Research Article
Low Dose Bupivacaine versus Prilocaine Regarding Hemodynamic Stability and Safety in Geriatrics: A Randomized, Double-Blind Comparative Study
Mohamed Ahmed Shawky*, Mohamed Ahmed Hamed, Yasser Salem Mostafa, Doaa Lotfy Abd El Baky and Omar Sayed Farghaly
Corresponding Author: Mohamed Ahmed Hamed, Department of Anesthesiology, Faculty of Medicine, Fayoum University, Egypt.
Received: December 30, 2024; Revised: January 08, 2025; Accepted: January 11, 2025 Available Online: Janauary 24, 2025
Citation: Shawky AM, Hamed AM, Mostafa YS, Abd El Baky DL & Farghaly OS. (2025) Low Dose Bupivacaine versus Prilocaine Regarding Hemodynamic Stability and Safety in Geriatrics: A Randomized, Double-Blind Comparative Study. Int J Anaesth Res, 7(1): 206-216.
Copyrights: ©2025 Shawky AM, Hamed AM, Mostafa YS, Abd El Baky DL & Farghaly OS. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Background: The most common adverse event of spinal anesthesia is post-spinal anesthesia hypotension, with an incidence of 16% to 33%. This study aimed to compare the impact of bupivacaine and prilocaine on hemodynamic stability and safety during orthopedic operations in older individuals.

Methods: A double-blind randomized controlled trial was done on a group of 100 cases who were scheduled to have elective knee and below-knee orthopedic procedures at Fayoum University Hospital. The patients were categorized into two equal groups (50 cases in each group): bupivacaine group who had been administered a low dose of 7.5 milligrams of hyperbaric bupivacaine 0.5%, and prilocaine group who had been given a low dose of 40 milligrams of intrathecal hyperbaric prilocaine, 2%.

Results:
A statistically insignificant variance has been observed among examined groups according to systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) at baseline, 10, 20, 30, 60, 90, and 120 minutes (P > 0.05), while there was significant decrease in bupivacaine group than prilocaine group regarding SBP and MAP after 5 min (P = 0.007, P = 0.001 respectively); moreover, there was statistically significant variance among the examined groups according to intensity of sensory block at 90 and 120 min (P = 0.013, P = 0.028 respectively), and motor block at 60, 90 and 120 min (P = 0.025, P < 0.001, P < 0.001  respectively). There was statistical significance regarding atropine and ephedrine use with lower doses in the prilocaine group (P < 0.05). The two study groups had a statistically significant variance in the return of sensory, motor, and bladder functions (P < 0.001).

Conclusion:
Concerning lower doses of atropine and ephedrine and faster recovery of sensory, motor, and urinary bladder function, the use of prilocaine for spinal anesthesia seems to be preferable to bupivacaine, especially in geriatrics.

Trial registration:
No protocol revisions or study amendments have been made since the trial’s inception, according to the information on ClinicalTrials.gov (NCT06382220), principal investigator: Mohamed Ahmed Hamed, date of registration: April 23, 2024.

Keywords:
Bupivacaine, Prilocaine, Hemodynamic stability, Geriatrics

Abbreviations:
SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; MAP: Mean Arterial Pressure; HR: Heart Rate; ERAS: Early Recovery After Surgery
BACKGROUND

Orthopedic operations are a rapidly expanding surgical field worldwide. In 2017, there was a global total of 22.3 million orthopedic surgical procedures conducted. It is projected that the yearly number of orthopedic treatments will grow by 4.9 percent each year, reaching approximately 28.3 million operations by 2022 [1].

Spinal anesthesia is commonly utilized in orthopedic surgery, particularly in procedures involving the lower limbs. Nevertheless, due to the elevated occurrence of bradycardia and hypotension, there is usually a potential danger, especially among the older population, given their compromised hemodynamic condition. Unilateral spinal anesthesia restricts the extent of the spinal block to the side of the body where the surgery is being performed, as most operations include just one lower limb. The most common adverse event of spinal anesthesia is post-spinal anesthesia hypotension, with an incidence of 16% to 33%. The effect of 
the dose of local anesthetics administered intrathecally on cardiac output changes in elderly patients is largely unknown [2-4].

Bupivacaine is the preferred choice for spinal anesthesia because of its reliable nature and few adverse effects. Nevertheless, the extended and uncertain duration of action of bupivacaine, often ranging from three to nine hours, can present challenges for accelerated recovery and discharge plans [5]. Bupivacaine has a rapid onset time for motor block and a prolonged duration of motor block. The major disadvantage of bupivacaine is the significant inter-individual variability, which results in clinically significant variations in the period of motor block, dermatomal spread, and onset time [6,7].

Prilocaine is a local anesthetic that is classified in the same family as bupivacaine. Over the past ten years, the usage of prilocaine by two percent has been increasingly prevalent in orthopedic operations, thanks to advancements in day operations. Prilocaine promotes a briefer impairment of motor function and reduces the probability of urine retention, thus improving the process of postoperative recovery. Typically, the doses given in spinal anesthesia range from twenty to eighty milligrams [8].

This investigation aimed to examine the use of bupivacaine and prilocaine as unilateral low-dose spinal anesthetics for below-knee orthopedic procedures in older individuals, with a focus on hemodynamic stability and safety.

METHODS

A double-blind randomized controlled trial was performed on a group of one hundred cases who have been scheduled to have elective knee and below-knee orthopedic procedures at Fayoum University Hospital (R550). The investigation retrospectively registered at clinicaltrials.gov with the number (NCT06382220; principal investigator: Mohamed Ahmed Hamed, date of registration: April 23, 2024). No protocol revisions or study amendments have been made since the trial’s inception. The study was conducted from April 2024 to October 2024. Before recruitment and randomization, the eligible cases provided full informed consent. Cases have been assigned to research groups utilizing a randomized central computer-generated sequence and an enclosed assignment. The assignment was held by an investigator who did not take part in the clinical treatment or gather information. The cases were then randomly divided into two groups, as follows: prilocaine group and bupivacaine group.

Inclusion criteria: participants aged sixty years or older, of both sexes, with American Society of Anesthesiologists (ASA) physical status I, II, or III who have been scheduled for elective knee and below knee orthopedic procedures spanning 40 to 60 min under spinal anesthesia.

Exclusion criteria: Cases with a height less than 1.55 meters or greater than 1.75 meters, along with additional neurological illnesses and spine anomalies, have absolute and relative contraindications to spinal anesthesia. These contraindications include cases with intracranial hypertension, major bleeding disorders, cases taking anticoagulant medication, those with local infections, dementia, and allergic reactions to local anesthetics.

Sampling: For sample size calculation, the online site https://select-statistics.co.uk was used. Depending on previous study done by Mehta [9], the proportion difference is expected to be 17.5% between the two groups in incidence of hypotension which is our primary outcome in this study, with a power of 80%, alpha error of 5%, and an allocation ratio of 1:1, we need to include 96 patients in the study (48 in each group). To compensate for the possible dropout of 5%, we increased the sample size to 100 patients (50 in each group).

Anesthetic technique:

Before the subarachnoid blocking procedure All patients have been subjected to history-taking, clinical examinations, and laboratory investigations. All cases were administered a Ringer's lactate infusion at a dose of five milliliters per kilogram, which was then maintained intraoperatively at a rate of five milliliters per kilogram per hour. Systolic blood pressure (SBP), heart rate (HR), mean arterial pressure (MAP), and diastolic blood pressure (DBP) have been measured and documented.

Bupivacaine Group: The study involved 50 cases who were administered a low dose of 7.5 milligrams of hyperbaric bupivacaine 0.5% (brand name: Marcaine®, AstraZeneca, Sweden) in a volume of two milliliters. This was achieved by diluting 1.5 milliliters of hyperbaric bupivacaine 0.5% with 0.5 ml of sterile distilled water.

Prilocaine group: a total of 50 cases have been administered a small dose of 40 milligrams of intrathecal hyperbaric prilocaine 2% (Takipril, Sunny Medical Group, Egypt, under license from Sintetica, Switzerland) in a volume of two milliliters.

The administration was done intrathecally at the lumbar levels L3-L4 or L4-L5, while the cases were in a lateral decubitus position with the operated side kept dependent. The cases remained in this position for 10 min prior to being turned supine. The injection has been administered precisely in the midline over a period of thirty seconds using a 25-gauge Quincke needle, following rigorous aseptic protocols. The investigation solution has been made by a different investigator, and its substance has been hidden from the anesthetist who administered it. The anesthesiologist who gathered the information was unaware of any of the experimental groups. If sufficient surgical anesthesia was not attained, the case underwent general anesthesia and was subsequently excluded from the current investigation.

Study outcomes:

Primary outcome:

The incidence of hypotension, defined as a decrease in SBP < 90 mmHg or a ≥30% below baseline which requires the administration of ephedrine in incremental doses of 3 mg. patients were divided into hypotensive and nonhypotensive groups.

Secondary outcomes:

Doses of atropine had been administered intravenously as a management of bradycardia (HR <50). The intensity of sensory and motor blocks, as well as the time it took for bladder function to return (the ability to urinate without difficulty), were measured and compared and the lengths of recovery from sensory and motor blocks have been determined.

Cases have been assessed, starting five minutes following the subarachnoid injection, with evaluations conducted furthermore at 10, 20, 30, 60, 90, and 120 min. The sensory block level has been assessed bilaterally utilizing a 25G needle and the pin-prick test. The intensity of sensory block has been determined using Hollmen scale [10]:

Grade 1: full sensation.

Grade 2: weak sensation.

Grade 3: recognized as light touch.

Grade 4: loss of sensation.

Motor block evaluations were conducted immediately following the analgesic evaluation. The intensity of the motor block has been determined using the Bromage scale [11]:

Bromage 0: able to move the whole lower limb.

Bromage 1: unable to lift his leg but able to flex his knee and ankle.

Bromage 2: unable to flex his hip and knee but able to flex his ankle.

Bromage 3:  unable to flex his hip, knee, and ankle but able to move his toes.

Bromage 4: complete paralysis

The period of the sensory block has been determined as the period from when the sensory block attained its peak level of dermatomal blockade until the recovery of the S2 dermatome. The length of the motor block was determined as the period during which the Bromage scale decreased from a score of four to a score of zero.

Statistical analysis:

For the statistical analysis, we used SPSS version 25.0 for Windows (Armonk, NY: IBM Corp). The Shapiro‒Wilk test was used to assess the normality of continuous variables. Continuous variables that were normally distributed were presented as the mean ± standard deviations. The student’s two-sample t test was used for comparisons. Continuous variables that were not normally distributed were presented as the median and interquartile range (25th percentile-75th percentile) and the Mann-Whitney test was used for comparisons. Categorical variables were shown as percentages and absolute numbers of cases. The χ2 test and Fisher’s exact test were used for contingency table analysis as appropriate. Two-sided p values were shown, and the limit of statistical significance was set to p < 0.05.

RESULTS

Of the 115 patients evaluated for eligibility, 11 did not meet the inclusion criteria, 4 refused to participate. Data for 100 patients were analyzed (Figure 1).

According to Table 1, a statistically insignificant distinction has been observed among the examined groups regarding age and gender.



According to Table 2, a statistically insignificant variance has been observed among examined groups according to SBP, DBP, MAP at baseline, 10, 20, 30, 60, 90, and 120 min, while there was significant decrease in bupivacaine group more than the prilocaine group regarding SBP and MAP after 5 min.

According to Table 3, the overall and interval incidence of hypotension when compared to baseline at each time point between the two study groups was statistically insignificant.



According to Table 4, a statistically insignificant variance has been observed among examined groups according to used amount of ephedrine at 10, 20, 30 and 60 min, Atropine used at 5, 60, 90, 120 min while there was significant decrease in prilocaine group than bupivacaine group regarding used amount of ephedrine at 5, 90, 120 min, Atropine used at 10, 20, and 30 min.

According to Table 5, a statistically significant variance has been observed among examined groups according to intensity of sensory block at 90 and 120 min.


According to Table 5, a statistically significant variance has been observed among examined groups according to intensity of motor block at 60 ,90 and 120 min.

According to Table 6, a statistically significant variance has been observed regarding sensory and bladder function return which is more rapid in prilocaine group.


DISCUSSION

We compared low dose bupivacaine 7.5 mg (hemi-spinal) with low dose 40 mg prilocaine in knee and below knee orthopedic interventions aiming to achieve maximal hemodynamical stability enhancing ERAS (early recovery after surgery), we found that these doses were sufficient for such interventions. Andrea [12] agreed with our study regarding the efficacy of 40 mg prilocaine in successful subarachnoid block for knee surgeries. A statistically insignificant variance has been observed among examined groups according to SBP, DBP and MAP at baseline, 10, 20, 30, 60, 90 and 120 minutes, while there was significant decrease in bupivacaine group than prilocaine group regarding SBP and MAP after 5 min [12].

Initial findings at 5 min are consistent with the study conducted by Black [13] that found a clinically meaningful reduction in systolic arterial pressure > 20% was observed in thirty-two percent of the participants (seven out of twenty-two) in the prilocaine group and in seventy-three percent of the subjects (nineteen out of twenty-six) in the bupivacaine group [13].

Our investigation corroborated the findings of Etriki [14], who concluded that a statistically insignificant variance has been observed in mean arterial pressure among the groups examined at baseline, 10, 25, 35, and 65 min. Nevertheless, they found that there was statistically insignificant variation at 5 min [14].

Age above 50 years has been described as an independent predictor of hypotension during anesthesia [15]. Not surprisingly, the incidence of post spinal hypotension in the geriatric population of our current study was 41%, whereas it was 18% in a recent retrospective study of patients aged 46 to 71 years [16]. The characteristic reduction in cardiovascular function with ageing explains the susceptibility to hypotension in elderly patients. First, the cardiac output decreases by almost 50% between the ages of 20 and 80 due to the loss of cardiac myocytes and interstitial fibrosis [17]. Second, vascular compliance decreases with age, leading to dysfunction of blood pressure regulation [18]. Additionally, preoperative hypovolemia caused by fasting, anemia, or dehydration and continuation of ACE-I/ARBs also makes geriatric patients prone to post spinal hypotension [19].

In addition, Nasr [20] investigated the time it takes for spinal anesthesia to take effect using hyperbaric prilocaine at 2% with 20 μg fentanyl versus hyperbaric bupivacaine 0.5% with 20 μg fentanyl in perianal surgeries. The investigation found that there was a statistically insignificant distinction in mean arterial pressure among the two groups at baseline, 10, 25, 35, and 65 min. Nevertheless, it did find insignificant variation after five minutes [20].

The results of our study indicated that there was statistically insignificant variance observed among examined groups according to ephedrine used at 10, 20, 30 and 60 min and atropine at 5, 60, 90, 120 min. while there was significant decrease in prilocaine group than bupivacaine group regarding used amount of ephedrine at 5, 90 and 120 min, Atropine at 10, 20, and 30 min. these results favors the use of prilocaine at that dose in day case surgeries.

There was statistically significant variance has been observed among examined groups according to intensity of sensory and motor block as there was significant decrease in prilocaine group than bupivacaine group according to intensity of motor block at 60, 90 and 120 min and sensory block at 90 and 120 min. Mohamed [21] could support our results who reported that at 60 min, there was statistically significant decrease in prilocaine and fentanyl group than bupivacaine and fentanyl group according to motor regression, while there was statistically insignificant variation at 120 min [21]. In addition, Fayed [22] found statistically insignificant distinctions among the tested groups in terms of motor level at ten, twenty, and thirty minutes. However, there was a significant decrease in the prilocaine group compared to bupivacaine group at 120 minutes. Nevertheless, they stated that there was an insignificant disparity after sixty minutes, but a significant variance after five minutes [22].

Amr [23] investigated to evaluate the time it takes for motor and sensory block to start, end, and last following spinal anesthesia with hyperbaric prilocaine two percent or bupivacaine half percent combined with dexmedetomidine throughout elective inguinal hernia repair operations [23]. The investigation found significant variations in motor level among the groups at sixty minutes. and reported a statistically significant distinction at 120 min. The results of our study indicated that there was significant decrease in prilocaine group than bupivacaine group among examined groups according to sensory duration, motor duration and bladder function, agreed with us Fayed [22] who found also significant decrease in prilocaine group than bupivacaine group regarding sensory length and motor length [22]. In accordance with the study conducted by Black [13], the average duration to start micturition was shorter in prilocaine group than bupivacaine group also [13].

LIMITATIONS

This study has several limitations. We could not generalize the results on all age groups due to nature of geriatric patient in their characteristic hemodynamic properties. Also, this study could not assess the length of hospital stay after spinal anesthesia. The benefits of shorter recovery time of hyperbaric prilocaine 2% can be seen more clearly if the study is conducted on outpatient surgical patients. Transient neurologic symptoms were not observed in our study; however, the study was powered to compare the recovery times of the sensory, motor and urinary bladder block between groups, so we are not able to comment on adverse events and this is a limitation of this study. We did not measure cost benefit comparison for the two groups to assess better suitability for day-case surgeries.

CONCLUSION

Our study showed that the two drugs at these described doses had almost the same hemodynamical profile, as there was a significant reduction of SBP and MAP in the bupivacaine group compared to the prilocaine group only at 5 min otherwise no difference was found at any time. Moreover, bupivacaine had longer sensory, motor duration and had statistically longer time to return of bladder function when compared to the prilocaine group, these results favor the use of prilocaine in day surgery in geriatrics.

ACKNOWLEDGEMENTS

Not applicable.

AUTHOR CONTRIBUTIONS

Data collection: MAS, MAH, OSF. Data analysis: YSM, DLA. Writing: MAS, YSM. Revising: YSM, MAH. Study design: MAS, DLA, OSF. Patient recruitment: MAH. All authors contributed equally to this work, corresponding author and the guarantor: MAH. The author(s) read and approved the final manuscript.

FUNDING

No sources of funding.

AVAILABILITY OF DATA AND MATERIALS

Are available from the corresponding author upon reasonable request.

DECLARATIONS

Ethics approval and consent to participate: The investigation received permission from the Fayoum university Ethics Committee (R550). Prior to recruitment and randomization, eligible cases signed full informed consent.

Consent for publication: Written informed consent was obtained from all patients.

Competing interests: No competing interest.

Author details: Department of Anesthesiology, Faculty of Medicine, Fayoum University, Fayoum 63511, Egypt.

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