Our study sheds light on the potential use of nicardipine in managing pituitrin-induced hypertension during laparoscopic myomectomy, a procedure aimed at reducing intraoperative bleeding. Pituitrin's cardiovascular side effects, including hypertension and arrhythmias, necessitate an effective and safe countermeasure, and nicardipine, a dihydropyridine calcium channel blocker, emerges as a promising solution.
Our study established the ED50 and ED95 of nicardipine for managing pituitrin-induced hypertension during laparoscopic myomectomy, providing essential guidance for anesthesiologists and surgeons when pituitrin administration is required. With an ED50 of 4.839 µg/kg and an ED95 of 5.308 µg/kg, we offer a quantitative framework for determining the appropriate nicardipine dosage, ensuring both effectiveness and safety while minimizing potential side effects.
These findings hold particular relevance in clinical settings where pituitrin is routinely administered, such as in China. Nicardipine, known for its safety profile, rapid onset of action, and the ability to maintain heart rate and cardiac output, proves to be an ideal choice for managing the cardiovascular responses induced by pituitrin.
Nicardipine has shown effectiveness and safety in managing acute hypertension following various conditions, including post-subarachnoid hemorrhage, severe antepartum hypertension, hypertensive emergencies[24]. Nicardipine is also a versatile medication used to maintain intraoperative hemostability, managing conditions like tracheal intubation or extubation-induced hypertension, chronic hypertension, and inducing controlled hypotension for specific surgical procedures[11]. However, the ideal dosage of nicardipine for managing pituitrin-induced hypertension remains uncertain, which is why we initiated this trial.
This study demonstrated that the DD50 of nicardipine in attenuating pituitrin-induced hypertension during laparoscopic myomectomy in patients was determined to be 4.839 µg/kg (95% CI: 4.569–5.099 µg/kg) using a sequential method for single injection. Furthermore, the ED95 was estimated to be 5.308 µg/kg (95% CI: 5.065–6.496 µg/kg). These findings provide quantitative support for the inhibitory impact of nicardipine on the pressor response to pituitrin in this clinical context.
One research, using Dixon's up and down sequential allocation, aimed to determine nicardipine's ED50 for mitigating hypertensive response during tracheal intubation induction[25]. The results showed that the ED50 values for nicardipine in three groups (thiopental, propofol, and etomidate) were 18.0 µg/kg, 6.2 µg/kg, and 16.7 µg/kg, respectively. Our study results demonstrated that the ED95 for intravenous nicardipine in treating pituitrin-induced hypertension is approximately 5.308 µg/kg with a 95% confidence level. Notably, the propofol group exhibited the lowest nicardipine requirement, which aligns closely with our research findings.
The hemodynamic response triggered by pituitrin follows a biphasic pattern, primarily influenced by its constituents—vasopressin and oxytocin. Vasopressin binds to V1 receptors, prompting contraction of vascular smooth muscles, thus raising blood pressure and inducing peripheral vasoconstriction[4, 26–28]. On the other hand, oxytocin receptors, present on endothelial cells, promote intracellular calcium ion increase, augmenting endothelial nitric oxide synthase activity and consequent vasodilation [29–31]. The interplay of vasopressin, with a longer half-life, and oxytocin concentration appears pivotal, often resulting in sustained elevation of blood pressure compared to the initial decrease[32]. In a recent study, the dose-response of nitroglycerin in preventing pituitrin-induced hypertension during laparoscopic myomectomy was investigated[33]. The results indicated that nitroglycerin effectively prevented pituitrin-induced hypertension, and specific doses were associated with a significant reduction in hypertension incidence. However, prophylactic nitroglycerin used prior to pituitrin-induced hypertension may lead to higher incidence of hypotension. Our study was designed to mitigate the hypertensive response that typically occurs approximately 1 minute after the intramyometrial injection of pituitrin[4]. This approach intentionally excludes patients who may experience oxytocin-induced hypotension, contributing to the safety of pituitrin administration.
Nicardipine, a water-soluble calcium channel antagonist, primarily exerts vasodilatory effects. In situations demanding rapid blood pressure control, intravenous nicardipine demonstrates a relatively swift onset and offset of action. The pharmacokinetics of nicardipine in patients with mild to moderate hypertension follow a linear pattern[34]. A large mount of studies investigate nicardipine's role in mitigating the intraoperative stress response. Intravenous nicardipine effectively controls acute intraoperative blood pressure across a spectrum of surgical procedures, encompassing cardiovascular, neurovascular, and abdominal surgeries[11]. It is particularly beneficial in intentional blood pressure reduction during surgeries where achieving hemostasis poses challenges, such as procedures involving the hip or spine [35]. Moreover, multiple studies demonstrate that intravenous nicardipine attenuates the hypertensive response without inducing tachycardia in anesthetized individuals following laryngoscopy and tracheal intubation [36, 37]. A well-designed, sizable study affirms nicardipine's ability to prevent cerebral vasospasm in patients with recent aneurysmal subarachnoid hemorrhage [38], consolidating evidence for its effectiveness in short-term hypertension treatment. This study presents the inaugural investigation into the median effective dose of nicardipine for averting pituitrin-induced hypertension during laparoscopic myomectomy.
Research indicates that intravenous nicardipine is as effective as, and in some cases, even superior to other medications used for emergency blood pressure reduction, such as nitroglycerin, in managing preoperative hypertension during surgery. Nicardipine offers specific advantages, including a stable dose-response effect and less hypotension and tachycardia[39]. Additionally, another study demonstrated that nicardipine has a higher likelihood of achieving the physician-specified SBP (systolic blood pressure) target range within 30 minutes compared to labetalol[40].
In our study, we utilized a sequential trial approach to determine the optimal dosage of nicardipine for managing pituitrin-induced hypertension during laparoscopic myomectomy. The adaptive nature of a sequential trial allowed us to efficiently evaluate medication responses within a relatively short time frame, which is especially crucial in a clinical context where rapid intervention is required to address hypertensive episodes induced by pituitrin[41].
The dose-response relationship is a fundamental concept that guided our investigation. Our aim was to find the most effective dosage of nicardipine, and the dose-response relationship, with a focus on quantal response, precisely reflects how different doses of the drug interact with the body. Understanding this relationship is critical for optimizing the therapeutic effect of nicardipine while minimizing any potential adverse outcomes[42].
Limitations of this study include: 1. We administered a single bolus of nicardipine without combining it with pump injections. It is possible that the antihypertensive effect of the drug gradually weakens several minutes after bolus injection. The combination of bolus and pump infusion requires further research. 2. The main drawback of the sequential trial is that the study results tend to be conservative, potentially delaying the clinical implementation for potentially beneficial procedures. Moreover, a larger sample size may be necessary for rare events. Therefore, this investigation is instructive as a pilot study for preventing pituitrin-induced cardiovascular adverse reactions in patients undergoing laparoscopic myomectomy with nicardipine.
In conclusion, nicardipine effectively inhibits pituitrin (6U)-induced cardiovascular adverse reactions in patients undergoing laparoscopic myomectomy, with an ED50 of 4.839 (95% confidence interval: 4.569–5.099) µg/kg and an ED95 of 5.308 (95% confidence interval: 5.065–6.496) µg/kg.
Figure 1 Flow-chart of the study.
Figure 2 The sequential trial utilizing nicardipine to alleviate hypertension induced by intramyometrial injection of pituitrin.
Figure 3 Dose-response Curve.
Figure 4 The Variations of SBP within 20 min after injection of pituitrin
Figure 5 The Variations of HR within 20 min after injection of pituitrin