A Prospective Open-Label Randomized Controlled Trial to Compare Intrathecal 1% 2-Chloroprocaine Versus 0.5% Bupivacaine in Ambulatory Elective Surgeries.

BACKGROUND: For an outpatient surgery, an ideal anesthetic drug should have a faster onset and shorter duration of action and minimal side effects. Although Bupivacaine is a drug of choice in spinal anesthesia but is not suitable for ambulatory surgeries. We aimed to compare 1% 2-chloroprocaine (2-CP) which is considered to be a short-acting agent with 0.5% hyperbaric bupivacaine as a spinal anesthetic agent in ambulatory surgeries.
MATERIALS AND METHODS: The study includes a prospective analysis of 60 patients who underwent ambulatory surgeries of <60 min and were randomly divided into two groups of 30 each: Group I - intrathecal injection of preservative-free formulation of 1% 2-CP 40 mg (4 mL) given and Group II - intrathecal injection of 0.5% hyperbaric bupivacaine 10 mg (2.0 mL) given time to reach surgical anesthesia, time for resolution of motor block, time for end of anesthesia, time to requirement of first postoperative analgesic, time to unassisted ambulation, time for micturition, and time to reach discharge readiness criteria, which were recorded.
RESULTS: We observed that in the CP group, onset time is early and there was more fast regression of surgical anesthesia in the CP group resulting in less time required for unassisted ambulation and less time for discharge from the hospital.
CONCLUSION: We concluded that 2-CP can be used for spinal anesthesia in shorter duration surgeries with early recovery from anesthesia and hence early discharge from the hospital. Copyright:

INTRODUCTION

In the present era, many procedures are performed as a day-care surgery under spinal anesthesia. For an outpatient surgery, an ideal anesthetic drug should have a faster onset and shorter duration of action and minimal side effects.[12] For many years, lidocaine was used clinically as a drug of choice due to its predictable time of onset and duration of action. There is reported incidence of transient neurological symptoms (TNSs) which are manifested as back pain radiating to lower extremities resulting in the withdrawal of this drug from clinical practice as it leads to short-term decreased quality of life in the patients.[345] Bupivacaine which is rarely associated with TNS became the drug of choice for spinal anesthesia. For the ambulatory surgeries, 0.5% hyperbaric bupivacaine has been tried for spinal anesthesia in smaller doses, but there are more chances of block failure,[6] and with the larger doses, its duration is unpredictable. Return of the bladder function is a matter of concern with this drug resulting in delayed discharge of patients from the hospital.[7] Procaine being a short-acting agent was also tried but showed limited success owing to its high failure rate and nausea.[8910]

2-Chloroprocaine (2-CP) which is an amino ester and is characterized by shorter latency and smaller duration of action was tried, but its use was associated with neurological deficits. Various studies done with 2-CP along with preservative, found that neurotoxicity is because of low pH and antioxidant.[1112]

Now, preservative-free pH-adjusted 1% 2-CP is available in the market and has been used for spinal anesthesia without any complications.[131415] Earlier studies proved that the use of preservative free 1% 2-CP in the dosage of 30–60 mg provides effective spinal blockade indistinguishable to lignocaine with reduced frequency of TNS.[1314] We hypothesized that 1% 2-CP can be used as a spinal anesthetic agent with faster recovery as compared to bupivacaine and early discharge from the hospital during ambulatory surgeries.

Keeping this in mind, we aimed to compare 1% 2-CP and 0.5% hyperbaric bupivacaine as a spinal anesthetic agent in ambulatory surgeries in terms of the time of onset of sensory blockade till T10, duration of sensory and motor blockade, time for unassisted ambulation, time for micturition, and discharge from the hospital to support our hypothesis.

MATERIALS AND METHODS

After receiving approval from the institutional ethics committee, the study was registered in the Clinical Trials Registry of India (CTRI/2020/03/023710). Sixty patients of age group 18–60 years with an ASA physical status I or II posted for infraumbilical ambulatory elective surgery of 45–60-min duration under spinal anesthesia were recruited. The sample size was calculated as per the following formula with conventional multiplier for alpha = 0.05 and conventional multiplier for power (b) = 0.8:

n = Sample size in each of the groups.

μ1 = Population mean in treatment Group I.

μ2 = Population mean in treatment Group II.

Hence, thirty patients were included in each group for power analysis of 80% and were divided into open-label fashion according to computer-generated randomization:

Group I (2-CP): Patients were given preservative-free formulation of 1% 2-CP 40 mg (4 mL) as a spinal anesthetic agent

Group II (bupivacaine): Patients were given 0.5% hyperbaric bupivacaine 10 mg (2.0 mL) as a spinal anesthetic agent.

Written informed consent was taken from all the patients who participated in the study. Exclusion criteria included patients with contraindications to spinal anesthesia, namely neurologic disease (multiple sclerosis, symptomatic lumbar herniated disc, spinal stenosis, fluid restriction (cardiac or renal insufficiency), allergy or intolerance to local anesthetics, or para-aminobenzoic acid; patients with known atypical plasma cholinesterase deficiency; and patients on oral anticoagulant therapy.

All patients were kept nil per orally for at least 6 h preoperatively. After arrival in the operating room, a 20G peripheral intravenous (i.v.) catheter was secured and approximately 10 mL.kg−1 of Ringer's lactate was infused for preloading. Intraoperative monitoring included noninvasive arterial blood pressure, electrocardiogram (five leads), and pulse oximetry. Spinal anesthesia was given under all aseptic conditions after local infiltration of the skin with 2% lidocaine with the patient in the lateral position, and the subarachnoid space was entered at the L3–4 or L4–5 interspace via the midline approach using a 26G Quincke's spinal needle. According to their randomization, patients received an intrathecal injection of either 0.5% hyperbaric bupivacaine 10 mg (2.0 mL) or a preservative-free formulation of 1% 2-CP 40 mg (4.0 mL). After the completion of the spinal injection, the patients were immediately turned to supine position. Sensory and motor block level was checked every 3 min for 15 min, every 5 min for 45 min, and every 10 min for 60 min and then every 15 min until complete regression of sensory block (up to S2).

Sensory block was assessed in a caudal to cephalad direction using the bilateral pinprick test with hypodermic needle, whereas motor block was assessed using the modified Bromage scale (0 = no block, full straight leg raise possible; 1 = unable to raise straight leg, 2 = unable to flex knee but able to flex ankle; and 3 = no motor movement, complete motor block). Surgery was started when loss of pain sensations up to T10 was achieved. If effect of spinal anesthesia wore off before completion of surgery injection midazolam 1–2 mg i.v. and injection ketamine 1–2 mg.kg−1 iv was administered and if the patient still complained of pain, general anesthesia was given to complete the surgery and it was considered as failure and not considered for study. The occurrence of clinically relevant hypotension (defined as a decrease in systolic arterial blood pressure 30% from baseline values) was treated with i.v. mephentermine. Clinically relevant bradycardia (defined as heart rate below 50 beats/min) was treated with i.v. atropine. Postoperative analgesia was administered with i.v. paracetamol, nonsteroidal anti-inflammatory drugs, and i.v. tramadol if the pain was intense and difficult to bear. Injection ondansetron 4 mg i.v. was administered for postoperative nausea and vomiting. Patients were discharged from the postoperative recovery room when they met the following criteria: a minimum stay of 60 min, stable hemodynamic variables, signs of motor block regression (Bromage 0–2), no i.v. analgesia within the previous 20 min, and normal consciousness level. After discharge from the recovery room, the patients were transferred to the surgical ward. Discharge from the hospital was possible when the patients reached all of the following criteria: complete regression of sensory block (up to S2 level) and motor block (Bromage 0), ability to void and walk without assistance, stable hemodynamics, no nausea or vomiting, pain controlled with oral medication, and ability to tolerate liquids by mouth.

The following data were recorded: time to reach surgical anesthesia, time for resolution of motor block, time for end of anesthesia, and time to requirement of first postoperative analgesic. Time to unassisted ambulation, time for micturition, and time to reach discharge criteria were also recorded. Patients were followed up and were asked for any headache, backache, and paresthesia in lower limbs after 24 h through telephonic discussion and 7 days after surgery when the patient came for routine follow-up.

A comparison of block regression over time was analyzed using a two-way analysis of variance for repeated measures. Student's t-test was used to compare the other variables, including the primary outcome (time to eligibility for discharge, time for complete regression of the sensory and motor blocks, duration of stay in the postoperative recovery room, and time to ambulation and micturition) and secondary outcomes (incidence of complications such as hypotension, bradycardia, postoperative nausea, and vomiting between the two groups).

RESULTS

Sixty patients were included in the study depending on the inclusion and exclusion criteria. In Group I, 1% 2-CP was used for spinal anesthesia, whereas in Group II, anesthesia was achieved with intrathecal 0.5% hyperbaric bupivacaine.

Regarding demographic variables, type, and duration of surgery, there was no significant statistical difference observed in both the groups, as shown in Table 1 (P > 0.05).

Table 1

Demographic variables

Variables	Group I 2- CP (n=30)	Group II B (n=30)	P
Age (years)	60±10	55±12	>0.05
Weight (kg)	70±10	75±12	>0.05
Height (cm)	160±10	155±10	>0.05
ASA physical status (I/II)	16/14	18/12	>0.05
Sex (female/male)	20/10	18/12	>0.05
Lower limb/abdominal procedure	16/14	17/13	>0.05
Surgery duration (min)	40±5	45±5	>0.05

2-CP=2-chloroprocaine

Spinal efficacy parameters: Primary outcome measures

Time to the onset of sensory and the motor block in Group I was 6 and 9 min, respectively, and in Group II was 7 and 8 min, respectively. Although time of onset was less in the CP group, on intergroup comparison, data were statically not significant (P > 0.05), as shown in Table 2.

Table 2

Spinal efficacy parameters

Parameters	Group I 2 CP (n=30)	Group II B (n=30)	P
Time to onset of sensory block up to T10 (min)	6	7	>0.05
Time to onset of motor block up to T10 (min)	8	9	>0.05
Time to end of motor block (min)	88	150	<0.05
Time to end of anesthesia (min)	95	190	<0.05
Time to unassisted ambulation (min)	130	220	<0.05
Time to first analgesic (min)	100	220	<0.05
Time to micturition (min)	160	350	<0.05
Time to discharge from hospital (min)	180	365	<0.05

2-CP=2-chloroprocaine

Time to end of motor block and time to end of anesthesia are 88 min and 95 min in Group I and 180 min and 190 min in Group II, respectively, as shown in Table 2, and the results were statistically significant (P < 0.05).), as shown in Table 2.

Mean time required for unassisted ambulation in Group I was 130 min and in Group II was 220 min. On statistical analysis, the difference was statistically significant (P < 0.05), as shown in Table 2.

Mean time until micturition was 160 min in Group I and 350 min in Group II. On intergroup comparison, time for first voiding was significantly less in Group I (P < 0.05), as shown in Table 2.

Similarly, mean time required for discharge from the hospital in Group I was 180 min and in Group II was 365 min, and the time required for discharge from the hospital was also significantly less in Group I, as shown in Table 2.

Mean time for the requirement of first analgesic dose is 100 min in Group 1 and 250 min in Group 11. These results were statistically significant (P < 0.05), and there was an early requirement of analgesics in Group I, as shown in Table 2.

Complications

In terms of complications which were considered as secondary outcomes of the study, there was no significant difference observed in terms of hypotension, bradycardia, and postoperative nausea and vomiting. No case of transient neurological symptoms was observed in any of the patients in any group, as shown in Table 3.

Table 3

Complications

	Group 2-CP (n=30)	Group B (n=30)	P
Hypotension	2/30	4/30	>0.05
Bradycardia	0/30	2/30	>0.05
TNS	-	-
Postoperative nausea and vomiting	2/30	1/30	>0.05

TNS=Transient neurological symptoms, 2-CP=2-chloroprocaine

DISCUSSION

The present study was conducted to compare intrathecal preservative free 40 mg of 1% 2-CP and 10 mg of 0.5% hyperbaric bupivacaine in infraumbilical ambulatory elective surgeries. The primary outcome was that there was more fast regression of sensory and motor blockade in the 2-CP group resulting in less time for unassisted ambulation and time of discharge from the hospital as compared to 0.5% hyperbaric bupivacaine.

The use of 2-CP was not done in the past because of high incidence of transient neurological symptoms due to low pH and antioxidant.[1112] In the study done by Yoos et al., it was found that preservative-free 2-CP provided safe and effective anesthesia in ambulatory surgeries without any incidence of transient neurologic function.[15] Furthermore, in the study done by Foldes and Mcnall, they found preservative free 2-CP successfully for spinal anesthesia in 214 patients.[16]

All the demographic variables, type, and duration of surgery were comparable in both the groups as we included patients having infraumbilical ambulatory surgeries of duration <60 min.

In the study done by Kopacz Dan J, he found that 40 mg and 60 mg provided rapid and reliable sensory and motor blockade, whereas 20 mg and 30 mg provided adequate sensory anesthesia for short duration surgeries but less motor blockade and sacral sparing.[17] Similarly, in the study done by Casati et al., they demonstrated that 40 and 50 mg of 1% 2-CP provided adequate surgical anesthesia and by lowering dose to 30 mg produced unreliable anesthesia and no decrease in discharge time.[18] Hence, we compared 40 mg of 2-CP with 10 mg bupivacaine in our study to support our hypothesis.

The onset times for sensory and motor blockade in our study were 6 and 8 min in the 2-CP group and 7 and 9 min, respectively, in the bupivacaine group. Although the result was not significant, there was a decreased time required to start surgery in the CP group. The results were in accordance with the study done by Camponovo et al. where they compared 50 mg of 1% 2-CP with 10 mg of 0.5% plain bupivacaine and found that 2-CP was comparable in terms of time of sensory blockade till T10 but had a faster onset of motor blockade.[19]

Time to end of motor blockade and duration of anesthesia was significantly less in the CP group as compared to the bupivacaine group, which was advantageous as this leads to a significant reduction in the duration of time for unassisted ambulation. Our results were in accordance with the study done by Componovo et al. where they found quicker recovery from anesthesia in the 2-CP group as compared to the bupivacaine group.[19] In another study done by Lacasse et al. in which they compared 40 mg of preservative-free 2-CP and 0.75% hyperbaric bupivacaine (7.5 mg) and found that 2-CP resulted in faster block resolution and earlier hospital discharge.[20]

In our study, urinary retention was a problem observed in the bupivacaine group only which leads to increased time required to reach discharge criterion in these patients as compared to the 2-CP group. This leads to reduced hospital stays in the 2-CP group as compared to the bupivacaine group resulting in cost-effectiveness and greater patient satisfaction. Breebaart et al. also found that spinal anesthesia with long-acting local anesthetics results in increased time required for first voiding as compared to spinal anesthesia with short-acting agents.[21] Similarly, in the study done by Camponovo et al. and Lacasse et al., they also observed problem of urinary retention in the bupivacaine group.[1920]

In any of the groups, no patient complained of pain during surgery, so no need of any sedation and general anesthesia supplementation was required. 2-CP provided adequate and reliable surgical anesthesia. This was in accordance with the study done by Yoos et al. where they compared 2-CP 40 mg with 7.5 mg bupivacaine in eight healthy volunteers and found that 2-CP can establish adequate duration and effect of block during ambulatory surgeries.[15]

As regression of anesthesia in the 2-CP group was fast, so there was early need of first analgesic requirement in the 2-CP group in postoperative area as compared to the bupivacaine group, but this was not the problem in shorter duration surgeries, and pain in the recovery period was managed well with multimodal analgesia.

In terms of complications, there occurred a lower incidence of hypotension and bradycardia in the 2-CP group though not statistically significant. No incidence of any transient neurological symptoms was seen in any of the groups. This finding is in agreement with various studies done earlier where they found no incidence of TNS with preservative-free 2-CP compared to 17%–33% with lignocaine.[2223]

Hence, we found that 2-CP can be used in short duration surgeries with early recovery and hence early discharge from the hospital. The limitation of our study was that the sample size was smaller and our study was not double blinded.

CONCLUSION

We concluded that 2-CP can be used for spinal anesthesia in shorter duration surgeries with early recovery from anesthesia and hence early discharge from the hospital resulting in decreased financial burden on the patient and greater patient satisfaction.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.