Pain management during the surgical process is one of the major topics of anesthesiology. Knowing the mechanism of early surgery-related complications entails adequate pain management and faster rehabilitation. To address this method of anesthesia, anesthetic drug selection, and dose modification are the essential components.
SA is well known relatively safe method of anesthesia induction. It is widely used in lower thoracic, abdominopelvic, and lower limb surgeries. Annually, it is employed in approximately 15 million surgeries (5% of surgical interventions)around the world(1, 2). SA was shown to have beneficial effects in the reduction of pulmonary complications, surgical site infections, the need for blood transfusion, thrombotic events, ICU admission, and inpatient care period(4).
Bupivacaine is a potent aminoacyl local anesthetic and a leading substance used for SA induction (11). Bupivacaine blocks nerve excitation by disabling voltage-gated sodium channels and antagonizing NMDA receptors in the dorsal horn(12). The pharmacologic features of bupivacaine are responsible for long-lasting anesthesia and sensory dissociation from motor blocks. A relatively low tachyphylaxis rate and poor placenta passage make it favorable for antinociceptive induction(13, 14). Hyperbaric (HB) bupivacaine hydrochloride has a greater density relative to the cerebral spinal fluid. in comparison with isobaric bupivacaine, HB-bupivacaine appeared to have brisk motor block initiation and a relatively shorter duration of sensory-motor block remission(7). The HB form attenuates the need for conversion to general anesthesia and supplemental analgesia without increasing the incidence of adverse effects (7).
Parallel to advantages, SA has several complications. Prominent peri-operative complications of HB-bupivacaine are hemodynamic instability and respiratory depression(2). Although individual reactions to HB-bupivacaine are idiosyncratic, more adverse reactions co-exist with higher-dose injections(8). However an inappropriate low-dose injection of the anesthetics followed by SA failure(15). Many efforts have been made to recognize the best dosage of HB-bupivacaine for SA, but the results are controversial.
We found that all three injected doses of HB-bupivacaine (A:12.5 mg/B:15 mg/C:20mg) were effective for induction of the Anesthesia required for lower limb orthopedic surgeries lasting up to 180 minutes. Our findings claim that the incidence of agitation, bradycardia, and hypoventilation did not vary between our study groups significantly, while for hypotension and N/V, we found an important between-group variation with a lower incidence in Group A relative to the others. Also clinically and statistically, the overall incidence rate of unwanted drug reactions was lower in group A of the participants. Our results imply that the decline of the systolic, diastolic, and mean arterial pressure are dose-dependent approximately. Conversely, respiratory rate and O2 saturation did not exhibit dose-dependent manners. Post-hoc analysis revealed that the majority of the meaningful inter-group differences happened 10–30 minutes after the injections, and the observed differences were more prominent between Groups A and C. Except for the injected drug dose, gender was found to be an important factor for anticipating the incidence of adverse effects. Our data suggested a protective effect of the female gender in unwanted drug reactions incidence.
Our findings on the efficacy of HB-bupivacaine in the induction of sensory-motor block (complete sensory-motor block without the additional intraoperative need for anesthesia) were in line with those of other studies. Picherski et.al in an RCT of lower limb orthopedic surgeries found 100% efficacy for the 15mg HB-bupivacaine solution on induction of the complete sensory-motor block. According to their results up to 73% of the patients did not need any additional intraoperative anesthesia(16). The difference between our results and the mentioned study probably originates from the various sample sizes and unequal drug brands and injected doses. Additionally, the patient's sensitivity to pain may influence the results of the additional need for intraoperative analgesia. Considering the adequate sensory-motor block in all study groups, our results support using a lower dose (12.5 mg) of HB-bupivacaine for SA in lower limb orthopedic surgeries.
Manouchehrian et al in a double-blinded RCT compared the efficacy of two doses of HB-bupivacaine 0.5% (10 mg and 12 mg) in cesarean section(15). They claimed that a lower dose of HB-bupivacaine was safer and more hypotension and bradycardia were associated with a higher dose of HB-bupivacaine. they concluded that a higher dose of HB-bupivacaine had more incidence of N/V.
Arzola et al in a meta-analysis investigated the efficacy of low-dose bupivacaine (≤ 8 mg) in spinal anesthesia for cesarean delivery(17). The associations of low-dose bupivacaine with a lower incidence of hypotension and N/V were concluded in this review. They also reported that low-dose bupivacaine was less effective for SA induction and associated with a higher risk of analgesic supplementation.
Age is another important indicator of adverse drug reaction incidence because of the pharmacodynamic features of HB-bupivacaine. The ED50% for HB-bupivacaine is reduced by advancing in age(18). Elderly people are more susceptible to induction of anesthesia and side effects by the use of HB-bupivacaine.
Prolonged immobilization after surgery is one of the most well-known risk factors for thromboembolic events. Layson et al demonstrated that a low-dose single shot of HB-bupivacaine provides a faster return of motor functions and better rehabilitation for patients in arthroplasty surgeries (19).
These findings necessitate more investigation to find the ideal dose of injected HB-bupivacaine for the induction of SA. Evidently, because of the multifactorial nature of adverse reactions incidence, a more precise evaluation should be conducted. Surgery duration, demographic features, patient’s medical history, American Society of Anesthesiologists (ASA) physical score, spinal cord level of SA induction, and β-blocker consumption are some of the known important factors for developing adverse effects after SA induction(9, 10).
The nature of the surgical procedures, the duration of the surgery, the different doses of injection, patient characteristics, and the technical issues of the injections are potentially important variables in finding the best dose of HB-bupivacaine in SA.
We tried to equalize these parameters among our study’s groups. Surgery time, demographic features, ASA score, and the spinal cord level for induction of SA didn’t have any significant differences in our study’s group. According to our results, injecting 12.5 mg of HB-bupivacaine for SA was a safe and efficient method for anesthesia induction in orthopedic surgeries of the lower limbs with surgery time of 45–180 minutes.
One source of weakness in this study which could have affected the measurements of the outcomes was inadequate information about participants’ past medical history and their routine drug consumption. Our information about these variables relied on patients' statements and it could affected by recall biases. Another limitation of our study is related to the sampling method. A large sample size study is needed to better evaluate the efficacy and adverse effects of HB-bupivacaine dosages. All of the participants were selected from a single center, and the patients had the same ethnicity for these reasons our findings were less generalizable. Also, our study does not contain the time of onset and duration of the anesthesia, further evaluation should be made to accurately compare the efficacy of these three dosage groups for induction of anesthesia.