In modern surgical practice, the approach toward daycare surgery is increasing. Short-acting drug chloroprocaine was abandoned because of associated transient neurological symptoms attributed to its preservative, sodium bisulfite. Its safety and efficacy were reestablished after the introduction of preservative-free chloroprocaine. Intrathecal dexmedetomidine and nalbuphine when added as an adjuvant improve sensory block characteristics and provide hemodynamic stability. Hence, we planned this study.
This study aimed to compare the effect of adding dexmedetomidine 10 μg versus nalbuphine 0.4 mg as an adjuvant to intrathecal 40 mg of 1% chloroprocaine for daycare surgeries performed under spinal anesthesia.
MATERIALS AND METHODS
This prospective, randomized, double blind study was conducted after obtaining approval from Institutional Ethical Committee of Mahatma Gandhi Medical College and Hospital, MGMCH/IEC/JPR/2019/70, dated 02/01/2020 and written informed consent from all the patients. The procedure followed guidelines laid down under Helsinki Declaration (2013). The duration of the study was between January 2020 and June 2021. A total of 150 patients were enrolled and were randomly divided into three groups of 50 each with the help of computer-generated randomization tables. There were no dropouts. The study drugs were prepared by anesthesia nurse and provided in prefilled syringes as per the group. Both the patients and the observer were blinded to the study groups which were as follows:
- Group C (n = 50) received 40 mg of 1% chloroprocaine (4 mL) and 1 mL normal saline, intrathecally
- Group NC (n = 50) received 40 mg of 1% chloroprocaine (4 mL) with nalbuphine 0.4 mg diluted to 1 mL in normal saline, intrathecally
- Group DC (n = 50) received 40 mg of 1% chloroprocaine (4 mL) with dexmedetomidine 10 μg diluted to 1 mL in normal saline, intrathecally.
The inclusion criteria were age 18–65 years, either gender, ASA PS classes II and III, below umbilical surgeries of duration 60–90 min, and those giving consent for surgery. Those patients having history of drug allergy, on psychotropic medications, with infection at the spinal site, and with spinal deformity and pregnant or lactating females were excluded from the study. On receiving the patient in the operating room, electrocardiogram, noninvasive blood pressure, and pulse oximetry were applied and continuously monitored. All patients were coloaded with around 1 L of balanced salt solution administered intravenous (i.v.) via 18G cannula. Patients were placed in sitting position, and under all aseptic precautions, lumbar puncture was performed at L3–L4 intervertebral space using a 25G Quincke's spinal needle, via midline approach. The study drugs were injected in the subarachnoid space after confirming free and clear flow of cerebrospinal fluid (CSF). Thereafter, the patients were immediately placed in the supine position. Monitoring of vital parameters was continued throughout the operative period. Midazolam 1 mg was administered i.v. in every patient for anxiolysis.
Sensory block was assessed using pinprick method by blunt needle every minute until the highest dermatome level (T10) reached and thereafter every 30 min till regression to S2 dermatome. Time to onset of sensory block and to attain peak sensory block level (T10 dermatome) was noted. Time to regression to S2 level was taken as an estimate of duration of sensory block. We also noted time to first demand of rescue analgesia.
Motor block was evaluated using modified Bromage scale (0 = no motor block, 1 = inability to lift extended legs; able to move knees and feet, 2 = inability to lift extended leg and move knee, able to move feet, 3 = complete block of motor limb) every minute until attainment of scale of 3 and thereafter every 30 min until complete regression of motor block. The onset of motor block was considered as attainment of Bromage 2 and duration of motor block as that of Bromage 0.
Sedation was assessed every 30 min until 6 h after completion of surgery, using Ramsay Sedation Score (1 = awake, 2 = cooperative, 3 = responds to command only, 4 = asleep-brisk response to light glabellar tap or loud auditory stimulus, 5 = sluggish response, 6 = no response).
Pain was assessed using 10-point visual analog scale (VAS) (0 = no pain … 10 = worst pain ever felt).
A modified Aldrete score was used for readiness to discharge from postanesthesia care unit (PACU) (activity level, respiration, circulation, consciousness, and oxygen saturation). Patients were discharged from the PACU after achieving a modified Aldrete score ≥9 and transferred to the ambulatory surgery unit.
The primary end point was time until complete recovery of sensory and motor block. The secondary end points were onset of sensory and motor blocks and time to reach peak levels and time to ambulation.
The sample size calculation was performed with SAS, version 9.2 of the SAS system for Windows (SAS Institute Inc., Cary, North Carolina, USA). This size was calculated to detect a difference in onset, duration, and time to complete regression of sensory and motor blockade between the groups and was based on pair-wise, two-sided Mann–Whitney U-test. An overall type I error of 5% with a Bonferroni correction, we used level of 1.667% for each pair wise comparison. The exact times until complete recovery of sensory and motor block for the different local anesthetics are not known in the literature. Instead, we based our sample size estimation on estimates for the ambulation time that were obtained from the literature. Using a conversion formula, a lognormal distribution for the time until complete block recovery was assumed for each group. With 50 subjects in each group, the power is at least 98% for each pairwise comparison to detect differences as large as described in the literature. The study has only been powered for the primary end point, which is the time until complete recovery of sensory and motor block.
It was performed with SAS, version 9.2 of the SAS system for Windows (SAS Institute Inc., Cary, North Carolina, USA). The qualitative data were entered as numbers and quantitative data as mean ± standard deviation (SD). The qualitative data were analyzed using Chi-square test whereas the quantitative one using Student's t-test and two-sided Mann–Whitney U-test. P < 0.05 was considered statistically significant.
Demographic parameters were comparable in all three groups [Table 1].
The duration of sensory block was prolonged with the use of adjuvants dexmedetomidine and nalbuphine compared to chloroprocaine alone. The prolongation was greater in Group DC compared to Group NC, the trend being group C < NC < DC (P < 0.001) [Table 2]. The duration of motor block revealed similar trends [Table 3]. The onset of sensory and motor block was earlier in Group NC compared to Group DC (Group C < NC < DC) (P < 0.001) [Tables 2 and 3, respectively]. The VAS score at 90 min was significantly more in Group NC compared to Group DC (P < 0.001) [Figure 1].
Patients of Group NC could be ambulated earlier than those of Group DC. Ramsay Sedation Score was comparable in all three groups at all points of time [Figure 2]. Hemodynamic variables were comparable, and there were no major side effects in either group.
Daycare surgery is gaining popularity in the modern world due to its various advantages. Besides being cost-effective, it reduces the burden on the health system. Patient satisfaction is also higher due to early recovery and short hospital stays. Surgeries below umbilical level are routinely performed under spinal anesthesia. Due to nonavailability of safe short-acting local anesthetic agent over the past years, spinal anesthesia was not preferred modality for daycare surgeries. Hence, such surgeries had to be conducted under general anesthesia which has its own limitations.
Most practitioners abandoned intrathecal lignocaine due to transient neurological symptoms. Chloroprocaine, another local anesthetic agent with short duration, was also abandoned because of its neurological complications attributed to sodium bisulfite, used as a preservative. Its safety and efficacy were reestablished after the introduction of preservative-free chloroprocaine. Goldblum and Atchabahian reported that preservative-free chloroprocaine was reliable local anesthetic compared to lidocaine. Its duration of action is 45–60 min.
Hejtmanek and Pollock concluded that preservative-free chloroprocaine in the dose of 40 mg intrathecally was effective in providing surgical anesthesia for ambulatory surgeries. In our study, we used 1% chloroprocaine 40 mg intrathecally.
Various drugs have been used as an adjuvant to local anesthetic agents to get better results. Intrathecal opioids can produce extensive analgesia, when used as adjuvants, and has the advantage of allowing early ambulation of patients because of their sympathetic and motor nerve-sparing activities. Nalbuphine is an opioid with agonist activity at the K receptors and antagonist activity at the mu receptors. In our study, we used chloroprocaine 40 mg with 0.4 mg nalbuphine as an adjuvant, intrathecally. Mukherjee et al. compared different doses of nalbuphine 0.2, 0.4, and 0.8 mg as an adjuvant with 12.5 mg hyperbaric bupivacaine in spinal anesthesia. The time of two-segment regression of sensory blockade and duration of effective analgesia was prolonged in Group C (0.4 mg nalbuphine) and Group D (0.8 mg nalbuphine) (P < 0.05). The incidence of side effects was significantly higher in Group D 0.8 mg (P < 0.05) compared with the other groups. Hence, nalbuphine used intrathecally is a useful adjuvant and, in a dose of 0.4 mg, prolongs postoperative analgesia without increased side effects.
Dexmedetomidine is a novel alpha-2 agonist. It produces analgesia by inhibiting release of C-fiber transmitters and by hyperpolarization of postsynaptic dorsal horn neurons. Halder et al. observed the effects of different doses of dexmedetomidine as an adjuvant in bupivacaine-induced subarachnoid block for traumatized lower limb surgery. 80 patients divided in two groups. Group D5 received 3 mL of 0.5% hyperbaric bupivacaine +5 μg dexmedetomidine. Group D10 received 3 mL of 0.5% hyperbaric bupivacaine +10 μg dexmedetomidine. They reported that dexmedetomidine increased sensory and motor block duration and time to first analgesic use in dose-dependent manner.
Our primary objectives were to compare the duration of sensory and motor blockade. The secondary objectives were to study the onset and time to complete regression of sensory and motor blockade and time to ambulation and to find out any complications such as hypotension, bradycardia, respiratory depression, nausea, vomiting, pruritus, and urinary retention and manage them.
On comparing Group NC and Group DC, we observed that onset of sensory block is prolonged in Group D (P ≤ 0.001).
Michael and Mehta observed the effect of bupivacaine 15 mg with 10 μg dexmedetomidine or 0.4 mg nalbuphine. They reported that the mean onset of sensory block in Group N was 6.3 ± 1.64 min and in Group D was 3.5 ± 1.10 min (mean ± SD) (P < 0.001). We used chloroprocaine which is isobaric compared to CSF. It can be a possible reason for that contrast results for delaying effect. We observed that addition of dexmedetomidine as an adjuvant prolongs the duration of motor block more than nalbuphine. This is in accordance with their results which showed that duration of motor block was greater in dexmedetomidine group (P < 0.001) (247.43 ± 28.538 and 184.17 ± 27.104 min, respectively) (mean ± SD). Furthermore, the onset of motor block in Group D and Group N was 8.73 ± 1.874 min and 6.23 ± 1.382 min, respectively (P < 0.001). Kim et al. observed that using dexmedetomidine as adjuvant to intrathecal bupivacaine 6 mg prolongs time to regression to S2 segment (P < 0.001). This is in accordance with our study.
On intergroup comparison between Group NC and Group DC, the time to onset of motor block was greater in dexmedetomidine group than nalbuphine group (P < 0.0001). Chatrath et al. studied the effect of adding dexmedetomidine 10 μg as adjuvant to hyperbaric bupivacaine versus hyperbaric bupivacaine alone, intrathecally, and found that the total duration of motor block was greater in the dexmedetomidine group (318.36 ± 9.374 min) versus using bupivacaine alone (146.94 ± 9.173 min) (P < 0.001). This is also in accordance with our study.
Michael and Mehta discussed the effect of dexmedetomidine 10 μg or nalbuphine 0.4 mg with 15 mg bupivacaine intrathecally, and they reported no significant changes were seen in heart rate, systolic blood pressure, and diastole blood pressure in both groups at all intervals (P > 0.05). These findings are in concordance with our study.
We conclude that the addition of adjuvants such as nalbuphine or dexmedetomidine intrathecally with chloroprocaine is safe and effective as it prolongs the sensory block. Nalbuphine is a better adjuvant drug for daycare surgeries compared to dexmedetomidine because of lesser prolongation of motor block and earlier ambulation.
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Conflicts of interest
There are no conflicts of interest.
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