European Journal of Cardiovascular Medicine

Spinal anesthesia, introduced into clinical practice by August Bier in 1898, has since become one of the most frequently employed regional anesthetic techniques in modern surgical practice. It is widely regarded as the gold standard for infraumbilical and lower limb surgeries due to its numerous advantages over general anesthesia. These include avoidance of airway manipulation and endotracheal intubation, maintenance of spontaneous ventilation, earlier recovery of gastrointestinal motility, reduced stress response to surgery, lower incidence of postoperative nausea and vomiting, and decreased risk of thromboembolic complications. Additionally, spinal anesthesia provides profound sensory and motor blockade with minimal systemic drug exposure, making it especially beneficial in patients where general anesthesia may pose higher risk [1,2].

However, hypotension remains one of the most frequent and clinically significant complications associated with spinal anesthesia. The principal mechanism involves sympathetic blockade leading to venodilation, decreased systemic vascular resistance, and pooling of blood in the lower extremities, which in turn reduces venous return, cardiac output, and ultimately arterial blood pressure. Severe hypotension may compromise perfusion to vital organs such as the brain, heart, and kidneys, particularly in elderly or high-risk patients, leading to adverse outcomes if not recognized and treated promptly. Therefore, anticipation, prevention, and timely management of spinal-induced hypotension are essential components of safe anesthetic practice [3,4].

Multiple preventive strategies have been investigated to counteract spinal-induced hypotension. Mechanical methods, such as leg elevation, Trendelenburg positioning, and leg wrapping with elastic bandages, aim to enhance venous return but often provide only partial benefit. Fluid preloading or co-loading with crystalloids or colloids is another commonly used approach; however, crystalloids require large volumes and have limited and short-lived efficacy due to rapid redistribution, while colloids, though more effective in maintaining intravascular volume, carry potential risks like allergic reactions and coagulation disturbances [4,5].

Pharmacologic prophylaxis using vasopressors has gained preference in recent years due to its predictable and sustained effect on maintaining blood pressure. Among the available agents, ephedrine is widely considered the vasopressor of choice in spinal anesthesia because of its mixed α- and β-adrenergic agonist activity. It increases blood pressure by enhancing myocardial contractility, heart rate, and peripheral vascular resistance, while simultaneously maintaining uteroplacental perfusion, which makes it especially suitable in obstetric anesthesia as well. Ephedrine can be administered as an intravenous bolus or continuous infusion, and several studies have demonstrated its efficacy in both prevention and treatment of spinal-induced hypotension with minimal adverse effects when used in appropriate doses [6,7].

Considering these pharmacologic and hemodynamic advantages, the present prospective randomized controlled study was undertaken to compare the prophylactic efficacy of intravenous ephedrine hydrochloride versus crystalloid preloading in the prevention of post-spinal hypotension and associated intraoperative complications such as nausea, vomiting, and shivering in patients undergoing elective lower abdominal and lower limb surgeries. The study also aimed to evaluate the hemodynamic stability, incidence of side effects, and overall clinical safety of both preventive approaches [7,8].

This study was conducted at Department of Anesthesia, Mahavir Institute of Medical Sciences, Vikarabad, Telangana, India from May 2024 to April 2025 Ethical approval was obtained from the Institutional Research Committee (IRC). Patients scheduled for elective lower abdominal and lower limb surgeries were enrolled. Individuals with systemic illnesses such as diabetes, hypertension, bleeding disorders, cardiac diseases, or anemia were excluded. Preoperative evaluation and written informed consent were obtained for all participants. Sedation was administered the night before surgery with lorazepam 1 mg orally and on the morning of surgery with diazepam 5 mg orally.

Patients were randomly assigned into two groups, each comprising 40 patients:

·         Group I: Received a prophylactic IV bolus of ephedrine 3 mg immediately after spinal anesthesia, followed by an infusion of ephedrine at 1 mg/min for 15 minutes.

·         Group II: Received crystalloid preloading at 20 ml/kg over 20 minutes prior to spinal anesthesia.

An 18 G intravenous cannula was inserted, and baseline hemodynamic parameters including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and SpO₂ were recorded in the operating room. Spinal anesthesia was administered in the left lateral position using a 23 G spinal needle at the L3–L4 interspace under strict aseptic precautions. After confirmation of cerebrospinal fluid flow, 4 ml of 0.5% hyperbaric bupivacaine along with 25 µg fentanyl was injected into the subarachnoid space. Patients were then placed supine with a 10-degree Trendelenburg tilt, and a small pillow was positioned under the shoulders.

The onset of sensory analgesia was assessed using the pinprick method, and the final dermatomal level was recorded 20 minutes after spinal block. HR, SBP, DBP, SpO₂, and ECG were monitored every 2 minutes for the first 20 minutes, followed by 10-minute intervals until the end of surgery. Patients were closely observed for any immediate or delayed complications.

Table 1. Type of study

Table 2. Level of Block

Table 3. Changes in Heart Rate (bpm)

Table 4. Changes in Systolic Blood Pressure (mmHg)

Table 5. Dose and time for rescue ephedrine

Table 6. Incidence of complications

Spinal anesthesia–induced hypotension is primarily managed by physiologic measures that improve venous return, thereby increasing preload and restoring cardiac output. Interventions such as head-down positioning, leg elevation (10–15 inches), or leg wrapping with elastic bandages alone do not completely prevent hypotension. Crystalloid administration can reduce the incidence of hypotension, but large volumes (>15 ml/kg) are often required, which may lead to undesirable effects such as increased central venous pressure, hemodilution reducing oxygen-carrying capacity, and release of atrial natriuretic peptide, which promotes diuresis and diminishes the hemodynamic benefit of volume loading. Considering these limitations, prophylactic pharmacologic intervention is often more effective than prehydration in preventing hypotension [9-11].

Among vasopressors, mixed adrenergic agonists such as ephedrine are particularly effective in correcting the non-cardiac circulatory effects of spinal anesthesia compared to pure α- or β-agonists. Several studies have demonstrated the efficacy of prophylactic IV ephedrine, administered as a bolus or infusion, in preventing hypotension without significant adverse effects. Based on this evidence, we conducted a prospective, randomized study to evaluate the safety and effectiveness of a prophylactic regimen of IV ephedrine, consisting of a 3 mg bolus immediately after spinal anesthesia, followed by an infusion of 1 mg/min for 15 minutes, compared with crystalloid preloading in reducing post-spinal hypotension, nausea, vomiting, and shivering [12-14].

Our study included 80 adult patients classified as ASA grade I or II, undergoing elective lower abdominal or lower limb surgeries. The groups were comparable in terms of age, sex ratio, and baseline characteristics. The onset of sensory analgesia was similar between groups (8.84 ± 2.32 min in the ephedrine group vs. 8.53 ± 1.96 min in the preloading group, p > 0.05). Sensory block reached the T6 level in 60% of patients in the ephedrine group and 63.33% in the preloading group, and the T8 level in 23.33% and 20% of patients, respectively [15,16].

In our study, preloading consisted of Ringer Lactate at 20 ml/kg over 20 minutes, consistent with protocols used by Sonia Ouergui et al. The total prophylactic ephedrine dose was 18 mg, administered as a 3 mg initial bolus followed by a 1 mg/min infusion over 15 minutes. This dosage aligns with previous studies such as Lionel Simon et al., who evaluated prophylactic boluses of 10–20 mg in cesarean sections, and Kang Y.G. et al., who compared IV ephedrine infusion versus bolus during spinal anesthesia and found that infusion maintained SBP without causing reactive hypertension, comparable to our findings [17,18].

In our study, hypotension was defined as a fall in SBP ≥30% from baseline. The incidence of hypotension was higher in the preloading group (23.33%) compared to the ephedrine group (6.66%). In the ephedrine group, decreases in SBP and DBP after 20 minutes were not statistically significant, whereas the preloading group experienced significant reductions (p < 0.001). Two patients in the ephedrine group and seven in the preloading group required more than one 3 mg bolus of ephedrine to restore SBP to 70% of baseline. The mean total dose of rescue ephedrine was 3 ± 0 mg in the ephedrine group versus 7.28 ± 1.6 mg in the preloading group (p < 0.05). The time to first rescue ephedrine was significantly longer in the ephedrine group (47.5 ± 3.5 min) compared with the preloading group (21.5 ± 4.6 min, p < 0.0002). These results are consistent with those reported by Noor M. Gajraj et al., where the incidence of hypotension was higher in the crystalloid group (55%) compared with the ephedrine infusion group (22%, p < 0.05), and the need for rescue ephedrine was greater in the crystalloid group [19,20].

High doses of prophylactic IV ephedrine may cause side effects such as reactive hypertension. In our study, 5 patients (16.66%) in the ephedrine group developed transient hypertension. An initial rise in heart rate was observed in both groups at 2 minutes, likely due to glycopyrrolate administration. In the preloading group, 4 patients (13.33%) developed bradycardia treated with IV glycopyrrolate, whereas 10 patients in the ephedrine group developed tachycardia (≥20% above baseline), which was managed with IV esmolol 20 mg. These findings are comparable to Iclal et al., who observed tachycardia in 52.4% of patients receiving IV ephedrine and 28.6% in the control group [20].

Regarding other complications, the incidence of nausea or vomiting was significantly lower in the ephedrine group (2%) compared with the preloading group (16%, p < 0.05), consistent with Rothenberg DM et al., who reported the antiemetic effects of ephedrine. Shivering occurred in 3.33% of patients in the ephedrine group versus 16.66% in the preloading group, in line with the findings of Youn Yi Jo et al., who showed that ephedrine infusion minimizes intraoperative hypothermia [21,22].

In summary, prophylactic IV ephedrine, administered as a small bolus followed by infusion, effectively reduces the incidence of hypotension, decreases the requirement for rescue vasopressors, and lowers the occurrence of nausea, vomiting, and shivering compared with crystalloid preloading, with minimal and manageable side effects.

Prophylactic intravenous ephedrine, given as a small initial bolus followed by continuous infusion, is a simple, cost-effective, and reliable approach to prevent hypotension, intraoperative nausea, vomiting, and shivering. Its effectiveness is comparable to crystalloid preloading, with only minor side effects such as transient tachycardia.

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