Caudal bupivacaine alone versus bupivacaine with ketamine to compare postoperative analgesia

Objective: to compare the effectiveness of caudal bupivacain alone and bupivacaine with ketamine in terms of duration of analgesia. Study Design: Randomized controlled trial. Duration and Place: Department of Anaesthesia Quid e Azam Medical College, Bahawalpur from May 2018 to May 2019. Methodology: Study was started after approval from local ethical committee a parental consent was obtained after complete information of study. Main outcome variables are duration of analgesia, pain score, Bromage score. Data analysis was done with SPSS version 23.1. P value ≤0.05 was taken as statistically significant. Results: The mean duration of analgesia and time taken to void urine after surgery of the Group A was 5.80±2.71 hours and 4.45±0.51 hours, respectively. While, the mean duration of analgesia and time taken to void urine after surgery of the Group B was 12.53±2.51 hours and 4.52±0.53 hours, respectively. Statistically significant was observed in duration of analgesia. P value 0.000. Conclusion: Combination of Ketamine 0.5 mg/kg and bupivacain 0.25% in a dose of 1 ml/kg prolonged the duration of postoperative analgesia toa significant range in comparison with bupivacaine 25% of 1 ml/kg alone.


Introduction
Pain is an unpleasant feeling which is most feard symptom of an illness. Human always keep trying to terminate or conquer this unpleasant feeling in any age group 1 . It is a very complicated phenomenon which cannot be described or diagnosed. It is necessary to control the pain in hospitalized patients for better outcomes or early recovery from the disease 2 . Coudal analgesia is a most popular effective and useful regional block in these days. Codual block is a regional analgesic technique mostly used for below diaphragmatic surgeries. It is found to be successful and effective 3 .
Among its disadvantages most common is short duration of action when a single injection of local anaesthetic was given, even bupivacain which is a long acting anaesthetic gives only 4 to 8 hours of analgesic effect 4,5 . To overcome this short duration of action codual catheter was inserted for repeated doses of anaesthetic agent but this method not too much popular because of high risk of infection 6 . Addition of ketamine to an anaesthetic agent enhance the duration of analgesia. Administration of epidural ketamine produce profound the analgesic affects at a level of spinal cord without any adverse effects.
Addition of preservative free drug like ketamine enhanced the time of post operative analgesic effects in patients of below diaphragm surgery 7 . Dose of ketamine caudal block is controversial, many previous studies determine the dose of ketamine but it was not justified properly. In a study Semple et al reported that 0.5mg per kg is an optimum dose of ketamine for caudal epidural blockade. This local anaesthetic effect is stimulated by N methyl D aspirate receptors antagonism also known as NMDA receptors 8 .
Use of ketamine may increase blood pressure and heart rate, because hallucinations raise intracranial and intraocular pressure and provoke acute porphyria 9 . In psychiatric patients ketamine administered with precautions, it increases the sedative effect of medicine in a dose dependent manner. Use of benzodiazepines diminishes the anti depressant role of ketamine. Other than NMDA receptors antagonism ketamine may actually on sigma receptors, muscrinic acetylcholine receptors and antagonized their effects 10 .

Methodology
Study was started after approval from local ethical committee a parental consent was obtained after complete information of study. Study was completed in Department of Anaesthesia Quid e Azam Medical College, Bahawalpur from May 2018 to May 2019.Patients of age more than 20 years, ASA status I and II and who were selected for below diaphragm surgery were selected for study. Patients with no sensitivity or allergy to bupivacain or ketamine or having caudal injection contraindication such as bleeding disorder, infection at the sight and vertebral column deformities were not included in study. Patients were divided into two groups A and B by lottery method. Patients in group A were given bupivacain 2.5% with dose of 1ml per kg and in group B were given bupivacain 0.25% with dose of 1ml per kg plus ketamine 0.5mg per kg preservative free. Bilateral IV lines of 18 G were inserted in dorsal veins of hands. Patients were kept for NPO six hours before surgery. All patients were undergone for general anaesthesia with thiopentone 5 to 6 mg per kg and inhalational N2o, oxygen and halothane gas. Caudal injection was given before start of surgery and then surgeon was allowed to perform surgery. Patient's non invasive blood pressure, ECG, spo2, heart rate was monitored. When surgical procedure was completed patients were shifted to recovery room and observed for one hour and then observations were done at one hour, four hours, six hours, twelve hours and 24 hours after shifting in ward. Analgesia duration was recorded by VAS core. Duration of analgesia was labeled as time between caudal injection and first analgesia requirement after surgery. Within 24 hours if analgesia was not required then duration of analgesia was noted as 24 hours. Bromage scale was used to evaluate the motor block.

Bromage scale:
Complete flexion of feet and knees and able to lift legs score 0. Legs cannot be extended or lifted but flexion of knees and feet is present score 1. Flexion of knees and feet both absent score 2. Complete absence of movement in legs and feet score 3.
Data analysis was done by putting data in SPSS version 24. Mean and standard deviation were presented for quantitative data like age, duration of analgesia. Qualitative data was presented as numbers and percentages like gender. Chi square and student t-test were applied to see association among variables. Probability value ≤ 0.05 was considered as significant.

Results:
Eighty patients were included in this study. The patients were further analyzed into two Groups as n=40 in Group A and n=40 in Group B. The mean age, weight and duration of surgery of Group A was 3.71±1.38 years, 11.42±1.86 kg and 47.62±3.76 minutes, respectively. Nature of surgery was observed as urethroplasty in n=16 (40%) patients, herniotomy in n=15 (37.5%) patients and orchidopexy in n=9 (22.5%) patients. While, the mean age, weight and duration of surgery of Group B was 3.50±1.55 years, 11.52±1.56 kg and 48.47±3.01 minutes, respectively. Nature of surgery was observed as urethroplasty in n=27 (67.5%) patients, herniotomy in n=9 (22.5%) patients and orchidopexy in n=4 (10%) patients. The difference of nature of surgery among the groups was significant (0.044). (Table.  I).
Pain score (postoperative) of both the groups at 1, 4, 6, 12 and 24 hours were shown in table II. The difference was statistically significant at 6 and 12 hours, (p=0.001) and (p=0.020), respectively. Bromage scale (postoperative) of both the groups at 1, 4, 6, 12 and 24 hours were shown in table III. The difference was not statistically significant at any of the hour among the groups.
The mean duration of analgesia and time taken to void urine after surgery of the Group A was 5.80±2.71 hours and 4.45±0.51 hours, respectively. While, the mean duration of analgesia and time taken to void urine after surgery of the Group B was 12.53±2.51 hours and 4.52±0.53 hours, respectively. Statistically significant difference was observed for duration of analgesia (p=0.000). (Table. IV).

Discussion:
Study was conducted by Semple et al 11 on efficacy and dose of ketamine in codual block and reported that addition of preservative free ketamine enhance the effect of 0.25% of bupivacain when given in epidural block and optimum dose of ketamine in codual block is 0.5mg per kg.
In the study doses of bupivacain and ketamine ate similar as in our study and conclusion can be compared with our study results and conclusion.
Another study was conducted by Naguib et al 12 and compared bupivacain 0.25% alone with bupivacain 0.2% plus 0.5mg per kg ketamine in children who were selected for inguinal herniotomy and concluded that there was not statistically significant difference between the groups in terms of quality and duration of analgesia. In combination group only 7% patients required rescue analgesia and in other group 20% patients required rescue analgesia.
A similar study was also conducted by Cook et al 13 and compared bupivacain 0.25% plus 0.5mg per kg ketamine with clonidine 2microgram per kg or epinephrine 5mg per ml and concluded that ketamine group provides longer duration of post operative analgesia as compared to clonidine and epinephrine group but in our study we compared ketamine combination bupivacain 0.25% alone but study results comparable with this study.
Another study was conducted by Martindale SJ et al 14  When we concern about the dose of ketamine in bupivacain 0.25% Panjabi et al 18 conducted a study and recommended that 0.5mg/kg is a standard dose of ketamine when added in bupivacain for better analgesic effect and sedation of patients. He compared 0.5mg/kg ketamine with 0.25 mg/kg ketamine and side effects also limited. In a study Nasr et al 19 reported that use of 0.5 mg/kg ketamine in 0.25% bupivacain provides sufficient effect of duration of analgesia.
In a study Findlow D et al 20 compare the bupivacain and combination of bupivacain with ketamine and reported that combination of ketamine plus bupivacain provides longer duration of analgesia about 20% greater time of analgesic effect. Results of this study are also identical to our study that for purpose of duration of analgesia combination of bupivacain and ketamine 0.5mg/kg is an ideal choice.

Conclusion:
Results of our study reveal that combination of Ketamine 0.5 mg/kg and bupivacain 0.25% in a dose of 1 ml/kg prolonge the duration of postoperative analgesia to a significant range in comparison with bupivacaine 25% of 1 ml/kg alone.