Abdominal hysterectomy is the second-most common surgery in females between the age of 25 and 50 years after cesarean section. It is associated with moderate-to-severe postoperative pain.[
1 ] 2
The administration of local anesthetics with additives such as dexmedetomidine into the wound before the incision (preemptive analgesia) has been demonstrated to reduce postoperative pain and improve the quality and duration of analgesia.[
3 4 5 6 7 8 ] 9
In this study, we hypothesized that preemptive local surgical site infiltration of dexmedetomidine would decrease the requirement of other analgesics in the postoperative period. The primary objective was to determine the duration of postoperative analgesia and the requirement of rescue analgesics in the postoperative period in patients undergoing abdominal hysterectomy.
SUBJECTS AND METHODS
After approval from the institutional ethics committee, a double-blind prospective observational analytical study was conducted in a tertiary care government hospital. The study is a part of Registered Trial Number CTRI/2019/09/021346. All the patients undergoing abdominal hysterectomy admitted during the period of 6 months fulfilling the inclusion criteria were considered samples. The sample size was calculated on the basis of the previous study.[
] At 95% significance level and 80% power, assuming a 30% increase in rescue analgesic consumption in Group 2, 37 patients were required in each group. To increase the power of the study, 40 patients in each group, a total of 80 patients were enrolled. Patients were randomly allocated into two groups of 40 each after obtaining written informed consent. Randomization was done by computer-generated numbers. 10
Group A – 40 patients receiving bupivacaine with dexmedetomidine
Group B – 40 patients receiving bupivacaine alone.
Patients included in the study were between the ages of 30 and 60 years undergoing elective abdominal hysterectomy under spinal anesthesia with American Society of Anesthesiologists (ASA) Grade 1 and 2. Those with documented allergies to any drugs, especially local anesthetics, morbid obesity, Raynaud's disease, hepatorenal insufficiency, and those receiving adrenoceptor agonists, antagonists, or narcotics before the operation were excluded from the study.
In the present study setting, the patient posted for abdominal hysterectomy under spinal anesthesia underwent a detailed preanesthetic evaluation the day before surgery followed by routine investigations. Written informed consent was taken before the scheduled operation from the patient and relatives. Patients were kept nil oral for 6 h before the surgery. Patients were monitored for baseline parameters in the operation theater.
A peripheral intravenous (IV) line was secured with 20-gauge IV cannula and lactated Ringer's solution was started as maintenance fluid. Spinal anesthesia was given with complete aseptic precautions using bupivacaine 0.5% 3 ml. Incision site/wound infiltration was done with bupivacaine (0.125%) 15 ml with dexmedetomidine 1 μg/kg or bupivacaine (0.125%) 15 ml alone before taking incision for abdominal hysterectomy.
The highest level of spinal anesthesia was achieved, level of spinal anesthesia after the end of surgery and 2 and 4 h after the surgery was noted. Patients were assessed for pain by visual analog scale (VAS 0–10: 0 – no pain and 10 – worst imaginable pain) at the time of arrival in the postanesthesia care unit and then at 2, 4, 6, 12, and 24 h after operation. Duration of analgesia was recorded which is the time from infiltration of bupivacaine 15 ml with dexmedetomidine 1 μg/kg or bupivacaine 15 ml alone to the need of rescue analgesia. Rescue analgesia was given with diclofenac sodium 75 mg intramuscular on demand or whenever the VAS score was ≥ 4.
The number of patients requiring rescue analgesia and total diclofenac consumption during the first 24 h after operation was recorded.
The level of sedation was assessed using a four-point Sedation Scale (0–3, 0 – awake and oriented, 1 - drowsy but responding to commands, 2 - sleepy but easy to arouse [by loud command or glabellar tap], and 3 - deep sleep and difficult to arouse).[
] The incidence and severity of postoperative nausea and vomiting (PONV) were assessed by four-point categorical scales (0 - none, 1 - mild, 2 - moderate, and 3 - severe). Metoclopramide 10 mg IV was given for severe nausea or vomiting. Any other adverse effect was also recorded. 10
Data were entered into a Microsoft Excel data sheet and were analyzed using SPSS 22 version software (IBM SPSS Statistics, Somers NY, USA). Categorical data were represented in the form of frequencies and proportions. The Chi-square test and Fisher's exact tests were used as a test of significance for qualitative data. Continuous data were represented as a mean and standard deviation; an independent
t-test was used as a test of significance to identify the mean difference between two quantitative variables. P < 0.05 was considered statistically significant. RESULTS
When age, weight, and ASA scores of the two groups were compared in
Table 1, there was no statistically significant difference and both groups were comparable. Table 1:
Demographic data and American Society of Anesthesiologists score of the patient
Mean VAS scores between Group A (bupivacaine with dexmedetomidine) and Group B (bupivacaine alone) patients at various time intervals were assessed and it was found that the mean VAS score of Group A patients was significantly less at each time interval when compared with that of Group B [Graph 1]. Group A had less score in initial hours compared to Group B but once Group B receives rescue analgesia, the score started decreasing in Group B as compared to Group A. When diclofenac consumption was compared, the total diclofenac consumption in Group A was less (95.63 [±33.92] mg) than that in Group B (150 [±0.0] mg) [Graph 2]. The difference was found to be significant.
The mean duration of surgery was 60–90 min.
The four-point categorical scale score for PONV of Group A showed a better score (lower score) which means nausea and vomiting were less in Group A as compared to Group B. However, the difference was not found to be significant [
Table 2]. The difference in the four-point Sedation Scale score of Group A and Group B was not found to be statistically significant. In Group A, 90% of patients were awake and 10% of patients were drowsy but responding to commands. When timings for the requirement of rescue analgesia were assessed, for Group A, rescue analgesia was required after 2 h in only 1 patient, 4 h in 10 (25%) patients, and at 6 h in 29 (72.5%) patients. However, in Group B, rescue analgesia was required immediately at 0 h in 6 (15%) patients and at 2 h at 34 (85%) patients [Graph 3]. The difference was found to be statistically significant. Statistical difference between the two groups comparing the highest level of spinal anesthesia achieved (T6 level); level of spinal anesthesia after the end of surgery and 2 and 4 h after the surgery was not significant. Table 2:
Comparison of four-point categorical scale for postoperative nausea and vomiting and four-point Sedation Scale score of patients between two groups
Pain is an unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage.
Postoperative pain has conventionally been managed using nonsteroidal anti-inflammatory drugs (NSAIDs) or opioid analgesics. However, NSAIDs are associated with an increased incidence of gastrointestinal problems, kidney dysfunction, and bleeding diathesis; opioids are known to increase the side effects, especially nausea, vomiting, respiratory depression, and sedation.[
11 12 ] 13
Accordingly, a variety of methods have been investigated to reduce postoperative pain, thus reducing analgesic use.
Preemptive analgesia is defined as a treatment that is initiated before surgery to prevent the establishment of central sensitization evoked by the incisional and inflammatory injuries occurring during surgery and in the early postoperative period. As preemptive analgesia has “protective” effect on the nociceptive system, it can be more effective than a similar analgesic treatment initiated after surgery. Consequently, preemptive analgesia can reduce immediate postoperative pain and also prevent the development of chronic pain by decreasing the altered central sensory processing.
The alpha-2 adrenergic receptor agonist dexmedetomidine, a nonopioid analgesic has sedative, analgesic, and anti-sympathetic effects, and is now widely used as an adjuvant in general anesthesia, nerve block anesthesia, topical anesthesia, and postoperative analgesia.[
] When given intravenously, it has a significant opioid-sparing effect as well as the decreased requirement of anesthetic agents.[ 14 11 ] Dexmedetomidine also has been used as an adjunct to local anesthetics for various nerve blocks.[ 15 ] Peripherally, α2-agonists produce analgesia by reducing the release of norepinephrine and causing α2-receptor-independent inhibitor effect on nerve fiber action potential.[ 12 ] Hence, the infiltration of dexmedetomidine in the surgical wound may help to avoid the adverse hemodynamic effects of IV administration while still providing postoperative analgesia. When dexmedetomidine and clonidine were added to lignocaine for nerve block, it enhanced the local anesthetic action of lignocaine through peripheral α-2A adrenoceptors.[ 16 ] 17
The results of this study indicate that the addition of dexmedetomidine to preemptive bupivacaine infiltration significantly reduces postoperative pain and diclofenac consumption, as compared to that in the group treated through mere bupivacaine infiltration, in patients undergoing abdominal hysterectomy. This can be explained by different mechanisms: inhibition of pain conduction in C-fibers, decreased in the production of inflammatory cytokines, the vasoconstrictive effect of 2 on vascular smooth muscle prolongs the time of analgesia, inhibition of tetrodotoxin-sensitive Na
+ channels, and the absorption of dexmedetomidine to systemic circulation resulting in supraspinal analgesia.[ 18 ] 19
The research done so far has shown good results for the use of dexmedetomidine in IV sedation (intensive care unit and operative patients), epidural, caudal anesthesia, and Bier's block.[
7 20 21 22 ] 23
A similar study conducted to evaluate the effect of dexmedetomidine added to ropivacaine infiltration on postoperative pain after inguinal herniorrhaphy concluded that dexmedetomidine added to ropivacaine infiltration reduces pain during the postoperative period after inguinal herniorrhaphy.[
] Another study to determine the postoperative analgesic effect of the addition of dexmedetomidine to 0.25% bupivacaine for local infiltration of the surgical wound concluded that wound infiltration of dexmedetomidine with bupivacaine provides superior pain relief compared to bupivacaine alone.[ 24 ] Similar findings were reported with the use of levobupivacaine.[ 10 ] We used 0.125% bupivacaine in our study. 25
Another double-blind study to evaluate the efficacy of local wound infiltration analgesia with ropivacaine and dexmedetomidine in tubercular spine surgery concluded that wound infiltration with ropivacaine, adrenaline, and dexmedetomidine before wound closure provided good postoperative analgesia with lower morphine requirement.[
Similar results were obtained in the present study. The patients who received dexmedetomidine as preemptive surgical site infiltration with bupivacaine before incision in abdominal hysterectomy had significantly reduced postoperative pain scores and diclofenac requirement when compared with those who received bupivacaine alone.
In the present study, we found that there was no significant difference in PONV between the two groups. Similar results were seen by Luan
et al.[ ] 27
No complications were noted in both the groups intraoperatively and postoperatively in our study.
In the present study, dexmedetomidine infiltration was not compared with IV dexmedetomidine, and only low-risk patients (ASA: 1–2) were studied. The duration of the hospital stay of both groups was not studied.
As per the observation seen in the present study, the number of patients requiring rescue analgesia and total diclofenac consumption during the first 24 h after operation was significantly less in the group who received bupivacaine with dexmedetomidine when compared with bupivacaine alone.
Therefore, it is suggested that the use of injection dexmedetomidine with bupivacaine at incision site wound infiltration gives better postoperative analgesia in abdominal hysterectomy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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