Randomized Controlled Study Comparing 2-Chloroprocaine and Bupivacaine for Spinal Anesthesia in Gynecological Surgeries.

Background: Ambulatory surgeries are increasing all over. While searching for an ideal anesthetic, the use of lidocaine was linked to a greater rate of transitory neurological symptoms and bupivacaine delays discharge due to a longer duration of motor blockade. 2-chloroprocaine (2CP) with a shorter duration of action is gaining popularity. We aimed to compare intrathecal bupivacaine and 2CP for the subarachnoid block for elective ambulatory gynecological surgeries.
Methods: A single-blind study was conducted on 90 patients comparing 40 mg 2CP and 10 mg 0.5% bupivacaine heavy measuring pinprick sensation, motor block, time to ambulation, and voiding of urine so as to get ready for discharge.
Results: In both groups, the beginning of sensory blockage occurred at a similar time, while motor blockade achieved was faster in the 2CP group. The resolution of motor blockade was 1.7 times faster in the 2CP group than in the bupivacaine group. Time taken for ambulation was delayed significantly in the bupivacaine group, i.e., 263.04 ± 29.08 min compared to the 2CP group, i.e., 225.44 ± 29.48 min which was a delay of almost 38 min. Voiding of urine was also delayed in the bupivacaine group by 60 min compared to the 2CP group and was significant finding leading to delay of discharge of patients. Adverse effects were comparable in both groups.
Conclusion: Intrathecal preservative-free 2CP provides satisfactory surgical block, and has a considerably faster rate of block regression, resulting in earlier ambulation and voiding, allowing the patient to be discharged from the hospital sooner as compared to intrathecal bupivacaine. Copyright:

INTRODUCTION

In the current scenario, many surgeries are now performed as day-care surgeries using subarachnoid block. An ideal spinal anesthetic medication for outpatient surgeries should have a more rapid onset, shorter duration of action, and fewer side effects, including a reduced risk of neurotoxicity.[12] Bupivacaine is a commonly used local anesthetic agent, which has been used in low doses (5–7.5 mg) for day-care spinal anesthesia by few practitioners. It avoids side effects which are associated with lidocaine, but has other nonfavorable effects such as delayed ambulation and urinary retention all of which may delay discharge after the day-care procedure. Other local anesthetics including levobupivacaine and ropivacaine were also tried but had similar unfavorable effects.[3456] Lidocaine was used by many in the past for day-care surgeries, due to its rapid onset and offset of action but soon its use was stopped due to higher incidences of transient neurological symptoms (TNS).[7]

Hence, the search for an anesthetic drug having ideal characteristics and adequate postoperative analgesia, which would allow discharge of pain-free patients after day-care procedure, continues.

2-chloroprocaine (2CP), a preservative-free amino ester local anesthetic with a rapid onset, better sensory and motor block, faster recovery time, and low side effects, can be used for shorter-duration day-care surgeries.[89]

Hence, we aimed to compare 2CP and low-dose bupivacaine in elective day-care surgeries.

METHODS

After obtaining approval from the institutional ethics committee and written informed consent from patients, this randomized single-blinded study was conducted in a tertiary care center from January 2019 to September 2020 on 90 patients undergoing gynecological surgical procedure of short duration (<60 min). The clinical research was done, following the ethical principles for medical research involving human subjects in accordance with the Helsinki Declaration 2013.

Patients of the age group 18–50 years of ASA I and II class posted for the elective gynecological procedure of shorter duration, such as dilatation and curettage, biopsies of vulva, cervix, and vagina, and hysteroscopy and tubal ligation were included in the study. While those patients, refusing to give consent, allergic to the local anesthetic agent, with any contraindication to regional anesthesia, with neurological diseases, with renal disease requiring fluid restriction, with cardiac disease, and those with atypical plasma cholinesterase were excluded from the study.

All patients were investigated according to the institutional protocol. Patient was randomly allocated into two groups using computer generated random allocation plan [Figure 1].

Figure 1

CONSORT flow diagram

Group 2C: 45 patients received injection 2CP 1% – 40 mg (4 ml) drug in subarachnoid space at L3-L4 intervertebral space.

Group B: 45 patients received injection of bupivacaine 0.5% heavy 10 mg (2 ml) drug in subarachnoid space at L3-L4 intervertebral space.

On arrival at odds ratio, patients were enquired about nonprofit organization status and multipara monitors including blood pressure (BP) cuff, electrocardiography (ECG), and pulse oximeter (SPO2) were attached and baseline reading of systolic BP (SBP), diastolic BP, mean BP (MAP), SPO2, and heart rate (HR) were recorded. Intravenous (IV) access was achieved with 20G IV cannula and preloading was done with 500 ml of Ringer's Lactate fluid. Premedication was done with injection of pantoprazole 40 mg and injection of ondansetron 4 mg IV.

Patients were given spinal anesthesia, under all aseptic precautions in sitting position with 25 G spinal needle in L2-L3 or L3-L4 space, through midline approach using either of two abovementioned drugs, according to randomization.

Patients were made supine after spinal anesthesia, and sensory and motor block was measured.

The timing of drug injection was recorded as “0” minute. After the spinal injection, a single observer tracked the progression of the spinal block until it met the requirements for home discharge. After the patient was put supine, the effectiveness of the sensory and motor block was evaluated every 3 min. The loss of pinprick feeling was used to determine sensory block. The Modified Bromage Scale was used to assess motor block. Patients who had no effect or had an insufficient spinal anesthetic effect were given general anesthesia and were removed from the research. The loss of pinprick feeling at T12 with a Modified Bromage score of 2 was considered the commencement of surgical anesthesia. Sensory and motor block progression was tracked every 3 min for the first 15 min, and then every 5 min for the next 15 min, then every 15 min for the next 30 min until the sensory block had regressed to the S2 dermatome. Serial assessments were made every 30 min until the home discharge criteria were met.

Block failure was defined as the inability to achieve a sensory block at T12 within 30 min of spinal injection. The patient's BP (both systolic and diastolic), ECG, and pulse oximeter values were all taken and noted during the operation. Hypotension was defined as a drop in SBP/MAP of more than 25% from baseline and was treated with IV mephentermine 6 mg. If necessary, the vasopressor medication was repeated, and total dose was recorded. Patients were given 0.6 mg IV atropine if their HR dropped below 50 beats/min and this treatment was repeated if necessary. Sedation/analgesia with injection of fentanyl 2 mcg/kg IV was given if the intraoperative quality of analgesia was unsatisfactory. The amount of time taken to ambulate (walk without assistance) and void urine was recorded.

Discharge criteria at our institute included stable vitals, tolerating clear liquids orally, absence of postoperative nausea and vomiting and pain, voiding of urine, and walking without support. Time to discharge from the hospital was measured from time of spinal anesthesia to first successful voiding of urine.

Inquiry was made telephonically for 7 days regarding the development of any side effects, especially TNS, which is defined as pain or abnormal sensations in gluteal area and radiating down toward lower limb.[7]

Statistical analysis

We hypothesized that 40 mg of 2CP would have faster recovery from spinal anesthesia than 10 mg of 0.5% bupivacaine. We calculated sample size using a previous study, considering time taken for receding of both motor and sensory effects of spinal anesthesia as the main outcome measure. The sample size was determined using a two-sided test with a power of 90% and an alpha of 0.05. A minimum of 45 patients in each group were required to achieve a 76-min decrease. The information was entered into IBM Corp, Released 2020. IBM SPSS Statistics for Windows, Version 20, Armonk, NY: USA. Frequency and percentage were used to express qualitative data. Nominal data comprised group category (Group 2C and Group B), gender of cases, diagnosis, comorbidity, general examination findings, and complications among other qualitative data. Quantitative data such as age, height, weight, sensory block, motor block, and sedation required are represented using mean +/−standard deviation, median, and (interquartile range). Comparison of quantitative data measured between group category (Group 2C and B) was made using unpaired t-test and P < 0.05 was considered statistically significant.

RESULTS

In our study, demographic variables were comparable in two groups [Table 1]. In the 2CP and bupivacaine groups, the meantime for onset of sensory block was 3.37 and 3.26 min, respectively. As indicated in Table 2, this data are not statistically significant (P > 0.05). In the 2CP and bupivacaine groups, the meantime for onset of motor block was 4.92 and 6.27 min, respectively, which is statistically significant (P < 0. 05).

Table 1

Demographic data

Parameter	Mean±SD		P
	Group 2C	Group B
Age	36.76±10.50	36.02±9.48	>0.05
BMI (kg.m−2)	25.39±4.27	26.27±3.93	>0.05
ASA grade (%)
I	34 (75.6)	36 (80)	>0.05
II	11 (24.4)	9 (20)

BMI=Body mass index, SD=Standard deviation, ASA=American Society of Anesthesiology

Table 2

Clinical characteristics of subarachnoid block

Parameter	Mean±SD		P
	2CP	Bupivacaine
Onset time of sensory block (min)	3.37±0.18	3.26±0.30	>0.05
Onset time of motor block (min)	4.92±0.64	6.27±0.65	<0.05
Time to reach maximum block height (min)	6.43±0.81	6.71±0.91	>0.05
Duration of motor block (min)	63.81±7.52	107.60±15.48	<0.05
Duration of sensory block (analgesia) min	81.32±10.06	161.61±7.49	<0.05
Intraoperatively requirement of sedation (%)	11 (24.4)	3 (6.7)	<0.05
Time taken for ambulation (min)	225.44±29.48	263.04±29.08	<0.05
Time taken for voiding of urine (min)	276.49±23.99	336.13±19.76	<0.05

SD=Standard deviation, 2CP=2chloroprocaine

Table 2 shows that motor onset was considerably faster (P < 0.05) in the 2CP group. In the 2CP and bupivacaine groups, the average duration of motor block was 63.81 and 107.60 min, respectively. This data demonstrate that the bupivacaine group has a considerably longer duration of motor block (P < 0.05).

In the 2CP and bupivacaine groups, the average duration of sensory block was 81.32 and 161.61 min, respectively. The 2CP group has a considerably faster resolution of sensory block (P < 0.05). In the 2CP and bupivacaine groups, the meantime to ambulate was 225.44 min and 263.04 min, respectively. This finding revealed a statistically significant increase in ambulation time in the bupivacaine group (P < 0.05). The average time it took to void urine was 276.49 min in the 2CP and bupivacaine groups; the time was 336.13 min and 336.13 min, respectively. Time taken for voiding of urine was significantly longer in the bupivacaine group (P < 0.05).

DISCUSSION

More and more procedures are being conducted on a daycare basis with progress in ambulatory surgeries. Spinal anesthesia being simple and cost-effective regional anesthesia technique is used widely. For years together, intrathecal lignocaine was used widely due to its rapid onset and shorter duration, but soon its use was stopped by many practitioners owing to the concern about TNS associated with it.[710] Later on hyperbaric bupivacaine in lower dose is being tried as an alternative, but even with smaller doses, the duration of action is prolonged and also may fail to provide adequate surgical anesthesia.[3] More so, may delay discharge of a patient due to urinary retention that is commonly encountered with it.[6] Hence, none of the local anesthetics available in clinical use can provide a block with faster onset, predictable duration, rapid recovery, and good surgical anesthesia with fewer side effects.[23] Hence, the search for an ideal local anesthetic lead to the present study comparing intrathecal preservative-free injection 2CP 1% – 40 mg (4 ml) and bupivacaine 0.5% heavy 10 mg (2 ml) in day-care procedures. Our primary outcome was intrathecal 2CP provides good surgical anesthesia and allows earlier discharge from the hospital than intrathecal bupivacaine.

Concern was raised regarding neurotoxicity caused by high dose of intrathecal 2CP, but later on, studies revealed the cause as sodium bisulfate and soon preservative-free 2CP was made available.[11121314] The study conducted by Yoos et al.[15] and Foldes and Macall[16] concluded that preservative-free 2CP is safe and effective in day-care anesthesia without any neurological sequelae.

In our study, demographic variables were comparable in two groups [Table 1]. Two groups were also comparable in terms of time of onset of sensory blockade as well as time to reach maximum blockade level [Table 2] although the onset of motor blockade was faster in the 2CP group, hence surgery in the 2CP group started earlier than the bupivacaine group.

Camponovo et al.[8] also demonstrated similar results where they found the onset of motor blockade was faster in the 2CP group than 10 mg of the bupivacaine 0.5% group. Laccase et al.[17] comparing 0.75% of bupivacaine 7.5 mg and 2CP 40 mg found that motor block resolution was faster with 2CP than in the bupivacaine group, which resulted in earlier discharge from the hospital. Similar results were also found in a study conducted by Componovo et al.[8] and Balwinderjit Singh et al.[18] Our results were in accordance with all these studies. We also found that the resolution of motor blockade was 1.7 times faster in the 2CP group than in the bupivacaine group.

Time taken for ambulation was delayed significantly in the bupivacaine group, i.e., 263.04 ± 29.08 min compared to the 2CP group, i.e., 225.44 ± 29.48 min, which was a delay of almost 38 min. Voiding of urine was also delayed in the bupivacaine group by 60 min compared to the 2CP group and was a significant finding, leading to delay of discharge of patients. Even after regression of block and ambulation, many patients could not completely void successfully in the bupivacaine group, leading to delay in discharge from day-care unit. This delay in voiding may be due to the failure of detrusor muscle contraction, due to a delay in sensory dermatomal regression to at least the S3 level. Laccase et al.[17] and Breebaart et al.[6] had similar findings in their studies, thereby demonstrating a longer time interval to void successfully after intrathecal administration of longer-acting local anesthetics than the shorter-acting one.

It is noteworthy that intraoperatively more number of patients required IV sedation [Table 3] in the 2CP group than in the bupivacaine group although most patients required it at the end of surgery when they had complained of pressure sensation at the operative site, suggesting early regression of sensory block. Furthermore, the requirement of analgesic was earlier in the 2CP group postoperatively. Patients were followed up telephonically for the first 24 h for the development of any pain/dysesthesia in lower limbs or buttocks after spinal anesthesia suggestive of TNS. None of the patients from any group had complained about TNS. This was due to the use of preservative-free 2CP and was in accordance with various previous studies conducted by Yoos et al.[19] and Palas et al.[20] Incidence of complications including hypotension and bradycardia were not significant in both groups and were comparable.

Table 3

Requirement of sedation

Intraoperatively: Requirement of sedation	Group 2C, n (%)	Group B, n (%)	P
Yes	11 (24.4)	3 (6.7)	<0.05
No	34 (75.6)	42 (93.3)
Total	45 (100)	45 (100)

One of the limitations of our study was that it was single-blinded study. Since the block was earlier to regress in the 2CP group, it was easy to identify it and there was no better way to blinding. Another limitation of our study was that we defined urinary retention by simple criteria of the need for catheterization instead of measuring actual bladder volume. According to Breebaart et al.[6] need for catheterization represents the final stage of bladder retention and voiding per SE does not exclude residual bladder volumes.

CONCLUSION

Intrathecal preservative-free 2CP provides satisfactory surgical block, has significantly faster regression of block, earlier ambulation, and voiding, and hence facilitates the faster discharge of the patient from the hospital as compared to intrathecal bupivacaine following day-care surgeries.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.