|Year : 2018 | Volume
| Issue : 2 | Page : 366-370
Intrathecal nalbuphine versus ketamine with hyperbaric bupivacaine in lower abdominal surgeries
Amar Parkash Kataria, Harjeet Singh, Brij Mohan, Milind Thakur, Vishal Jarewal, Sabeena Khan
Department of Anesthesiology and Intensive Care, Government Medical College, Amritsar, Punjab, India
|Date of Web Publication||14-Jun-2018|
Dr. Harjeet Singh
Department of Anaesthesia, D17/1212, Street No. 2, Kartar Nagar, Chheharta, Amritsar, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Spinal anesthesia is an effective method of anesthesia with fewer side effects. The main limitations include the shorter duration of action and shorter postoperative analgesia when performed only with local anesthetics. Aim: The aim of this study is to compare adjuvants nalbuphine and ketamine to hyperbaric bupivacaine in spinal anesthesia with respect to the duration of analgesia, sensory and motor onset, hemodynamic status, and side effects. Settings and Design: This was a prospective, randomized, double-blind study. Materials and Methods: After ethical committee's clearance and informed consent, 90 patients of the American Society of Anesthesiologists physical status I and II were randomly allocated in three groups N, K, and B who received 3 ml hyperbaric bupivacaine with 0.8 mg nalbuphine, 3 ml hyperbaric bupivacaine with 25 mg ketamine (preservative free), and 3 ml hyperbaric bupivacaine with 0.5 ml normal saline, respectively. Statistical Analysis: Data were analyzed using paired t-test. Results were analyzed and compared to previous studies. SPSS-22 version of software was used, released 2013, IBM Corp., Armonk, NY, USA. Results: Mean duration of analgesia in Group N, K, and B was 290 ± 6.09, 220 ± 5.03, and 154 ± 6.04 min, respectively. Mean time of sensory onset in Group N, K, and B was 2.08 ± 0.34, 3.5 ± 0.25, and 4.5 ± 0.37 min, respectively. Time of motor onset was 7.60 ± 0.58, 7.79 ± 0.37, and 7.82 ± 0.53 min in Group N, K, and B, respectively. Conclusion: Nalbuphine is an effective adjuvant in spinal anesthesia with respect to sensory onset, duration of analgesia, and hemodynamic stability.
Keywords: Hyperbaric bupivacaine, ketamine, nalbuphine, spinal anesthesia
|How to cite this article:|
Kataria AP, Singh H, Mohan B, Thakur M, Jarewal V, Khan S. Intrathecal nalbuphine versus ketamine with hyperbaric bupivacaine in lower abdominal surgeries. Anesth Essays Res 2018;12:366-70
|How to cite this URL:|
Kataria AP, Singh H, Mohan B, Thakur M, Jarewal V, Khan S. Intrathecal nalbuphine versus ketamine with hyperbaric bupivacaine in lower abdominal surgeries. Anesth Essays Res [serial online] 2018 [cited 2020 Apr 3];12:366-70. Available from: http://www.aeronline.org/text.asp?2018/12/2/366/234419
| Introduction|| |
Pain as described by International Association for Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage.” The surgical stress response is maximum during the postoperative period and affects almost every part of the body systems. Postoperative pain is associated with many negative outcomes such as ventilation problems, patient discomfort, cardiovascular events, endocrine disorders, and poor wound healing. It is an important factor in regulating patients outcome in postoperative period. Initially, general anesthesia was the only anesthetic modality available for all kind of surgeries irrespective of site and duration of surgery.
Regional anesthesia with spinal and epidural blocks have been used for a long time for various surgical procedures and pain relief. The first spinal anesthesia was given by Karl August Bier in 1898 at Royal surgical hospital of the University of Kiel, Germany. He performed it by injecting 3 ml of 0.5% cocaine solution in subarachnoid space. Many drugs have been used since then. bupivacaine  came afterward with longer duration of action and less central nervous system side effects, and nowadays, it is the most commonly used intrathecal drug. The subarachnoid block has emerged as an effective and convenient method of anesthesia for lower limb and lower abdominal surgeries. It is simple to use with intense motor and sensory blockade, good muscle relaxation, no loss of consciousness, minimum physiological changes with few side effects such as postoperative respiratory depression, nausea, vomiting, drowsiness, etc. Patients undergoing spinal anesthesia alone with local anesthetic agents experience pain once the effect is over. Hence, various adjuvants have been used along with local anesthetics in spinal anesthesia to prolong the postoperative analgesia. The adjuvants most commonly used are opioids, ketamine, alpha 2 adrenergic agonists, midazolam etc.
Nalbuphine  is a semi-synthetic opioid with mixed μ antagonist and κ agonist properties. The use of nalbuphine can prove to be a boon because when used singly or in combination with other agents it has the potential to maintain or even enhance opioid-based analgesia while simultaneously mitigating the common mu-opioid side effects. Nalbuphine binds to kappa opioid receptors in the brain and spinal cord to produce analgesia. It prolongs the duration of analgesia without affecting the motor and autonomic nervous system.
Ketamine, a noncompetitive N-Methyl-D-aspartate (NMDA)-receptor antagonist, exhibits analgesic properties. There are two enantiomers S (+) ketamine and R (+) ketamine. The S (+) ketamine is the active compound. Ketamine has other actions, some of which also may contribute to its analgesic effect. These include interactions with calcium and sodium channels, dopamine receptors, cholinergic transmission, and noradrenergic and serotoninergic reuptake (intact descending inhibitory pathways are necessary for analgesia), together with opioid like and anti-inflammatory effects. Ketamine has been used intrathecally also as an adjuvant to local anesthetic, and it has been seen that it provides better surgical conditions with good analgesia and cardiovascular stability.
This study was designed to compare the efficacy of nalbuphine and ketamine as adjuvants to hyperbaric bupivacaine in spinal anesthesia in lower abdominal surgeries with respect to sensory onset, duration of analgesia, motor onset, and side effects. This study will also compare the groups with control group that contains bupivacaine alone. The study was conducted after getting approval from Hospital Ethical Committee.
| Materials and Methods|| |
This study was conducted as prospective double-blinded, randomized controlled trial on 90 patients of age group 18–60 years of the American Society of Anesthesiologists Grade I and II after obtaining approval from Hospital Ethical Committee. The study was done after obtaining informed consent from the patients. The exclusion criteria included unwillingness, coagulation disorders and neurological disorders, any signs of sepsis, previous injury, deformity or previous surgery of spine, morbid obesity, any anticipated difficulty in regional anesthesia, any allergy to study drug, pregnancy and lactation, and any life-threatening disease.
Patients were divided into three groups of 30 each, Group N (3 ml of 0.5% hyperbaric bupivacaine with 0.8 mg nalbuphine diluted in 0.5 ml normal saline), Group K (3 ml of 0.5% hyperbaric bupivacaine with 25 mg preservative-free ketamine diluted in 0.5 ml normal saline) and Group B (3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml normal saline). Sample size was calculated taking into account the parameters such as duration of analgesia, sensory onset, hemodynamic stability, and side effects after consultation from statistician and the power of the study was >85%. All the patients were kept fasting for 6 h before surgery. Patients were reassessed on the day of surgery in the preoperative room. In the operation theater, multipara monitor was attached to the patient to monitor heart rate (HR), noninvasive blood pressure, oxygen saturation (SpO2), respiratory rate (RR), and electrocardiogram. Patients were preloaded with Ringer lactate solution at 10 ml/kg after securing intravenous line. Premedication was given as injection glycopyrrolate 0.2 mg and injection midazolam 0.04 mg/kg body weight by intravenous route just before the surgery.
The patient was put in lateral decubitus position; back of the patient was painted with povidine-iodine solution. Area was draped with sterile sheet. L3 and L4 space were located (in case of difficulty L2 and L3 space). Skin wheal was raised with 2% lignocaine (plain). Quincke spinal needle number 25G was introduced into subarachnoid space through midline approach. Successful dural puncture was confirmed by withdrawing the stylet to verify free flow of cerebrospinal fluid (CSF). Syringe loaded with study drug was attached to hub of the needle and after aspiration of CSF whole of drug was injected in to the CSF. The drugs under study were prepared by another investigator to facilitate double blinding. After giving the drug intrathecally, the spinal needle was taken out, and the patients were made supine immediately and were given O2 at 6 L/min through face mask. The anesthesiologist who performed the technique recorded the intraoperative data and followed up patients postoperatively until discharged from postanesthesia care unit.
Sensory block was assessed by loss of sensation to pinprick in the midline using a 22G blunt hypodermic needle every 2 min up to 10 min, at an interval of 5 min up to 30 min, every 15 min up to 120 min, half hourly up to 240 min, thereafter hourly till 12 h of surgery. Time from injection of local anesthetic in intrathecal space up to the time when the patient does not feel the pinprick at T10 level was taken as time of sensory onset. The highest dermatome showing analgesia was taken as the level of analgesia. The degree of motor block was assessed at the same interval as sensory level by the modified Bromage score. Bradycardia (defined as HR <60 beats/min) was treated with injection atropine sulfate 0.3 mg intravenously. Hypotension (defined as systolic blood pressure [SBP] <20% less than baseline value) was treated with intravenous ephedrine as per required and additional Ringer's lactate solution. Continuous hemodynamic monitoring was done needle every 2 min up to 10 min, at an interval of 5 min up to 30 min, every 15 min up to 120 min, half-hourly up to 240 min, thereafter hourly till 12 h of surgery. Pain was assessed by visual analog scale (VAS) score [Figure 1]. Sedation was assessed by Ramsay sedation scale [Table 1].
The interpretations of visual linear analog scale will be explained 1 day before the operation to the selected patients taken for study to determine the quality of analgesia in the postoperative period. This will be carried out with 0–10 cm line. The first-end mark “0” means “no pain” and the end marked “10” means “severe pain.” The patients will be asked to mark the severity of pain experienced. Rescue analgesia will be given if VAS score >3.
All the parameters were entered in master chart and analyzed using SPSS software. Variable parameters were analyzed using Chi-square test, and continuous parameters were analyzed using unpaired t-test. P < 0.05 was considered statistically significant, P < 0.001 was highly significant and P > 0.05 was considered nonsignificant.
| Observations and Results|| |
A total of 90 patients were enrolled in the study of age group 18–60 years. The demographic data and surgical profile of the groups were comparable [Table 2]. 1 (3.33%) patient in Group N and 2 (6.67%) patients developed bradycardia intraoperatively. No patient showed bradycardia in Group K. The mean HR and RR remained stable and comparable at all measured intervals, and the difference was statistically nonsignificant (P > 0.05). The mean SBP and diastolic blood pressure (DBP) was stable and comparable at all measured intervals with the difference being nonsignificant (P > 0.05) between the groups except at 8, 10, and 15 min intervals when the mean SBP was significantly low in Group B as compared to Group N and K [Figure 2] and [Figure 3]. The HR, RR, SBP, DBP, and SpO2 were comparable postoperatively, and no significant difference was observed. The difference in the sedation score between Group N, Group K, and Group B was statistically nonsignificant (P > 0.05) intraoperatively and postoperatively. Postoperative VAS scores at different time intervals were significantly lower in Group N and Group K as compared to Group B, indicating superior analgesia.
The mean time to onset of sensory block to T10 dermatome was 2.08 ± 0.34 min in Group N, 3.5 ± 0.25 min in Group K and 4.5 ± 0.37 min in Group B. The difference between the groups (N and K, N and B, K, and B) was highly significant (P< 0.001) and nalbuphine containing Group N has the shortest time of onset of sensory block [Figure 4]. The mean time taken to attain maximum sensory level was 6.30 ± 1.02 min in Group N, 6.77 ± 0.86 min in Group K, and 7.10 ± 0.99 min in Group B. The difference was significant between the groups (P< 0.05) with nalbuphine group taking least time to achieve the max sensory level [Figure 4].
|Figure 4: Meantime of sensory onset (minutes) and mean time to achieve maximum sensory level (minutes)|
Click here to view
The mean time to achieve maximum motor block was 7.60 ± 0.58 min in Group N, 7.79 ± 0.37 min in Group K and 7.82 ± 0.53 min in Group B. The difference was statistically nonsignificant in all the groups although Group N had shortest time. The mean total duration of motor block in Group N, Group K, and Group B was 148.87 ± 6.80 min, 148.70 ± 586 min, and 146.80 ± 4.62 min, respectively. The difference between the groups was nonsignificant.
The time of request of first dose of rescue analgesia (duration of analgesia) in Group N was 290 ± 6.09 min, Group K was 220 ± 5.03 min, and Group B was 154 ± 6.04 min. The difference in the groups was highly significant (P< 0.001) [Figure 5]. The mean numbers of rescue analgesia doses were 2.2 ± 0.42 in Group N, 2.6 ± 0.61 in Group K, and 3.8 ± 0.47 in Group B. Difference was highly significant (P< 0.001), patients in Group N and Group K required less doses of rescue analgesia as compared to Group B.
Hypotension was observed in 1 (3. 33%) patient in Group N, 1 (3.33%) patient in Group K and 4 (13. 33%) patients in Group B. Bradycardia was seen in 1 (3.33%) patients in Group N, 0 (0%) patient in Group K, and in 2 (6.67%) patients in Group B. There was no incidence of pruritus. Nausea/vomiting was seen in 1 (3.33%) patients in Group N, 1 (3.33%) patients in Group K, and 3 (10%) patients in Group B; the difference was statistically nonsignificant. Other side effects such as urinary retention, shivering, headache, and backache were also recorded [Table 3].
| Discussion|| |
Effective pain control has become very essential for optimum care of patients in the postoperative period. Provision of good analgesia in postoperative period may go a long way in alleviating pain and faster recovery. Spinal anesthesia is a simple technique which uses local anesthetics in small doses which provides reliable surgical anesthesia, good muscle relaxation, and analgesia. These advantages of spinal anesthesia are masked by its limited duration of action and patient may start feeling pain after the effect wears off.
The efficacy of the local anesthetic can be enhanced by adding adjuvant to it. The adjuvants used can be opioids, α agonist, or ketamine, etc., Nalbuphine is an opioid, highly lipid soluble with agonist action at the κ-opioid receptor and antagonist at the μ-opioid receptor. It improves the quality of intraoperative analgesia and provides prolonged duration of analgesia post operatively. Ketamine is an anesthetic agent with multiple actions. It has potent analgesic properties, and its mode of action include noncompetitive antagonism at NMDA receptors.
The mean time to onset of sensory block to T10 dermatome and the time taken to attain maximum sensory level was lowest in Group N and the difference was significant. A study conducted by Shakooh and Bhosle  with nalbuphine as an adjuvant with bupivacaine showed that the onset of sensory block was faster and time taken to attain complete sensory block was shorter in the nalbuphine group. The difference was statistically significant as concluded in our study.P Sivatharshini and Shekaran  also conducted a similar study with 25 mg ketamine as an adjuvant. It was seen that mean time for onset of sensory and duration of sensory block was significantly earlier in group containing ketamine than bupivacaine alone as observed in our study.
The mean time taken to achieve maximum motor block of Bromage 3 was earlier in Group N, but the results were comparable and statistically nonsignificant. In a study done by Mukherjee et al., it was seen that onset of motor block was early in group containing 0.8 mg nalbuphine and duration of motor block was also more in that group, but the difference was insignificant as seen in our study also. In a study done by Jain et al., it was observed that there was early onset of motor block in ketamine group along with longer duration of motor block although the difference was insignificant, as observed in our study.
The duration of analgesia was more in Group N than Group K and Group B. The difference was highly significant statistically (P< 0.001). Kumaresan and Raj  in his study observed that the duration of analgesia was significantly prolonged in group containing nalbuphine, similar to our study. Hemanth N et al. also observed that the duration of analgesia was significantly more in group containing ketamine than the bupivacaine alone. Similar kinds of results have been observed in our study.
Jyothi et al. conducted a study and concluded that the use of nalbuphine along with bupivacaine caused no gross hemodynamic disturbances even with increasing doses, in concordance with our study. Sivatharshini and Shekaran  in a study observed that patients were hemodynamically more stable in group containing ketamine as an adjuvant than bupivacaine alone as observed in our study also.
Other side effects monitored were shivering, urinary retention, headache, backache, and respiratory depression. In a study conducted by Gupta et al., it was seen that the addition of nalbuphine improved intraoperative analgesia without causing any undue side effects and complications, analogous to the observation in our study. Another study was performed by Khezri et al., which showed no central nervous system complication or any other undesired side effects with ketamine similar to the observation in our study.
| Conclusion|| |
It was concluded from our study that bupivacaine when combined with nalbuphine or ketamine provided adequate spinal block for lower abdominal surgeries. Both the groups were effective in providing adequate anesthesia and analgesia along with good hemodynamic stability, but bupivacaine with nalbuphine group was better than ketamine group and bupivacaine alone group with respect to the prolonged duration of analgesia, prolonged duration of sensory block with early onset, and lesser side effects.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]