|Year : 2017 | Volume
| Issue : 4 | Page : 913-920
Comparison of the efficacy and safety of morphine and fentanyl as adjuvants to bupivacaine in providing operative anesthesia and postoperative analgesia in subumblical surgeries using combined spinal epidural technique
Owais Mushtaq Shah, Kharat Mohammad Bhat
Department of Anesthesiology, Sheri Kashmir Institute of Medical Sciences (Deemed University), Srinagar, Jammu and Kashmir, India
|Date of Web Publication||28-Nov-2017|
Owais Mushtaq Shah
Department of Anesthesiology, Sheri Kashmir Institute of Medical Sciences (Deemed University), Soura, Srinagar - 190 011, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: The combined spinal epidural (CSE) technique involves intentional subarachnoid blockade and epidural catheter placement during the same procedure to combine their individual best features, to reduce the total drug dosage and avoid their respective disadvantages. The addition of opioids to local anesthetics (bupivacaine) for CSE anesthesia (CSEA) is increasingly common to enhance the block. Neuraxial fentanyl is more potent and has shorter duration of action than morphine which provides prolonged anesthesia and analgesia, however at the cost of increased incidence of adverse effects like delayed respiratory depression. Aims and Objectives: The aim is to compare the efficacy and safety of morphine and fentanyl as adjuvants to bupivacaine in subumblical surgeries using CSE technique. The characteristics of sensory and motor block, intergroup variations in pain, cardiorespiratory parameters, and adverse effects were compared between the two groups. Materials and Methods: A total of 60 patients belonging to physical status American Society of Anesthesiologists Classes I and II, aged 18–60 years were randomized into two groups: Group A (n = 30) received intrathecal 0.5% heavy bupivacaine 12.5 mg and morphine 2.85 μg/kg; Epidural Anesthetic bolus (when required/T11Regression) 8 ml 0.25% isobaric bupivacaine and 0.04 mg/kg morphine; Epidural Analgesic bolus (postoperative visual analog scale [VAS] score >30) 5 ml 0.125% isobaric bupivacaine and 0.04 mg/kg morphine and Group B (n = 30) received intrathecal 0.5% heavy bupivacaine 12.5 mg and fentanyl 0.35 μg/kg; Epidural Anesthetic bolus (when required/T11Regression) 8 ml 0.25% isobaric bupivacaine and 0.7 μg/kg fentanyl; Epidural Analgesic bolus (postoperative VAS score >30) 5 ml 0.125% isobaric bupivacaine and 0.7 μg/kg fentanyl. Results and Conclusion: Group A had significantly prolonged two segment regression time, T11 regression time, lower mean VAS score, prolonged effective analgesia, and required lesser number of epidural boluses in 24 h as compared to Group B (P < 0.001). There were no significant differences between the groups considering onset of sensory block, duration of motor block, median maximum sensory block level achieved after spinal component (T6), median highest sensory block level achieved after epidural anesthetic bolus (T7-4seg enhancement after regression to T11), cardiorespiratory parameters and adverse effects. None of the patients had respiratory depression nor was there any failure of spinal/epidural component of CSEA. Thus, addition of morphine to bupivacaine in CSEA produced prolonged effective anesthesia and postoperative analgesia compared to addition of fentanyl to bupivacaine without producing undue adverse effects.
Keywords: Bupivacaine, combined spinal epidural anesthesia, fentanyl, morphine
|How to cite this article:|
Shah OM, Bhat KM. Comparison of the efficacy and safety of morphine and fentanyl as adjuvants to bupivacaine in providing operative anesthesia and postoperative analgesia in subumblical surgeries using combined spinal epidural technique. Anesth Essays Res 2017;11:913-20
|How to cite this URL:|
Shah OM, Bhat KM. Comparison of the efficacy and safety of morphine and fentanyl as adjuvants to bupivacaine in providing operative anesthesia and postoperative analgesia in subumblical surgeries using combined spinal epidural technique. Anesth Essays Res [serial online] 2017 [cited 2021 Nov 30];11:913-20. Available from: https://www.aeronline.org/text.asp?2017/11/4/913/209984
| Introduction|| |
Combined spinal epidural anesthesia (CSEA) offers advantages over the epidural or single injection spinal anesthesia alone. The singularity lies in its ability to combine the rapidity, density, and reliability of the subarachnoid block with the flexibility of epidural block to titrate a desired sensory level, vary the intensity of the block, control the duration of anesthesia, and deliver postoperative analgesia and has an added advantage of requiring lower dose of epidural top ups. The addition of opioids to local anesthetics (e.g., bupivacaine) for spinal anesthesia is increasingly common both to enhance anesthesia and to provide postoperative analgesia. Fentanyl is a phenyl piperidine derivative, synthetic opioid agonist which is 75–125 times more potent, 800 times more lipid soluble and it has faster onset of action (5 min intrathecal, 10 min epidural) and relatively short duration of action (2–4 h). Morphine is a hydrophilic phenanthrene derivative and its onset is slow compared to the lipophilic opioids (15 min intrathecal, 30 min epidural) and it has a significantly longer duration of action (approximately 12–24 h). However, it has the potential to cause adverse effects, especially delayed respiratory depression and hence requires careful selection of patients and vigilance protocol.
Aims and objectives
To compare the efficacy and safety of morphine and fentanyl as adjuvants to bupivacaine in providing operative anesthesia and postoperative analgesia in subumbilical surgeries using CSE technique.
To compare between the groups:
- The characteristics of sensory and motor block
- Intergroup variations in pain and the total number of epidural boluses required in 24 h period
- Alteration in vital signs (noninvasive blood pressure [BP], heart rate, respiratory rate, SpO2)
- Adverse effects.
| Materials and Methods|| |
This randomized double-blind prospective study to compare the efficacy and safety of morphine and fentanyl as adjuvants to bupivacaine in providing operative anesthesia and postoperative analgesia in subumblical surgeries using CSE technique was conducted in the Department of Anesthesiology and Critical care SKIMS from 2013 to 2015. This study was conducted after approval by the Institutional Ethics Committee and Helsinki Declaration of 1975 as revised in 2000 was adhered to. An informed written consent was obtained from all the patients for participation in this study. Latest CONSORT guidelines were adhered to.
Sixty patients admitted in our hospital undergoing subumblical surgeries (lower limb [orthopedic, plastic], perineal, gynecological, lower abdominal) under CSEA in the age group of eighteen to 60 years belonging to physical status American Society of Anaesthesiologists (ASA) Classes I and II of either sex were included in the study.
ASA physical status >II, emergency surgeries, all contraindications for regional Anesthesia like those with bleeding disorders, coagulopathy, allergic to amide anesthetics, increased intracranial tension, infection at local site, patient refusal for the procedure.
The various parameters studied were onset time of sensory (T10) and time taken to complete motor block, maximum sensory block level achieved and time taken to achieve it, two segment regression of sensory block, regression time to T11/time of administration of first epidural bolus for anesthesia (when required), duration of motor block, maximum sensory block level achieved after epidural anesthetic bolus, intergroup variations in pain, cardiorespiratory parameters, total number of epidural boluses required in 24 h period, sedation score and adverse effects.
A thorough preanesthetic assessment was performed before the day of surgery as per pro forma. Standard NPO guidelines and monitoring protocol were followed such as electrocardiogram, Noninvasive BP, and pulse oximetry. Intravenous (i.v.) access was established and Ringer's lactate solution (10 ml/kg) was used for preloading before the block. Patients were randomized into one of the two groups using systematic random sampling which was computer generated:
- Group A (n = 30) intrathecal 0.5% heavy bupivacaine 12.5 mg (2.5 ml) and morphine sulfate 2.85 μg/kg (200 μg equated in 0.5 ml in average adult)
- Group B (n = 30) intrathecal 0.5% heavy bupivacaine 12.5 mg (2.5 ml) and fentanyl 0.35 μg/kg (25 μg equated in 0.5 ml in average adult).
In all patients, using an aseptic technique in the sitting position, 2 ml of 1% lidocaine was infiltrated into the subcutaneous area of the lumbar 3–4 interspace. The epidural space was identified by the loss of resistance technique with 0.9% saline solution using an 18-G Tuohy needle. Spinal tap was performed using a 27-G 120 mm Quincke spinal needle which was introduced inside the Tuohy needle (needle through needle technique). After intrathecal injection of the study drugs, a 20-G soft tip epidural catheter with 3 lateral eyes was introduced 3–5 cm into the epidural space in all patients. The test solution was prepared by an anesthesiologist not involved in the study. The patients were randomly allocated (n = 30 per group) to receive the test solution. After the intrathecal injection, the patients were returned to the position for surgery. Oxygen 6 L/min was administered through face mask. Heart rate, respiratory rate, SpO2, and noninvasive arterial BP were recorded every 2nd min for first 10 min, then at 5-min interval for 30 min, at 15-min interval up to 60 min, then every half hourly for 4 h and every 4 hourly for rest of 24 h after giving spinal block except after administering epidural anesthetic bolus in which vitals were recorded after every 5 min for first 30 min. Sensory Block level as assessed using pinprick and the degree of motor block assessed according to the modified Bromage score* was recorded every minute for the first 10 min. The onset of sensory block was defined as the time between injection of intrathecal anesthetic and absence of pain at the T10 dermatome as assessed by sterile pinprick. Time to complete motor block was defined as modified Bromage score of 3. Complete motor block recovery was defined when modified Bromage score was 0.
In case of insufficient cephalad spread to T10 level or regression of block to T11 level, incremental epidural boluses were injected comprising 8 ml of 0.25% isobaric bupivacaine and 0.04 mg/kg of morphine (3 mg equated in 2 ml in average adult) in Group A or 8 ml of 0.25% isobaric bupivacaine and 0.7 μg/kg of fentanyl (50 μg equated in 2 ml in average adult) in Group B.
Patients were monitored for pain using visual analog scale (VAS) scores every 5 min for first 30 min, at 15 min interval up to 60 min, then every half hourly for 4 h and every four hourly for rest of 24 h after giving spinal block. The patients who had a postoperative VAS score above 30 were administered an epidural bolus dose including 5 ml of 0.125% isobaric bupivacaine and 0.04 mg/kg of morphine (3 mg equated in 2 ml in average adult) in Group A or 5 ml of 0.125% isobaric bupivacaine and 0.7 μg/kg of fentanyl (50 μg equated in 2 ml in average adult) in Group B. Total number of epidural boluses required in 24 h period was recorded. The epidural catheter was removed at the end of the 24th h. *Modified Bromage Scale: 0 = No motor block, 1 = inability to increase extended legs 2 = inability to flex knees, 3 = inability to flex ankle# VAS: 0–100 (0 = No Pain, 100 = Agonizing) 0 = No pain, 10–30 = Mild pain, 40–60 = Moderate pain, 70–100 = Severe pain. Hypotension defined as systolic arterial pressure <90 mmHg or when mean arterial BP decreased more than 25% from the baseline value was treated by increasing the i.v. infusion rate and if necessary, administering incremental doses of 6 mg of ephedrine i.v. atropine 0.02 mg/kg i.v was administered for heart rate below 50 beats/min. Sedation was assessed using Subjective Sedation Scale as: Grade 0: Awake conscious no sedation to slightly restless, Grade 1: Calm and compose, Grade 2: Awake on verbal command, Grade 3: Awake on gentle tactile stimulation, Grade 4: Awake on vigorous shaking, Grade 5: Unarousable. Any untoward incident or adverse effects such as nausea, vomiting, hypotension, bradycardia, respiratory depression, pruritus, dry mouth, dizziness, shivering, headache, failure of spinal component, and failure of epidural component were recorded.
IBM SPSS (Statistical Package for the Social Sciences) Statistics 20.0 and Microsoft Excel were used to carry out the statistical analysis of data. Data were analyzed using descriptive statistics, namely, means, standard deviations, and percentage. G*Power: Statistical Power Analyses for Windows and Mac was used to keep the power of study 80% and thus, sample size was considered 60 patients (30 in each group). The Student's independent t-test and repeated measurement analysis were employed. Chi-square test and Fisher's exact test, whichever appropriate, was used. Data were presented using bar, line and pie diagrams. The value of P < 0.05 was considered statistically significant.
| Observations and Results|| |
As illustrated in [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6] and [Figure 1], [Figure 2], [Figure 3], [Figure 4].
|Table 4: Enhancement of block after epidural bolus in combined spinal.epidural anesthesia in various studies|
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|Table 5: Intergroup comparison of intensity of pain as measured using visual analog scale at different time intervals|
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|Figure 1: Comparison of intra and postoperative mean arterial pressure between the two groups|
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|Figure 2: Comparison of intra and postoperative heart rate between the two groups|
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|Figure 3: Comparison of intra and post operative oxygen saturation between the two groups|
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|Figure 4: Comparison of intra and postoperative respiratory rate between the two groups|
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| Discussion|| |
Mean time taken to T10 sensory blockade and complete motor block was similar among the groups (P = 0.263 and 0.158, respectively, being statistically nonsignificant). In both the groups, median maximum sensory block level achieved after spinal component of CSEA was T6 and there was no significant difference in time taken to reach maximum dermatomal level (P = 0.067). Furthermore, there was no significant difference in the duration of motor block among the groups (P = 0.154). The study results are similar to Karaman et al. 2011, who used 0.5% hyperbaric bupivacaine 2 ml intrathecally with 200 μg of morphine/25 μg of fentanyl to examine the effects of fentanyl and morphine, alone and in combination, as adjuncts to spinal anesthesia for elective cesarean section. In their study, they observed that the time taken to achieve T10 sensory block was 4.1 ± 1.7 min in morphine group and 3.8 ± 1.4 min in fentanyl group which was statistically insignificant (P > 0.05) and that time taken to reach maximum sensory block level was 7.6 ± 2.3 min in morphine group versus 7.5 ± 2.1 min in the fentanyl group which was again statistically insignificant (P > 0.05). Furthermore, they observed that there was no significant difference among the groups in the duration of motor block (278 ± 16.5 min in morphine group versus 225 ± 32.9 min in the fentanyl group, P > 0.05). Naveen Kumar et al. 2014 noted in their study that the time taken to complete motor blockade was 6.25 ± 0.42 min in morphine group (2.75 ml of 0.5% bupivacaine + 0.25 mg of morphine equated in 1 ml given intrathecally). In the study done by Jagtap et al. 2014 time taken to complete motor block was 6 ± 3.6 min in fentanyl group (15 mg 0.5% bupivacaine with 25 mcg fentanyl given intrathecally). In the study done by Holmström et al. 1999, median highest sensory block level achieved after spinal component of CSEA was T6 (3.5–4 ml of 0.5% hyperbaric bupivacaine +0.2 mg of morphine given intrathecally and 20–90 mg of bupivacaine epidurally whenever required till satisfactory block level is achieved). In the study done by Reddy et al. 2013, it was observed that the median highest sensory block level achieved after spinal component of CSEA was T6 in bupivacaine-fentanyl group (3 ml of 0.5% hyperbaric bupivacaine given intrathecally and 0.125% bupivacaine with fentanyl 2 μg/ml epidurally whenever required).
Regression by two segment dermatomal level was significantly slower in Group A than Group B (P < 0.001). Regression time to T11 was significantly prolonged in Group A as compared to Group B (P < 0.001). The result was comparable to the study done by Karaman et al. 2011 in which they found that the mean regression time to T10 was 164 min in Group A and 148.9 min in Group B. In the study by Naveen Kumar et al. 2014, mean two segment regression time was 113.20 ± 5.83 min in the morphine group. Median highest sensory block level achieved after epidural anesthetic bolus in CSEA was T7 in Group A (T6–T8) and T7 (T6–T8) in Group B of patients which was given on block regression to T11; 3–5, average-4 segment enhancement-differences being comparable between the two study groups and statistically nonsignificant (P = 0.817). CSEA often produces a more extensive block than expected, and the epidural dose needed to extend the block is often lower compared to doses needed with epidural anesthesia alone., This observation has two possible explanations., First, the alleviation of subatmospheric pressure by the Tuohy needle before injection of the local anesthetic can reduce the volume of the subarachnoid space in the dural sac and extend the level of spinal anesthesia. Second, diffusion of local anesthetic molecules from the epidural to the subarachnoid space through the dural hole is possible, due to dural sac compression after injection of local anesthetic in the epidural space. Comparison of enhancement of block after epidural bolus in CSEA in various studies is shown in [Table 4]. In this study, epidural anesthetic bolus of 8 ml of 0.25% bupivacaine +3 mg of morphine equated in 2 ml making total volume of 10 ml was given in Group A and 8 ml of 0.25% bupivacaine +50 μg of fentanyl equated in 2 ml making total volume of 10 ml was given in Group B on regression of sensory block to T11 in 50 patients (25 patients in each group due to prolonged duration of surgery in them). Maximum level of sensory blockade increased in all patients in each group by 3–5 segments-average 4 segments, P = 0.817 (statistically nonsignificant).
Intergroup variations in pain and the total number of epidural boluses used in 24 h period: Although wide variations were seen in pain score, however, Group A had lower VAS scores than Group B [Table 5] at almost all time intervals, the differences being statistically significant (P < 0.05). However at 180 min and 960 min, differences between the groups were comparable and statistically nonsignificant (P > 0.05). Furthermore, at 150 min VAS score was higher in Group A than Group B (P < 0.001-statistically significant). This may be partly explained by the fact that mean regression time to T11 in Group B was 140.53 ± 4.470 min. Thus, epidural anesthetic bolus was administered in 25 patients in Group B at that time which would explain lower VAS score in them at 150 min as compared to Group A although still not being clinically significant enough to intervene if on the basis of analgesia only (VAS <40 in both groups). In addition, mean regression time to T11 in Group A was 165.03 ± 8.257 min. Thus, epidural anesthetic bolus was administered in 25 patients in Group A at that time which would explain nonsignificant differences in VAS scores at 180 min between the two study groups. Mean duration of effective analgesia was significantly longer in Group A than Group B (960 min in Group A vs. 480 min in Group B). Total number of epidural boluses used in 24 h were significantly lower in Group A than Group B (P < 0.001). In meta-analysis done by Pöpping et al. 2012 about opioids added to LA for single-shot intrathecal anesthesia in patients undergoing minor surgery, morphine (0.05–2 mg), and fentanyl (10–50 μg) added to bupivacaine were most frequently tested. Duration of postoperative analgesia was prolonged with morphine (weighted mean difference 503 min; 95% confidence interval [CI] 315–641) and fentanyl (weighted mean difference 114 min; 95% CI 60–168). Morphine decreased the number of patients requiring opioid analgesia after surgery and decreased pain intensity to the 12th postoperative h. Akanmu et al. 2013 observed in their study about analgesic effects of intrathecally administered fentanyl in spinal anesthesia for lower limb orthopedic surgeries that the duration of effective analgesia (time from injection of intrathecal drug to time of request for analgesic, i.e., VAS score >40) in bupivacaine-fentanyl group was 276.23 ± 26.21 min. Mean VAS score in bupivacaine-fentanyl group was 33.00 ± 4.35 (25 μg of fentanyl added to 10 mg of 0.5% hyperbaric bupivacaine intrathecally). In the study done by Karaman et al. 2011, it was observed that time to first analgesic requirement in morphine group was 20.5 ± 6.7 h, where as in fentanyl group, it was 4.2 ± 3.9 h, the differences between the groups were statistically significant, P < 0.05. Siti Salmah and Choy 2009 conducted a study to determine the effect of intrathecal morphine 0.1 mg as compared with intrathecal fentanyl 25 μg in terms of analgesia and duration for postoperative pain relief after Cesarean section and observed that the VAS for pain and the cumulative patient-controlled analgesia (PCA) morphine requirement were both significantly lower in Group 1 (P < 0.05) during the 24 h study. Sedation score and adverse effects: There were no significant variations in sedation score, systolic BP, diastolic BP, heart rate, respiratory rate, and SpO2 between the two groups and were comparable and stable. There was no significant difference in the incidence of adverse effects in the two groups (P > 0.05). None of the patients in either group had respiratory depression in 24 h nor was there any failure of spinal or epidural component of CSEA. The differences between the two groups were comparable and statistically nonsignificant (P > 0.05). On each occasion, the BP returned to normal after one or two increments of IV ephedrine 6 mg and an infusion of 500 mL of NaCl 0.9%. Five patients needed treatment for bradycardia (1 in Group A and 4 in Group B) with atropine Dahl et al. revealed in their retrospective study which included 485 patients, that the incidence of pruritus is very high but similar in all opioid groups. The most feared complication of opioid administration is respiratory depression. Ko et al. reviewed the use of the term “respiratory depression” and found that there is no clear definition, leading to difficulty and confusion when comparing available studies. The incidence is infrequent for doses commonly used clinically, but it is dose dependent for both hydrophilic and lipophilic opioids. Detection of respiratory depression after neuraxial opioids may be difficult. Respiratory rate may or may not decrease, and significant hypercapnia can occur despite a normal respiratory rate. Pulse oximetry may be valuable, but the most reliable clinical sign appears to be a depressed level of consciousness. The optimal neuraxial opioid dose is a balance between the conflicting demands of providing optimal analgesia while minimizing dose-related adverse effects. Dose-response studies show that neuraxial morphine appears to have an analgesic ceiling. The optimal “single shot” intrathecal dose of morphine appears to be 100–200 μg and the clinical recommendation is not to exceed 300 μg to prevent the late respiratory depression and the ideal “single shot” epidural morphine dose is 2.5–3.75 mg. Intrathecal fentanyl in doses of 10–30 μg is commonly used in spinal anesthesia. Bolus doses of 50–100 μg of fentanyl may be used epidurally. There are conflicting data about the incidence of late respiratory depression after intrathecal opioid administration. In a prospective study on 856 patients, there were eight cases of respiratory depression after 0.2 mg intrathecal morphine. Swart et al. reported one case of respiratory depression at postoperative 14 h after the administration of 0.1 mg intrathecal morphine in addition to bupivacaine in thirty patients undergoing cesarean section with spinal anesthesia. This respiratory depression was attributed more to postoperative parenteral opioid consumption (24 mg morphine) by PCA than spinal opioid. In different studies with hyperbaric bupivacaine plus different doses of fentanyl no respiratory depression was determined. Abouleish et al. 1988 conducted a study to demonstrate the effects of adding 0.2 mg preservative-free morphine sulfate in 0.2 ml solution to hyperbaric spinal bupivacaine in patients undergoing cesarean section and observed that the incidence of nausea in study group was 47%, vomiting 6%, and pruritis 65% and there was no evidence of respiratory depression after giving morphine intrathecally. Reddy et al. 2013 found that 8% of patients in fentanyl-bupivacaine group had nausea/vomiting and the bupivacaine-fentanyl group was associated with nonsignificant hemodynamic changes and none of the patients experienced respiratory depression. In the study done by Karaman et al. 2011, it was observed that there were no significant differences among the groups in the incidences of intraoperative and postoperative nausea, vomiting, cardiorespiratory parameters, and pruritus. In morphine group 40% of patients had pruritis, 45% had nausea, 60% were awake and 40% drowsy, whereas in fentanyl group 55% of patients had pruritis, 25% had nausea, 45% of patients were awake, 45% drowsy, and 10% were asleep but arousable (differences between the groups being comparable and statistically in significant, P > 0.05).
Limitations of the study
Latency of onset of action and potency of morphine and fentanyl could not be studied exclusively because it was masked by the action of local anesthetic and urinary retention could not be assessed because in our institution all patients were catheterized for 24 h postoperatively. Since pain is a subjective phenomenon with wide variability of responses among the individuals, it is difficult to standardize the variable.
| Conclusion|| |
- Addition of both morphine ad fentanyl to bupivacaine in CSEA required lesser total volume of epidural anesthetic top up for block enhancement upon regression thereby confirming the novelty of technique
- Addition of morphine to bupivacaine produced prolonged effective anesthesia and postoperative analgesia compared to addition of fentanyl to bupivacaine without producing undue adverse effects in CSEA.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]