|Year : 2015 | Volume
| Issue : 3 | Page : 370-376
Epidural dexmedetomidine, tramadol, or neostigmine for postoperative pain after major breast surgeries
Mohamed Amr Abusabaa, Mohamad H Hamada MD , Mostafa A Abo El Enin, Salah M Kamal
Department of Anesthesia and Intensive Care, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||01-Nov-2014|
|Date of Acceptance||18-Mar-2015|
|Date of Web Publication||29-Jul-2015|
Mohamad H Hamada
8 Family Houses, El Obor City, Qalubia
Source of Support: None, Conflict of Interest: None
It is postulated that the beneficial effects of epidural analgesia result from attenuation of stress response and provision of good postoperative analgesia. We added dexmedetomidine, tramadol, or neostigmine to bupivacaine in thoracic epidural anesthesia to evaluate their effect on perioperative cortisol level, postoperative analgesia, time to ambulation, and complications.
Patients and methods
Eighty female patients scheduled for major breast surgery were divided into four equal groups (20 patients each) in a randomized double-blinded manner. Thoracic epidural anesthesia was induced. In group C 15 ml of 0.5% bupivacaine (control group), in group D 15 ml of 0.5% bupivacaine +75 μg of dexmedetomidine, in group T 15 ml of 0.5% bupivacaine +75 mg of tramadol, and in group N 15 ml of 0.5% bupivacaine +75 μg of neostigmine were given. Perioperative cortisol level, postoperative analgesia, time to ambulation, and complications were assessed.
Demographic data and surgical characteristics were similar in all groups. Patients in groups D and T had lower pain scores compared with patients in groups C and N at all time points in the following 24 h postoperatively. Hence, patients in groups D and T consumed a lower dose of bupivacaine in the postoperative period compared with patients in groups C and N. There was a highly significant reduction in the mean time to postoperative ambulation in groups D, T, and N compared with group C.
Dexmedetomidine is superior to tramadol and neostigmine in providing hemodynamic stability, excellent attenuation of stress response, prolonged postoperative analgesia, and early mobilization with minimal undesirable side effects.
Keywords: dexmedetomidine, neostigmine, postoperative pain, thoracic epidural anesthesia, tramadol
|How to cite this article:|
Abusabaa MA, Hamada MH, Abo El Enin MA, Kamal SM. Epidural dexmedetomidine, tramadol, or neostigmine for postoperative pain after major breast surgeries. Ain-Shams J Anaesthesiol 2015;8:370-6
|How to cite this URL:|
Abusabaa MA, Hamada MH, Abo El Enin MA, Kamal SM. Epidural dexmedetomidine, tramadol, or neostigmine for postoperative pain after major breast surgeries. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 Sep 21];8:370-6. Available from: http://www.asja.eg.net/text.asp?2015/8/3/370/161707
| Introduction|| |
General anesthesia is the technique normally used for breast surgeries. The downside of general anesthesia includes inadequate pain control, a high incidence of nausea and vomiting, and increasing length of hospitalization. Other controversial effects of general anesthesia in oncologic patients are related to depression of the immune system. Thoracic epidural block is frequently used in plastic surgeries of the breast, and there are also some reports on its use in oncologic surgeries of the breast . Analgesic effect of α2 agonists is mostly mediated at the spinal level; neuraxial administration of dexmedetomidine was found to have potent analgesic effect. A few clinical studies have examined the epidural administration of dexmedetomidine in thoracic and upper abdominal surgery. Epidural dexmedetomidine potentiates neuraxial local anesthetics, decreases intraoperative anesthetic requirements, and improves postoperative analgesia, thus reducing postoperative pulmonary complications  . Epidural tramadol produces analgesia by binding to certain opioid receptors (μ-opioid receptor) in addition to inhibition of reuptake of norepinephrine and serotonin in the spinal cord; its exact mechanism of action is not completely known. Epidural tramadol can produce effective analgesia in patients undergoing major abdominal surgery without any serious side effects  . Epidural neostigmine provides analgesia through M1 and M2 receptors in the spinal cord, inhibiting the breakdown of acetylcholine. It also prolongs and intensifies the analgesia through release of nitric oxide in the spinal cord. It prolongs motor block when combined with a local anesthetic  . This study aimed to compare the effects of dexmedetomidine, tramadol, and neostigmine injected into the thoracic epidural space as adjuvants to bupivacaine to manage postoperative pain after major breast surgeries as regards hemodynamic changes, respiratory changes, postoperative analgesia, and stress response.
| Patients and methods|| |
After ethical committee approval and after obtaining informed consent from patients, this study was carried out in Al-Azhar University Hospitals on 80 female patients aged between 20 and 60 years who were of ASA physical status I or II and scheduled for major breast surgery. Patients were divided into four equal groups (20 patients each) in a randomized double-blinded manner (computerized) using closed envelopes. In group C 20 patients received thoracic epidural anesthesia (TEA) with only 15 ml of bupivacaine hydrochloride 0.5% (Bucain, Germany) (control group). In group D 20 patients received TEA with 15 ml of 0.5% bupivacaine in addition to 75 μg of dexmedetomidine hydrochloride (Precedex, Hospira Inc., Lake forest, USA). In group T 20 patients received TEA with 15 ml of 0.5% bupivacaine in addition to 75 mg of tramadol hydrochloride (Tramal, Germany). In group N 20 patients received TEA with 15 ml of 0.5% bupivacaine in addition to 75 μg of neostigmine methylsulfate. Patients who had a history of coagulation defect, heart failure, respiratory diseases, neurological or psychiatric diseases, patients with a history of previous thoracic spine surgery, those on steroid therapy, and those with suprarenal gland dysfunction were excluded from the study. Evaluation of complete blood picture, coagulation profile, liver and kidney function tests, evaluation of random blood sugar, ECG, and echocardiography (if required) were carried out. All patients were informed about the visual analog scale (VAS) before the procedure. An 18-G intravenous cannula was inserted. All patients were given 2 mg midazolam intravenously 1 h before arrival at the operation theater as premedication, and upon arrival at the operation room 500 ml of normal saline was infused as a preload. A blood sample was obtained for measurement of serum cortisol level (baseline value). All patients were monitored by five-lead ECG, non invasive blood pressure (NIBP), and pulse oximetry. Vital data were obtained and recorded as baseline values. After skin preparation and disinfection, while the patient was in the sitting position, 5 ml of lidocaine 2% was used for local infiltration of the skin and subcutaneous tissue at the entry point at the level of the T4-T5 interspace (paramedian approach was used 1 cm lateral and 1 cm above the lower spine). An epidural 18-G Tuohy needle (Portex Epidural Minipack; Smiths Medical ASD Inc., 10 bowman drive keene, NH 03431 pete hirte 1265 grey fox rd st. paul, MN 55112, USA) was inserted and advanced slowly and cautiously until loss of resistance, and then a soft epidural catheter was inserted 5 cm within the thoracic epidural space. A test dose with 3 ml of 2% lidocaine plus 15 μg of epinephrine was injected to confirm the catheter placement. After fixation of the epidural catheter at the back, the patients were placed in the supine position and administered the local anesthetic and its adjuvants as mentioned before, aiming to block the somatosensory level from C8 to T8. When two segment regressions occurred, 5 ml of 0.5% bupivacaine in 15 ml saline was injected. In case of failed block, patchy block, or dural tap, general anesthesia was used to complete the surgical procedure, and these patients were excluded from the study and replaced with other patients. For this comparative study, all patients were continuously monitored intraoperatively and 24 h postoperatively. We defined an intraoperative reduction of mean arterial blood pressure or heart rate by more than 20% of baseline values as hypotension or bradycardia, respectively. Bradycardia was treated with increments of intravenous 0.5 mg atropine and hypotension with increments of intravenous ephedrine (5 mg). The time and level of complete sensory block for regional anesthesia was assessed by pinprick. Patients were assessed at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 24 h after operation for mean arterial blood pressure, heart rate, respiratory rate, first analgesic requirement, total analgesic requirement/24 h, time to ambulation, and postoperative pain using the VAS, which is a horizontal 10-cm VAS with ends marked as 0 (no pain) and 10 (worst imaginable pain). A volume of 10 ml of bupivacaine 0.125% was injected through an epidural catheter if the VAS score was greater than 3. The cortisol level was assessed preoperatively, 1 h after skin incision, and finally after 24 h postoperatively. Postoperative complications (postoperative nausea and vomiting (PONV), itching, somnolence, urine retention, and dry mouth) were also assessed.
The minimal sample size was calculated to be 80 (four groups of 20 patients each) with type I error 0.05 (α) and type II error 0.1 (β) by power of test 10% by Medcalc program V3.2 (Microsoft Partner MedCalc Software bvba Acacialaan 228400 Ostend, Belgium).
Statistical presentation and analysis was carried out, using the mean and SD for normal quantitative data, tested by analysis of variance (parametric test), and median and interquartile range for nonparametric data, tested by the Kruskal-Wallis test, and the χ2 -test for qualitative data. P value was considered nonsignificant if greater than 0.05, significant if less than 0.05, and highly significant if less than 0.001. Data were analyzed using statistical package for the social sciences (SPSS, version 17; SPSS Inc., Chicago, Illinois, USA).
| Results|| |
Demographic data [Table 1] showed no significant difference between groups as regards patient weight, height, ASA physical status, total duration of anesthesia, operative time, and type of surgical procedure. In the current study vital data were recorded at T0 (after finishing the surgical procedure), every 1 h in the following 12 h, and then at 24 h. [Figure 1] and [Figure 2] show that there was significant change in mean arterial blood pressure and heart rate in the first 6 h after surgery (P < 0.05), but in the second 6-h period as well as at 24 h there was no significant change among the four groups (P > 0.05). In groups D and T reduction in mean arterial blood pressure was more prominent than in groups C and N. Postoperative respiratory rate showed no statistically significant difference in the baseline values of the four groups and over the time course of the study (P > 0.05). There was a highly significant change among groups with respect to pain score (P < 0.001), except at 6, 8, and 10 h postoperatively, when there was no statistically significant change (P > 0.05). Further, patients in groups D and T had lower pain scores compared with group C. However, patients in group N had lower pain scores than those in group C but higher scores than patients in groups D and T [Table 2]. As regards first need to analgesic dose, there was a highly significant increase in the mean time in groups D, T, and N compared with group C and in group D compared with group N (P < 0.001). Also there was significant change between groups D and T and between groups T and N (P < 0.05) [Table 3]. There was a highly significant decrease in the mean dose of bupivacaine required as epidural analgesia in the 24 h after surgery in groups D, T, and N compared with group C (P < 0.001) [Table 4]. There was also a highly significant change between two groups (P < 0.001). There was a highly significant reduction in the mean time to postoperative ambulation in groups D, T, and N compared with group C and in group D compared with group N (P < 0.001). There was a significant change between groups D and T, and between groups T and N (P < 0.05). However there was no significant change between groups D and T (P > 0.05) [Table 5]. Baseline serum cortisol levels showed no difference among groups (P > 0.05), but after 1 h from skin incision there was increase in serum cortisol level in all groups with variable degrees, with marked elevation in group C compared with the other groups. There was a highly significant change among groups (P < 0.001). At 6 h postoperatively, serum cortisol started to decline to reach preoperative values in groups D, T, and N compared with group C, which was still high (P < 0.001) [Figure 3]. As regards perioperative complications there were two patients who had dural tap and 10 patients with patchy or failed block. Those 12 patients converted to general anesthesia (GA) and were replaced by other patients to complete each group of 20 patients. Two cases in group T developed nausea and two cases had vomiting. In group N one case had nausea and one case had vomiting. As regards dry mouth, four cases in group D had dry mouth and thirst sensation; no other patients in the other groups had the same complication. As regards hypotension, two cases in group D had hypotension with systolic blood pressure less than 90 mmHg compared with groups T and N (only one case in each group). No case in all groups had pruritus or urine retention.
|Table 2: Median (interquartile range) postoperative pain score in the four groups (baseline) and within 24 h of surgery|
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|Table 3: Mean ± SD/h of time to fi rst rescue analgesic dose in the four groups|
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|Table 4: Total dose of bupivacaine in mg required within 24 h postoperatively|
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|Table 5: Postoperative ambulation per hour in the four groups (mean ± SD)|
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| Discussion|| |
This study was decided to compare between different drugs (dexmedetomidine, tramadol, and neostigmine) when used as adjuvants to bupivacaine in TEA in patients undergoing major breast surgeries. The patients in this study were divided into four groups (20 patients each). The four groups were nearly similar regarding their basic data (age, sex, body weight, height, ASA classification, and operative conditions).
As regards hemodynamics, mean arterial blood pressure and heart rate decreased considerably in all groups, with variable degrees, during the first 30 min of surgery, and then on subsequent readings there was a gradual return of blood pressure toward baseline values. In groups D and T reduction in mean arterial blood pressure was more prominent than in groups C and N. This is in agreement with the results of a study by Jain et al.  , which showed a significant fall in pulse rate and mean arterial pressure 10 ± 5 min after epidural dexmedetomidine, which lasted throughout the study period. Kiran et al.  showed that epidural neostigmine decreases the mean arterial blood pressure and pulse rate by 15% from baseline. Paranjpe et al.  studied the addition of 50 mg tramadol to a mixture of lidocaine and bupivacaine in epidural anesthesia in lower limb surgeries, and found that there was significant reduction in heart rate and mean arterial blood pressure in the first hour of surgery, which is in agreement with the results of the present study.
As regards respiration and oxygenation there were no harmful effects such as hypoventilation or hypoxemia recorded in any case of this study and there were no statistically significant differences among groups. This is in agreement with many studies that used epidural dexmedetomidine, tramadol, and neostigmine as adjuvants to local anesthetic drugs - for example, the research by Oriol-LÓpez et al.  , who studied epidural dexmedetomidine in regional anesthesia to reduce anxiety, the research by Paranjpe et al.  , who studied epidural tramadol with low-dose local anesthetics for anesthesia and postoperative analgesia in orthopedic patients, and that by Mamta et al.  , who studied two different doses of epidural neostigmine coadministered with lignocaine for postoperative analgesia and sedation.
As regards the time to first rescue postoperative analgesic topup, there was remarkable difference among the four groups. Patients in group C (the control group) experienced higher pain scores compared with the other groups and had faster onset of postoperative pain (2 ± 0.7 h) compared with groups D, T, and N, which were 5 ± 0.8, 3.5 ± 0.8, and 3 ± 0.7 h, respectively. Further, the frequency of topup doses of epidural analgesia consumption of local anesthetic in the following 24 h was higher in group C (84.3 ± 10.6 mg/24 h) compared with groups D, T, and N, which were 31.25 ± 6.4, 40.6 ± 5.5, and 53 ± 5.5 mg/24 h, respectively. Sukhminder et al.  in their study on epidural dexmedetomidine in lower limb orthopedic surgeries found that the first rescue topup analgesic dose was needed at 6.1 ± 0.4 h, which is similar to the result of our study. The difference may be due to the use of ropivacaine 0.75% instead of bupivacaine 0.5% in our study. Baraka et al.  in their study on epidural tramadol after cesarean section found that administration of 100 mg of epidural tramadol prolonged the mean time to first rescue analgesic dose to 4.5 ± 3.1 h, which is similar to the mean value in our study (3.5 ± 0.8 h). The difference can be due to the use of a larger dose of tramadol in their study compared with our study (75 mg) and due to the different time of injection, as they gave epidural tramadol at skin closure, whereas we gave epidural tramadol before the start of surgery. Kiran et al.  found that addition of 100 μg of neostigmine to a mixture of lidocaine/bupivacaine in lower abdominal surgeries prolonged the time to first rescue epidural analgesia to about 5 h; however, in our study the mean time to first rescue epidural analgesic was 3 h only. This may be due to the different doses used in the two studies.
In the current study we found that patients in groups D and T had lower pain scores compared with patients in groups C and N at all times in the following 24 h so that patients in groups D and T consumed a lower dose of bupivacaine in the postoperative period compared with patients in groups C and N. Sukhminder et al.  found a remarkable synergistic effect between dexmedetomidine and the local anesthesia (LA). Not only were they able to decrease the dose of local anesthetic in both groups but also the duration of postoperative analgesia was significantly prolonged in the dexmedetomidine group with lower consumption of analgesia in the postoperative period. Baraka et al.  found that patients who received epidural tramadol had lower pain scores with significantly lower consumption of additional analgesic medications. Selcen et al.  found that the neostigmine group had lower pain scores and consumed a lower dose of local anesthetic compared with the control group (bupivacaine alone), which is concordant with the current study.
The current study showed reduction in the mean time to postoperative ambulation in groups D, T, and N compared with group C and in group D compared with group N (P < 0.001). There was a significant difference between groups D and T, and between groups T and N (P < 0.05). However, there was no significant difference between groups D and T (P > 0.05). Carli et al.  concluded that the superior quality of pain relief provided by epidural analgesia had a positive impact on out-of-bed mobilization, bowel function, and intake of food, with long-lasting effects on exercise capacity and health-related quality of life.
Serum cortisol was studied for evaluation of stress response to surgery. There was no difference among groups as regards baseline values, but at 1 h after skin incision and 6 h postoperatively there was marked variability in reduction of stress response in groups D, T, and N compared with group C. Patients in group D had the lowest serum cortisol levels in postincision samples; the level of cortisol tended to decline in the postoperative period. Patients in groups T and N also had lower levels of serum cortisol compared with group C but the level in group T was lower than that in group N. Aggo et al.  found that bupivacaine-based epidural anesthesia significantly reduces the stress response to surgical stimuli when compared with isoflurane-based tracheal general anesthesia. Murakawa et al.  suggested that continuous epidural infusion of morphine was adequate for postoperative pain relief and had a suppressive effect on plasma cortisol levels compared with a systemic analgesic regimen. Eiji et al.  concluded that preincisional epidural neostigmine suppressed the stress responses during the early period of surgery and produced postoperative analgesic effects, which were assessed by the level of plasma cortisol and the VAS score, respectively. With respect to postoperative complications, 10% of cases in group T developed nausea and 10% of cases developed vomiting. Baraka et al.  reported nausea and vomiting in 20% of patients on tramadol, which is similar to our study. Demiraran et al.  in their study on epidural tramadol in children found that 25% had nausea and vomiting, whereas Yasemin et al.  in their study on epidural tramadol after lumbar microdiscectomy found a higher incidence of postoperative nausea and vomiting (PONV) (40%), which is higher than that in our study. In group N, 5% of cases had nausea and 5% of cases had vomiting. This was higher than the figures calculated by Kiran et al.  , who found that the incidence of nausea and vomiting in their study had remarkably reduced to 2%, and when we compared the current study with that by Chittora et al.  we found that the result in this study was nearly similar to theirs (5-10%). In contrast, no case in group D had PONV, which may be due to the possible antiemetic property of dexmedetomidine as proved by Tufanogullari et al.  . Twenty percent of cases in group D had dry mouth; this proportion is similar to Sukhminder et al.'s  study, who found that 16% of cases had dry mouth. Two cases in group D had hypotension with mean blood pressure less than 60 mmHg compared with groups T and N in which only one case had hypotension in each group. This hypotension was successfully managed with intravenous infusion of 500 ml crystalloids.
| Conclusion|| |
Dexmedetomidine is superior to tramadol and neostigmine in providing hemodynamic stability, excellent attenuation of stress response, prolonged postoperative analgesia, and early mobilization, with minimal undesirable side effects.
| Acknowledgements|| |
The authors are grateful to all doctors at the Anaesthesia Department of El Hussein University Hospital for their participation in this study.
Conflicts of interest
| References|| |
Doss NW, Ipe J, Crimi T, Rajpal S, Cohen S, Fogler RJ, et al
. Continuous thoracic epidural anesthesia with 0.2% ropivacaine versus general anesthesia for perioperative management of modified radical mastectomy. Anesth Analg 2001; 92:1552-1557.
Elhakim M, Abdelhamid D, Abdelfattach H, Magdy H, Elsayed A, Elshafei M. Effect of epidural dexmedetomidine on intraoperative awareness and post-operative pain after one-lung ventilation. Acta Anaesthesiol Scand 2010; 54:703-709.
Demiraran Y, Kocaman B, Akman RY. A comparison of the postoperative analgesic efficacy of single-dose epidural tramadol versus morphine in children. Br J Anaesth 2005; 95:510-513.
Lauretti GR, de Oliveira R, Reis MP, Juliâo MC, Pereira NL. Study of three different doses of epidural neostigmine coadministered with lidocaine for postoperative analgesia. Anesthesiology 1999; 90:1534-1538.
Jain D, Khan RM Kumar D, Kumar N. Perioperative effect of epidural dexmedetomidine with intrathecal bupivacaine on haemodynamic parameters and quality of analgesia. South Afr J Anesth Analg 2012; 18:105-109.
Kiran MD, Sanikop CS, Kotur PF. Randomized control trial of neostigmine and placebo as adjuvants to compound mixture of lignocaine and bupivacaine for epidural analgesia in lower abdominal surgeries. Indian J Anesth 2006; 50:448-451.
Paranjpe JS, Gaikwad SA, Patil MS, Bandgar SP, Deshpande TS. Epidural tramadol with low dose local anesthetics for anesthesia and postoperative analgesia in NYHA class III orthopaedic patients - a prospective randomized controlled study. J Pharm Biol Sci 2013; 5:18-22.
Oriol-López SA, Maldondo-Sanchez KA, Hennandez-Bernal CE. Epidural dexmedetomidine in regional anesthesia to reduce anxiety. Anesthesiology 2008; 31:271-277.
Mamta H, Chandra G, Bhatia VK, Singh D, and Bhaskar P. A comparative study of two different doses of epidural neostigmine coadministered with lignocaine for post operative analgesia and sedation. Research papers 2010; 26:461-464.
Bajwa SJ, Arora V, Kaur J, Singh A, Parmar SS. Comparative evaluation of dexmedetomidine and fentanyl for epidural analgesia in lower limb orthopedic surgeries. Saudi J Anaesth. 2011; 5:365-370.
Baraka A, Jabbour S, Ghabash M, Nader A, Khoury G, and Sibai A. A comparison of epidural tramadol and epidural morphine for postoperative.Can J Anaesth. 1993; 40:308-13.
Selcen T, Topcu I, Ekici NZ, Cagler H, Erincler T. Comparison of analgesic activity of the addition of neostigmine and fentanyl to bupivacaine in post operative analgesia. Saudi journal of anesthesia 2006; 27:1199-1203.
Carli F, Mayo N, Klubien K, Schricker T, Trudel J, Belliveau P. Epidural analgesia enhances functional exercise capacity and health-related quality of life after colonic surgery: results of a randomized trial. Anesthesiology 2002; 97:540-549.
Aggo AT, Fyneface-Ogan S, Mato CN. The differential impact of two anesthetic techniques on cortisol levels in Nigerian surgical patients. Niger J Clin Pract 2012; 15:68-74.
Murakawa T, Nagao H, Baba S, Kudo T, Matsuki A, Oyama T, et al.
Effect of continuous epidural infusion of morphine for postoperative analgesia on pituitary-adrenocortical function. Masui 1989; 38:625-631.
Eiji M, Saito H, Kurata Y, Takinami M, Tanifuji Y. Postoperative Analgesic Effect of Epidural Neostigmine, and the Responses of Plasma Cortisol and Interleukin-6 .Anesthesiology 2001; 95: Anesthesiology 2002; 96: A915.
Demiraran Y, Kocaman B, Akman RY. A comparison of the postoperative analgesic efficacy of single-dose epidural tramadol versus morphine in children. Br J Anaesth 2005; 95:510-513.
Yasemin ª, A APAN, Gokºen OZ, Cetin A. Epidural tramadol infiltration decreases postoperative analgesic consumption after lumbar microdiscectomy. Turk J Med Sci 2012; 42:395-401.
Chittora SP, Fareed A, Sharma R. A comparative analysis of neostigmine as an additive to lignocaine for postoperative analgesia in intrathecal and epidural anesthesia. Indian J Anest 2003; 47:185-189.
Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, et al
. Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesth Analg 2008; 106:1741-1748.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]