|Year : 2017 | Volume
| Issue : 2 | Page : 107-111
A comparative study of intravenous patient-controlled analgesia with tramadol alone and tramadol plus dexmedetomidine for major lower abdominal surgery
Neeta Abhay Kavishvar, Bhavesh H Prajapati
Department of Anaesthesiology, Government Medical College and New Civil Hospital, Surat, Gujarat, India
|Date of Web Publication||6-Sep-2017|
Neeta Abhay Kavishvar
Flat 2/B Pararthana Apartment, Ravishankar Sankul, Bhatar Char Rasta, Surat - 395 017, Gujarat
Source of Support: None, Conflict of Interest: None
Background: Different techniques are used to provide postoperative pain relief to the patients. The patient-controlled analgesia (PCA) has come out as promising option. The main advantage of it is a stable plasma concentration of analgesic drug and the control of medication in patients' hand. Morphine has been used extensively for postoperative analgesia, but almost no respiratory depression makes tramadol equally popular for postoperative analgesia. Alpha-2 agonist-like dexmedetomidine can have additive analgesic effect. The above background was the base of planning this study to evaluate the effect of dexmedetomidine added to tramadol for postoperative analgesia. Materials and Methods: This prospective study was conducted in sixty female patients undergoing lower abdominal surgery. All patients were given spinal anesthesia for surgery. When effect of spinal anesthesia wear off and the patient had verbal rating score (VRS) more than three PCA was started. In Group T, all patients received tramadol 1 mg/kg followed by PCA tramadol. In Group D, all patients received tramadol 1 mg/kg and dexmedetomidine 0.5 mcg/kg followed by PCA having combination of tramadol and dexmedetomidine. VRS for pain, total consumption of tramadol, and side effects were recorded for 24 h postoperatively. Results: VRS for pain was comparable in both the groups. PCA demand and total dose of tramadol were less in group who received tramadol with dexmedetomidine. There was no significant difference in occurrence of side effects. Conclusions: The combination of dexmedetomidine with tramadol reduces the tramadol requirement for postoperative analgesia.
Keywords: Dexmedetomidine, patient-controlled analgesia, postoperative analgesia, tramadol
|How to cite this article:|
Kavishvar NA, Prajapati BH. A comparative study of intravenous patient-controlled analgesia with tramadol alone and tramadol plus dexmedetomidine for major lower abdominal surgery. Indian J Pain 2017;31:107-11
|How to cite this URL:|
Kavishvar NA, Prajapati BH. A comparative study of intravenous patient-controlled analgesia with tramadol alone and tramadol plus dexmedetomidine for major lower abdominal surgery. Indian J Pain [serial online] 2017 [cited 2020 May 28];31:107-11. Available from: http://www.indianjpain.org/text.asp?2017/31/2/107/214118
| Introduction|| |
Pain is the most important concern for the patient and anesthesiologist in the perioperative period. Adequate pain relief is a right of the patient and it is an obligatory duty of the doctor. There are different techniques to provide postoperative pain relief such as intramuscular or intravenous (IV) opioids, nonsteroidal anti-inflammatory drug, per rectal administration of drugs, intrathecal/epidural opioid, or local anesthetic agent. Intermittent IV and intramuscular use of opioid is most widely practiced method, but many a times, it is not adequately effective.
Patient-controlled analgesia (PCA) is becoming popular these days as it allows patient to self-administer small bolus dose of opioid making it possible to achieve effective blood concentration as per a particular patient's requirement. PCA technique also avoids peaks and valleys in drug concentration. Another advantage is that it minimizes the time delay between perception of pain and administration of medication and lowers total analgesic dose requirement. Patient feels that he/she is in control of his/her pain management which increases his satisfaction about pain management. The effectiveness and safety of PCA with number of opioids have already been demonstrated; however, the ideal opioid has not been yet found.
Morphine is a gold standard opioid analgesic, most commonly used in PCA system. Tramadol is a popular agent for postoperative pain relief as it almost does not have any respiratory depression. The most disturbing side effects of tramadol are nausea and vomiting, which can reduce the effectiveness of tramadol as an analgesic. Dexmedetomidine a potent alpha-2 adrenoreceptor agonist can add the effect of analgesia without increasing the incidence of side effects. These observations lead to the concept that the combination of an opioid and dexmedetomidine may improve postoperative patient comfort with PCA. There are studies in literature in which dexmedetomidine was combined with opioids such as morphine and meperidine, but during literature search, hardly any study could be found of combination of tramadol and dexmedetomidine.
Hence, this prospective randomized double-blind study was designed to evaluate the effect of dexmedetomidine added to tramadol in PCA. It was designed to note whether adding dexmedetomidine to tramadol reduces the total dose of tramadol and improves analgesia and/or reduces the side effects.
| Materials and Methods|| |
After obtaining the Institutional Ethics Committee approval, this prospective study was conducted in sixty female patients of age group 23–60 years, American Society of Anesthesiologist Class 1-2, who were scheduled for elective abdominal surgery. Preanesthetic examination of patients was done a day before the surgery. Detailed history was elicited and systemic examination was done to rule out major systemic illness. Routine investigations such as hemoglobin, random blood sugar (RBS), renal function tests, and electrocardiogram were done. Patients with following conditions were excluded from the study such as allergy to study drug, inability to use PCA pump, long-term use of opioid drug, history of chronic pain, hepatic dysfunction, renal dysfunction, hypertension, ischemic heart disease, heart block, respiratory disease, patients on antidepressant or beta blockers, history of postoperative nausea and vomiting, and history of motion sickness.
Before surgery, all patients were given demonstration of and explained about PCA and instructed how to use PCA pump. Patients were also explained about 0–10 verbal rating score (VRS), where 0 represented no pain and 10 worst pain imaginable.
Patients were randomly divided by computer-generated random numbers into two groups to receive injection tramadol in Group T and injection tramadol plus dexmedetomidine in Group D as postoperative analgesic medication through PCA pump. All patients were premedicated with injection glycopyrrolate 0.2 mg IV and injection midazolam 1 mg IV 30 min before the surgery. Preoperative vitals (pulse, blood pressure) were recorded inside the operation theater. All patients were given spinal anesthesia with injection bupivacaine (0.5%) and adequate level of anesthesia was achieved. After completion of surgery, all patients were given injection ondansetron 4 mg IV and then shifted to the postoperative recovery room. In postoperative recovery room, all patients were observed for regression of spinal anesthesia. When the regression level of spinal anesthesia was L1 and patients complained of pain with VRS >3, loading dose of injection tramadol 1 mg/kg IV was given to Group T and Group D received injection tramadol 1 mg/kg + injection dexmedetomidine 0.5 μg/kg IV diluted in 10 ml normal saline (NS).
Fifty ml syringe in the PCA pump contained the following study drug:
- Group T: Injection tramadol 250 mg (5 ml) +injection NS (45 ml)
- Group D: Injection tramadol 250 mg (5 ml) + injection dexmedetomidine 250 μg (2.5 ml) + injection NS 42.5 ml.
Thus, the solution in PCA syringe contained injection tramadol 5 mg/ml in case of Group T and injection tramadol 5 mg plus injection dexmedetomidine 5 μg/ml in case of Group D. The bolus dose and PCA syringe were prepared by an independent person. The investigator who was supposed to collect data was blinded to the Group to which the patient belongs. Patient himself was also blinded to the content of PCA. Patients were instructed to use PCA pump when they feel pain with VRS >3.
The loading dose is defined as minimum dose to produce appreciable analgesia without causing side effects. The demand dose depends on the agent used for the analgesia. The lockout period is the minimum allowable period between PCA bolus doses. It depends on the pharmacokinetic property of the agent used. The purpose of lockout period is to make sure that most of the effect of bolus dose is reached before further dose is received by the patient by pressing the button. Maximum allowable drug in 4 h is important to prevent patient from receiving excessive dose of the medication causing serious side effects. The above-mentioned PCA settings mainly depend on the analgesic medication.
PCA pump setting was adjusted at 2 ml bolus with 10 min lockout period, with maximum dose of 100 mg for injection tramadol and 100 μg of dexmedetomidine plus 100 mg of tramadol in 4 h in Group T and D, respectively. Patients were assessed at 1, 2, 4, 8, 12, and 24 h after the operation with the following parameters, pulse, blood pressure, SpO2, sedation score, nausea, PCA demand, and good demand. If the patient has to be assessed at night when the patient is supposed to be sleeping, then the assessment was done 2 or 3 h before or after to the scheduled time of assessment. VRS was assessed as 0–10. Sedation was assessed with five-point score [Table 1].
All patients' total demand, good demand, and total drug delivered in milligram were recorded. All patients were asked about patient satisfaction score to be graded as poor, good, and excellent. Patients were observed for nausea, vomiting, sedation, dry mouth, respiratory depression, bradycardia, hypotension, arrhythmia, etc., in postoperative ward for 24 h.
The sample size was calculated as 30 in each group by considering reduction in tramadol dose by 20%, with power of study was 0.8 and significance level of 0.05.
Primary outcome measures such as total demand, good demand, total dose of tramadol used, VRS score, and secondary outcome measures such as blood pressure, heart rate, incidence of complication, and patient satisfaction score were analyzed using Student's t-test and Chi-square test. Mann–Whitney test was also applied to observations of total demand, good demand, and total dose of tramadol.
| Observation and Results|| |
Patients in both the groups were comparable for age (39.8 ± 8.84 and 39.7 ± 7.15 years) and weight (50.16 ± 4.04 and 50.9 ± 5.73 kg). All patients were female patients undergoing lower abdominal gynecological surgery. 90% of the females were operated for abdominal hysterectomy and 10% for laparotomy for various gynecological indications.
During the study period, the mean VRS score at 1 h after starting PCA was 4.8 ± 1.4 in Group T and 4.0 ± 1.36 in Group D. The difference was statistically significant (P< 0.05). The mean VRS score at 2, 4, 8, and 16 h was comparable between two groups (P > 0.05). At 24 h, when patients were assessed for pain, mean VRS score was 1.66 ± 1.51 in Group T and 0.63 ± 1.21 in Group D. Thus, both tramadol (Group T) and tramadol plus dexmedetomidine (Group D) provided comparable analgesia. In this study, sedation was assessed by five-point score [Table 1], not a single patient had sedation score more than 2 at any time during the study period in both the group. Mean pulse rate, mean systolic blood pressure, and mean diastolic blood pressure were compared between Group T and Group D. It was noted that the difference between the two groups was statistically not significant. Mean oxygen saturation was more than 97% in both the groups during the study period.
The [Table 2] shows the demand of PCA. When it was compared at 1 h in both the groups, the difference was statistically not significant (P > 0.05) When the demand at 2, 4, 8, 16, and 24 h in both the groups were compared, the difference was statistically significant (P< 0.05) (Student's t-test); the number of demands was significantly more in tramadol only group than tramadol plus dexmedetomidine group.
Good demand is a demand which releases the bolus dose of analgesic drug. That means that PCA button was pressed after lockout period. [Table 3] presents the patients' good demand in Group T and Group D at various time intervals. When the good demands in both the groups were compared, the difference was not statistically significant at 1 and 2 h after starting PCA (P > 0.05). At 4, 8, 16, and 24 h after starting PCA, the good demands were significantly less when dexmedetomidine was combined with tramadol (P< 0.05) (Student's t-test).
[Table 4] shows the total dose of tramadol in mg in Group T and Group D at various time intervals.
After each case, the dose of tramadol in mg and dexmedetomidine in microgram were calculated from the data obtained from PCA pump. Total tramadol used in 24 h in Group T was 182.4 ± 82.5 mg compared to 137.6 ± 45.61 mg in Group D. The difference was statistically significant. When data of 24 h in both group were compared with Mann–Whitney test for demand, good demand, and dose in mg, P < 0.05. Hence, the difference was statistically significant. In Group D, total dose of dexmedetomidine used was 137.66 ± 45.61 μg in 24 h.
Four patients had nausea in Group T and five patients had nausea in Group D. Chi-square test was applied and it showed that there was no statistical significant association between the occurrence of nausea and postoperative analgesic medication in this study.
All the patients at the end of study were asked about their satisfaction score for postoperative analgesia which was graded as poor, good, and excellent. In tramadol group, 28 patients had good or excellent satisfaction score and only 2 were graded as analgesia poor. In dexmedetomidine group, 29 patients were satisfied with the technique (good or excellent score) except one patient.
When the satisfaction score in both the groups was compared, the difference was not statistically significant (P > 0.05).
Side effects such as vomiting, dry mouth, respiratory depression, bradycardia, hypotension, and arrhythmia were not observed in both the groups.
| Discussion|| |
Pain following lower abdominal surgery for various gynecological conditions is very hard to treat. Spinal anesthesia is the most common anesthesia for these surgeries. Intrathecal additives are also widely used to provide analgesia, but they are also not without side effects. Many of the female patients being anxious about the surgery are the candidates who are difficult to satisfy about the postoperative pain regimen. PCA gives control of the pain management in patient's hand, which may be one of the factors which can make it an effective method of postoperative analgesia.
Pain arising from lower abdominal surgery has both visceral and somatic components. Opioid is the best choice as analgesic in this situation. Morphine is gold standard among the opioids and it is widely used with PCA.
Ideal analgesic for PCA should have rapid onset of action. It should be highly effective in relieving pain, have an intermediate duration of action, no tolerance, or dependence, have minimum side effects or adverse drug interactions.
Tramadol is a synthetic opioid, a weak centrally acting analgesic drug. It inhibits neuronal reuptake of noradrenaline and 5 hydroxytryptamine (5 HT) and it facilitates 5 HT release. Thus, it provides analgesia through dual mechanism. It has poor affinity to the mu receptor, so it is unlikely to cause respiratory depression. It is a widely used analgesic for postoperative pain, especially of moderate to severe painful condition. Silvasti et al. and Hadi et al. concluded that PCA with tramadol is equally effective as PCA morphine in controlling postoperative pain.
It is the most popular agent used by IV route in hospital where this study was done, for postoperative analgesia. When most of the patients are shifted to ward after operation, it is important to use analgesic drug having good safety profile.
Hence, this study was planned to evaluate injection tramadol a popular agent as patient-controlled analgesic medication.
The concept of multimodal analgesia is based on using different classes of analgesic together which can alleviate pain though discrete mechanism of action targeting the pain from all sides. This will reduce the dose of analgesics and its side effects.
Opioid being traditional and prevailing analgesic for postoperative pain control but has drawbacks such as respiratory depression, nausea, vomiting, and pruritus.
Dexmedetomidine is a potent α2 adrenoreceptor agonist with α1:α2 selectivity ratio of 1:1600 and it has sedative, anxiolytic, anesthetic sparing effect. The other important quality of dexmedetomidine is that it does not produce respiratory depression. Above characteristics of dexmedetomidine led to the concept of combining it with opioid for postoperative analgesia. It can enhance the analgesia produced by opioid and reduce the requirement of opioid, thus by decreasing the side effects. Combination of opioids such as morphine and pethidine with dexmedetomidine are studied by many. Dexmedetomidine and morphine for IV PCA resulted in superior analgesia when compared to morphine alone.
Hakki Unlugence and Hadi et al. concluded that analgesia produced by tramadol and morphine is comparable. Tramadol can be a good alternative to morphine for postoperative analgesia.
It was observed that initial analgesia was better with dexmedetomidine group. Analgesia provided by dexmedetomidine is through its action on α2 adrenoreceptor at spinal cord as well as supraspinal sites. It also provides antinociception by inhibition of conduction of nerve signals through C and A delta fibers and local release of encephalin. Dexmedetomidine is having specific effect in which patient is sedated but arousable. The loading dose of dexmedetomidine leading to anxiolysis and conscious sedation might have contributed for first 2 h lesser VAS score in dexmedetomidine group than tramadol group. This property is beneficial in postoperative period.
The PCA demand noted at 2, 4, 8, 16, and 24 h in both the groups and compared, it was significantly less in tramadol with dexmedetomidine group (P< 0.05). When good demand were compared in both the groups at 4, 8, 16 and 24 h after starting PCA, it was less in group who received dexmedetomidine along with tramadol.(P< 0.05)
The total dose of tramadol received in 24 h was 182.4 ± 82.5 mg in Group T and 137.66 ± 45.61 mg in Group D (P< 0.05). Tramadol consumption was reduced by almost 25% when dexmedetomidine was added to tramadol.
Thus, the addition of dexmedetomidine to tramadol significantly reduces the demand for PCA and reduces the total requirement of tramadol.
Nub T Altindis. et al. (2008) observed that meperidine consumption was reduced in meperidine pus dexmedetomidine group than meperidine only group for postoperative PCA after elective abdominal surgery. Lin et al. (2009) noted dexmedetomidine group required 29% less morphine during the first 24 h postoperative period.
Dexmedetomidine itself has analgesic property through its action on spinal cord and peripheral α2 receptors. Analgesia produced by tramadol is through action on μ receptors and action on 5 HT. Mechanism of action of both tramadol and dexmedetomidine of providing analgesia is different; hence, when both the agents are used together, additive effect occurs. This is the reason for reduced requirement of tramadol in dexmedetomidine group.
It is a well-known fact that pain has emotional component. Female patients undergoing abdominal hysterectomy or laparotomy are anxious and emotionally labile. Dexmedetomidine by its anxiolytic properties can take care of this and make whatever analgesia more effective.
When discussing about complication related to the study, it can be stated that none of the patients had vomiting, dry mouth, respiratory depression, bradycardia, hypotension, arrhythmia, etc., in postoperative ward for 24 h in both the groups. Five patients in Group D and four patients in Group T had nausea (P > 0.05).
It is a known fact that tramadol causes nausea and vomiting; hence, in this study, prophylactic injection ondansetron was given before starting postoperative analgesic.
It was hypothesized that addition of dexmedetomidine will reduce the requirement of tramadol and by that reduce the most disturbing side effect, nausea and vomiting.
As it has been observed that though the tramadol requirement has reduced, but incidence of nausea was comparable between both the groups. The study with more number of patients can answer this question in better way or female patients with gynecological operations are as such more susceptible to emetogenic episode.
This study was done in hospital where many of the patients are from low socioeconomic class and poorly educated. It was observed that it was not easy to make them understand the concept of PCA and how to use PCA. If PCA is not the routine method of postoperative analgesia even the nursing staff may require training.
Patient's satisfaction for postoperative analgesia was comparable for both groups for this study. Patient satisfaction is multifactorial. It is not the analgesia, but many other factors such as surgery, side effects, and patient care in perioperative period had significant effect on it. The concept of PCA is that when the patient himself is in control of his pain naturally, the level of satisfaction will be more.
Thus, it can be concluded that analgesia produced by PCA tramadol and PCA tramadol plus dexmedetomidine is almost comparable. Dexmedetomidine added to PCA tramadol reduces the requirement of tramadol without much side effect.
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[Table 1], [Table 2], [Table 3], [Table 4]