INTRODUCTION:

Spinal anaesthesia, or sub-arachnoid block (SAB), is widely used for lower limb and lower abdominal surgeries. It has been the mainstay of regional anaesthesia in developing countries, especially India. Starting with cocaine way back in 1898, various local anaesthetics have been used to achieve intrathecal blockade. However, nowadays, bupivacaine is being extensively used and produces an adequate sensory and motor blockade.¹ However, it has its disadvantages and side effects, such as cardiac and central nervous system toxicity.²

Local anaesthetics’ acute and most serious adverse effects involve the cardiovascular and central nervous systems.³ They are usually because of accidental intravascular injections or an apparent overdose. These adverse effects have prompted a search for drugs with lesser toxicity.

Newer long-acting local anaesthetics (ropivacaine, levobupivacaine) have recently been introduced for clinical use. The claimed benefits are reduced cardiac toxicity on overdose and more specific effects on sensory rather than motor nerve fibres.^4-7 Ropivacaine was found to have less cardiotoxicity than bupivacaine in animal models. Unlike bupivacaine, ropivacaine has been developed and marketed as the pure S (-) enantiomer of ropivacaine. It is less lipophilic than bupivacaine. This property is associated with a decreased potential for CNS toxicity and cardiotoxicity.⁸ Hyperbaric ropivacaine 0.75% has been introduced in India in 2022. Besides being well tolerated and safe, ropivacaine has a short time to onset of anaesthesia. It results in a sensory and motor blockade of a duration appropriate for the indication or procedure.

In this study, we compare the efficacy of 22.5 mg (3ml) of 0.75% hyperbaric ropivacaine with a control group using 15 mg (3ml) of 0.5% hyperbaric bupivacaine. 

REVIEW OF LITERATURE:

Whiteside et al.⁹ in 2003 compared the clinical efficacy of hyperbaric ropivacaine with that of bupivacaine commercially available hyperbaric preparation. They observed that All blocks were adequate for the proposed surgery, but there were significant differences between the two groups in mean time to onset of sensory block at T10 (ropivacaine 5 min; bupivacaine 2 min; P<0.005), median maximum extent (ropivacaine T7; bupivacaine T5; P<0.005) and mean duration of sensory block at T10 (ropivacaine 56.5 min; bupivacaine 118 min; P=0.001). Patients receiving ropivacaine mobilised sooner (ropivacaine mean 253.5 min; bupivacaine 331 min; P=0.002) and passed urine sooner (ropivacaine mean 276 min; bupivacaine 340.5 min; P=0.01) than those receiving bupivacaine. More patients in the bupivacaine group required treatment for hypotension (>30% decrease in systolic pressure; P=0.001). They found that ropivacaine 15 mg in glucose 50 mg ml-1 provides reliable spinal anaesthesia of shorter duration and less hypotension than bupivacaine. The recovery profile for ropivacaine may be of interest given that more surgery is being performed in the day-case setting.

Kallio et al.¹⁰ in 2004 carried out a study in which they compared plain intrathecal solutions containing ropivacaine 15 and 20 mg versus bupivacaine 10 mg in a prospective, randomised, double-blinded study. This study included 90 ambulatory lower-extremity surgery patients who received 2 ml of ropivacaine 1%, ropivacaine 0.75%, or bupivacaine 0.5%. All patients in the hyperbaric group achieved T10 dermatome analgesia but only 64% (18/28) of the plain group. T10 analgesia was reached in 5 min (median, range 5–20 min) in the hyperbaric group vs 10 min (5–45 min) in the plain group (P=0.022), and complete motor block in 10 min (5–45 min) vs 20 min (5–60 min) (P=0.003), respectively. The hyperbaric group had a longer duration of analgesia at T10; 83 min (5–145 min) vs 33 min (0–140 min) (P=0.004). Duration of the sensory block from the injection of the anaesthetic to complete recovery was shorter in the hyperbaric group than in the plain group, 210 min (120–270 min) vs 270 min (210–360 min) (P<0.001), as was the duration of motor block, 120 min (5–150 min) vs 210 min (120–330 min) (P<0.001). They found that patients of the hyperbaric group attained discharge criteria earlier than those of the plain group (P=0.009). Compared with the plain solution, 15 mg of intrathecal hyperbaric ropivacaine produced a faster onset, greater success rate of analgesia at the level of T10 dermatome, and faster recovery of the block.

Camera et al.¹¹ in 2007 conducted a study to determine the median effective dose (ED50) for a motor block of intrathecal ropivacaine, levobupivacaine, and bupivacaine and to define their motor-blocking potency ratios. As assessed using up-down analysis, intrathecal ED50 for the motor block was 5.79 mg for ropivacaine (95% CI 4.62–6.96), 4.83 mg for levobupivacaine (95% CI 4.35–5.32) and 3.44 mg for bupivacaine (95% CI 2.55–4.34) (P<0.001). The relative motor blocking potency ratios were ropivacaine/bupivacaine 0.59 (95% CI, 0.42–0.82), ropivacaine/levobupivacaine 0.83 (95% CI 0.64–1.09), and levobupivacaine/bupivacaine 0.71 (95% CI 0.51–0.98). They concluded that there is a clinical profile of potency for the motor block for the pipecoloxyxylidines when administered spinally: low, intermediate and high for ropivacaine, levobupivacaine and bupivacaine, respectively.

Mantouvalou et al.¹² in 2008 performed a study to compare the anaesthetic efficacy and safety of three local anaesthetic agents: racemic bupivacaine and its two isomers: ropivacaine and levobupivacaine, in patients undergoing lower abdominal surgery. One hundred fifty patients, ASA I-III, were randomised to receive an intrathecal injection of three local anaesthetic solutions. The onset of motor block was significantly faster in the bupivacaine group than in the ropivacaine group and almost the same in the levobupivacaine group (P < 0.05). Ropivacaine presented a shorter motor and sensory block duration than bupivacaine and levobupivacaine (P < 0.05). 

Sanchez et al.¹³ in 2009 compared the effects of intrathecal isobaric ropivacaine (IR) versus isobaric bupivacaine (IB) in a dose ratio of 3:2 in non-ambulatory urologic and orthopaedic surgery. One hundred seventeen patients scheduled for surgery were randomised and assigned in a double-blind fashion to receive either 15mg of IR (n=58) or 10 mg of IB (n= 59). They concluded that the motor blockade was longer in the Intrathecal bupivacaine Group (266.5+/- 29.5) compared to the Intrathecal ropivacaine Group (226.4 ± 22.3 min), p < 0.001. They found the duration of the motor blockade to be prolonged with bupivacaine (15 mg) when compared with ropivacaine (21.5 mg).

VRR Chari et al.¹⁴ in 2013 carried out a study in which they compared intrathecal isobaric solution containing ropivacaine 21.5 mg versus hyperbaric bupivacaine 15 mg in a prospective, randomised, double-blinded study. This study included 100 ambulatory lower-extremity surgery patients who received 3 ml of ropivacaine 0.75% or bupivacaine 0.5%. They observed that the sensory onset was significantly delayed in the Ropivacaine group (42.6 ± 11.39 min) compared to the Bupivacaine group (18.4 ± 6.53 min), P<0.001. The motor onset was also significantly delayed in the Ropivacaine group (55.54 ± 13.01 min) compared to the Bupivacaine group (27.5 ± 8.03 min), P<0.001. The peak sensory time was significantly delayed in the Ropivacaine group (10.92± 2.60 min) compared to the Bupivacaine group (7.38 ± 1.69 min), P<0.001. The peak motor time was also significantly delayed in the Ropivacaine group (8.92 ± 2.41 min) compared to the Bupivacaine group (4.82 ± 1.22 min), P<0.001. The two dermatomal sensory segment regression was significantly prolonged in the Ropivacaine group (117.2 ± 12.5 min) compared to the Bupivacaine group (108.5 ± 10.61 min), P<0.001. The duration of motor blockade was significantly prolonged in the Bupivacaine group (190.2 ± 28.37 min) compared to the Ropivacaine group (149.7±8.60 min), P<0.001. Intrathecal plain ropivacaine might be superior to bupivacaine in terms of a more extended sensory block and a shorter motor block duration. They concluded that 0.75% isobaric ropivacaine can be safely used in the lower limb and lower abdominal surgeries, especially in cases where early ambulation is desired.

 AIMS AND OBJECTIVES:

PRIMARY OBJECTIVE:

To compare the onset and duration of sensory and motor block in patients undergoing lower abdominal and lower limb surgeries when hyperbaric 0.75% ropivacaine or hyperbaric 0.5 % bupivacaine are used for spinal anaesthesia.

SECONDARY OBJECTIVE:

To observe hemodynamic changes following administration of hyperbaric ropivacaine and bupivacaine.

MATERIAL AND METHODS:

The study will be conducted after institutional ethics committee approval. Written informed consent from patients will be obtained.

STUDY SITE:

Manipal hospital, Old Airport Road, Bangalore 560017.

 STUDY POPULATION:

Forty-four patients of either gender older than 18 years of American Society of

Anaesthesiologists (ASA) physical status I and II undergoing lower abdominal

and lower limb surgeries will be studied.

STUDY DESIGN:

A prospective randomised study.

INCLUSION CRITERIA:

·         Age between 18 years - 70 years undergoing lower abdominal and lower limb surgery under subarachnoid block.

·         Patients willing to get enrolled in the study.

·         ASA physical status I or II.

 EXCLUSION CRITERIA:

·         ASA III and IV

·         Contraindications to spinal anaesthesia

·         Known hypersensitivity to local anaesthetics

·         Presence of hemodynamically relevant cardiovascular co-morbidities 

·         Presence of spinal deformities/disability / handicap

·         Pregnancy

STUDY PERIOD:

This study will be conducted over two years (2022-2024). 

Sample size:

44 (22 in each group)

SAMPLE SIZE CALCULATION:

 A study by V.R.R.Chari et al.14 found the peak sensory onset of hyperbaric bupivacaine time to be 7.38±1.69 mins. The sample size was calculated using the online calculator http://powerandsamplesize.com/Calculators/Compare-2-Proportions/2-Sample-Equality using the 2-mean method, with type 1 error rate α to be 5% and power 1-β to be 0.80 is 22 in each group.

SAMPLE DESIGN:

44 people will be randomly divided into 2 groups. 1 group will receive 3ml (15mg) of 0.5% hyperbaric Bupivacaine, and the other group will receive 3 ml (22.5mg) of 0.75% hyperbaric Ropivacaine.

 METHODOLOGY:

Patients undergoing lower limb surgeries and lower abdominal surgeries who fulfil the inclusion and exclusion criteria will be included in the study.

Preoperatively: A thorough pre-anaesthetic assessment and classification as per ASA status will be conducted before the operation. A fasting period of 6 hours or overnight fasting will be ensured for all patients. Written informed consent will be taken from all patients. The patients will be explained the anaesthetic procedure and the possible complications related to the procedure. The patients will be told that they may leave the study if they wish at any time.

On the day of surgery: patients will be preloaded with 10ml/kg of the crystalloid solution via a large bore IV cannula which will be started 10 minutes before giving the block. Standard monitors will be connected for continuous monitoring of BP, Pulse, oxygen saturation (SpO2) and ECG. Baseline vitals will be recorded. All drugs and equipment required for a spinal block, resuscitation equipment and emergency drugs will be readily available before giving the block.

Patients included in the study will be randomly divided into 2 groups by sealed envelope technique. The study drug will be administered by an anaesthesiologist who will not be involved in the data collection. The block characteristics will be assessed by an independent investigator blinded to the group allocation. 

Bupivacaine group: In this group, patients will receive an intrathecal injection of 3 ml (15 mg)of 0.5% hyperbaric Bupivacaine.

Ropivacaine group: In this group, patients will receive an intrathecal injection of 3 ml 22.5 mg of 0.75% hyperbaric Ropivacaine. 

 Spinal anaesthesia will be performed in a sitting position using a 27G Whitacre spinal needle via the midline approach in the L3-L4 or L4-L5 space, following the current protocol for spinal anaesthesia for lower abdominal and lower limb surgeries. After the injection of spinal medication, the patient will be turned supine. 

Time of onset and level of sensory analgesia:

Block, defined as a lack of sharp sensations to pinprick, will be assessed on both sides of the trunk using pinprick in a standardised manner on each patient, using a standardised explanation. Pinprick will be assessed using a short bevel 25 gauge applied initially on the clavicle, which will be used as a reference point. Then beginning at L1, in the mid-clavicular line, a pinprick will be applied to the skin every 2cm each time, asking the patient if she can feel the prick and moving more cephalad until sensations perceived are as sharp as that felt at the reference point. The onset of anaesthesia will be marked by achieving a dermatomal block of T10-T12. The maximum cephalic height of the block and the time interval to achieve it will be recorded by loss of pinprick sensation at this level.

Time of onset and duration of motor block:

The modified Bromage scale will be used to assess the degree of motor blockade.

Degree of motor blockade (modified Bromage scale):

Assessment of sensory loss and motor block scores will be made at 1 minute, after the spinal during the first 10 mins, then at 15 mins intervals between 30 and 120 mins and after that at 30 minutes intervals until complete recovery. Complaints of chest discomfort, nausea, vomiting and alteration of sensorium will be watched and recorded every hour. Regression of the block to the S2 level will be recorded by pinprick to determine the duration of the block.

Fall of SBP>20% of baseline or DBP >10% will be considered hypotension. Hypotension will be treated with intermittent boluses of injection Ephedrine 6mg IV. HR>20% of baseline will be considered bradycardia and treated with atropine 0.6 mg IV. Spo2 fall of below 95% will be treated with O2 via mask 4 - 6 litre. 

Subsequently, the patient will be transferred to the Post Anaesthesia Care Unit (PACU), where residual sensory blockade will be monitored, and its wearing-off time will be noted (when sensation to pinprick regressed by two-dermatome segment – T5). The residual motor blockade will be monitored, and its wearing-off time will be noted (when the patient starts to lift legs against gravity – T6). Patients will be transferred from the PACU after recording the two-segment sensory regression and motor wear-off time. Post-operative side effects like nausea, vomiting, urinary retention and transient neurological deficits in limbs will be noted.

PARAMETERS TO BE STUDIED:

a) Onset of anaesthesia (Time taken to achieve a block height of T10-T12)

b) Time taken for peak sensory block.

c) Duration of anaesthesia (Time of regression of block to S2 level)

d) Complications (Hypotension, bradycardia, nausea and vomiting)

e) Any other post-operative complications.

STUDY TOOLS:

a) 27G Whitacre spinal needle

b) Spinal drugs (0.5% heavy Bupivacaine & 0.75% heavy Ropivacaine)

c) Standard monitors (ECG, non-invasive blood pressure monitoring, HR, Spo2)

REFERENCES:

1. Covino BG. Pharmacology of local anesthetic agents. Br J Anaesth1986;58:701-716.

2. KashimotoS ,Kume M and Kumazawa. Functional and metabolic effects of bupivacaine and lignocaine in the rat heart-lung preparation. Br J Anaesth1990;65:521-526.

3. Reynolds F. Adverse effects of local anesthetics. Br J Anaesth1987;59:78-95.

4. McDonnaldSB , Liu SS, Kopacz DJ, Stephenson CA. Hyperbaric spinal ropivacaine: a comparison to bupivacaine in volunteers. Anesthesiology 1999;90:971-7.

5. Malinovsky JM, Charles F, Kick O, Lepage JY, Malinge M, Cozian A, et al. Intrathecal anesthesia: Ropivacaine versus Bupivacaine. AnaesthAnalg2000;91:1457-60.

6. Alley EA, Kopacz DJ, McDonald SB, Liu SS. Hyperbaric spinal bupivacaine: a comparison to racemic bupivacaine in volunteers. AnaesthAnalg2002;94:188-93.

7. Cox GR, Faccenda KA, Gilhpooly C, Bannister J, Scott NB, Morrisson LMM. Extradural S (-)-Bupivacaine: comparison with racemic RS-Bupivacaine. Br J Anaesth 1998;80;289-93.

8. Abouleish EJ, Elias M, Nelson C. Ropivacaine induced seizure after extradural anesthesia. BrJAnaesth1998;80:843-844.

9. Whiteside JB, Burke D, Wildsmith JAW. Comparison of ropivacaine 0.5% (in glucose 5%), with bupivacaine 0.5% (in glucose 8%) for spinal anaesthesia for elective surgery. Br J Anaesth2003;90:304-8.

10.Kallio H, Snall ET, Tuomas CA, Rosenberg PH. Comparison of hyperbaric and plain ropivacaine, 15 mg in spinal anaesthesia for lower limb surgery. Br J Anaesth2004;93:664–9.

11. Camorcia M, Capogna G, Berritta, Columb MO. The relative potencies for motor block after intrathecal ropivacaine, levobupivacaine and bupivacaine. Anesth Analg. 2007;104:904–7.

12.Mantouvalou M, Ralli S, Arnaoutoglou H, Tziris G, Papadopoulos G. Spinal anesthesia: comparison of plain ropivacaine, bupivacaine and levobupivacaine for lower abdominal surgery. Acta Anaesthesiol Belg. 2008;59:65-71

13.Hinojosa-Sánchez O, Alamilla-Beltrán I, HaAlonsoR, Solano-Moreno H, Alvarez-Villaseñor AS, Ramírez-Contreras JP et al. Subarachnoid blockade with Ropivacaine versus Bupivacaine in urologic and orthopaedic surgery. Rev Med Inst Mex Seguro Soc.2009;47:539-44.

14.ChariVRR, Sah P, Wani N.Comparison between intrathecal isobaric ropivacaine 0.75% with hyperbaric bupivacaine 0.5%: a double- blind, randomized controlled study. Anaesth Pain Intensive Care. 2013;17:261–6.

DATA COLLECTION FORM

Name:                                                                                      Sex                                                      Age:                            Date:

Height:                                                                                                Weight:                                    ASA class:

Level of block achieved (pin prick method):

Mean time of onset of sensory analgesia at:

1) T10

2) T6

Degree of motor blockade (modified Bromage scale):

Hypotension: Yes / No

Bradycardia: Yes / No

Nausea and vomiting: Yes /No

Other complications:

PARTICIPANT INFORMATION SHEET

1. Participant Information: You are invited to participate in this research project. Please read this information carefully. Ask questions about anything you don’t understand or want to know more about. Participation in this research is voluntary. If you don’t wish to participate, you don’t have to.

Once you understand what the project is about and if you agree to participate, you may be asked to sign the consent form. By signing the consent form, you indicate that you understand the information and that you give your consent to participate.

2. Study title: A prospective randomised study of comparison between 0.5% hyperbaric bupivacaine and 0.75% hyperbaric ropivacaine for subarachnoid block in patients undergoing lower abdominal and lower limb surgeries

3. Procedure and purpose of the study: To measure anterior neck soft tissue thickness by ultrasound and evaluate its correlation with difficult laryngoscopy and difficult tracheal intubation.

4. Risks and benefits: There are no special risks involved in this study. You will not be paid for participation.

5. Privacy, Confidentiality and Disclosure of Information: Any information obtained in connection with this research that can identify you will remain confidential and only be used for this research project.

6. Participation is Voluntary: Participation in any research project is voluntary. If you do not wish to participate, you are not obliged to. If you decide to take part and later change your mind, you are free to withdraw from the project at any stage.

7. Contact for further information: Thank you for taking the time to read the information about this study. Before you sign this form, you can ask a question about the research or how it is done, possible research-related complications

CONTACT DETAILS:

DR.LAKSHMIPRABA.M.      

DNB Resident

Department of Anaesthesiology

Manipal Hospitals, Old Airport Road, Bangalore

Mobile: +91 9080089073

GUIDE:

DR.VINAYAK P S 

Consultant Anaesthesiologist

Manipal Hospitals, Old Airport Road, Bangalore

SUBJECT INFORMED CONSENT FORM

Informed consent form to participate in the study

STUDY TITLE: A PROSPECTIVE RANDOMISED STUDY OF COMPARISON BETWEEN 0.5% HYPERBARIC BUPIVACAINE AND 0.75% HYPERBARIC ROPIVACAINE FOR SUB ARACHNOID BLOCK IN PATIENTS UNDERGOING LOWER ABDOMINAL AND LOWER LIMB SURGERIES

SUBJECTS’S HOSPITAL NO: _________________

DATE OF BIRTH / AGE (in years): _____________________

                                                 SUBJECT INITIAL BOX

1. The content of the above consent form and

the procedure have been explained in a language

known to me, and I have understood the same.

2. I understood that my participation in the study is

voluntary and that I am free to withdraw at any time

without my medical care or legal rights being affected.

3. I agree not to restrict the use of any data or results

that arise from this study provided such use is only

for the scientific purpose(s)

4. I agree to take part in the above study

5. I have received a copy of the signed and dated informed

Informed Consent Signatures

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Printed name of subject ______________________ (Person Signing to complete)

Witness Signature (or thumb impression) ______________________________

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Investigator’s Signature (or thumb impression) ___________________________

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