocaine for IVRA. Anesth Analg 2004;98:835-40.

[26] Bekker A, Sturaitis MK. Dexmedetomidine for neurological surgery. Neurosurgery. 2005; 57:1-10.

[27] Suneet Kathuria, Shikha Gupta, and Ira Dhawan. Dexmedetomidine as an adjuvant to ropivacaine in supraclavicular brachial plexus block. Saudi J Anaesth. 2015 Apr-Jun; 9(2): 148-154.

[28] Grossi P, Allegri M. Continuous peripheral nerve blocks: state of the art. Curr Opin Anaesthesiol 2005; 18: 522-26.

[29] Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg 2011; 113: 904-25.

[30] Riazi S, Carmichael N, Awad I, Holtby RM, McCartney CJ. Effect of local anaesthetic volume (20 vs 5 ml) on the efficacy and respiratory consequences of ultrasound-guided interscalene brachial plexus block. Br J Anaesth. 2008; 101:549-56.

Ilke Kupeli (1), Ufuk Kuyrukluyildiz (2), Sara Tas (3), Zehra Bedir (4), Aysin Selcan (5)

(1.) MD., Assist. Prof., Anesthesiology and Reanimation Department, Erzincan University, Erzincan,Turkey, ilkeser2004@gmail.com

(2.) MD., Assist. Prof., Anesthesiology and Reanimation Department, Erzincan University, Erzincan,Turkey, drufuk2001@gmail.com

(3.) MD., Public Health Department, Erzincan University, Erzincan,Turkey, saratas_1984@hotmail.com

(4.) MD., Anesthesiology and Reanimation Department, Mengucek Gazi Training and Research Hospital, Erzincan,Turkey, dr.zehra.25@hotmail.com

(5.) Prof. Dr., Anesthesiology and Reanimation Department, Bagcilar. Training and Research Hospital, Istanbul,Turkey, aysinalagol@yahoo.com

Cite this article as: Kupeli I, Kuyrukluyildiz U, Tas S, Bedir Z, Selcan A. Does Patient-Controlled Infraclavicular Perineural Dexmedetomidine Increase the Duration of Postoperative Analgesia?. Clin Exp Health Sci 2018

Correspondence Author/Sorumlu Yazar: Ilke Kupeli E-mail/E-posta: ilkeser2004@gmail.com
Table 1: Mean age of the groups (*)

             Group    N (*1)    Mean    Std. Deviation (**1)     p

Age (years)     1      30       43,40     12,615                0.456
                2      30       45,73     11,435

(*) t Tests, (*1): patient number (**1): standard deviation

Table 2: Gender of groups (*)

                    Group 1     Group 2    Total     p

       Male (n*2)   16          17         33
       Female (n)   14          13         27       0.799
Total               30          30         60

(*) Chi-Square Tests, (*2) : number of subject

Table 3: Systolic and diastolic arter pressure and heart rate of the
groups according to time

               Systolic Arter Pressure
               Group 1                    Group 2

  0.minute     133,50 [+ or -] 16,2       127,87 [+ or -] 21,0
 30.minute     131,67 [+ or -]15,5        129,23 [+ or -] 17,6
 60.minute     131,47 [+ or -]14,1        126,83 [+ or -] 18,0
 90.minute     134,20 [+ or -] 15,5       127,20 [+ or -] 16,8
120.minute     130,63 [+ or -] 15,2       127,13 [+ or -] 16,3
  4. hour (*)  132,83 [+ or -] 12,7 (*)   127,20 [+ or -] 13,3 (*)
  6. hour (*)  135,63 [+ or -] 16,4       124,67 [+ or -] 13,8
  8. hour      132,67 [+ or -] 13,1       133,00 [+ or -] 12,6
 12. hour (*)  137,00 [+ or -] 14,1       140,67 [+ or -] 15,7
 24. hour (*)  128,00 [+ or -] 14,7 (*)   124,67 [+ or -] 15,4 (*)

                Systolic Arter Pressure   Diastolic Arter Pressure
                p                         Group 1

  0.minute     .251                       86,63 [+ or -] 11,3
 30.minute     .574                       84,77 [+ or -] 11,1
 60.minute     .273                       82,53 [+ or -] 8,6
 90.minute     .100                       83,27 [+ or -] 9,6
120.minute     .395                       83,07 [+ or -] 11,5
  4. hour (*)  .100                       84,47 [+ or -] 8,6  (*)
  6. hour (*)  .007 (**)                  87,83 [+ or -] 13,1 (*)
  8. hour      .920                       82,50 [+ or -] 8,9
 12. hour (*)  .347                       86,67 [+ or -] 13,0 (*)
 24. hour (*)  .329                       80,00 [+ or -] 10,1 (*)

               Diastolic Arter Pressure
               Group 2                    p

  0.minute     79,37[+ or -] 14,3        .347
 30.minute     79,90 [+ or -] 10,3       .943
 60.minute     77,20 [+ or -] 11,1       .388
 90.minute     77,30 [+ or -]10,2        .976
120.minute     75,63 [+ or -] 8,4        .302
  4. hour (*)  76,33 [+ or -] 11,5 (*)   .000 (**)
  6. hour (*)  78,33[+ or -] 10,5 (*)    .003 (**)
  8. hour      83,00 [+ or -] 9,1        .832
 12. hour (*)  88,67 [+ or -] 10,4 (*)   .674
 24. hour (*)  77,33 [+ or -] 8,2 (*)    .301

                Heart Rate
                Group 1               Group 2               p

  0.minute      69,70 [+ or -] 14,8   73,73 [+ or -] 7,6   .190
 30.minute      70,90 [+ or -] 14,8   73,90 [+ or -] 8,5   .342
 60.minute      70,70 [+ or -] 15,7   74,07 [+ or -] 7,2   .290
 90.minute      71,20 [+ or -] 15,5   74,20 [+ or -] 8,0   .352
120.minute      70,63 [+ or -] 13,4   75,53 [+ or -] 6,6   0.79
  4. hour (*)   71,90 [+ or -] 9,9    76,33 [+ or -] 7,0   0.51
  6. hour (*)   73,30 [+ or -] 13,7   75,70 [+ or -] 6,7   .395
  8. hour       72,17 [+ or -] 12,3   80,27 [+ or -] 8,2   .004 (**)
 12. hour (*)   74,47 [+ or -] 12,5   83,40 [+ or -] 8,0   .002 (**)
 24. hour (*)   70,47 [+ or -] 10,7   77,07 [+ or -] 8,0   .002 (**)
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Title Annotation:Original Article / Ozgun Arastirma
Author:Kupeli, Ilke; Kuyrukluyildiz, Ufuk; Tas, Sara; Bedir, Zehra; Selcan, Aysin
Publication:Clinical and Experimental Health Sciences
Article Type:Report
Date:Sep 1, 2018
Words:3657
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