European Journal of Cardiovascular Medicine

Spinal anaesthesia offers reliable and efficient analgesia during the perioperative phase.(1)For orthopaedic surgeries of lower limb, spinal anaesthesia is a simple, affordable and ideal approach because it offers quick onset and efficient sensory and motor block along with reduced stress response and fewer thromboembolic events.(2)

Bupivacaine, though was the preferred drug for sub-arachnoid block has a notably extended duration of motor block which lengthens the time spent in the PACU. Furthermore, bupivacaine has greater neurological and cardiac toxicity.(3) from severe over doses or unintentional intravascular injections leading to sudden cardiac arrest even refractory to resuscitation.

Ropivacaine and Levobupivacaine are newer amide local anaesthetic drugs which are pure levo-isomers and cause lesser CNS and cardiovascular adverse effects, attributed to their three-dimensional structure.(4)Ropivacaine is known for its lesser lipophilicity than bupivacaine. Hence, poorly penetrates the large myelinated motor fibres and results in a decreased motor block and a reduced potential for CNS and cardiovascular toxicity.(5) Levobupivacaine on the

other hand has a reduced potential to block inactivated Na+ K+ channels and also has a quicker rate of dissociation. Most human, in vivo and in vitro pharmacodynamic research on nerve block show that levobupivacaine is less likely to cause cardiovascular and CNS toxicity than bupivacaine while maintaining a similar potency.(6)

Several theoretical and experimental clinical research have examined the clinical characteristics and toxicity of these drugs using various dosages. Even though certain distinctions have been noted, it is too soon to tell how these qualities will affect clinical practice. Many of these studies conducted have used isobaric preparations of these drugs and there is less evidence to compare the clinical efficacy of hyperbaric preparations of these drugs. Therefore, the purpose of my study is to examine the therapeutic effectiveness of equipotent solutions of 0.75% hyperbaric Ropivacaine with 0.5% hyperbaric Levobupivacaine in spinal anaesthesia. Null hypothesis of my study is that there is no statistically significant difference in the duration of analgesia achieved by 0.75% hyperbaric ropivacaineand 0.5% hyperbaric levobupivacaine for spinal anaesthesia in lower limb orthopaedic surgeries.

The aim of this study is to compare the block characteristics between 0.75% hyperbaric ropivacaine and 0.5% hyperbaric levobupivacaine for spinal anaesthesia in patients undergoing orthopaedic surgeries of lower limb. The primary objective being comparison of the duration of analgesia and the secondary objectives are to compare the onset and regression of sensory and motor blocks between the two groups along with their effect on hemodynamic parameters.

This ‘randomized, double-blinded (patient and observer), single hospital-based’ study was conducted after taking approval from the Institutional Ethical Committee and fulfilling all the norms. Informed and written consent was obtained from the participants of the study. This study was registered with Clinical Trial Registry- India (CTRI/2024/03/064415).

Patients scheduled for elective orthopaedic surgeries of lower limb under spinal anaesthesia aged between 18-60 years, ASA grade 1 and 2, expected duration of surgery less than 3 hours and agreeing to the informed and written consent were included in the study. The patients refusing consent, with history of allergic reactions to Local Anaesthetics, coagulopathy, neurological disorders, severe cardio, respiratory, hepatic and renal disease or spinal deformity and patients with previous spinal surgery were excluded from our study.

Based on previous study (7) ,considering the duration of analgesia as 143.2 ± 20.3 mins, to detect a difference of 15 mins with level of significance 5%and power of study80%, 29 patients were needed in each group. Considering an attrition rate of 20%, we have taken 35 patients each in both groups, which makes the sample size (n) = 70 patients.

Patients were randomly allocated into two groups, Group A and Group B, by a computer-generated random sequence using block randomization with blocks of variable sizes. Concealment of allocation was ensured with the use of opaque sealed envelope technique. For Group A (n = 35); 15mg 0.5% (3 ml) hyperbaric Levobupivacaine and for Group B (n = 35) 22.5mg 0.75% (3 ml) hyperbaric Ropivacaine was prepared.

After shifting the patient into operation theatre table an intravenous line with 18G cannula was established, the routine monitoring devices were applied and the baseline vital parameters were recorded. Under all aseptic and antiseptic precautions the prepared drug was administered intrathecally over 10 seconds. Immediately after delivering the drug, the needle was pulled out and the patient was then laid down in supine position.

Considering the time of intrathecal injection as zero the onset of sensory block, time to reach maximum dermatomal level of sensory block, time for regression of two dermatomes, time for regression of sensory block to T12, onset of motor block, time to reach Bromage 3, duration of motor block and duration of analgesia was recorded:(8)The level of sensory block achieved was estimated in the anterior axillary line bilaterally, as lack of cold sensation using alcohol swab. Recordings were taken after every 3 minutes for the initial 15min then after every 5 minutes for the following 30 min and then at every 15 minutes till regression of sensory block to T12 level. Pain assessment using NRS Score was done at 2 hours, 4 hours, 6 hours and 8 hours in the postoperative period. Rescue analgesia was administered when the NRS score reached 4 or more than 4, with inj. diclofenac sodium 75 mg IM and the time was noted.(8)The level of motor block achieved was recorded using modified Bromage scale(9)at every 3 min interval for the initial 15 min, then at 5 min intervalsfor next 30 min and then at every 15 minutes till complete regression of motor block.

Any haemodynamic adverse events occurring during surgery was also recorded. Hypotension was treated with iv infusion of Ringer lactate 200ml and iv bolus of 6 mg mephentermine. Iv atropine (0.5 mg) was used to treat bradycardia. The patients were also assessed for any possible adverse effects such as nausea, vomiting, pruritus, headache or any other related complications.

The data that was collected was then entered into MS-Excel spreadsheet and analysis of the data was performed. Descriptive and inferential statistics were used for analysis. The SPSS software version 21.0 was utilised to perform the statistical analysis. Statistical significance between the groups were interpreted as:-

p-value>0.05=not significant,

p-value<0.05= significant.

The flow of patients in our study depicted in the consort diagram

Patient characteristics are summarised in Table 1, with no significant difference in demographics.

Table 1: Demographic variables and Duration of surgery

The onset of sensory block differed significantly between the groups.The maximum upper spread of sensory block reaching T6 was observed in 34.28% of patients in Group A and 28.57% of those in Group B. Though the time to reach maximum level of sensory block did not differ significantly between the groups, but the time for 2 segment regression of sensory block and the mean time for regression of sensory block to T12 was significantly different between the groups.

The mean time for onset of motor block, time to reach Bromage 3 and the mean duration of motor block showed significant difference.

There was no significant differences between the groups regarding duration of analgesia and postoperative NRS pain scores.

In this study, it is seen that systolic blood pressure varies significantly (p<0.05) at 5mins, 10mins and 75mins between the two groups. The diastolic blood pressure varies significantly (p<0.05) at 5mins, 30mins and 180mins between the two groups. The variation of heart rate remained statistically insignificant (p<0.05) at between the two groups.

It was found in our study that 2 patients (5.71%) in Group A presented with nausea compared to 1 patient (2.85%) in Group B (p-value=0.5551). None of the patients had bradycardia in Group A whereas 1 patient (2.85%) in group B had bradycardia requiring injection atropine. Hypotension was observed in 2 patients group A and 3 patients in group B (p-value=0.6425) which required treatment with vasopressors. One patient in group A experienced shivering compared to none in group B (p value<0.05).

We have used hyperbaric levobupivacaine 0.5% (15mg) for Group A and hyperbaric ropivacaine 0.75%(22.5mg) for Group B as past studies (10,12)  have suggested Levobupivacaine to be 1.5 times more potent than Ropivacaine. In our study the mean duration of analgesia was found to be comparable for the two drugs, similar to that found by Dionel et al(15).However, J. F. Luck et al.(14)found the median duration of sensory block to be significantly longer for levobupivacaine compared to ropivacaine which may be attributed to the use of non-equipotent doses of the two drugs in their study. could be the probable reason for such difference.

In our study, the mean time of onset of sensory block for levobupivacaine was longer than that for ropivacaine similar to that found by Athar et al.(11). The findings from various authors about the onset of sensory blocks show ample variations with some having no significant difference.(14) while others concluding the difference to be significant.(7).The discrepancies in the results of various investigations regarding onset time may be due to factors such as sample size, demographic composition, methodology, drug dosage and baricity.

In both the groups in our study, sensory block has reached the median maximum dermatomal height of T7. The use of hyperbaric solutions of both drugs in our study could be the probable factor behind such comparable results. Many previous studies have concluded hyperbaric drugs to produce more reliable sensory and motor blocks.(16)

Although the mean time to reach maximum level of sensory block was longer in levobupivacaine group than ropivacaine, we found the distribution to be statistically not significant which is consistent with the findings by J. F. Luck et al.(14) However, the study that was conducted by Athar et al(11) found the mean time for reaching maximum level of sensory block to be significantly longer with levobupivacaine. The use of isobaric preparations of the study drugs was probably the reason behind such significant difference between the two groups.

In our study the mean time for 2 segment regression of sensory block and the mean time for regression of sensory

block to T12 was significantly longer in levobupivacaine group compared to the ropivacaine group. Mantouvalou et al. (13) and Athar et al.(11) found similar results in their study. However, the mean time for regression of sensory block to T10 in the study conducted by Gautier et al.(17)was comparable in the levobupivacaine and ropivacaine groups which could be attributed to the difference in sample population which included only pregnant patients and applied methodology such as isobaric drugs with sufentanil as adjuvant and dilution of drugs with normal saline to produce equal volume.

Our study found the onset of motor block to Bromage 1and the time for motor block to reach Bromage 3 and was significantly faster in ropivacaine group. Some studies have found slower onset of motor block and slower time for motor block to reach Bromage 3 with the difference statistically not significant Mantouvalou et al.(13) by J. F. Luck et al(14) which again might be attributed to the non-equipotent dose of drugs used. Our study found that the mean duration of motor block was significantly shorter for ropivacaine compared to levobupivacaine. In the studies conducted by Mantouvalou et al.(13)J. F. Luck et al.(14) and Athar et al(11) also found similar results. The median post-operative NRS score was found to be comparable between the two groups. The study conducted by Gautier et al.(17)also found the score of quality and VAS to be similar in both the groups.

Decrease in BP and HR are the two most commonly observed side effects of neuraxial blocks. It was noted in our study that both the ropivacaine and levobupivacaine groups experienced a brief drop in blood pressure, although the incidence of ‘transient hypotension’ was found to be slightly higher in the ropivacaine group. However, cases were swiftly treated without resulting in any serious repercussions. The overall haemodynamic parameters were found to be comparable in both the groups. The increased incidence of transitory hypotension reported with ropivacaine may be related to the faster attainment of maximum block height compared to levobupivacaine, resulting in a drop in blood pressure. Similar findings were also evident in the study conducted by Parpaglioni et al.(18)With respect to minor side effects such as dry mouth, nausea/ vomiting, shivering etc. no significant difference between two groups were observed.

Limitations-

The study does have some significant drawbacks. Our inclusion criteria was adults who are generally healthy and it's unclear how it will affect patients who have associated comorbidities. Age, height and weight-based dose standardisation were not done in this study. The quality of block and patient recover profile (time for mobilisation and time for micturition) was not assessed in our study.

We accept the null hypotheses of our study and conclude that there is no significant difference with respect to the duration of analgesia between hyperbaric solutions of 0.75% ropivacaine and 0.5% levobupivacaine when used for spinal anaesthesia in patients undergoing elective lower limb orthopaedic surgeries .Spinal anaesthesia with hyperbaric 0.75% ropivacaine produces faster onset of sensory block. However, the maximum dermatomal height of sensory block and the time required to achieve maximum dermatomal height are comparable between both the drugs. Hyperbaric 0.75% ropivacaine also produces faster onset of motor block and the regression of both sensory block as well as motor block is significantly faster with hyperbaric 0.75% ropivacaine compared to hyperbaric 0.5% levobupivacaine. Both the drugs are comparable with respect to haemodynamic parameters and adverse effects.

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