Efficacy of caudal butorphanol
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《美国医学杂志》
Department of Anesthesiology, King George's Medical University, Lucknow, India
Abstract
Objective : To evaluate the efficacy of butorphanol with or without bupivacaine for caudal epidural anesthesia in children undergoing infraumbilical surgery. Methods : Sixty ASA physical status I and II patients of either sex aged 1-10 yr were randomized to one of three groups. Group L received 1 ml/kg of 0.25% bupivacaine; Group B received 1 ml/kg of 25 μg/kg butorphanol diluted in normal saline; and Group LB received 1 ml/kg of 25 μg/kg butorphanol in combination with 0.25% bupivacaine, in caudal epidural anesthesia. Hemodynamic variables (HR and MAP) and respiratory rate were monitored in all patients. Sedation score, pain score and requirement of rescue analgesia were recorded at preset time intervals alongwith post-operative complications. Results : There was no difference among the groups regarding sedation scores, requirement of rescue analgesia and post-operative complications. Mean duration of analgesia was maximum in group BL (14.5 ± 3.5 hr, P<0.001), than in group L (8.8 ± 4.8 hr) and group B (6.8 ± 2.9 hr). Conclusion : The addition of 25 μg/kg butorphanol to bupivacaine resulted in superior analgesia with a longer period compared with caudal bupivacaine and butorphanol alone, without an increase of side effects.
Keywords: Pediatric surgery; Caudal epidural anesthesia; Butorphanol; Bupivacaine
In the past two decades, there has been a considerable progress in the understanding of infants' and children's perception of pain and responses to pain.[1] A parallel noteworthy advancement has occurred in the knowledge of anatomy, physiology, and pharmacology of regional anesthetic techniques in infants and children. Some of these techniques are now an integral part of perioperative and procedure-related pain management in children of all ages.[2]
Caudal anesthesia/analgesia is a wide-spread anesthetic technique for intraoperative and postoperative analgesia during lower limb, perineal and lower abdominal procedures. Administration of local anesthetic with or without opioids (morphine) has been widely used in caudal blocks till date. The present prospective, randomized double blind trial was conducted to evaluate caudal butorphanol with or without bupivacaine regarding its analgesics characteristics and postoperative complication in children undergoing infraumbilical surgery
Materials and Methods
After obtaining local ethics committee approval and written informed-parental consent, 60 patients of either sex were studied, who were ASA I - II, aged 1 to 10 yr, undergoing infraumbilical surgery of one to two hr duration ( i.e. hernia repair, orchiopexy, low ARM, colostomy or ileostomy closure, cystolithotomy, uretheroplasty etc). Patients receiving sedation, opioids/analgesics and patients in whom caudal analgesia was contraindicated, were excluded from the analysis. Patients with failed caudal block were also excluded from the study. No premedication was given to any of the patients. After cannulation of a vein, intravenous drip was started at a rate of 10 ml/kg. Before caudal, IV ketamine 1 mg/kg with atropine 0.01 mg/kg and midazolam 0.1 mg/kg was given to make the patients cooperative during the procedure/block. Standard intraoperative monitors were applied like NIBP, ECG, pulse oximeter, and nasopharyngeal temperature probe. The patients were randomly allocated to one of the three groups using a table of random numbers:
Group L : received 1 ml/kg of 0.25% bupivacaine in caudal epidural anesthesia
Group B : received 25 μg/kg of butorphanol diluted in saline to get total volume of 1 ml/kg in caudal epidural anesthesia
Group LB : received 1 ml/kg freshly made mixture of 0.25% bupivacaine and 25 μg/kg of butorphanol in caudal epidural anesthesia
No other perioperative peroperative analgesia was given. Patients were unaware of their treatment groups. All the patients received 50% oxygen in air by ventimask. Heart rate and blood pressure were recorded by the noninvasive technique. When the patient was awake in the perioperative room, the heart rate, arterial pressure, peripheral oxygen saturation, respiratory rate and pain score were recorded by a blinded observer who was not aware about the group to which the patient belong. A modified objective pain score, given a maximum score of 10 table1, was used to assess pain over a 5-minute period every hour.[3] Given below in the table2 are listed the demographic data of the patients. Respiratory rate and a four point sedation score (0 = eyes open spontaneously, 1=eyes open on speech, 2 = eyes open when shaken, 3= unarousable) were also measured every hour table3. Supplemental analgesia was given at the score of 3 4 in the form of paracetamol (20 mg/kg) syrup. Postoperative complications or adverse events like episodes of nausea/ vomiting, facial flushing/sweating, pruritus, urinary retention, or psychomimetic behaviour were noted, if they occurred table4. The data was subjected to the statistical analysis using Pearson's chi- square test or student 't' test to obtain the results.
Previous studies reported a mean duration of analgesia of 8 hours with an SD of 4 hr with the use of bupivacaine for caudal analgesia.[4] We hypothesized that if a mean duration of analgesia of 15 hr with an SD of 5 hr would be achieved with bupivacaine - butorphanol combination, a sample size of 20 patients was determined to provide 99% power for two-tail 't' test at the level of 5% significance. The p value of <0.05 was taken as statistically significant.
Results
Regarding the demographic data of the patients, all the three groups were identical (i.e. age, sex ratio, weight, ASA physical status and duration of surgery) table2. Although sedation score was maximum in group BL than group L & B, there was no statistical significance table3. None of the patients in any of the three groups had respiratory depression ( i.e. respiratory rate similar in all the groups). There was no difference among the groups regarding hypotension after the caudal anesthesia in any of the three groups. Four patients (20%) in group B and 2 patients (10%) in group L required additional analgesia immediately after surgery in the postoperative room, but there was no statistical significance among the groups. There was no significant difference between the three groups in mean hourly sedation scores table3.
Mean duration of analgesia was significantly higher in group BL than in group L and group B (P<0.001). The incidence of emesis (nausea/vomiting) was higher in both butorphanol groups (B & BL) than in the bupivaciane group (group L); the differences were not statistically significant table4. The incidence of pruritus, sweating, urinary retention and psychomimetic behaviour was slightly more in both butorphanol groups (B and BL) than in the local anesthetic group (group L), but the difference was not statistically significant.
Discussion
The present study's results demonstrated that butorphanol 25 μg/kg added to caudally administered local anesthetics significantly increased the duration of postoperative analgesia in patients undergoing elective infraumblical surgery. There has been one study in the literature of butorphanol use for caudal anesthesia/analgesia in pediatric population undergoing genitourinary procedure.[5] It was found that requirement of rescue analgesia in post anesthesia care unit and total numbers of morphine doses administered were significantly less in patients in whom butorphanol 30 μg/kg was added to bupivacaine in caudal epidural analgesia. Our study's findings are consistent with their findings but the differences from the present study were: they had used 0.25% bupivacaine with 1: 200,000 epinephrine and caudal epidural analgesia along with general anesthesia. In another study, butorphanol has also been used in patients of cerebral palsy undergoing elective orthopedic operations, and it was found to be safe and useful for postoperative pain control in children.[6]
Butorphanol is a totally synthetic compound of the nalorphine cyclazocine series. It is a mixed agonist - antagonist with intrinsic activity at receptors of the muopioid type (morphine like). It is also an agonist at kappa opioid receptors. Its interactions with these receptors in the CNS apparently mediate most of its pharmacological effects, including analgesia. Butorphanol has an analgesic action similar to that of morphine, with less respiratory depression, less nausea and vomiting, no undesirable psychomimetic effects and the provision of perioperative amnesia.[7] One of the interesting findings of the present study is the paucity of side effects associated with caudal butorphanol as mentioned in the literature.[7] Its high lipid solubility and high affinity for opioid receptors are additional factors that contribute to the paucity of side effects with its use.[8] High lipid solubility increases diffusion in the spinal cord and limits the amount of drugs remaining in the CSF, capable of reaching the brainstem where side effects are detected.[9] In a recent trial it has been demonstrated that there were less chances of complication or side effects with caudal analgesia as compared to parenteral use of analgesics or penile block in patients for circumcision.[10]
For the pediatric caudal epidural analgesia, other opioids like morphine[6], buprenorphine[6], fentanyl[11] and tramadol[4],[12] have been used. Drug like clonidine has also been used but its use in caudal analgesia resulted in significant prolongation of duration of postoperative analgesia, with the side effects like bradycardia and urinary retention.[13] Caudal epidural use of morphine, buprenorphine or butorphanol in a study did not increase the frequency of side effects such as nausea, vomiting etc., and need for rescue analgesia was also less in these patients within 24 hours after operation.[6] Addition of fentanyl citrate to bupivacaine in caudal epidural block in children did not influence the stress response to surgery, nor did it improve the analgesic intensity of the caudal block as described in literature.[11]
The use of tramadol in combination with 0.25% bupivacaine resulted in a significant increase in the analgesia time in one study[4] and no increase in another.[12] In the present study, caudal administration of bupivacaine with the addition of butorphanol resulted in significant increase in analgesia time than bupivacaine or butorphanol alone. The sedation scores although high in butorphanol bupivacaine combination group were not statistically significant as has been described with caudal tramadol in combination with bupivacaine.[4] Incidence of side effects among the groups was also not statistically significant as seen with tramadol in literature[4],[12]. The duration of analgesia with tramadol bupivacaine combination was 13.5 + 2.2 hr[11], but with butorphanol bupivacaine combination it was 14.5 + 3.5 hr in the present study. So it can be well stated that butorphanol bupivacaine combination is comparable with tramadol bupivacaine combination regarding the duration of analgesia, incidence of side effects and sedation score.
Conclusion
From the present experience, finally it can be concluded that caudal administration of bupivacaine, with the addition of butorphanol, is a reasonably safe and effective means for pediatric caudal epidural anesthesia in children undergoing infraumblical surgery to increase the duration of analgesia without an increase in the side effects. However, it is believed that larger series of patients will provide better information of its efficacy and other side effects.
References
1. Anand KJ, Coskun V, Thrivikraman KV et al. Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav 1999; 66 : 627.
2. Dalens B. Regional anesthesia in infants, children and adolescents. 2nd ed. London, Baltimore; Williams and Wilkins, Waverly Europe, 1995.
3. Wolf AR, Hughes D, Wade A, Mather SJ, Prys-Roberts C. Postoperative analgesia after pediatric orchiopexy : evaluation of a bupivacaine morphine mixture. British J Anesthesia 1990;64 : 430-435.
4. Senel AC, Akyol A, Dohman D, Solak M. Caudal bupivacaine-tramadol combination for postoperative analgesia in pediatric herniorrhaphy. Acta Anesthesiol Scand 2001; 45 (6) : 786-789.
5. Lawhorn CD, Stoner JM, Schmitz ML, Brown RE Jr, Stewart FW, Volpe P, Shirey R. Caudal epidural butorphanol plus bupivacaine versus bupivacaine in pediatric outpatient genitourinary procedures. J Clin Anesth 1997; 9 (2) : 103-104.
6. Ohta K, Katsuno M, Kawana S, Namiki A. Epidural opioids for post-operative pain control in pediatric patients with cerebral palsy. Masui 1993; 42(5): 664-668.
7. Sung Y-F, Weinstein MS, Ghani GA. Balanced anesthesia : A comparison of butorphanol and morphine. Southern Medical Journal 1984 ; 77 : 180-182.
8. Abdoud TK, Moore M, Zhu J, Murakawa K et al. Epidural butorphanol or morphine for the relief of postcesarean section pain: ventilatory responses to carbon dioxide. Anesth Analg 1987; 66 : 887-893.
9. Bromage PR, Campresi EM, Durant PAC, Nielsen CH. Rostral spread of epidural morphine. Anesthesiology 1982; 56 : 431-436.
10. Allan CY, Jacqueline PA, Shubhda JH. Caudal epidural block versus other methods of postoperative pain relief for circumcision in boys. Cochrane Database Syst Rev 2003; (2) : CD 003005.
11. Gaitini LA, Somri M, Vaida SJ, Yanovski B, Mogilner G et al. Does the addition of fentanyl to bupivacaine in caudal epidural block have an effect on the plasma level of catecholamines in children. Anesth Analg 2000; 90 (5) : 102-133.
12. Prosser DP, Davis A, Booker PD, Murry A. Caudal tramadol for postoperative analgesia in pediatric hypospadias surgery. Br. J Anaesth 2000; 85 (5) : 805-807.
13. Lee JJ, Rubin AP. Comparison of a bupivacaine-clonidine mixture with plain bupivacaine for caudal analgesia in children. Br J Anesth 1994; 72 : 258-268.(Singh Vinita, Kanaujia As)
Abstract
Objective : To evaluate the efficacy of butorphanol with or without bupivacaine for caudal epidural anesthesia in children undergoing infraumbilical surgery. Methods : Sixty ASA physical status I and II patients of either sex aged 1-10 yr were randomized to one of three groups. Group L received 1 ml/kg of 0.25% bupivacaine; Group B received 1 ml/kg of 25 μg/kg butorphanol diluted in normal saline; and Group LB received 1 ml/kg of 25 μg/kg butorphanol in combination with 0.25% bupivacaine, in caudal epidural anesthesia. Hemodynamic variables (HR and MAP) and respiratory rate were monitored in all patients. Sedation score, pain score and requirement of rescue analgesia were recorded at preset time intervals alongwith post-operative complications. Results : There was no difference among the groups regarding sedation scores, requirement of rescue analgesia and post-operative complications. Mean duration of analgesia was maximum in group BL (14.5 ± 3.5 hr, P<0.001), than in group L (8.8 ± 4.8 hr) and group B (6.8 ± 2.9 hr). Conclusion : The addition of 25 μg/kg butorphanol to bupivacaine resulted in superior analgesia with a longer period compared with caudal bupivacaine and butorphanol alone, without an increase of side effects.
Keywords: Pediatric surgery; Caudal epidural anesthesia; Butorphanol; Bupivacaine
In the past two decades, there has been a considerable progress in the understanding of infants' and children's perception of pain and responses to pain.[1] A parallel noteworthy advancement has occurred in the knowledge of anatomy, physiology, and pharmacology of regional anesthetic techniques in infants and children. Some of these techniques are now an integral part of perioperative and procedure-related pain management in children of all ages.[2]
Caudal anesthesia/analgesia is a wide-spread anesthetic technique for intraoperative and postoperative analgesia during lower limb, perineal and lower abdominal procedures. Administration of local anesthetic with or without opioids (morphine) has been widely used in caudal blocks till date. The present prospective, randomized double blind trial was conducted to evaluate caudal butorphanol with or without bupivacaine regarding its analgesics characteristics and postoperative complication in children undergoing infraumbilical surgery
Materials and Methods
After obtaining local ethics committee approval and written informed-parental consent, 60 patients of either sex were studied, who were ASA I - II, aged 1 to 10 yr, undergoing infraumbilical surgery of one to two hr duration ( i.e. hernia repair, orchiopexy, low ARM, colostomy or ileostomy closure, cystolithotomy, uretheroplasty etc). Patients receiving sedation, opioids/analgesics and patients in whom caudal analgesia was contraindicated, were excluded from the analysis. Patients with failed caudal block were also excluded from the study. No premedication was given to any of the patients. After cannulation of a vein, intravenous drip was started at a rate of 10 ml/kg. Before caudal, IV ketamine 1 mg/kg with atropine 0.01 mg/kg and midazolam 0.1 mg/kg was given to make the patients cooperative during the procedure/block. Standard intraoperative monitors were applied like NIBP, ECG, pulse oximeter, and nasopharyngeal temperature probe. The patients were randomly allocated to one of the three groups using a table of random numbers:
Group L : received 1 ml/kg of 0.25% bupivacaine in caudal epidural anesthesia
Group B : received 25 μg/kg of butorphanol diluted in saline to get total volume of 1 ml/kg in caudal epidural anesthesia
Group LB : received 1 ml/kg freshly made mixture of 0.25% bupivacaine and 25 μg/kg of butorphanol in caudal epidural anesthesia
No other perioperative peroperative analgesia was given. Patients were unaware of their treatment groups. All the patients received 50% oxygen in air by ventimask. Heart rate and blood pressure were recorded by the noninvasive technique. When the patient was awake in the perioperative room, the heart rate, arterial pressure, peripheral oxygen saturation, respiratory rate and pain score were recorded by a blinded observer who was not aware about the group to which the patient belong. A modified objective pain score, given a maximum score of 10 table1, was used to assess pain over a 5-minute period every hour.[3] Given below in the table2 are listed the demographic data of the patients. Respiratory rate and a four point sedation score (0 = eyes open spontaneously, 1=eyes open on speech, 2 = eyes open when shaken, 3= unarousable) were also measured every hour table3. Supplemental analgesia was given at the score of 3 4 in the form of paracetamol (20 mg/kg) syrup. Postoperative complications or adverse events like episodes of nausea/ vomiting, facial flushing/sweating, pruritus, urinary retention, or psychomimetic behaviour were noted, if they occurred table4. The data was subjected to the statistical analysis using Pearson's chi- square test or student 't' test to obtain the results.
Previous studies reported a mean duration of analgesia of 8 hours with an SD of 4 hr with the use of bupivacaine for caudal analgesia.[4] We hypothesized that if a mean duration of analgesia of 15 hr with an SD of 5 hr would be achieved with bupivacaine - butorphanol combination, a sample size of 20 patients was determined to provide 99% power for two-tail 't' test at the level of 5% significance. The p value of <0.05 was taken as statistically significant.
Results
Regarding the demographic data of the patients, all the three groups were identical (i.e. age, sex ratio, weight, ASA physical status and duration of surgery) table2. Although sedation score was maximum in group BL than group L & B, there was no statistical significance table3. None of the patients in any of the three groups had respiratory depression ( i.e. respiratory rate similar in all the groups). There was no difference among the groups regarding hypotension after the caudal anesthesia in any of the three groups. Four patients (20%) in group B and 2 patients (10%) in group L required additional analgesia immediately after surgery in the postoperative room, but there was no statistical significance among the groups. There was no significant difference between the three groups in mean hourly sedation scores table3.
Mean duration of analgesia was significantly higher in group BL than in group L and group B (P<0.001). The incidence of emesis (nausea/vomiting) was higher in both butorphanol groups (B & BL) than in the bupivaciane group (group L); the differences were not statistically significant table4. The incidence of pruritus, sweating, urinary retention and psychomimetic behaviour was slightly more in both butorphanol groups (B and BL) than in the local anesthetic group (group L), but the difference was not statistically significant.
Discussion
The present study's results demonstrated that butorphanol 25 μg/kg added to caudally administered local anesthetics significantly increased the duration of postoperative analgesia in patients undergoing elective infraumblical surgery. There has been one study in the literature of butorphanol use for caudal anesthesia/analgesia in pediatric population undergoing genitourinary procedure.[5] It was found that requirement of rescue analgesia in post anesthesia care unit and total numbers of morphine doses administered were significantly less in patients in whom butorphanol 30 μg/kg was added to bupivacaine in caudal epidural analgesia. Our study's findings are consistent with their findings but the differences from the present study were: they had used 0.25% bupivacaine with 1: 200,000 epinephrine and caudal epidural analgesia along with general anesthesia. In another study, butorphanol has also been used in patients of cerebral palsy undergoing elective orthopedic operations, and it was found to be safe and useful for postoperative pain control in children.[6]
Butorphanol is a totally synthetic compound of the nalorphine cyclazocine series. It is a mixed agonist - antagonist with intrinsic activity at receptors of the muopioid type (morphine like). It is also an agonist at kappa opioid receptors. Its interactions with these receptors in the CNS apparently mediate most of its pharmacological effects, including analgesia. Butorphanol has an analgesic action similar to that of morphine, with less respiratory depression, less nausea and vomiting, no undesirable psychomimetic effects and the provision of perioperative amnesia.[7] One of the interesting findings of the present study is the paucity of side effects associated with caudal butorphanol as mentioned in the literature.[7] Its high lipid solubility and high affinity for opioid receptors are additional factors that contribute to the paucity of side effects with its use.[8] High lipid solubility increases diffusion in the spinal cord and limits the amount of drugs remaining in the CSF, capable of reaching the brainstem where side effects are detected.[9] In a recent trial it has been demonstrated that there were less chances of complication or side effects with caudal analgesia as compared to parenteral use of analgesics or penile block in patients for circumcision.[10]
For the pediatric caudal epidural analgesia, other opioids like morphine[6], buprenorphine[6], fentanyl[11] and tramadol[4],[12] have been used. Drug like clonidine has also been used but its use in caudal analgesia resulted in significant prolongation of duration of postoperative analgesia, with the side effects like bradycardia and urinary retention.[13] Caudal epidural use of morphine, buprenorphine or butorphanol in a study did not increase the frequency of side effects such as nausea, vomiting etc., and need for rescue analgesia was also less in these patients within 24 hours after operation.[6] Addition of fentanyl citrate to bupivacaine in caudal epidural block in children did not influence the stress response to surgery, nor did it improve the analgesic intensity of the caudal block as described in literature.[11]
The use of tramadol in combination with 0.25% bupivacaine resulted in a significant increase in the analgesia time in one study[4] and no increase in another.[12] In the present study, caudal administration of bupivacaine with the addition of butorphanol resulted in significant increase in analgesia time than bupivacaine or butorphanol alone. The sedation scores although high in butorphanol bupivacaine combination group were not statistically significant as has been described with caudal tramadol in combination with bupivacaine.[4] Incidence of side effects among the groups was also not statistically significant as seen with tramadol in literature[4],[12]. The duration of analgesia with tramadol bupivacaine combination was 13.5 + 2.2 hr[11], but with butorphanol bupivacaine combination it was 14.5 + 3.5 hr in the present study. So it can be well stated that butorphanol bupivacaine combination is comparable with tramadol bupivacaine combination regarding the duration of analgesia, incidence of side effects and sedation score.
Conclusion
From the present experience, finally it can be concluded that caudal administration of bupivacaine, with the addition of butorphanol, is a reasonably safe and effective means for pediatric caudal epidural anesthesia in children undergoing infraumblical surgery to increase the duration of analgesia without an increase in the side effects. However, it is believed that larger series of patients will provide better information of its efficacy and other side effects.
References
1. Anand KJ, Coskun V, Thrivikraman KV et al. Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav 1999; 66 : 627.
2. Dalens B. Regional anesthesia in infants, children and adolescents. 2nd ed. London, Baltimore; Williams and Wilkins, Waverly Europe, 1995.
3. Wolf AR, Hughes D, Wade A, Mather SJ, Prys-Roberts C. Postoperative analgesia after pediatric orchiopexy : evaluation of a bupivacaine morphine mixture. British J Anesthesia 1990;64 : 430-435.
4. Senel AC, Akyol A, Dohman D, Solak M. Caudal bupivacaine-tramadol combination for postoperative analgesia in pediatric herniorrhaphy. Acta Anesthesiol Scand 2001; 45 (6) : 786-789.
5. Lawhorn CD, Stoner JM, Schmitz ML, Brown RE Jr, Stewart FW, Volpe P, Shirey R. Caudal epidural butorphanol plus bupivacaine versus bupivacaine in pediatric outpatient genitourinary procedures. J Clin Anesth 1997; 9 (2) : 103-104.
6. Ohta K, Katsuno M, Kawana S, Namiki A. Epidural opioids for post-operative pain control in pediatric patients with cerebral palsy. Masui 1993; 42(5): 664-668.
7. Sung Y-F, Weinstein MS, Ghani GA. Balanced anesthesia : A comparison of butorphanol and morphine. Southern Medical Journal 1984 ; 77 : 180-182.
8. Abdoud TK, Moore M, Zhu J, Murakawa K et al. Epidural butorphanol or morphine for the relief of postcesarean section pain: ventilatory responses to carbon dioxide. Anesth Analg 1987; 66 : 887-893.
9. Bromage PR, Campresi EM, Durant PAC, Nielsen CH. Rostral spread of epidural morphine. Anesthesiology 1982; 56 : 431-436.
10. Allan CY, Jacqueline PA, Shubhda JH. Caudal epidural block versus other methods of postoperative pain relief for circumcision in boys. Cochrane Database Syst Rev 2003; (2) : CD 003005.
11. Gaitini LA, Somri M, Vaida SJ, Yanovski B, Mogilner G et al. Does the addition of fentanyl to bupivacaine in caudal epidural block have an effect on the plasma level of catecholamines in children. Anesth Analg 2000; 90 (5) : 102-133.
12. Prosser DP, Davis A, Booker PD, Murry A. Caudal tramadol for postoperative analgesia in pediatric hypospadias surgery. Br. J Anaesth 2000; 85 (5) : 805-807.
13. Lee JJ, Rubin AP. Comparison of a bupivacaine-clonidine mixture with plain bupivacaine for caudal analgesia in children. Br J Anesth 1994; 72 : 258-268.(Singh Vinita, Kanaujia As)