Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
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Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
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Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.

Dr. Anuradha
On Jan 2020

Important Notice

Original article / research
Year : 2023 | Month : June | Volume : 17 | Issue : 6 | Page : UC58 - UC62 Full Version

Spinal Anaesthesia for Ambulatory Perianal Surgeries: A Comparison between Short Acting and Long Acting Local Anaesthetics

Published: June 1, 2023 | DOI:
Navin Gandhi, Mohan Sundaram, Ashok Kulasekhar, Subramaniam Anand, Arun Kumar

1. Postgraduate, Department of Anaesthesia, Chettinad Hospital and Research Institute, Chennai, Tamil Nadu, India. 2. Postgraduate, Department of Anaesthesia, Chettinad Hospital and Research Institute, Chennai, Tamil Nadu, India. 3. Head, Department of Anaesthesia, Chettinad Hospital and Research Institute, Chennai, Tamil Nadu, India. 4. Professor, Department of Anaesthesia, Chettinad Hospital and Research Institute, Chennai, Tamil Nadu, India. 5. Professor, Department of Anaesthesia, Chettinad Hospital and Research Institute, Chennai, Tamil Nadu, India.

Correspondence Address :
Dr. Mohan Sundaram,
No. 16A, Kumar Street, Kanchipuram-631501, Tamil Nadu, India.


Introduction: Chloroprocaine (ester group) is a preservative-free local anaesthetic which is available as isobaric solution. It is being recently popularised in spinal anaesthesia for its shorter duration of action which plays a significant role in the early ambulation and voiding functions, which is the primary essence in ambulatory surgery. Intrathecal Bupivacaine is the most commonly used drug for its block characteristics, taking into account not only the fast initiation of sensory and motor blockade but also faster sensory and motor regression.

Aim: To compare the block characteristics between 1% Chloroprocaine and 0.5% Bupivacaine in patients undergoing perianal surgeries under spinal anaesthesia.

Materials and Methods: This randomised, interventional double blinded study was carried out in Chettinad Hospital and Research Institute, Kelambakkam, Chennai, Tamil Nadu, India, from April 2020 to August 2021. The patients were split into two groups of 34 each. Group 1: Patients received 30 mg of 1% Chloroprocaine intrathecally. Group 2: Patients received 10 mg of 0.5% Bupivacaine intrathecally. In both the groups the onset, duration of both sensory and motor blocks, intraoperative haemodynamic, two segment regression time, time to ambulation and micturition, the time to eligibility for discharge from hospital was evaluated. Independent sample t-test, Chi-square test and Fisher’s-Exact test were employed to compare the distribution of qualitative variables between the groups.

Results: Total of 68 participants 31 (45.6%) males and 37 (54.4%) females), 34 in each group 1 and group 2 were analysed. Both groups contained maximum patients in >45 years age group, 12 (35.2%) in each group. Demographic and anthropometric parameters of patients in both the groups were comparable. Mean time of ambulation after spinal anaesthesia in the Group 1 was 137.65±9.15 minutes and in Group 2 was 193.38±8.14 minutes (p-value <0.05). Mean time taken to return of voiding function the Group 1 was 157.06±16.05 minutes and in Group 2 was 213.53±10.26 minutes (p-value <0.05). Mean time taken for Post-Anaesthetic Discharge Scoring System (PADSS) score >9 in Group 1 was significantly less (165.29±13.59 minutes) than Group 2 (219.41±9.52 minutes). Mean time duration for request of first rescue analgesic in Group 1 was significantly faster (104.71±8.69 minutes) than Group 2 (157.79±8.81 minutes). There was no significant difference in haemodynamic changes between the study groups.

Conclusion: Chloroprocaine has proved to be better than Bupivacaine. It has proven to provide adequate surgical anaesthesia, it leads to early regression of motor and sensory blocks, faster un-assisted ambulation and micturition. Time to rescue analgesia was earlier in the Group 1 when compared to Group 2.


Bupivacaine, Chloroprocaine, Day care surgeries, Subarachnoid block

The incidence of perianal surgeries varies among institutions, accounting for more than 5% of General surgical procedures. Commonly done perianal surgeries like lateral sphincterotomy, haemorrhoidectomy, fistulectomy are of short duration (less than one hour) (1). However, in terms of effective recovery and airway management, regional anaesthesia has massive benefits over general anaesthesia. Frequent post-operative negative impacts of general anaesthesia, such as post-operative nausea and vomiting, giddiness might be mitigated by confining the anaesthetised region to the surgical field (2). Because it delivers a stable anaesthetic action with a quick onset of effect, spinal anaesthesia is an appropriate anaesthetic choice for ambulatory procedures of the infraumbilical region (3).

Duration of spinal anaesthesia with 15-20 mg of hyperbaric Bupivacaine ranges from 90 to 200 min (4). In order to reduce the duration of surgical anaesthesia for day care surgeries lower dose of 10 mg of 0.5% hyperbaric Bupivacaine is routinely used. However, a few of their properties, such as delayed ambulation and the likelihood of retention of urine, may restrict it being used for ambulatory surgery (5). The perfect anaesthetic should have a rapid onset as well as offset of its action in order to enable rapid patient discharge with the least number of adverse effects possible. Therefore, in the ambulatory context, determining the correct local anaesthetic for spinal anaesthesia is essential (6).

Chloroprocaine (ester group) preservative free local anaesthetic with a very short half-life, available as isobaric solution has been recently used in spinal anaesthesia for its shorter duration of action. This drug was first made available in 1952 and has since been widely used for spinal anaesthesia. It wasn’t until 1956 that sodium bisulfite was put into commercial chloroprocaine formulation as a preservative (7). For obstetric patients, the medication was administered as an epidural anaesthetic. Several instances of neurologic impairments linked to inadvertent intrathecal injections of high volumes of chloroprocaine during labour analgesia were described in the 1980s (8).

Considering this and the paucity of studies in the Indian set-up, intrathecal 1% preservative free chloroprocaine has been used in this study for short duration perianal surgeries lasting less than one hour. These preservatives resemble para-aminobenzoic acid. Because of this, allergic reactions may be due to preservative stimulation of antibody formation rather than a response to the local anaesthetic (9).

The purpose of this study was to evaluate the efficacy of 1% Chloroprocaine 30 mg over 0.5% hyperbaric Bupivacaine 10 mg intrathecally in perianal surgeries. The primary outcome measures were the time taken to reach eligibility for discharge from Post Anaesthesia Care Unit (PACU). The secondary outcomes were the block characteristics (onset and regression of sensory and motor block), the haemodynamic changes and the time taken to request of first rescue analgesic.

Material and Methods

It was a, randomised, interventional double blinded study carried out at Chettinad Hospital and Research Institute in Kelambakkam, Chennai, Tamil Nadu, India, from April 2020 to August 2021, under the Department of Anaesthesiology. The Institutional Human Ethical Committee reviewed and approved the study- IHEC No: 009/IHEC /Feb.2020, dated 22-03-2020, CTRI/2021/07/034845. Prior to enrolment all study participants were explained the risks and benefits associated with the study in a language they understand, following which an informed written consent was obtained. Anonymity was maintained with regards to information of study participant.

The enrolled 68 participants were randomly allocated into two groups (34 patients in each group) using a computer-generated randomisation code. Group 1 (n=34): Patients received 30 mg of 1% Chloroprocaine (3 mL) intrathecally. Group 2 (n=34): Patients received 10 mg of 0.5% Bupivacaine (2 mL) intrathecally (Table/Fig 1).

Inclusion criteria: American Society of Anaesthesiology (ASA) Grade-I and ASA Grade-II, age 18-65 years, Body Mass Index (BMI) of the patient <35, both elective and emergency surgeries, duration of surgery < 60 minutes.

Exclusion criteria: Coagulopathy and other bleeding disorder, increased intracranial pressure, patient allergic/sensitive to local anaesthetic agents, pregnant and lactating patients, patients with peripheral neuropathy were excluded from the study.

Study Procedure

All patients underwent routine pre-operative assessment in the pre-anaesthetic assessment clinic and were assessed again the day before surgery. Those who fulfilled the eligibility criteria were enrolled, after explaining the study and the risks associated with the interventions in the language they understood.

The patients were advised fasting of six hours for a light meal, two hours for clear liquids prior to surgery and pre-medicated with Tablet Ranitidine 150 mg the night before surgery and 6 am on the day of surgery. On arrival, in the pre-anaesthetic room, one hour prior to wheeling inside the operation theatre, all patients were encouraged to void the bladder, the consent forms were re-checked, an 18 Gauge (G) intravenous (i.v.) access secured and the patients were pre-loaded with 500 mL of ringer lactate solution.

Once the patient was shifted inside the operating room, routine monitors for haemodynamic monitoring (3-lead Electrocardiogram (ECG) monitoring, heart rate, blood pressure, oxygen saturation) were attached and baseline vital signs were recorded. The appropriate study drug according to the randomised code was pre-loaded and kept in a sterile syringe by anaesthesiologist not involved in the study.

All patients were made to sit, with arms hugging a pillow, their neck flexed and both legs stretched out on the operation table. Their lumbar region was painted with antiseptic solution and draped. The intervertebral space to which the drug to be given was identified and 1-2 mL of 2% lignocaine local anaesthetic was infiltrated in the skin and subcutaneous tissue and after that subarachnoid block was performed with 26 G Quincke needle using median approach. After the lumbar puncture, the continuous flow of cerebrospinal fluid was ascertained.

Each of the 68 patients was given the study drug intrathecally over 10-15 seconds. The patients were placed in supine position immediately after the injection, and this time was defined as ‘zero’. The patients were placed in supine position for a minimum of at least three minutes before any positional change. All patients were given a hot air forced convective warmer blanket with a temperature of 40ºC. Thereafter, investigator assessed all of the following parameters. An anaesthesiologist who was not involved in the trial prepared pre-filled marked syringes with the study drug. The composition of the injections and the group allocation were unknown to the anaesthesiologist who performed the intervention and recorded the observations.

Level of sensory blockade was assessed by loss of cold sensation, using cotton swab dipped in cold saline.

The grading used for sensory blockade-

• Grade-0: Normal Sensation to cold cotton swab.
• Grade-1: Dull sensation to cold cotton swab.
• Grade-2: Sensation felt.

Time taken for onset of sensory block (level L1), time taken for sensory block to level T10 and maximum level of sensory blockade and time taken for it are duly noted. Level of motor blockade was assessed using Modified Bromage score. Time taken to onset of complete motor block (score 1) was duly noted.

All haemodynamic parameters such as heart rate, blood pressure {Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP)}, SpO2, were monitored every three minutes for first 15 minutes and then every five minutes for first one hour and then every 15 minutes for 90 minutes. In the event of failed subarachnoid block or inadequate anaesthesia duration during procedure, the patient will be given general anaesthesia and excluded from the study group. Any hypotension due to spinal anaesthesia was managed with intravenous fluids or injection Ephedrine as needed.

Patients were put in lithotomy position and surgery started and duration of surgery was noted. Postoperatively, patients were shifted to PACU for further monitoring. Time taken to request of first rescue analgesic was noted. Patients were asked to rate their pain using a 100 mm Visual Analogue Scale (VAS) till they reported a VAS >3 and the patient was given rescue analgesic (Inj. Paracetamol 1 g intravenously). Time taken to un-assisted ambulation was noted. Time to spontaneous voiding of urine was noted. Patients were observed in the PACU till micturition.

Patients were started on liquids and soft solid diet from 180 minutes from starting of anaesthesia, provided there was no contraindication to start oral diet on a surgical aspect. Common side effects like nausea, bradycardia, vomiting, hypotension, shivering, urticaria, if any, were noted. Postoperatively, eligibility to discharge from hospital was calculated based on Post Anaesthesia Discharge Scoring System (PADSS) (10). A score >9 is fit for discharge. PADSS has been modified to ensure a higher level of safety, thus the “vital signs” criteria must never score lower than two, and none of the other five criteria must ever be equal to 0, even if the total score reaches nine.

Degree of sensory regression, motor regression was recorded every five minutes till one hour and every 15 minutes till four hours. Time for two-segment sensory regression, complete sensory regression to level S2 and complete motor regression (score 6) were noted.

Statistical Analysis

Independent sample t-test was used in order to compare two means. Chi-square test and Fisher’s-Exact test was employed to compare the distribution of qualitative variables between the groups. In case if one characteristic is measured multiple times along the timeline, two way Repeated Measures Analysis Of Variance (RMANOVA) was used as inferential statistic. All tests were two tailed and results were considered statistically significant if the p-value is <0.05. Continuous variables were expressed as mean and standard deviation. Description of categorical variables were expressed as frequency and proportion. The data were entered using Microsoft Office Excel 2010 and analysed using Statistical Package for Social Sciences (SPSS) software version 24.0.


Demographic and anthropometric parameters of patients in both the groups were comparable. In both the groups’ females were more than males (Table/Fig 2). Mean time of ambulation after spinal anaesthesia in the Group 1 was 137.65±9.15 minutes and in Group 2 was 193.38±8.14 minutes (p-value <0.05). Mean time taken to return of voiding function the Group 1 was 157.06±16.05 minutes and in Group 2 was 213.53±10.26 minutes (p-value <0.05).

Mean time taken for PADSS score >9 was found to be significantly low in Group 1 when compared to Group 2 (Table/Fig 3).

Onset of sensory block among the Group 1 was longer than that of the Bupivacaine Group 2. Mean time to attain Sensory level T10 among the Group 1 was faster than that of the Group 2 (Table/Fig 4).

Mean time to attain complete motor block among the Group 1 was faster than that of the Group 2, though not statistically significant (Table/Fig 5).

Mean time for two-segment regression from peak block and time for sensory regression to level S2 among the Group 1 was significantly faster than that of the Group 2 (Table/Fig 6).

The mean duration of motor block was significantly low in Group 1 when compared to Group 2 (Table/Fig 7).

Mean heart rate of study participants both the groups showed a declining trend. The change in heart rate in both the groups was found to be similar over the surgical process (Table/Fig 8).

MAP of study participants both the groups showed a declining trend. The change in MAP in both the groups was found to be similar over the surgical process (Table/Fig 9).

Mean time duration to request of first rescue analgesic was significantly lesser in Group 1 when compared to Group 2 (Table/Fig 10).

In this study the only complication reported was shivering. Other complications like nausea, bradycardia, vomiting, hypotension and urticaria were not reported in both the group.


The present randomised interventional double-blinded study carried out with an aim to evaluate the block characteristics between 1% Chloroprocaine versus 0.5% hyperbaric Bupivacaine in spinal anaesthesia for short duration perianal surgeries. Outcome of the study Chloroprocaine for perianal surgeries of short duration resulted in an adequate surgical anaesthesia and at the same time quicker recovery from anaesthesia and early hospital discharge when compared with 10 mg of hyperbaric 0.5% Bupivacaine. Few previous studies also discuss the comparative toxicities and side effects, useful for deciding the anaesthetic agents [11-13]. Mean time of ambulation after spinal anaesthesia in the Chloroprocaine group was faster than the Bupivacaine group. This was similar to the study done by Gys B et. al. Their study also concluded faster motor and sensory regression as compared to prilocaine. (14).

Lacasse MA et al., who studied the effect of 30 mg chloroprocaine and 10 mg Bupivacaine in healthy volunteers and found that mean time to ambulation was 225+56 minutes and 265+65 in respective groups and stated mean time to ambulation was earlier in chloroprocaine group. This proves that patients who were given Chloroprocaine can be ambulated early than Bupivacaine group patients (15).

Mean time taken to return of voiding function the Chloroprocaine group was faster than Bupivacaine group This was similar to the study done by Smith KN et al., who found the mean time to micturition in 30 mg Chloroprocaine group was 167+47 minutes and Prabhakar A et. al., found that 10 mg Bupivacaine in spinal had mean time to micturition of 241+14 minutes [4,5]. Lacasse MA et al., stated that mean time of voiding after spinal anaesthesia was earlier in Chloroprocaine group than Bupivacaine similar which was analogous with our study (15).

Rescue analgesic: The mean time duration to request for first rescue analgesic was found to be low in Chloroprocaine Group when compared to Bupivacaine group. Patients required analgesics earlier in Chloroprocaine Group. This was similar to study conducted by Lacasse MA et al., who stated patients in 30 mg Chloroprocaine group experienced more pain, earlier in PACU and required rescue analgesic faster than Bupivacaine group as the level regressed faster (15). The association of anaesthetists from various countries all together explained the skin antisepsis for central neuraxial blockade, in their previous literature (16).

PADSS scoring: The mean time taken for PADSS score >9 was found to be low in Chloroprocaine Group when compared to Bupivacaine group This was similar to the results of Lacasse MA et al., Campbell JP et. al. and Camponov C et. al. who stated that readiness to home discharge was earlier with chloroprocaine group when compared to Bupivacaine group (15),(16),(17). In this study the only complication reported was shivering.. Other complications like nausea, bradycardia, vomiting, hypotension and urticaria were not reported in both the group. In contrast to various other previous studies depicting toxicities in their literature [8,9,16].


One of the limitations of this study is that Chloroprocaine is an ultra short acting drug so even though blinded we can predict the drug given to each patient by the time taken for the regression of block. The selection and information bias due to the above limitation was avoided by randomisation and collecting data under supervision of guide. An additional limitation of this study was determining the precision of the sensory level of the block within two dermatomal levels. This was reduced by having the same blinded observer responsible for collecting data all the time during the entire study.


Intrathecal administration of 30 mg of 1% 2-Chloroprocaine for perianal surgeries of short duration resulted in an adequate surgical anaesthesia and at the same time quicker recovery from anaesthesia and early hospital discharge when compared with 10 mg of hyperbaric 0.5% Bupivacaine. So, it can be effectively used for ambulatory perianal surgeries of shorter duration.


This research was a thesis project done in Chettinad Hospital and Research Institute, Chennai.

1. Dr. Navin Gandhi, was the principal investigator of this study.
2. Dr. Mohana Sundaram had the chief role in manuscript preparation, visualisation and data presentation.
3. Dr. Ashok Kulasekhar was the guide for this study. He provided resources and helped with study conception and data curation
4. Dr. S Anand was the co-guide for this study and helped in methodology and formal analysis of the study.
5. Dr. Arun Kumar supervised the overall study and helped in computation.


Ghisi D, Boschetto G, Spinelli AM, Giannone S, Frugiuele J, Ciccarello M, et al. Spinal anaesthesia with chloroprocaine HCl 1% for elective lower limb procedures of short duration: A prospective, randomised, observer-blind study in adult patients. BMC Anesthesiology. 2021;21(1):01-08. [crossref][PubMed]
Singh B, Anand A, Attri JP. A prospective open-label randomized controlled trial to compare intrathecal 1% 2-chloroprocaine versus 0.5% bupivacaine in ambulatory elective surgeries. Anesthesia, Essays and Researches. 2020;14(2):266. [crossref][PubMed]
Vishnu B, Babu M, Ravi T, Kumar. Comparison of 0.5% bupivacaine and 1% 2-chloroprocaine for spinal anaesthesia for ambulatory surgeries: A prospective, observer blinded, Randomized, controlled trial. International Journal of Scientific Research. 2019;8(4):2277-79.
Smith, KN, Kopacz DJ, Susan MB. Spinal 2-chloroprocaine: A dose-ranging study and the effect of added epinephrine. Anesthesia & Analgesia; 2004;98(1); 81-88. [crossref][PubMed]
Prabhakar A, Lambert T, Kaye RJ, Gaignard SM, Ragusa J, Wheat S, et al. Adjuvants in clinical regional anesthesia practice: A comprehensive review. Best Practice & Research Clinical Anaesthesiology. 2019;33(4):415-23. [crossref][PubMed]
Barrington MJ, Uda Y. Did ultrasound fulfill the promise of safety in regional anesthesia? Current Opinion in Anesthesiology. 2018;31(5):649-55. [crossref][PubMed]
Shah J, Votta-Velis EG, Borgeat A. New local anesthetics. Best Practice and Research Clinical Anaesthesiology. 2018;32(2):179-85. [crossref][PubMed]
Wolfe RC, Spillars A. Local anesthetic systemic toxicity: Reviewing updates from the American society of regional anesthesia and pain medicine practice advisory. Journal of Peri Anesthesia Nursing. 2018;33(6):1000-05. [crossref][PubMed]
Li J, Duan R, Zhang Y, Zhao X, Cheng Y, Chen Y, et al. Beta-adrenergic activation induces cardiac collapse by aggravating cardiomyocyte contractile dysfunction in bupivacaine intoxication. PloS one. 2018;13(10):e0203602. [crossref][PubMed]
Iskander A, Gan TJ. Novel analgesics in ambulatory surgical patients. Current Opinion in Anesthesiology. 2018;31(6):685-92.[crossref][PubMed]
Neal JM, Woodward CM, Harrison TK. The American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic toxicity: 2017 version. Regional Anesthesia & Pain Medicine. 2018;43(2):150-53. [crossref][PubMed]
Wong GK, Pehora C, Crawford MW. L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: An experimental study in rats. Canadian Journal of Anesthesia/Journal Canadien D’anesthésie. 2017;64(3):270-79. [crossref][PubMed]
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Gys B, Lafullarde T, Gys T, Janssen L. Intrathecal prilocaine, 2-chloroprocaine and bupivacaine for ambulatory abdominal wall herniorrhaphy: A prospective observational study. Ambul Surg. 2017;23:08-12.
Lacasse MA, Roy DJ, Forget J, Vandenbroucke F, Seal RF, Beaulieu D. Comparison of bupivacaine and 2-chloroprocaine for spinal anaesthesia for outpatient surgery: A double-blind randomized trial. J Can Anesth 2011;58:384-391. [crossref][PubMed]
Membership of the Working Party; Campbell JP, Plaat F, Checketts MR, Bogod D, Tighe S, Moriarty A, Koerner R. Safety guideline: Skin antisepsis for central neuraxial blockade: Association of Anaesthetists of Great Britain and Ireland Obstetric Anaesthetists’ Association Regional Anaesthesia UK Association of Paediatric Anaesthetists of Great Britain and Ireland. Anaesthesia. 2014;69(11):1279-86. [crossref][PubMed]
Camponovo C, Wulf H, Ghisi D, Fanelli A, Riva T, Cristina D, et al. Intrathecal 1% 2-chloroprocaine vs 0.5% bupivacaine in ambulatory surgery: A prospective, observerblinded, randomized, controlled trial. Acta Anaesthesiol Scand. 2014;58(5):560-566.[crossref][PubMed]

DOI and Others

DOI: 10.7860/JCDR/2023/60319.18123

Date of Submission: Sep 19, 2022
Date of Peer Review: Dec 10, 2022
Date of Acceptance: Feb 11, 2023
Date of Publishing: Jun 01, 2023

• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

• Plagiarism X-checker: Sep 22, 2022
• Manual Googling: Jan 24, 2023
• iThenticate Software: Feb 07, 2023 (12%)

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