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Hyperbaric spinal ropivacaine in lower limb and hip surgery: A comparison with hyperbaric bupivacaine.

Objectives: In this clinical study hyperbaric ropivacaine in spinal anaesthesia for lower limb and hip surgery was evaluated and results obtained were compared with those using hyperbaric bupivacaine. Methodology: Two hundred patients scheduled for lower limb and hip surgery were randomly divided into two groups of 100 patients each. These patients received a spinal injection of either 3ml (15mg) of 0.5% hyperbaric ropivacaine or 3ml (15mg) of 0.5% hyperbaric bupivacaine using 25G Quincke type spinal needle. The parameters studied were onset and total duration of sensory block, onset and total duration of motor block, quality of intraoperative anaesthesia, hemodynamic alterations, and any intraoperative and postoperative complications. Results: The mean onset of sensory block (6±1.3min vs. 3±1.1min; p value<0.05) and motor block (13±1.6min vs. 9±1.3min; p value< 0.05) was significantly slower in ropivacaine group as compared to bupivacaine group. The total duration of sensory block was significantly shorter in ropivacaine group (160±12.9min) than in bupivacaine group (260±16.1min; p value <0.05). The mean duration of motor block was also shorter in ropivacaine group compared to bupivacaine group (126±9.2min vs. 174±12.6min; p value<0.05). Conclusion: The quality of anaesthesia was excellent in both the groups. In conclusion, a solution of ropivacaine (hyperbaric) can be used for spinal anaesthesia and is comparable with hyperbaric bupivacaine in terms of quality of block, but has shorter recovery profile.


INTRODUCTION
Bupivacaine, an amino amide compound, was synthesized and introduced into the clinical practice in 1963 and proved to be a very effective long acting local anaesthetic agent. In 1979, Albright drew attention to the dangers of the longer acting local anaesthetic agents, bupivacaine and etidocaine, in case they gained accidental intravascular access 1 . However, studies in animals 2 indicate that bupivacaine, when injected intravascularly, induces a dose and rate dependent depression of drug elimination, resulting in re-entrant arrhythmias and cardiac depression, sometimes culminating in cardiac arrest. These shortcomings of this otherwise novel local anaesthetic resulted in the development of more new anaesthetic agent 'ropivacaine'. Isomers of this local anaesthetic are reported to be least toxic as compared to racemic compounds 3 .
Ropivacaine, a new amino-amide local anaesthetic agent is similar in chemical structure to bupivacaine 3,4 . It is presented as a single-enantiomer and has been used extensively for the local infiltration, epidural, and peripheral blocks. Extensive clinical data have shown that ropivacaine is effective and safe for regional anaesthetics techniques such as epidural and brachial plexus block 5 . However hyperbaric ropivacaine has been little studied in intrathecal anaesthesia. The purpose of this study was to evaluate the efficacy and safety of hyperbaric ropivacaine in spinal anaesthesia and to compare it with hyperbaric bupivacaine in lower limb and hip surgeries.

MATERIAL AND METHODS
The study was performed at Govt. Medical College Srinagar, after institutional approval and after obtaining informed written consent of the patients undergoing lower limb and hip surgery under spinal anaesthesia. Inclusion criteria were age ≥ 40 and ≤ 75 years and American Society of Anesthesiologists (ASA) physical status classification I -II. Exclusion criteria were bleeding disorders, neurological, disorders, reluctance to get operated under spinal anaesthesia, local skin infection, severe back deformities, raised intracranial pressure, moderate to severe valvular lesions. The patients were divided into two groups of 100 patients each under: Group R (Ropivacaine Group): This group consisted of 100 patients who received 3ml intrathecal injection of 0.5% hyperbaric ropivacaine. Group B (Bupivacaine Group): This group consisted of 100 patients who received 3ml intrathecal injection of 0.5% hyperbaric bupivacaine. Preanaesthetic evaluation was done at least 24 hours prior to surgery. Tablet alprazolam 0.25mg to 0.5mg night before surgery was prescribed to the patients. Patients were advised to be nil orally from midnight before surgery. On the day of surgery, intravenous line was established on the non-dominant hand using 16G size intravenous cannula and intravenous fluid (Ringer lactate) started. The multi-channel monitor (Mindrays-BeneVeiw T8, Instromedix India) was attached and base line parameters viz pulse rate, blood pressure (systolic, diastolic & mean) ECG (lead II, V) and SpO 2 were recorded. Under all aseptic precautions, the subarachnoid blocks were performed using 25G Quincke spinal needle at L3-L4 intravetebral space. After the block, vitals were monitored every 2 minute up to 16 minutes and thereafter, every 5 minutes interval till completion of surgery. Oxygen 4L/min was administered through Hudson facemask throughout the procedure. The onset of sensory block to T10 level was taken as the time from injection of anaesthetic solution to start of loss of sensation to pin prick at T10 level. The sensory block was tested at every 2 minute intervals till the establishment of the block and every 5minutes during surgery. Total duration of sensory block was taken as complete recovery of sensory block. After the completion of the surgery, the sensory block was tested at 15minute intervals till its complete regression. Motor block was assessed using modified Bromage scale by asking the patient to flex the limb at hip, knee, and ankle joints (Grade 0: No paralysis, Grade1: Inability to raise extended leg, can bend knee, Grade 2: Inability to bend knee, can flex ankle, Grade 3: No movement). Onset time of motor blockade was taken as the time to acquire complete motor block (grade 3) after the intrathecal injection of local anaesthetic and total duration was taken as time to regain complete recovery from motor block. Quality of intraoperative anaesthesia was assessed using "Four Grade Scale" 6 which is defined as:-

Excellent:
No supplementary sedative or analgesia required. Good: Only sedative required Fair: Both sedative and analgesic required. Poor: General anaesthesia and tracheal intubation required.
Bradycardia (heart rate <60 beats/min) when encountered, was recorded and treated with intravenous atropine which was administered in small incremental doses. Hypotension (systolic blood pressure <30% from baseline) when encountered, was recorded and treated with intravenous ephedrine which was administered in small incremental doses. The patients were observed for first 24 hours for nausea, vomiting and any other complications.
Data were entered and analyzed with the Graph Pad.com (version 5, 2010). Data were presented as median (range), mean or frequencies, as appropriate. Nominal patient's characteristics and the duration of surgery were compared using the Fisher's exact test. A Bonferroni correction was applied for multiple two-way testing. In all categories P<0.05 was considered statistically significant. Pulse and blood pressure were compared using Multiple comparison test (Dennett test), q value >2.740 considered statistically significant (p value<0.05).

RESULTS
The characteristics of the two groups were comparable in terms of age, sex, weight, gender and ASA classification ( Table 1).
The mean onset of sensory block at T10 level (6±1.3min vs. 3±1.1min; p value<0.05) and motor block (13±1.6min vs.9±1.3min; p value< 0.05) was significantly slower in ropivacaine group as compared to bupivacaine group (Table. 2) (Figure.2). The mean duration of sensory block was significantly shorter with ropivacaine group (160±12.9min) than with bupivacaine group (260±16.1min; p value <0.05). The mean duration of motor block was also shorter in ropivacaine group compared to bupivacaine group (126±9.2min vs. 174±12.6min; p value<0.05) (Figure 2). The intraoperative quality of anaesthesia was excellent and similar in both groups. However it was fair in 1% in bupivacaine group and 3% patients in ropivacaine group. It was statistically insignificant between the two groups (p value>0.05). None of the patients in both the groups had poor quality of anaesthesia (Table. 2).
Hypotension was the most common side effect in both groups. There was a significant difference in the incidence of hypotension between the two groups (p value<0.05).
In bupivacaine group, 66 patients (66%) developed hypotension while in ropivacaine group only 19 patients (19%) developed hypotension (Table. 2) (Figure.3). The incidence of bradycardia, nausea, vomiting and shivering during intraoperative period did not differ significantly between the two groups (p value>0.05) ( Table 2). The two groups did not differ significantly in regards as nausea and vomiting (p value>0.05).

DISCUSSION
The present study confirmes the findings of a previous studies 7,8 that a glucose-containing solution of ropivacaine can produce predictable and reliable spinal anaesthesia for a wide range of surgical procedures. However present study is in variance with the results of the two early clinical studies, which have described blocks with ropivacaine inadequate for surgery 9,10 . The variance can be because these authors have used glucose-free solutions of ropivacaine. The variation confirms that the addition of glucose to solution of ropivacaine has the same effect as with other drugs 11,12,13,14 . In present study, the hyperbaric solution of 0.5% ropivacaine was prepared aseptically by mixing 5ml of 0.75% isobaric ropivacaine (Ropin ® , Neon, India) with 2ml of 25% dextrose and 0.5ml sterile water at room temperature. This gave a total volume of 7.5ml and resulting in a final glucose concentration of 6.6% in hyperbaric ropivacaine solution with specific gravity of 1.02450 at room temperature 15 .
In the present study, the onset of both sensory and motor block was delayed in ropivacaine group as compared to bupivacaine group. The total duration of sensory and motor block was also shorter in ropivacaine group as compared to bupivacaine group. The present study correlates with various authors 16,17,18,19,20 who also found earlier onset of sensory block to T10 level and longer duration of sensory block with hyperbaric spinal bupivacaine compared to hyperbaric spinal ropivacaine, which was statistically significant. This may be because of higher lipid solubility and slightly higher protein binding of bupivacaine as compared to ropivacaine. Lipid solubility is important determinant of local anaesthetic activity. The onset time of conduction block is directly correlated with the lipid solubility of local anaesthetic 21,22 . Increased lipid solubility increases sequestration of local anaesthetic in myelin and other surrounding neural compartments. Thus, action is increased as absorption of local anaesthetic molecule into myelin and surrounding neural compartments creates a depot for slow release of local anaesthetic 23 . This observation may be explained by a correlation between lipid solubility and both sodium channel receptor affinity and ability to alter sodium channel conformation by direct effects on lipid cell membranes. In general, the more lipid soluble and longer acting agents have increased protein binding. The lesser lipid solubility of ropivacaine may cause this drug to penetrate the large myelinated A fibers more slowly than the more lipid soluble bupivacaine 24 . It is also postulated that because ropivacaine is less lipophilic it has a greater effect on the non-myelinated pain fibres rather than the myelinated motor fibers 25 . Although the patients' satisfaction to recovery of motor block was not assessed clinically and objectively in this study, earlier recovery with spinal ropivacaine is associated with more patient satisfaction 20,26 .
We found no evidence of any late sequelae such as backache or other transient symptoms in this study and this correlates with the previous studies of ropivacaine when used in spinal anaesthesia 7,15 .
In the present study, intrathecal ropivacaine produced excellent intraoperative anaesthesia, indistinguishable from spinal bupivacaine. Statistically the difference in quality of anaesthesia was insignificant between the two groups. The present study correlates with those of Osama-Al-Abdulhadi et al 26 and J.F Luck et al 27 who also found statistically insignificant difference in quality of anaesthesia between ropivacaine and bupivacaine when given intrathecally.
Hypotension was the most common side effect in both groups. There was a significant difference in the incidence of hypotension between the two groups. The studies of various authors 6,28,15 supports our results of low incidence of hypotension in hyperbaric ropivacaine but the exact cause of low incidence of hypotension as compared to bupivacaine is not established. The intraoperative and postoperative complications (bradycardia, nausea, shivering, vomiting) did not differ significantly between the two groups.

CONCLUSION
A solution of ropivacaine (hyperbaric) can be used for spinal anaesthesia and is comparable with hyperbaric bupivacaine in terms of quality of block, but has shorter recovery profile. Values are expressed as mean ± standard deviation (SD) or no. of patients