Dexmedetomidine is a relatively novel alpha -2 receptor agonist having sympatholytic properties which provides excellent hemodynamic stability during surgery without affecting respiration. But its antinociceptive property has not been studied much.
Aim: To study the effects of intra operative infusion of Dexmedetomidine on perioperative analgesics requirement in patients undergoing laparoscopic surgery with evaluation of sedation and recovery characteristics.
Material and methodology: Total 50 subjects posted for elective laproscopic surgery were selected and divided in group D and C, 25 in each. D group was subjects were given an initial loading dose of dexmedetomidine 1 μg/kg over 30 min prior to induction of anesthesia, followed by an infusion at 0.6 μg/kg/hr. The infusion was discontinued when surgery ended. Group P patients received the same volume of 0.9% saline as loading dose, followed by a saline infusion intraoperative. Sevoflurane was given in both the groups for maintenance of anesthesia. Requirement of analgesic in postoperative period was estimated along with visual analog sand sedation score.
Results: In D group 20 out of 25 subjects required either one or two doses of analgesic while in C group 19 out of 25 subjects required either three or four doses. This difference was statistically significant (P<0.05). Duration of analgesia was 8.32 ± 1.55 hours in D group while 1.20 ± 0.35 hours among C group (P<0.05). Conclusion: Dexmedetomidine provides excellent analgesia without causing sedation.
Key words: Dexmedetomidine, analgesia, sevoflurane, laproscopy
INTRODUCTION: To prevent surgical pain and hemodynamic responses of laryngoscopy, intubation various pharmacological agents are being used as an adjuvant in general anesthesia these involve,
β-blockers i.e. Atenolol , Esmolol
α-2 adrenoreceptor blockers i.e. Clonodine , Dexmeditomidine
Opioids i.e. Fentanyl , Remifentanyl
Vasodialators i.e. Nitroglycerine , Nicardipine
Alpha-2 agonists such as dexmedetomidine are known to reduce anesthetic requirements and because of sympatholytic properties they provide good hemodynamic stability during the intraoperative period. [1] Dexmedetomidine decreases plasma epinephrine and norephineprine level perioperative.[2, 3] It also attenuates hypertensive responses associated with surgical Stimulation. [4] These clinical characteristics make this intravenous agent a potentially attractive adjunct for general anesthesia and in the neurological intensive care unit (ICU). In addition patients treated with dexmedetomidine were discharged from the post anesthesia care unit earlier. [5] Analgesic effect of dexmedetomidine is qualitatively different as compared to opioids and can be used as an alternative to opioids in general anaesthesia. [6, 7, 8] so we decided to evaluate the usefulness of the anti-nociceptive property of dexmedetomidine.
AIMS AND OBJECTIVES:
To study the effects of intra operative infusion of Dexmedetomidine on perioperative analgesics requirement in patients undergoing laparoscopic surgery.
To evaluate for sedation and Recovery characteristics.
MATERIAL AND METHODOLOGY:
Present prospective randomized blinded placebo controlled study was conducted on 50 patients aged 35 to 65 with American Society of Anesthesiologists (ASA) status of 1 and 2 and scheduled for laparoscopic abdominal surgery in Hospital. 50 patients divided randomly in two groups.
1) Group D received dexmedetomidine infusion (n =25)
2) Group C received 0.9% sodium chloride as placebo (n =25)
Written informed consent from each subject and approval of institutional ethics committee was taken before commencement of the study.
EXCLUSION CRITERIA:
• Patients using α2-adrenergic receptors antagonists or any other antihypertensive drugs.
• Patients having dysrhythmia by ECG.
• Body weight more than 100 Kg
• Height less than 150
• Heart rate <50/min, first or second- or third degree heart block.
• Patients having cardiac dysfunction, hepatic or renal disease,
• Known allergy to dexmedetomidine.
• Participation in another drug study during the preceding 1 month.
• Patient’s refusal
All the patients underwent a detailed pre anesthetic check-up before surgery and all the routine and specific investigations were noted. The patients were electively kept nil per oral for 6 hours before surgery and prior to operation patients were explained about the procedure. After the patient was shifted to the theatre, standard monitors like ECG, NIBP, and pulse oximetery were applied. Intravenous line secured with one 18 gauge cannula and another 20 gauge for infusion of study drug in all the patients and intravenous fluid was started.
• PREMEDICATION:
All patients were preoxygenated with 100% oxygen for 5 minutes using Bain’s circuit and received,
Inj. Ondansetron 0.15 mg/kg IV
Inj. Glycopyrrolate 0.004 mg/kg IV
Inj. Fentanyl 1 μg/kg IV to group D and 2 μg/kg IV to group P
• Induction:
Achieved with thiopentone 3 to 5 mg/kg IV. Vecuronium 0.1 mg/kg IV was given to facilitate tracheal intubation.
• Maintenance:
It was achieved with 0.5 to 2% (end-tidal concentration) sevoflurane in 60% nitrous oxide and 40% oxygen. In each case, the aim was to maintain mean arterial blood pressure (MAP) within 80–120% of baseline values. Mean arterial blood pressure rise of more than 20% above baseline was treated by administering a 2 μg/kg IV bolus of fentanyl and raising the end-tidal sevoflurane concentration to 2%. Mean arterial blood pressure drop of more than 20% below baseline was treated initially with reduction of the end-tidal sevoflurane concentration to 0.5%. Supplemental boluses of vecuronium 0.05 mg/kg IV were administered as required maintaining muscle relaxation during surgery. Each Group D patient received an initial loading dose of dexmedetomidine 1 μg/kg over 30 min prior to induction, followed by an infusion started at 0.5 μg/kg/hr. The infusion was discontinued when surgery ended. Group C patients received the same volume of 0.9% saline as a sham loading dose, followed by a saline infusion.
Upon completion of surgery, each patient was extubated when they were able to execute simple verbal commands. All subjects were transferred to the postoperative care unit (PACU), where they were monitored for vitals and received nasal O2 supplementation. Degree of pain was determined by 11 point ‘visual analog scale (VAS).’ [9] VAS measures severity of pain ranging from 0(no pain) to 10(worst pain imaginable). In this method patient decides how severe pain he/she is having and accordingly suggest numbers between 0-10. It was explained to the patients that this score will be used after the end of surgery to assess their pain.
Diclofenac sodium 2mg/kg IV was administered for rescue analgesia as a bolus dose if the pain score at rest remained higher than 3. Sedation levels were also recorded using the ‘Ramsay sedation scale.’ [10] In this system,
1 = agitated and uncomfortable,
2 = cooperative and orientated,
3 = can follow simple directions,
4 = asleep but strong response to stimulation,
5 = asleep and slow response to stimulation, and
6 = asleep and no response to stimulation.
VAS and RSS was recorded at following time intervals postoperative. 10min, 30min,60min,90min,120 min,6hr, 12hr, 18hr, 24hr. Recovery characteristics were assessed using modified post anesthetic discharge scoring system[11] (0 to 15) at 20 minutes after tracheal extubation.
Emergence time [12] was measured as the time interval between sevoflurane discontinuation and the time to open eyes spontaneously or on verbal commands.
Extubation time [12] was measured as the time interval between sevoflurane discontinuation and extubation (performed when the patient obeyed verbal commands, demonstrated purposeful movement, and had adequate spontaneous breathing).
Modified post anesthetic discharge scoring system:
Category Score = 2 Score = 1 Score = 0
BP and Heart rate ± 20% of preoperative
Value ± 20-40% of preoperative
value
± 40 % preoperative
value
Activity Steady gait, no dizziness or meets preoperative level Requires assistance Unable to ambulate
Nausea and vomiting No or minimal Moderate, treated with parenteral medicines Severe , continuous despite treatment
Pain Minimal or no pain moderate Severe
Bleeding None Moderate
(1 episode) Severe (2 or more than 2 episodes)
Higher the score better recovery.
Each Observer who recorded data was blinded with respect to patients’ group allocation. The observer was never the anesthesiologist providing clinical care of the patient.
STATISTICAL ANALYSIS:
Results obtained from the study were expressed in mean ± SD, for non-parametric data Chi square test was applied and for numeric data with continuous variables ‘T’ test was applied. “P” value less than 0.05 was considered as statistically significant. Statistical analysis was done with EPI info software (version 3.5.3, 2011, centers for disease control and prevention, Atlanta, GA, USA)
RESULTS: Both the groups were comparable for demographic data and characteristics of surgery and no significant difference were found in these parameters (P>0.05) [Table 1]. All the subjects in the both the groups required rescue analgesia during postoperative period. However, those who were given dexmedetomidine intraoperative needed significantly lesser number of doses of analgesic. (P<0.05)
In D group majority of subjects 20/25 required either one or two doses of analgesic while in C group majority 19/25 required either three or four doses. This difference was statistically significant. (P<0.05) [Table 2]. VAS was also significantly less throughout postoperative period among D group as compared to C group (P<0.05) [Table 3].
A statistically significant difference was found in duration of analgesia. First dose of rescue analgesic among D group patients needed after 8.32hours postoperative while only after 1.20hours among C group (P<0.05) [Table 4].
Sedation was more among D group (P<0.05) [Table 5], but recovery was also better in dexmeditomidine administered group. (P<0.05) [Table 6].
DISCUSSION:
Primary outcome from my study is, need of diclofenac sodium as rescue analgesia and VAS remained less among the patients who were given dexmedetomidine intraoperative.
The activation of α2-adrenergic receptors by dexmedetomidine in the dorsal horn of the spinal cord inhibits the release of substance P, a nociceptive mediator, resulting in primary analgesic effects as well as potentiating of opioid-induced analgesia. Our findings are similar to study done by Gurbet A et al. [13] and Khaled Taha [14], where they proved intraoperative administration of dexmedetomidine reduces postoperative morphine requirement. Another study done by Nevriye salman et al. [15] also showed total number of doses of rescue analgesic reduces with dexmedetomidine usage.
The analgesic effects of dexmedetomidine observed in our study correlate well with previous findings in both animals and humans. Experiments with thermal pain models in animals by Kayser V et al. [16] and Hall JE et al. [17] have shown that systemic administration of clonidine or dexmedetomidine has significant analgesic effects. Cortinez et al. [6] showed that a 0.6 ng/mL target control infusion (equivalent to 0.5 μg/kg) of iv dexmedetomidine had analgesic effects in humans. These doses of dexmedetomidine are similar to the amounts which patients received in the current study. However, conflicting results were 6documented in one study in an experimental model of secondary hyperalgesia, where volunteers who received clonidine at a dose known to produce moderate to severe sedation experienced no anti-hyperalgesic or anti-allodynic effects. [18]
Arain et al. [19] compared the efficacy of dexmedetomidine with morphine for postoperative analgesia after major inpatient surgery. They found both groups had similar pain scores but the morphine group required 66% more morphine to achieve the analgesic effect.
Venn et al. [20] investigated the postoperative effects of postoperatively administered dexmedetomidine in 119 cardiac surgery and general surgery patients who required mechanical ventilation and sedation in an intensive care unit. They found dexmedetomidine had an analgesia-sparing effect and resulted in reduced need for rescue sedation. In our study, we observed that the dexmedetomidine group had significantly lower Diclofenac requirements than the placebo group during the first 24 hour after abdominal surgery. One explanation for this postoperative analgesia with dexmedetomidine may be the anxiolytic and thymoanaleptic properties of α2-agonists, which act on the emotional component of postoperative pain. [21]
We also found that need of 1st dose of rescue analgesic was delayed with intraoperative dexmedetomidine use. (Table 4)
Dexmedetomidine did cause some amount of sedation, but It did not cause any delay in recovery of the patient from anesthesia in fact recovery was better among D group. The sedation was also not that severe so as to warrant any interference from our side.
These results in our study were similar to one study of D.P.Bhattacharjee, Sushil Nayek et al. [22] where they found that Dexmedetomidine caused sedation but did not cause any delay in recovery time. KN Gopal Krishna et al. [12] also found recovery is better in Dexmeditomidine administered group. However In another study of Toni Uhrich et al. [23] it was found that small dose Dexmedetomidine infusions caused sedation, impairment of memory and psychomotor performance.
Conclusion:
We conclude that continuous infusion of dexmedetomidine during laproscopic surgery significantly reduces the amount of Diclofenac sodium that patients require to remain comfortable postoperative. Dexmedetomidine produces some amount of sedation in the patients, but the sedation was not significant enough to delay recovery from anesthesia.