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Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 9  |  Issue : 3  |  Page : 391-396  

Safety and analgesic efficacy of intravenous dexmedetomidine in arthroscopic knee surgery


1 Department of Anaesthesiology, All Institute of Medical Sciences, New Delhi, India
2 Department of Orthopaedics, All Institute of Medical Sciences, New Delhi, India

Date of Web Publication8-Sep-2015

Correspondence Address:
Riddhi Kundu
All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: Nil., Conflict of Interest: There are no conflicts of interest.


DOI: 10.4103/0259-1162.161820

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   Abstract 

Context: Dexmedetomidine, a highly selective alpha-2 agonist has been used as an adjuvant analgesic in vascular, bariatric, and thoracic surgery. We assessed the efficacy of intravenous dexmedetomidine as an analgesic adjunct to local anesthetic infiltration for control of postoperative pain in arthroscopic knee surgery. Settings and Design: This was a randomized control study performed in a Tertiary Care Hospital. Materials and Methods: Forty-five adult patients scheduled for anterior/posterior cruciate ligament reconstruction were randomized into three groups. Group B (bupivacaine group) received bupivacaine intraarticularly and normal saline by the intravenous route. Group D (dexmedetomidine group) received Intravenous dexmedetomidine and normal saline intraarticularly. Group BD (bupivacaine + dexmedetomidine group) received a combination of intravenous dexmedetomidine and intraarticular bupivacaine. Patient's cardiorespiratory parameters, time to first rescue, total rescue analgesic consumption in first 24 h, visual analog scale for pain were assessed. Statistical Analysis: The data were analyzed using analysis of variance and Chi-square test. Results: The time to first request for rescue analgesia was significantly prolonged in Group D and Group BD patients (P < 0.05) compared to Group B. Total rescue analgesic consumption was least in Group BD. Group D and Group BD patients had lower heart rate and systolic and diastolic blood pressure values. Conclusion: Intravenous dexmedetomidine in combination with intraarticular bupivacaine decreased perioperative analgesic requirement in patients undergoing arthroscopic knee surgery. However, monitoring and vigilance are essential if dexmedetomidine is used as part of a multimodal analgesic regimen in view of its hemodynamic side effects.

Keywords: Arthroscopic knee surgery, bupivacaine, dexmedetomidine


How to cite this article:
Kundu R, Dehran M, Chandralekha, Trikha A, Nag H L. Safety and analgesic efficacy of intravenous dexmedetomidine in arthroscopic knee surgery. Anesth Essays Res 2015;9:391-6

How to cite this URL:
Kundu R, Dehran M, Chandralekha, Trikha A, Nag H L. Safety and analgesic efficacy of intravenous dexmedetomidine in arthroscopic knee surgery. Anesth Essays Res [serial online] 2015 [cited 2021 Jan 17];9:391-6. Available from: https://www.aeronline.org/text.asp?2015/9/3/391/161820




   Introduction Top


Arthroscopic knee surgery is associated with significant postoperative pain, thereby limiting the early discharge of the patient. To control the pain regional nerve blocks, systemic analgesics, intraarticular infiltration of local anesthetics, and magnesium have been used.[1],[2],[3] Multimodal analgesia techniques may enhance postoperative recovery, decrease the duration of hospital stay and facilitate early convalescence. Alpha adrenoceptor agonist clonidine has been shown to provide effective analgesia after arthroscopic knee surgery.[4],[5],[6],[7] Dexmedetomidine has eight times more affinity for alpha-2 receptors as compared to clonidine. It is well-known for its sedative, analgesic, and anxiolytic properties. In addition, it has significant anesthetic and opioid sparing properties.[8],[9],[10],[11],[12],[13] It is devoid of respiratory depressant action or addictive potential.[1],[14] The central analgesic effects of dexmedetomidine are primarily due to its interaction at alpha-2a receptors in the locus coeruleus of brain and spinal cord, here the drug attenuates nociceptive signal transduction.[1],[15],[16] However, the peripheral analgesic effect has not been fully defined. Dexmedetomidine has been reported to enhance central and peripheral neural blockade by local anesthetics.[17],[18],[19] It has been used as an adjuvant analgesic in vascular, bariatric, and thoracic surgery. Intraarticular infiltration of dexmedetomidine has been used either alone or in combination with local anesthetics to provide postoperative analgesia in arthroscopic knee surgeries with reasonable success.[20],[21],[22],[23],[24] The intraarticular route of drug administration has predominantly relied on the direct local action of dexmedetomidine on the free nerve terminals in the joint space for producing analgesia. Dexmedetomidine in addition to its peripheral effects has well-recognized central mechanisms of analgesia.[15],[16] Therefore, we hypothesized that the adjunctive use of intravenous dexmedetomidine in combination with local anesthetic infiltration is expected to minimize postoperative pain by acting at both central and peripheral sites.

This prospective double blind randomized controlled study was designed to assess the efficacy of intravenous dexmedetomidine as an analgesic adjunct to intraarticular local anesthetic infiltration for control of postoperative pain in arthroscopic knee surgery and to study its side effects profile.


   Materials and Methods Top


This double-blind prospective randomized study was conducted in the Department of Anesthesiology, All India Institute of Medical Sciences, New Delhi, following Institutional Ethics Committee approval. After obtaining written informed patient consent, 45 adult American Society of Anesthesiologists (ASA) I-II patients between 20 and 60 years of age scheduled for anterior/posterior cruciate ligament reconstruction were recruited for the study, from May 2012 to April 2013. Patients with significant cardiac or respiratory disease, renal, or hepatic dysfunction, hypertensive patients on alpha-methyldopa, clonidine, or beta blockers, patients on chronic nonsteroidal anti-inflammatory drugs therapy (>3 months continuous therapy), those who received opiates in last 24 h were excluded from the study. Patients selected were divided into three groups by computer generated randomization. Group B (bupivacaine group) received bupivacaine intraarticularly and normal saline by the intravenous route. Group D (dexmedetomidine group) received intravenous dexmedetomidine and normal saline intraarticularly. Group BD (bupivacaine + dexmedetomidine group) received a combination of intravenous dexmedetomidine and intraarticular bupivacaine.

The preanesthetic evaluation was carried out for all patients a day prior to surgery. Premedication with tablet diazepam (0.1 mg/kg to a maximum of 10 mg) was given the night before surgery and on the morning of surgery. In the preoperative visit, each patient was explained about the purpose of study, and the 10 point visual analog scale (VAS) for the assessment of pain postoperatively (where 0 = no pain, 10 = worst imaginable pain). The nurses were asked to note the time when they required the first rescue analgesia in the postoperative period.

All patients received conventional general anesthesia with endotracheal intubation. Intraoperative monitoring included a 5-lead electrocardiogram, pulse oximeter, capnography, and noninvasive blood pressure (NIBP). Induction with fentanyl (2 µg/kg body weight), propofol (2.5–3 mg/kg body weight), and vecuronium (0.1 mg/kg body weight) was used to facilitate endotracheal intubation. Anesthesia was maintained with oxygen: Nitrous oxide (1:1), isoflurane, vecuronium, and fentanyl infusion (0.5 µg/kg/h). Fentanyl infusion was stopped at the end of surgery. One gram intravenous paracetamol was given toward the end of surgery and every 6 hourly thereafter for first 24 h. The study drugs prepared were given prior to skin closure. All the test solutions were prepared by a team member who was not involved in data recording.





  • Group B: Received receive 20 ml of 0.25% bupivacaine intraarticularly and 20 ml of normal saline by intravenous route over 60 min
  • Group D: Received intravenous dexmedetomidine loading dose 1 µg/kg body weight over 10 min followed by 0.5 µg/kg/h for next 50 min in 20 ml normal saline and 20 ml of normal saline intraarticularly
  • Group BD: Received dexmedetomidine loading dose 1 µg/kg body weight over 10 min followed by 0.5 µg/kg/h for next 50 min in 20 ml normal saline and 20 ml of bupivacaine 0.25% intraarticularly.


Patient's baseline parameters including heart rate (HR), respiratory rate (RR), NIBP, oxygen saturation (SpO2) were recorded before anesthesia induction, after extubation, on arrival at the postanesthesia care unit (PACU), and every 30 min interval for first 2 h postoperatively and subsequently at 4, 6, 12, and 24 h. Time to first rescue analgesia provided with ketorolac (0.5 mg/kg intravenous) at a VAS score of >3 and total rescue analgesic consumption in first 24 h were noted. Patients are having breakthrough pain in spite of ketorolac or requiring frequent dosing (<6 hourly intervals) were planned for intravenous fentanyl boluses (0.5 µg/kg). The VAS pain scores were assessed at the same time intervals. In the PACU, continuous monitoring was done to detect and treat any adverse events such as bradycardia (>20% fall from baseline/<50 beats/min), hypotension (>20% fall from baseline), respiratory depression (<12 breaths/min), desaturation (SpO2 < 95%), hypertension (>20% rise from baseline), and any other complications.

Analysis of the recorded parameters was done with SPSS software package for Windows version 21.0 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp.). All the data were presented as means ± standard deviation, when the values were normally distributed. When the data were not in a normal distribution, logarithmic transformation was applied, and corrected values were used. The hemodynamic variables such as HR, systolic, and diastolic blood pressure (BP), RR, SpO2, VAS scores, and analgesic requirements were compared among the three groups using one-way analysis of variance and post-hoc analysis by Bonferroni. The incidence of hypotension, postoperative nausea and vomiting (PONV) and bradycardia were compared using Chi-square test.


   Results Top


The three groups were found to be similar in demographic characteristics including age, sex, weight, and ASA physical status, duration of anesthesia, and surgery [Table 1]. Baseline cardiorespiratory variables were also comparable between the groups [Table 2].
Table 1: Characteristics of patients

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Table 2: Baseline cardiorespiratory variables

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Patients in Group B had significantly higher HR postextubation and postoperatively till 4 h after surgery compared with the other two groups (Group D and Group BD) (P < 0.05) [Figure 1]. Systolic and diastolic BPs were also significantly higher in Group B compared to the other two groups (Group D and Group BD) at 0 and 60 min following surgery [Figure 2] and [Figure 3]. However, there was no statistically significant difference in hemodynamic variables between Group D and Group BD at all-time intervals studied. There was no statistically significant difference in the RR or SpO2 postoperatively in between the groups. No patient in any group developed oxygen desaturation or respiratory depression.
Figure 1: Heart rate changes in the postoperative period

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Figure 2: Systolic blood pressure changes in the postoperative period

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Figure 3: Diastolic blood pressure changes in postoperative period

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The mean pain VAS scores were higher in Group B as compared to the other two groups in the immediate postoperative period [Figure 4], which reached statistically significance only between Group B and Group BD at 60 min postoperatively (P = 0.024).
Figure 4: Visual analog score in the postoperative period

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The time of 1st rescue analgesia required was significantly longer in Group BD (mean 98.67 ± 59.114 min) and Group D (mean 84.00 ± 61.91 min) compared to Group B (mean 37.67 ± 19.353 min) (P = 0.001). This data were not normally distributed. Hence, log transformation was applied, using corrected values. The total ketorolac consumption was different between the three groups (P < 0.05) [Figure 5]. However, post-hoc analysis revealed a statistically significant difference only between Group B and Group BD (P = 0.017). No patients in any group required fentanyl for breakthrough pain.
Figure 5: Total rescue analgesia in the postoperative period

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Four patients (26.7%) in Group D and 3 patients (20%) in Group BD developed significant bradycardia. All patients were managed with atropine intravenous bolus. No patient in Group B developed bradycardia. However, on statistical analysis incidence of bradycardia was not found to be statistically significant. All patients developed bradycardia during study drug infusion and none thereafter. The lowest HR recorded was 42 beats/min, in a patient of Group D. Only one patient in Group D developed hypotension (>20% decline in baseline BP) along with bradycardia, and was managed with intravenous fluid bolus of 250 ml ringers lactate and atropine.

One patient in each Group BD, Group D and Group B (6.7%) developed hypotension during study drug infusion. The patient in Group B was managed with 300 ml intravenous fluid bolus of ringers lactate while each patient in Group D and Group BD required ephedrine 3 mg along with 200 ml intravenous fluid bolus of ringers lactate.

Two patients in Group B (13.33%) and 1 patient in each Group D (6.67%) and Group BD (6.67%) had PONV. However, the difference was not statistically significant between the three groups (P = 0.177). No other side effect was observed in any group.


   Discussion Top


In our study, use of intravenous dexmedetomidine in conjunction with intraarticular bupivacaine was found to decrease the perioperative ketorolac requirement in patients undergoing arthroscopic knee surgery. However, the incidence of hypotension and bradycardia were more frequent with use of intravenous dexmedetomidine.

Previous studies have evaluated the analgesic efficacy of dexmedetomidine through intraarticular, intravenous routes, and buccal/intramuscular premedication for knee arthroscopies.[3],[20],[21],[22],[23],[24],[25],[26],[27] However, we are unaware of any study that has tried to evaluate the adjunctive use of intravenous dexmedetomidine with intraarticular bupivacaine in arthroscopic knee surgery.

Dexmedetomidine has been recommended to be used as a bolus followed by an infusion. Some researchers have used only infusion and found that it causes less hemodynamic perturbations.[27] However, it takes a minimum of 8 h to reach steady state plasma concentration without the bolus. Therefore, a bolus followed by an infusion was used in our study. The analgesic effects of dexmedetomidine could be mediated through supraspinal, spinal, and peripheral actions. Dexmedetomidine used intraoperatively during tourniquet inflation would have acted only through spinal and supraspinal mechanisms. Therefore, the infusion was started at the end of surgery and continued postoperatively to elicit its interaction with intraarticular infiltration of bupivacaine in addition to its well-recognized central mechanisms of analgesia. The duration of infusion was decided on the basis of a study by Gómez-Vázquez et al.[3] Previous studies have compared intraarticular infiltration of dexmedetomidine to local anesthetic infiltration in knee arthroscopies.[20],[22] Total rescue analgesic consumption and VAS scores for pain were comparable in both the studies. Combining dexmedetomidine with local anesthetic infiltration, however, provided superior analgesia.[22] Though intraarticular dexmedetomidine provided effective analgesia, safety concerns about its local adverse effects must be clarified before recommending its intraarticular use. Dexmedetomidine is believed to provide analgesia by acting through spinal, supraspinal, and peripherial sites.[28] Therefore, the intravenous route for drug administration was used in this study.

This attenuation of hemodynamic response to extubation seen in Group D and Group BD is explained by the sympatholytic effect of dexmedetomidine.[29] This would have also contributed to bradycardia and hypotension seen in the groups receiving dexmedetomidine. Dexmedetomidine use has been associated with constant PaO2, PCO2 values even at high doses in healthy volunteers.[14],[28] We found comparable SpO2 values and RRs in all the groups in our study. However, oxygen by facemask at 4 L/min flow was given to all our patients in the postoperative period. Time to 1st rescue analgesia was significantly prolonged in Group BD (mean 98.67 min) and Group D (mean 84.00 min) compared to Group B (mean 37.67 min). The continuation of dexmedetomidine postoperatively period may have coincided with its peak plasma levels leading lead to lower VAS scores and delayed request for rescue analgesic in Group D and Group BD as compared to Group B. The time to 1st request was, however, shorter when compared to a previous study by Das et al. who used dexmedetomidine, fentanyl, and ropivacaine through intraarticular route.[23] Analgesia provided postoperatively by subarachnoid block may have contributed to the delayed request for analgesia in comparison to our study, in which general anesthesia was used in all patients.

Systemic administration (pre-, intra-, and post-operative) of dexmedetomidine is associated with a potentiation of both systemic analgesics, particularly opioids and a local anesthetic sensory block in neuraxial and perineural routes. The total ketorolac consumption was different in the three groups. However, further analysis revealed a statistically significant difference only between Group B and Group BD (P < 0.05). This would mostly be due to the synergistic action between dexmedetomidine, bupivacaine, and fentanyl in Group BD. This decreased ketorolac consumption even after stopping the infusion in this study may be possibly due to the persistent effect of dexmedetomidine after discontinuing the infusion as proposed by few researchers.[12] The incidence of PONV was comparable between the groups. However, patients were given ondansetron prophylactically in all three groups, and this might have resulted in a decreased incidence of PONV in all three groups. The overall safety profile of dexmedetomidine in aspects of nausea, vomiting, respiratory depression and sedation is in agreement with previous literature.[23],[14]


   Conclusion Top


Intravenous dexmedetomidine in combination with intraarticular bupivacaine was found to decrease the perioperative ketorolac requirement in patients undergoing arthroscopic knee surgery. However, systemic dexmedetomidine in such doses can induce unwanted hemodynamic side effects (e.g., hypotension and bradycardia). Therefore, a high level of monitoring and vigilance is essential postoperatively if dexmedetomidine is used as part of a multimodal analgesic regimen.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]


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[Pubmed] | [DOI]



 

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