Efficacy of Different Doses of Intrathecal Chloroprocaine as Anaesthetic for Ureterorenoscopic Lithotripsy

Introduction

Day care surgeries like ureterorenoscopic surgeries (URSL) for ureteric calculus are done under spinal anaesthesia (SA).^1,2,3 Intrathecal preservative free 1% chloroprocaine is shown to have faster onset, regression of the block, shorter time to ambulation, and earlier discharge from hospital.⁴

Literature suggested 30-60 mg of intrathecal chloroprocaine for procedures lasting 60 minutes or less. The purpose of our study was to identify the ideal dosage of intrathecal chloroprocaine in surgeries like URSL. Therefore, we compared the efficacy of three different doses (40, 45 and 50 mg) of chloroprocaine for URSL, after confirming from pilot study that 30 mg was inadequate.

Methods

In this prospective, non-randomized, comparative study, 105 patients of either sex belonging to ASA 1 and 2, aged between 18 to 60 years, with ureteric calculus >8 mm posted for URSL under SA were enrolled after obtaining institutional ethics committee approval and informed consent. The study was conducted from Jan 2018 to Dec 2018. Exclusion criteria included patients allergic to chloroprocaine, CNS infection, spine deformities, bleeding diathesis and coagulopathy, pre-existing neurological deficits of lower extremities, active upper and lower urinary tract infections.

On the day prior to surgery, all enrolled patients underwent pre-anaesthetic check-up, investigation review, and nil per oral advice as per ISA guidelines. Patients were pre-medicated with tab Ranitidine 150 mg and Diazepam 10 mg orally night prior to surgery. On arrival to the operating room, patients were reassessed and basic vitals like oxygen saturation (SpO2), heart rate (HR) and non-invasive blood pressure (NIBP) were recorded.

Patients were scheduled to receive the study drug (preservative free 1% chloroprocaine) by an independent resident/consultant not involved in the study. No randomization, blinding or allocation concealment was done.

Group A patients received 4 mL (40mg), Group B received 4.5 mL (45mg) and Group C received 5 mL (50mg) of chloroprocaine.

Intravenous access was secured with 20G cannula and patient was preloaded with fluid Ringer’s lactate at 10 mL/kg over 20 minutes. After recording baseline vitals, under aseptic precaution, SAB was performed at L3-L4 interspace in left lateral position with 25G Quincke’s needle. After confirmation of free flow of CSF, the study drug was administered over 10-15 seconds. Immediately after the injection, patients were turned supine and supplemented with 100% oxygen by facemask. Patients were immobilised for 5 minutes till the study drug fixation was confirmed. Then patients were put in lithotomy position and surgery was commenced. Monitoring included HR, Systolic blood pressure (SBP), Mean arterial pressure (MAP), SpO2 every minute for first 5 minutes, every 5 minutes for next 20 minutes, then every 10 minutes till the end of surgery and postoperatively, every 15 minutes till the patients complained of pain.

Sensory block was assessed by pinprick method using hypodermic needle and motor block by modified Bromage scale. Both the sensory and motor blocks were assessed every minute for first 5 minutes, then every 5 minutes for next 20 minutes and thereafter every 10 minutes until two segment regression from peak block and recovery of sensory blockade till S2 level and motor blockade of Bromage scale recovered to 0.

Onset of sensory blockade was defined as the time taken from the deposition of study drug till patient does not feel pin prick sensation at L1 level. Maximum height of sensory blockade was the time taken from deposition of drug till the attainment of maximum sensory blockade level. Duration of sensory blockade was defined as the time taken for two segment regression from peak block and complete recovery from anaesthesia when sensory block regresses to S2 level. Onset of motor blockade was the time from the deposition of the study drug till attainment of Bromage scale 3. (Modified Bromage scale: 0-full flexion of knees and feet, 1- just able to flex the knees, full flexion of feet, 2-unable to flex the knees, but some flexion of feet is possible and 3- unable to move legs or feet). Duration of motor block was the time taken from the onset of motor block till the patients attained Bromage scale 0. Any adverse effects like hypotension, bradycardia, nausea, vomiting and shivering were noted and treated accordingly.

Hypotension was defined as decrease in SBP of < 90 mmHg or decrease by > 30% of the baseline value and was treated with mephentermine 6 mg intravenous (iv) boluses and i.v fluid rush. Bradycardia was defined as heart rate of < 50 beats/min and was treated with atropine 0.6 mg iv. Nausea and vomiting was treated with Inj ondansetron 4 mg i.v and shivering with Inj butorphanol 1 mg i.v. In case patient complained of pain during the surgery, inj fentanyl 50 µg i.v was given and study was terminated.

Patients were instructed to report if anyone developed headache, backache or abnormal sensation in the buttocks or lower limb.

Casati et al.,⁵ concluded that 40 to 50 mg of plain chloroprocaine 1% provided adequate SA for lower limb outpatient procedures lasting 45 to 60 min, whereas 30 mg resulted in a spinal block of insufficient duration. We did a pilot study on 12 cases with dosage of 40, 45 and 50 mg and with preliminary data analysis, with the need to get a power of 80%, confidence interval of 90% and precision/error of 1%, in consultation with statistician and applying the below formula, the sample size was calculated as 35 in each group.

n=2(Zα +Zβ )2 -σ2 /(X1 – X2 )2

Data was analysed by using ANOVA and post hoc analysis by Bonferroni test. Stata version 14 statistical software was used for analysis. p< 0.05 was considered as statistically significant. Results The three groups were comparable with respect to demographic variables and duration of surgery. (Table 1).

The onset of sensory blockade at L1 was comparable between the three groups (p>0.05) (Table 2). The sensory block was prolonged in group C (100.14±6.58 min), when compared to group A & B (94.88±4.11 & 81.86±3.22 min) which was statistically significant (p<0.001) (Figure 1). The maximum cephalad spread of the drug reached T8 level in all the three groups. However, the time taken to reach T8 level was comparable in all the three groups (Table 2). The onset of motor blockade was comparable in all the three groups (p>0.05) and pro-longed duration was observed in group C (86.14±3.85 min) which was statistically significant (p<0.001) compared to group A and B (Figure 2). However the differences in the values between the three groups appeared clinically insignificant.

Time to discharge after recovery from sensory block (Table 2), procedure related complications and hemodynamic parameters were comparable between the groups (p>0.05) (Figure 3-5)

Discussion

With the development of minimally invasive techniques, the use of ambulatory surgery has grown rapidly, necessitating the search for the ideal short acting SA drug that provides rapid onset of action, adequate potency and predictable duration with decreased side effects. Ambulatory surgery has several advantages when compared to inpatient surgery such as reduced waiting time, lesser cancellations, lower hospital costs, rapid resumption of daily activities and lower risk of nosocomial infection.⁴

The use of URSL for the treatment of ureteric calculi is gradually increasing. As it is minimally invasive and associated with less pain, it may be considered as a suitable procedure for an outpatient setting.²

Considering that ambulatory surgery involves discharge on the day of surgery, recovery of the patient is perhaps the most important factor in determining the anaesthetic technique. SA is commonly preferred for performing URSL. It provides adequate anesthesia for the patient and good relaxation for the surgical procedure, advantages of awake patient, adequate post operative analgesia and early recovery.² Furthermore, one can avoid the side effects associated with GA such as nausea, vomiting, dizziness, residual muscle relaxation, and airway related complications.^6-8

However, when using SA, an appropriate LA and its dosage must be administered in order to avoid delays in hospital discharge. While long or intermediate acting LA agents prolong the recovery, the high incidence of TNS associated with intrathecal lidocaine led to most practitioners abandoning its use.^9-13 With the introduction of preservative free chloroprocaine, it is now possible to provide short duration SA that shows adequate sensorimotor blockade and quicker recovery.^14-17 The goal of this study was to identify the ideal dosage of chloroprocaine that provides optimal anaesthetic requirement in an ambulatory setting such as URSL by comparing the effects of three different doses of the drug.

The three doses of chloroprocaine were decided after careful review of various studies.^18,19 The most commonly used doses were 30 mg, 40 mg and 50 mg. Casati et al., concluded that 40 to 50 mg of plain chloroprocaine 1% provided adequate SA for lower limb outpatient procedures lasting 45 to 60 min, whereas 30 mg resulted in a spinal block of insufficient duration.⁵

A pilot study done on 10 patients showed that 30 mg of 1% chloroprocaine was insufficient to provide adequate surgical anaesthesia for URSL. Therefore, the three doses chosen for comparison were 40 mg, 45 mg and 50 mg in the present study.

Regarding the onset of sensory block, we noted that the onset of sensory blockade at L1 was fastest in group C with 3.48±0.56 min and slowest in group A with 5.05±0.68 min; however the values were comparable (p>0.05). The trend showed that as the volume of the drug increased, onset of sensory blockade was faster. These findings were similar to the study conducted by Camponovo et al., in which it was observed that the mean time for onset of sensory block was 5 min with 50 mg chloroprocaine and 6 min with 10 mg Bupivacaine.²⁰

Regarding maximum level of sensory block, authors in another study used 40 mg chloroprocaine in their study and found the sensory block up to T9.²¹ In our study, we noted the highest level of sensory block attained was T8 ranging from 75-85% of cases in all of the groups with group C attaining fastest in 6.08±0.65 min and group A and B in 7.94±0.68 min and 7.51±0.7 min, respectively (p >0.05), which was similar to the study conducted by Hejtmanek et al., in which the median block height with 30-60 mg isobaric chloroprocaine was T8.22 The fact that even though the maximum level of sensory block in majority of the cases in different groups were similar, the time to attain this maximum height differed. It shows that volume of drug has effect on the speed of cephalic distribution of the drug. Also in this study, none of the patients required conversion to general anaesthesia because of inadequate drug action. This showed that the selected doses of chloroprocaine were sufficient for this type of ambulatory surgeries.

The duration of sensory block was also similar in the present study and the results reported by others. Total mean duration of sensory block was found to be 100.14±6.5 minutes in group C, 81.86±3.²² minutes in group A and 94.86±4.11 minutes in group B which was statistically significant (p<0.001). Similar results were also seen in the study conducted by Casati et al.⁵ They found that duration of sensory blockade was 69, 85 and 97 minutes with 30, 40 and 50 mg of 2-chloroprocaine respectively.To know the effect of varying concentration of the drug by keeping the volume of the drug constant, further studies are required and this can be considered as one of the limitation of the study.

Onset of motor blockade was defined as the time taken to attain Bromage scale 3. There was no significant difference (p>0.05) in the onset of motor block in different groups. It was found that the onset was fastest in group C (9.8±1.68 min) and slowest in group A (10.71±1.79 min). A study by Yoos and Kopacz also found to have similar findings regarding mean time for the onset of motor block.21 There was a dose dependent increase in the duration of mean motor block and maximum of 86.14±3.8 min seen in group C which was statistically significant compared to the other two groups (p<0.001). A study conducted by Anarase and Bhalerao et al., showed that that the motor block duration with 50 mg 2-CP was 95±30 minutes.²³ This observation further highlights the adequacy of intrathecal chloroprocaine for ambulatory surgeries of short duration.

The time taken for complete sensory recovery (up to S2) and ambulation was found to be similar to that of a study by Hetjmanek et al. in which the mean time to ambulation with 30-60 mg Chloroprocaine was found to be 115±33 min.²²

Peri-operative hemodynamic variation, incidence of nausea and vomiting were comparable between the groups (p>0.05). None of the patients developed long term complications like TNS, or other neurological sequelae.

The limitations of the study included small and limited study sample. It was an observational study and lacked randomization, blinding and allocation concealment. Large scale randomization study will be required to determine the precision of the sensory level of the block within two dermatome levels and further delineate its safety as spinal anaesthetic choice of drug.

Conclusion

We conclude that preservative free 1% chloroprocaine is safe for intrathecal administration in ambulatory surgeries like URSL in dose ranges of 40-50 mg with ideal anaesthetic conditions, minimal hemodynamic disturbances and minimal short term and long term side effects.

Conflict of interest

The authors declare that they have no conflicts of interest for publication of this article.