Comparative efficacy of butorphanol versus nalbuphine for balanced anaesthesia and post- operative analgesia in patients undergoing laparoscopic surgery

This randomized double blind study was conducted in 60 patients, aged 20-60 years of age, of ASA physical status I and II scheduled to undergo elective laparoscopic surgeries. They were randomized and allotted into two groups. Group B received Inj Butorphanol 20 mcg/kg IV (n=30) and Group N received Inj Nalbuphine 0.2mg/kg IV (n=30), before induction of anesthesia with propofol. Intra-operative haemodynamic stability was assessed by monitioring heart rate, systolic and diastolic blood pressure. Post-operatively, pain was assessed using the VAS scale, and sedation was assessed using the Ramsay Sedation Score. Heart rate and diastolic blood pressures were lower in Group B after intubation, after insufflation of CO2, after 30 minutes, after 45 minutes, after extubation and during the post-operative period. Systolic blood pressure was lower in Group B after intubation, after insufflation of CO2, after 30 minutes and after 45 minutes. VAS pain scores were significantly lower in Group B at 6 hours and 8 hours post-operatively. Ramsay sedation scores were higher in Group B at 1hr, 2hrs, 4hrs, 6hrs and 8hrs postoperatively. From this study, it was concluded that Inj. Butorphanol 20 μg /kg was more efficacious when compared to Inj. Nalbuphine 0.2mg/kg as an analgesic for use in laparoscopic surgeries because of its ability to produce prolonged analgesia and better hemodynamic stability.


Introduction
Nalbuphine 1 is a semi-synthetic opioid agonistantagonist. Indicated for the relief of moderate to severe pain. It can also be used as a supplement to balanced anaesthesia. Butorphanol 2 is a morphinan-type synthetic agonistantagonist opioid analgesic. The most common indication for butorphanol is management of moderate to severe pain, as a supplement for balanced general anaesthesia. Butorphanol is also quite effective at reducing post-operative shivering.
Laparoscopic surgeries are also known as minimally invasive surgical procedures which are performed with assistance of video camera and several thin instruments. To perform a laparoscopic surgery, pneumoperitoneum should be created by insufflation with air or carbon dioxide. The created pneumoperitoneum causes several pathophysiological changes during surgery such as increase in systemic and pulmonary vascular resistance and extreme patient positioning.
Laparoscopic surgeries are commonly performed due to advantages like less post-operative pain and faster postoperative recovery. In this study, we compared Butorphanol and Nalbuphine as the analgesic component of balanced anaesthesia for laparoscopic surgeries.

Materials and Methods
After obtaining Institutional Ethical Committee approval, 60 consecutive patients posted for elective laparoscopic surgeries were enrolled for the study.

Preanaesthetic Evaluation
All patients underwent a routine pre-anaesthetic checkup as per the institutional protocol. An informed valid consent was taken from all the patients. Patients were given tab. Ranitidine 150mg and tab. Alprazolam 0.25mg the previous night. Nil per oral status of 8hrs was maintained for all patients.

Study Groups
The patients were randomized and allotted into two groups using a random number table. Group B received Inj Butorphanol 20 mcg/kg IV (n=30) and Group N received Inj Nalbuphine 0.2mg/kg IV (n=30) before induction.

Procedure Details
Venous access was secured with an 18 gauge intravenous cannula in the dorsum of the non-dominant hand. Ringer lactate solution was started at the rate of 4ml/kg/hr. Noninvasive blood pressure cuff, pulse oximeter and electrocardiography monitor (lead II and V5) were connected and basal parameters like heart rate, blood pressure and oxygen saturation were noted.
Group B or Butorphanol group: these patients were given Inj. Butorphanol 20mcg/kg intravenously 10 minutes before induction.
Group N or Nalbuphine group: these patients were given Inj. Nalbuphine 0.2mg/kg intravenously 10 minutes before induction.
Patients were pre oxygenated for 3 minutes with 100% oxygen followed by induction with Inj. propofol 2mg/kg. Neuromuscular blockade was achieved with Inj. Vecuronium bromide. Patient's trachea was intubated with appropriate sized endotracheal tube. Anaesthesia was maintained with 50% N2O, 50% O2 and Sevoflurane 1.5%. A lubricated Ryle's tube was then inserted to decompress the stomach.

Parameters Observed and Analyzed
Hemodynamic stability during the surgery was assessed by the following parameters-Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), End tidal Carbon dioxide (EtCO2) and oxygen saturation. These were observed and recorded at baseline, after administering the drug, after intubation, insufflation of CO2, 30 and 45 minutes after intubation. Heart rate and blood pressures were also recorded after extubation, and at 1hr, 2hrs, 4hrs, 6hrs and 8hrs post-operatively.
At the end of surgery, residual neuromuscular blockade was reversed with Inj. Neostigmine 0.05 mg/kg and Inj. Glycopyrolate 0.01 mg/kg intravenously. After extubation, vital parameters, sedation and pain scores were recorded. The VAS scale 3 was used to assess pain and the RAMSAY 4 score was used to assess sedation.
Patient was then shifted to the PACU. Vital parameters, sedation and pain scores were assessed at 1, 2, 4, 6 and 8 hours postoperatively. Patients were given Inj. Fentanyl 0.5mcg/kg intravenously when the VAS score was >3, which was repeated until the pain subsided.

Statistical Tools
The information collected regarding all the selected cases were recorded in Master Charts 1 and 2. Data analysis was done with the help of computer using Epidemiological Information Package (EPI 2008).
Using this software, range, frequencies, percentages, means, standard deviations, chi square and 'p' values were calculated. Kruskal Wallis chi-square test was used to test the significance of difference between quantitative variables and Yate's test for qualitative variables. A 'p' value less than 0.05 was taken to denote significant relationship.

Observations and Results
There was no statistically significant difference found between the two groups with respect to age and gender distribution. The heart rate was comparable between the two groups at baseline and after administering the drug. However, heart rate was significantly lower in group B after intubation, after insufflation of CO2, after 30 minutes, after 45 minutes, after extubation and during the post-operative period. The systolic blood pressure was comparable between the two groups at baseline, after extubation and during the postoperative period. However, it was significantly lower in Group B after intubation, after insufflation of CO2, after 30 minutes and after 45 minutes. The diastolic blood pressure was comparable between the two groups at baseline and after administering the drug. However, it was significantly lower in Group B after intubation, after insufflation of CO2, after 30 minutes, after 45 minutes, after extubation and during the post-operative period. Comparing post-operative pain scores between the two groups, there was no significant difference in the VAS pain scores at 1 hour, 2 hours and 4 hours post-operatively.
However, patients in Group B had significantly lower VAS pain scores at 6 hours and 8 hours post-operatively. Comparing the post-operative Ramsay sedation scores, the scores were significantly higher in the butorphanol group at 1 hour, 2 hours, 4 hours, 6 hours and 8 hours postoperatively.

Discussion
In our study, we found that Butorphanol and Nalbuphine were both cardio stable. However, Heart rate was significantly lower in group B (Butorphanol group) after intubation, after insufflation of CO2, after 30 minutes, after 45 minutes, after extubation and during the post-operative period. Systolic and Diastolic Blood Pressures were significantly lower in Group B after intubation, after insufflation of CO2, after 30 minutes and after 45 minutes. This shows that Butorphanol is more effective than Nalbuphine in attenuating the sympathetic response to direct laryngoscopy and endotracheal intubation and in blunting the surgical stress response.
Rao satyanarayana V, Srinivas B, Muralidar A et al 5 compared butorphanol and fentanyl for balanced anaesthesia in patients undergoing laparoscopic surgeries under general anaesthesia. Fifty patients of ASA I & II scheduled for elective laparoscopic surgery were randomized to butorphanol group and fentanyl group. There was significant rise in systolic & diastolic blood pressure after intubation in fentanyl group compared to butorphanol group.
R.K. Verma, S. Jaiswal, et al 6 compared butorphanol and fentanyl in total intravenous anaesthesia in laparoscopic cholecystectomy. In this study, patients received either inj. fentanyl 2 µg/kg or butorphanol 25µg/kg. All the patients were induced with inj. propofol and muscle relaxation with vecuronium. Anaesthesia was maintained by oxygen and propofol infusion. Suppression of sympathetic response to laryngoscopy and intubation was found to be better with Butorphanol than Fentanyl.
The above two studies had concluded that Butorphanol was more efficacious than Fentanyl in attenuating the haemodynamic stress response to direct laryngoscopy and endotracheal intubation Tariq M A, Iqbal Z, Qadirullah, et al 7 studied the efficacy of nalbuphine in preventing hemodynamic response to laryngoscopy and intubation. The nalbuphine group showed significantly lesser increase in mean arterial pressure and heart rate compared to control group after laryngoscopy and orotracheal intubation. They concluded that nalbuphine prevents marked rise in heart rate and mean arterial pressure associated with laryngoscopy and intubation.
In our study, there was no significant difference in the VAS pain scores between the two groups at 1 hour, 2 hours and 4 hours post-operatively. However, patients in Group B (Butorphanol Group) had significantly lower VAS pain scores at 6 hours and 8 hours post-operatively. This shows that Butorphanol provides longer duration of analgesia compared to Nalbuphine. Also, the Ramsay sedation scores were significantly higher in the Butorphanol group at all the time points post-operatively. There was no significant effect in oxygen saturation post-operatively.
F.N. Minai and F.A. Khan, et al 8 compared morphine and nalbuphine for intraoperative and post operative analgesia. They concluded that nalbuphine in a dose of 0.2mg/kg provided better analgesia and greater hemodynamic stability, as a component of balanced anaesthesia in lower abdominal surgery, with a lower incidence of nausea and vomiting in postoperative period compared to morphine 0.1 mg/kg.
The previous literature, however does not contain any study comparing Butorphanol and Nalbuphine for balanced anaesthesia. In our study, both Nalbuphine and Butorphanol provided good analgesia. The duration of analgesia was longer with Butorphanol than with Nalbuphine.