|Year : 2014 | Volume
| Issue : 2 | Page : 163-169
Comparison of dexmedetomidine versus propofol for maintenance of anesthesia during invasive procedures in pediatric oncology patients: a controlled randomized double-blind study
Ahmad Ramzy Shaaban, Sahar Kamal, Mahmoud M. Okasha
Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||02-May-2013|
|Date of Acceptance||02-Nov-2013|
|Date of Web Publication||31-May-2014|
Ahmad Ramzy Shaaban
Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
We designed our study to compare the effects of dexmedetomidine infusion versus propofol infusion on perioperative hemodynamics, sedation, pain, and recovery scores for invasive procedures in pediatric oncology patients.
Patients and methods
Forty children, 6-12 years of age, ASA I or II with hematological cancer, were randomized to receive either dexmedetomidine or propofol infusion during anesthesia for diagnostic or prognostic short-duration procedures. All patients received ketamine 0.5 mg/kg intravenously before the start of the procedure. Increments of ketamine (0.33 mg/kg, intravenously) was given to maintain the sedation score 5-6 using the Ramsay score. Routine vital signs, oxygen saturation, time for induction of sedation, total incremental doses of ketamine, time for spontaneous eye opening after stopping the infusion, recovery excitation score, and pain score were recorded.
Induction and recovery times were significantly shorter in the propofol/ketamine group. Although there was significant difference in heart rates between the two groups with lower rates for the dexmedetomidine/ketamine group, patients in the dexmedetomidine/ketamine group had significant lesser excitation score and lower pain score than patients in the propofol/ketamine group.
Dexmedetomidine/ketamine infusion provides hemodynamic stability, lower recovery excitation, and pain scores, although recovery time is prolonged when compared with propofol/ketamine infusion in invasive procedures in pediatric oncology patients. Thus, it represents an alternative sedoanalgesic choice for this population.
Keywords: Dexmedetomidine, invasive procedure, oncology, pediatric, propofol
|How to cite this article:|
Shaaban AR, Kamal S, Okasha MM. Comparison of dexmedetomidine versus propofol for maintenance of anesthesia during invasive procedures in pediatric oncology patients: a controlled randomized double-blind study. Ain-Shams J Anaesthesiol 2014;7:163-9
|How to cite this URL:|
Shaaban AR, Kamal S, Okasha MM. Comparison of dexmedetomidine versus propofol for maintenance of anesthesia during invasive procedures in pediatric oncology patients: a controlled randomized double-blind study. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 Oct 27];7:163-9. Available from: http://www.asja.eg.net/text.asp?2014/7/2/163/133387
| Introduction|| |
Many children receiving treatment for hematological cancer undergo painful diagnostic and therapeutic procedures such as bone marrow aspiration and lumbar puncture with or without intrathecal chemotherapy, which are considered one of the most stressful parts of treatment for the patients and their families .
Poorly controlled procedural pain in children with cancer is associated with the development of a number of anxiety-related symptoms, depression, and diminished analgesic effects for subsequent procedures ,. The WHO and the American Academy of Pediatrics recommend general anesthesia or the use of combination analgesia and sedative drugs during painful procedures in pediatric oncology patients .
Studies examining different methods of sedation for children undergoing painful procedures have shown different results. Propofol has emerged as an effective sedative/anesthetic for invasive procedures in children with cancer ,. Although 57% of pediatric cancer patients receiving repeated procedural sedations with propofol alone report distress behavior before the procedure, 22% state fear of pain and 17% convey fear of the sedation itself .
Dexmedetomidine is a highly selective α2-adrenergic agonist with both sedative and analgesic properties, which is approved by the Food and Drug Administration for short-term (<24h) sedation in adult patients in the ICU. It is not approved for use in children yet; however, there are a growing number of published reports describing the administration of dexmedetomidine during anesthesia in adults and children .
We hypothesized that dexmedetomidine could be effectively used as a sedative/analgesic agent for children requiring the above procedures. This study was designed to compare the hemodynamic stability and the recovery profile of dexmedetomidine with propofol for these brief invasive procedures.
| Patients and methods|| |
After receiving institutional review board approval, 40 patients scheduled for bone marrow biopsy and diagnostic or therapeutic lumbar puncture were included in this study. After a detailed explanation of the procedure, informed consent was obtained from all legal guardians. Children between 6-12 years diagnosed as either acute lymphocytic leukemia or acute myeloid leukemia with American Society of Anesthesiologist (ASA) physical status I-II were eligible for inclusion in the study.
The exclusion criteria included ASA physical status III-IV, age less than 6 years or more than 12 years, congenital heart disease, cardiomyopathy, any rhythm other than sinus rhythm, liver or renal disease, upper respiratory infection, behavioral problems, and patients on anticoagulant, β-blocker, clonidine, or digoxin therapy.
Randomization was determined in advance of the study using a randomization table created by computer software to assign the numbers between 1 and 40 to the two groups. Allocation was concealed using opaque sealed envelopes that were opened just before induction of general anesthesia.
For group A (n = 20), patients were assigned to receive propofol infusion and ketamine, which is the standard regimen for the hospital, and for group B (n = 20), patients were assigned to receive dexmedetomidine infusion and ketamine.
Patients in both groups were premedicated by metoclopramide (0.1 mg/kg, intravenous).
Standard monitoring (electrocardiogram, pulse oximetry, and noninvasive blood pressure) was applied to all patients (Datex Ohmeda S/5 Avance).
In group A, propofol infusion was started at a rate of 2 mg/kg over 10 min then the infusion rate of 50 μg/kg/min was adjusted until patient fall asleep and reach a sedation score 5-6 according to the Ramsay sedation score  [Table 1].
In group B, dexmedetomidine (Precedex; Abbott) infusion was started at a rate of 0.5 μg/kg, intravenous, for 10 min, and this was based on doses used during ICU sedation . Then, a continuous infusion of 0.5 μg/kg/h was adjusted until patient fall asleep and the sedation score became 5-6 and be able to be positioned.
Immediately before the procedure, 0.5 mg/kg ketamine was administered intravenously to reduce the procedural pain in both groups.
In both groups, incremental doses of ketamine 0.3 mg/kg were administered intravenously to maintain sedation score 5-6. Oxygen administration was applied through oxygen mask at 6 l/min, both in the beginning and after completion of the procedure. The Ramsay sedation score was recorded in 5-min intervals consecutively.
By the end of the procedure, the infusion drugs were stopped and patients were transferred to the postanesthesia care unit (PACU) for recovery.
A single observer, who was blinded to the treatment assignment, was present throughout the procedure and recovery periods. Blinding was assured by concealing the infusion pump and tubing using green towels and by standardizing the two infusion protocols such that each required only one adjustment, at 10 min after they were started. At the completion of the anesthetic, the intravenous tubing was flushed with saline to eliminate any residual propofol to maintain observer blinding.
Systolic and diastolic blood pressure, heart rate, and peripheral oxygen saturation (SpO 2 ) were recorded perioperatively at 5-min intervals in both groups. Time for induction of sedation (measured from the start of drug infusion until patient fall asleep), time for spontaneous eye opening (from cessation of drug infusion until spontaneous eye opening), and the total incremental doses of ketamine were recorded.
Recovery excitement score developed by Keegan et al.  was used by the observer to assess the degree of agitation upon emerge from sedation [1 (none)-awake and calm, cooperative; 2 (mild)-crying occasionally; 3 (moderate)-irritable/restless, screaming, inconsolable; and 4 (marked)-combative, disoriented, thrashing]. Parents were invited to accompany their children in the PACU after an initial admission and stabilization phase.
Pain assessment was performed in the PACU by Wong-Baker FACES Pain Rating Scale  [Figure 1] at 5-min interval; face 6 and above were an indication for the use of rescue analgesics in the form of 0.5 μg/kg fentanyl intravenously.
Patients were considered ready for discharge from PACU when they attained the Aldrete score of 9-10  [Table 2] and were free of pain, nausea, or vomiting.
The complications observed both during and after the procedure were recorded. Bradycardia and hypotension were defined as more than or equal to 20% decline from the baseline parameters, and the treatment plan was to decrease the infusion rate of the sedative drugs and to administer 10 ml/kg dextrose 5% in 0.45% normal saline as a bolus for hypotensive episodes. Glycopyrolate at a dose of 5 μg/kg was given intravenously for bradycardia. Desaturation (or respiratory depression) was defined as less than or equal to 94% and was planned to be treated by increasing FIO 2 . Other complications include partial airway obstruction, which requires intervention such as jaw thrust or chin lift, or complete airway obstruction with absence of air flow, which requires insertion of proper-sized airway, jaw thrust or chin lift, and assisted bag ventilation.
After post-hoc power analysis of the postoperative recovery score, with power 0.95, effect size 2.3, and α = 0.05, 19 participants per group were required. This was rounded upward to 20.
Data were statistically described in terms of mean ± SD or frequencies (number of cases) and percentages when appropriate. Data were tested for normality using the Kolmogorov-Smirnov test. The independent Student's t-test was used to compare parametric variables, the Mann-Whitney U-test for nonparametric variables (recovery scores), and Kaplan-Meier survival analysis for the frequency of ketamine given intraoperatively. P values less than 0.05 was considered statistically significant. All statistical calculations were performed using computer programs statistical package for the social science (SPSS, version 15; SPSS Inc., Chicago, Illinois, USA) for Microsoft Windows.
| Results|| |
Between March 2012 and August 2012, 40 children from 6 to 12 years of age were enrolled in the study; 25 were girls and 15 were boys.
There were statistically significant differences between patients who received propofol/ketamine infusion and those who received dexmedetomidine/ketamine infusion regarding induction time, recovery time, dose, and frequency of administration of ketamine.
The propofol/ketamine group had shorter induction and recovery times (12.2 ± 1.39 vs. 14.05 ± 1.63 min and 15.10 ± 2.40 vs. 17.45 ± 2.08 min, respectively). In addition, incremental doses of ketamine and the frequency of administration to keep sedation score around 5-6 were significantly lower in the propofol/ketamine group (12.65 ± 5.97 vs. 24.65 ± 9.85 mg and 1.60 ± 0.68 vs. 2.45 ± 0.60, respectively) [Table 3].
The mean heart rate in both groups reached its highest level preoperatively (112.75 ± 4.94 and 105.60 ± 9.75), decreased intraoperatively (99.10 ± 8.52 and 88.85 ± 11.96), and increased again in the PACU (100.69 ± 8.14 and 94.15 ± 8.65) in the propofol/ketamine and dexmedetomidine/ketamine groups, respectively [Table 4]. These changes in the heart rate over time were not statistically significant in the two groups (F = 0.87, P = 0.472) [Figure 2].
The mean systolic blood pressure in both groups reached its highest level preoperatively (90.20 ± 9.42 and 96.40 ± 8.58 mmHg), decreased intraoperatively (83.45 ± 3.39 and 83.35 ± 4.35 mmHg), and increased again in the PACU (87.45 ± 3.88 and 87.50 ± 5.32 mmHg) in the propofol/ketamine and dexmedetomidine/ketamine groups, respectively [Table 4].
These changes in the systolic blood pressure over time were statistically significant in the two groups (P = 0.002). However, there was no significant difference in mean systolic blood pressure between the two groups (87.033 and 89.083 mmHg; P = 0.161) [Figure 3].
The mean diastolic blood pressure reached its highest level preoperatively (56.30 ± 8.13 and 58.30 ± 8.34 mmHg), decreased intraoperatively (45.20 ± 6.04 and 52.10 ± 8.00 mmHg), and increased again in the PACU (51.80 ± 7.99 and 54.30 ± 8.67 mmHg) in the propofol/ketamine and dexmedetomidine/ketamine groups, respectively [Table 4].
The changes in the diastolic blood pressure over time were statistically significant in the two groups (P = 0.002) [Table 4]. However, there was no significant difference in mean diastolic blood pressure between the two groups (51.10 and 54.90 mmHg; P = 0.112) [Figure 4].
The mean O 2 saturation readings were stable for the two groups preoperatively (98.05 ± 0.94 and 98.55 ± 0.68%), intraoperatively (98.60 ± 1.39 and 98.85 ± 0.98%), and in the PACU (99.15 ± 0.81 and 98.85 ± 0.81%) in the propofol/ketamine and dexmedetomidine/ketamine groups, respectively [Table 4].
No significant change was observed in the mean O 2 saturation over time in the two groups (P = 0.083). In addition, there was no significant difference in the mean O 2 saturation between the two groups (98.600 and 98.75%; P = 0.393) [Figure 5].
Three patients became desaturated (SpO 2 <94%) in the propofol/ketamine group and one patient in the dexmedetomidine/ketamine group as a result of airway obstruction, which required jaw thrust and insertion of oral airway and reduction in the rate of drug infusion.
The recovery excitation score in patients of the dexmedetomidine/ketamine group was none to mild (1.40 ± 0.59); this was significantly lower than in patients of the propofol/ketamine group with mild to moderate score (2.10 ± 0.44; P = 0.000) [Table 5]. One patient in the dexmedetomidine/ketamine group had moderate score in comparison with three patients in the propofol/ketamine group.
|Table 5:Recovery excitement score, pain score, total amount of rescue analgesics, and time of stay in postanesthesia care unit|
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In general, no child needed restraints and their mild agitation required no treatment.
Patients in the dexmedetomidine/ketamine group had significant lower pain scores (0.50 ± 0.88) than patients in the propofol/ketamine group (1.30 ± 1.34) (P = 0.03); this was reflected on the dose of rescue fentanyl given with significant smaller dose in the dexmedetomidine/ketamine group (6.85 ± 3.8 μg) than in the propofol/ketamine group (17 ± 7.32 μg) (P = 0.00) [Table 5].
The length of stay in the PACU was highly significantly shorter in patients receiving propofol/ketamine infusion than those receiving dexmedetomidine/ketamine infusion; patients were ready for discharge within 59.35 ± 8.21 min in the propofol/ketamine group compared with 76.75 ± 11.06 min in the dexmedetomidine/ketamine group (P = 0.00) [Table 5].
| Discussion|| |
The purpose of our study was to compare the clinical effects and the recovery profile of dexmedetomidine/ketamine combination with propofol/ketamine for invasive procedural sedation in pediatric oncology patients.
In the current study, the time for induction of sedation and time of recovery after dexmedetomidine/ketamine were statistically significantly longer than after propofol/ketamine by 2 min. Induction dose was given slowly by infusion to minimize the changes in cardiovascular parameters, although more rapid induction bolus was possible.
The recovery-related agitation was significantly higher after propofol/ketamine, whereas smooth recovery pattern was observed after dexmedetomidine/ketamine. This is consistent with the sedation patterns reported with dexmedetomidine during mechanical ventilation where patients tend to be calm and comfortable when left alone, but are easily arousable when stimulated . That is why we have added ketamine as an adjuvant sedative analgesic and also to lower the rate of infusion.
In addition, the limited analgesic effects of dexmedetomidine and the nil one for propofol, both may not be the ideal sole agent for painful procedures, and a combination with ketamine may be effective in such scenarios.
The results of the current study revealed that patients sedated with dexmedetomidine/ketamine required significantly more ketamine as incremental doses than patients sedated with propofol/ketamine; these results coincides with results of Tosun et al.'s  study that compared dexmedetomidine/ketamine with propofol/ketamine in children with cyanotic congenital heart disease undergoing cardiac catheterization. Patients sedated with dexmedetomidine/ketamine required more supplemental doses of ketamine and had longer recovery time than patients sedated with propofol/ketamine combination. Adult studies  have shown that intraoperative use of dexmedetomidine decreases postoperative opioid consumption. However, this reduction in opioid requirements has been recently shown in only one pediatric study in which intravenous dexmedetomidine was used . Our results suggest that combination of dexmedetomidine with ketamine can potentiate their analgesic effects that lead to significant lower pain score postoperatively, and a decrease in the need for rescue fentanyl given more than propofol/ketamine combination group.
Despite the limited data, combination of dexmedetomidine/ketamine makes a pharmacologic sense as the two medications have the potential to balance the hemodynamic and adverse effects of the others. dexmedetomidine may prevent tachycardia, hypertension, salivation, and emergence phenomena from ketamine, whereas ketamine may prevent bradycardia and hypotension that have been reported with dexmedetomidine ,.
In the current study, we observed no significant change in O 2 saturation over time for the two groups, with four episodes of mild hypoxia (SpO 2≤94%) occurring in both groups: three cases occurred in the propofol/ketamine group, whereas one case in the dexmedetomidine/ketamine group. Those results suggest that neither dexmedetomidine nor propofol depress respiration excessively in children, when used in the dose range and manner used in this study. Respiratory inductance plethysmography used in another study , demonstrated that those problems were obstructive and not central and the decrease resulted predominantly from a decreased tidal volume with less effect on respiratory rate. A study conducted by Jayabose et al.  concluded that hypoxia was rare and never enough to warrant intubation in propofol-based anesthesia.
No side effects or complications were attributed to either the dexmedetomidine/ketamine group or the propofol/ketamine group. Nausea and vomiting did not occur after either treatment, based on the antiemetic effect of propofol . However, we could not establish that dexmedetomidine had antiemetic effect with a small number of children in each group.
The study conducted by Christopher et al.  suggested that the time to full recovery was significantly longer after dexmedetomidine administration than after propofol by 15 min. Thus, the time to PACU discharge after dexmedetomidine exceeded that after propofol; this is in favor of our results. However, their results regarding heart rate at all times in the dexmedetomidine group were significantly lower than baseline, whereas heart rate in the propofol group did not differ significantly from baseline at any time. In contrast, our results revealed more heart rate stability.
The disadvantage of dexmedetomidine/ketamine combination was the sign of prolonged time to discharge from PACU (15 min) in comparison with propofol/ketamine combination, explained by the short elimination half life of propofol compared with that of dexmedetomidine of 2 h.
The study conducted by Christopher et al.  suggested that the time to full recovery of full responsiveness was significantly greater after dexmedetomidine administration than it was after propofol by 15 min. Thus, the time to PACU discharge after dexmedetomidine exceeded that after propofol also, which coincides with our results. However, their results regarding heart rate at all times in the dexmedetomidine group was significantly less than baseline, whereas heart rate in the propofol group did not differ significantly from baseline at any time. This is in contrast to our results that revealed no statistically significant difference in heart rate between the two groups, which can be explained by addition of ketamine to dexmedetomidine in our study group.
We observed that there was significant decrease in systolic and diastolic blood pressure in the propofol/ketamine group than in the dexmedetomidine/ketamine group, which is similar to the results of the study conducted by Christopher et al.  in which the systolic and the diastolic blood pressure were significantly decreased in the propofol group than in the dexmedetomidine group, despite addition of ketamine.
A prospective study conducted by Berkenbosch et al. , on evaluation of dexmedetomidine for noninvasive procedural sedation in children, reported that the recovery pattern from sedation was smooth with no agitation or disorientation, and they observed that the length of recovery period is relatively long (69 min) compared with agent such as propofol, which is consistent with our results. In addition, Guler et al.  reported the benefits of dexmedetomidine administration just before the end of adenotonsillectomy procedures, which was a decreased incidence of emergence agitation compared with a placebo group.
We concluded that combination of dexmedetomidine/ketamine can be an excellent alternative to propofol/ketamine regimen in invasive procedural sedation with smooth recovery, stable cardiovascular parameters, and little clinical importance of prolonged recovery time and PACU discharge.
| Acknowledgements|| |
Conflicts of interest
| References|| |
|1.||Ellis JA, Spanos NP. Cognitive-behavioral interventions for children′s distress during bone marrow aspirations and lumbar punctures: a critical review. J Pain Symptom Manage 1994; 9:96-108. |
|2.|| Ljungman G, Gordh T, Sörensen S, et al. Pain in paediatric oncology: interviews with children, adolescents and their parents. Acta Paediatr 1999; 88:623-630. |
|3.|| Weisman SJ, Bernstein B, Schechter NL. Consequences of inadequate analgesia during painful procedures in children. Arch Pediatr Adolesc Med 1998; 152:147-149. |
|4.|| Zeltzer LK, Altman A, Cohen D, et al. Report of the subcommittee on the management of pain associated with procedures in children with cancer. Pediatrics 1990; 86:826-831. |
|5.|| Jayabose S, Levendoglu-Tugal O, Giamelli J, et al. Intravenous anesthesia with propofol for painful procedures in children with cancer, J Pediatr Hematol Oncol 2001; 23:290-293. |
|6.|| Hertzog JH, Dalton HJ, Anderson BD, et al. Prospective evaluation of propofol anesthesia in the pediatric intensive care unit for elective oncology procedures in ambulatory and hospitalized children. Pediatrics 2000; 106:742-747. |
|7.|| Barbi E, Badina L, Marchetti F, et al. Attitudes of children with leukemia toward repeated deep sedations with propofol. J Pediatr Hematol Oncol 2005; 27:639-643. |
|8.|| Mukhtar AM, Obayah EM, Hassona AM. The use of dexmedetomidine in pediatric cardiac surgery. Anesth Analg 2006; 103:52-56. |
|9.|| Ramsay MA, Savage TM, Simpson BR. Controlled sedation with alphaxalone-alphadolone. BMJ 1974; 2:656-659. |
|10.|| 1 Tobias JD, Berkenbosch JW. Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J 2004; 97:451-455. |
|11.|| 1 Keegan NJ, Yudkowitz FS, Bodian CA. Determination of the reliability of three scoring systems to evaluate children after general anesthesia. Anaesthesia 1995; 50:200-202. |
|12.|| 1 Wong D, Baker C. Pain in children: comparison of assessment scales. Pediatr Nurs 1988; 14:9-17. |
|13.|| 1 Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg 1970; 49:924-934. |
|14.|| 1 Belleville JP, Ward DS, Bloor BC, et al. Effects of intravenous dexmedetomidine in humans: I sedation, ventilation and metabolic rate. Anesthesiology 1992; 77:1125-1133. |
|15.|| 1 Tosun Z, Akin A, Guler G, et al. Dexmedetomidine-ketamine and propofol-ketamine combinations for anesthesia in spontaneously breathing pediatric patients undergoing cardiac catheterization. J Cardiothor Vasc Anesth 2006; 20:515-519. |
|16.|| 1 Tobias JD, Berkenbosch JW. Initial experience with dexmedetomidine in pediatric aged patients. Paediatr Anaesth 2002; 12:171-175 |
|17.|| 1 Bulow NM, Barbosa NV, Rocha JB. Opioid consumption in total intravenous anesthesia is reduced with dexmedetomidine: a comparative study with remifentanil in gynecologic videolaparoscopic surgery. J Clin Anesth 2007; 19:280-285. |
|18.|| 1 Al-Zaben KR, Qudaisat IY, Al-Ghanem SM, et al. Intraoperative administration of dexmedetomidine reduces the analgesic requirements for children undergoing hypospadius surgery. Eur J Anaesthesiol 2010; 27:247-252. |
|19.|| 1 Luscri N, Tobias JD. Monitored anesthesia care with a combination of ketamine and dexmedetomidine during magnetic resonance imaging in three children with trisomy 21 and obstructive sleep apnea. Paediatr Anaesth 2006; 16:782-786. |
|20.|| 2 Bloor BC, Ward DS, Belleville JP, et al. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology 1992; 77:1134-1142. |
|21.|| 2 Derek K, Sucullus I, Budak ET, Yeyen S, et al. A comparison of dexmedetomidine versus midazolam for sedation, pain, and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol 2010; 27:648-652. |
|22.|| 2 Christopher H, Frederick B, Kristin J, et al. A comparison of dexmedetomidine-midazolam with propofol for maintenance of anesthesia in children undergoing MRI. Anesth Analg 2008; 107:1832-1839. |
|23.|| 2 Berkenbosch JW, Wankum PC, Tobias JD. Prospective evaluation of dexmedetomidine for noninvasive procedural sedation in children. Pediatr Crit Care Med 2005; 6:435-439. |
|24.||2 Guler G, Akin A, Tosun Z, et al. Single-dose dexmedetomidine reduces agitation and provides smooth extubation after pediatric adenotonsillectomy. Paediatr Anaesth 2005; 15:762-766. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]