Ephedrine

After the patients entered the operating room, a Datex-Ohmeda anesthesia monitor was connected to monitor the entropy index. The stateentropy (SE), reactionentropy (RE), and SPI values were monitored using a GE Healthcare monitor (Helsinki, Finland). Both groups received target-controlled infusion (TCI) of dexmedetomidine (Dex) 0.8 μg/kg/10 minutes, intravenous tropisetron 5 mg, and intramuscular penehyclidine hydrochloride 0.1 mg/kg. After sedation, “eye sign” (Fig. 2A) and “infantile sign”(Fig. 2B) changes were assessed. According to the requirements of the surgical field, unilateral/bilateral QLB surgery was performed through the anterior approach under local anesthesia with ultrasound guidance. After the target site was determined, 0.50% lidocaine (Hebei Tiancheng Pharmaceutical Co., Ltd., Cangzhou, Hebei, China; approval number: H13022313; specification: 5 mL: 100 mg) and 0.20% ropivacaine (Shijiazhuang Siyao Co., Limited, Shijiazhuang, Hebei, China; approval number: H20203107; specification: 10 mL: 100 mg) in 20 ml 0.9% normal saline were injected into each side of group F. In group C, 20 mL 0.9% normal saline was injected on each side. Fifteen minutes after administration, the level of sensory block was assessed in all subjects using acupuncture.^{[12 (link)]}After testing the block level, the anesthesiologist on duty opened the sealed envelope marked 2 and decided whether to administer the OFA based on the block plane test results. Total intravenous anesthesia was used in both groups. Anesthesia was induced and maintained with TCI of propofol 3 to 3.5 μg/mL and intravenous rocuronium 0.6 mg/kg in group F, or with TCI of propofol 3 to 3.5 μg/mL and remifentanil (Yichang Humanwell Pharmaceutical Co. Ltd., Yichang, Hubei, China; approval number: H20030197; specification:1 mg) 2 to 4 ng/mL and intravenous rocuronium 0.6 mg/kg in group C. Then, the 2 groups were fitted with a laryngeal mask airway 3 to 5 according to body weight, and 0.3 mg/kg rocuronium was added intermittently according to the need of surgery to maintain the entropy index value of 40 to 65 and SPI value of 30 to 50.
When blood pressure was low and the heart rate was slow, ephedrine and atropine were administered for symptomatic treatment. Patients in both groups received intravenous flurbiprofen axetil 50 mg during skin suturing, followed by patient-controlled intravenous analgesia with esketamine 0.015 mg/(kg·h) (total dose ≤ 50 mg) + flurbiprofen 200 mg + Dex 100μg + tropisetron 5 mg + 0.9%NS to 100 mL, 2 mL/h. Electrocardiography, BP, pulse oxygen saturation (SPO₂), P_ETCO₂, SE, RE, SPI, Steward score, extubation time, awake time, as well as the propofol, Dex, rocuronium, and diltiazem dosages were monitored in both groups.

The first patient recruited received a concentration of 0.25% with fixed volume (14ml for male and 12ml for female), based on clinical practice and previous studies. Subsequently, if a patient had an inadequate block, the ropivacaine concentration was increased by 0.05% in the next subject. Following Stylianou et al. [7 (link), 8 (link)], we randomize the next patient with probability b = (1-T)/T to the next lower volume and 1-b = 0.89 to the same volume, where T = 0.90 in the MEV90.If a patient had a successful block, the next subject was randomized with probability b = 0.11 to the next lower concentration and 1-b = 0.89 to the same concentration.
Stylianou et al. [7 (link)–9 (link)] performed extensive trials and found that the estimated probability of toxicity associated with the recommended dose is stabilized with a sample size of at least 20 and best at over 40. Following this, we choose the sample size of 45 to accommodate potential dropout. To estimate MEC₉₀, a minimum of 45 positive responses were required [7 (link), 8 (link)]. Thus, we prospectively recruited patients until 45 successful blocks were accomplished, and a set of 44 sealed envelopes (with the random volume assignments inside for successful blocks) were opened. The envelopes were prepared by a resident who took no further part in the study. The MEC₉₀ was calculated using isotonic regression, and the 95% confidence interval (CI) was derived from the 2000 bootstrap replicates. Data were further analyzed using isotonic regression and bootstrapping CI to estimate the minimum effective concentration required to produce a successful block in 95% and 99% of patients (MEC95 and MEC99) [7 (link), 8 (link)].
The observer also recorded noninvasive systemic arterial blood pressure, measured with an automatic cycling device, and heart rate (HR), from the electrocardiogram during and after the caudal injection and during the operation. Hypotension was defined as a decrease in systolic blood pressure by 30% of the preanesthetic value or a systolic blood pressure less than 90 mm Hg. Hypotension was treated by administering ephedrine 3 mg or metaraminol 0.2 mg i.v. based on the HR of patients with increase infusion of crystalloid fluids. Bradycardia (<55 bpm) was treated by administering 0.3–0.5 mg atropine i.v.

Prior to the CP, patients were informed about the possibility of IPP, PPP, and PONV. They were trained on the use of the Numeric Pain Rating Scale (NRS) to report pain. On a scale from 0 to 10, 0 indicated no pain, and 10 indicated the worst pain imaginable. Patients were also evaluated for the risk of PONV using the APFEL score before the procedure in order to ensure the homogeneity of the groups. Apfel score is a widely recognized risk score having broad applicability in predicting the incidence of PONV in adults undergoing anesthesia for various types of surgical procedures. Female gender, history of motion sickness or PONV, nonsmoking status, and the use of postoperative opioids were recognized to constitute the independent risk factors of occurrence of PONV. If none, one, two, three, or four of these risk factors were present, the incidences of PONV were estimated as follows: 10%, 21%, 39%, 61%, and 79%, respectively [48 (link),49 (link)].
Prior to the induction of ISA, 10 mL/kg of Optylite Solution (Fresenius Kabi, Kutno, Poland) was administered intravenously. At the induction of ISA, performed according to the current guidelines of the ASA Committee on Quality Management and Departmental Administration regarding the definition of general anesthesia and the levels of sedation/analgesia (43), patients in all groups received a bolus of 1 mcg/kg of FNT (Fentanyl WZF, 50 mcg/mL; 2m, Polfa Warsawa, S.A, Warsaw, Poland) intravenously, and all patients were subsequently induced with 0.5 mg/kg of propofol every 2 min until the depth of sedation reached SE < 70 in the SE and AoA groups and until the eyelash reflex was lost in the control group. During maintenance, additional boluses of 0.5 mg/kg of propofol were administered intravenously in the SE and AoA groups with a target value of 60–70 and using conventional methods in the control group. In the event of inadequate analgesia, confirmed by an increase in SPI >15 from baseline values in the AoA group or an increase in mean blood pressure and heart rate >30% from baseline values in the SE and control groups, additional boluses of 0.5 mcg/kg of FNT were given intravenously at 2-min intervals until a normalization of SPI values in the AoA group or a normalization of hemodynamic parameters in the SE and control group.
Intraprocedural monitoring included pulse oximetry (SpO₂), electrocardiography (ECG), non-invasive blood pressure monitoring of systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), RE and SE, and SPI, according to group allocation. A single dose of 10 mg of ephedrine (Ephedrinum hydrochloricum WZF 25 mg/mL; 1 mL Polfa Warsawa, Poland) was administered if MAP decreased <60 mmHg, and a single dose of 0.5 mg of atropine (Atropinum sulfuricum WZF 1 mg/mL; 1 mL Polfa Warsawa, Poland) was administered if HR decreased <45 bpm, at 3 min intervals, until the abovementioned values returned to the normal level.
Postoperatively, patients were evaluated during the first 24 h for incidence of PONV and pain intensity using the NRS scale, and patients’ and endoscopists’ satisfaction was graded using a specially designed satisfaction scale. In the case of PPP, to meet each patient’s specific needs, postoperative analgesia was provided according to the current guidelines of the Polish Society of Anesthesiology and Intensive Therapy [30 (link)].
The statistical analysis perioperative period was divided into three stages: Stage 1: before the induction of ISA; Stage 2: CP; Stage 3: observance after the CP in a postanesthesia care unit (PACU) until full patient recovery from ISA.

Upon enrolment, the patients arriving at the operation theatre without premedication were given 8 ml kg⁻¹ Ringer’s solution via an intraoperative maintenance infusion of 4 ml kg⁻¹ h⁻¹. Standard physical monitoring was performed using an automated non-invasive blood pressure (BP) monitor, 5-lead ECG and pulse oximetry. Systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and HR were recorded at intervals of 5 min during the entire operation. To objectively record the baseline parameters, baseline measurements were defined using the average of three readings obtained at an interval of 5 min before induction in the supine position on the operation bed.
PNB (femoral and sciatic nerve blocks) was performed under ultrasound guidance combined with a nerve stimulator (MultiStim SENSOR, PAJUNK, Geisingen, Germany). If electrical stimulation of ≤ 0.5 mA elicited a visible motor response in the quadriceps femoris for femoral nerve or in the gastrocnemius for sciatic nerve, approximately 20 ml of ropivacaine hydrochloride (3.5 mg ml⁻¹) (Naropin, AstraZeneca AB, Sodertalje, Sweden) was injected. The block was considered satisfactory after confirming the presence of complete motor and sensory blocks. The presence of a motor block was assessed using the modified Bromage scale for the lower limb (0: normal motor function; 1: ability to only move the toes; and 2: inability to move the knee, ankle and toes), with a Bromage score of 2 indicating a complete block. The presence of a sensory block was assessed via the pin-prick method using a 26G hypodermic needle along the midline of the lower limb [15 (link)]. A successful sensory block was defined as a complete lack of pain sensation at the surgical field level. Patients who successfully achieved a complete block were randomly administered with 1.5 µg kg⁻¹ h⁻¹ DEX [16 (link)] (H20090248, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, China) or 50 µg kg⁻¹ h⁻¹MID (H10980025, Jiangsu Nhwa Pharmaceutical Co., Ltd, Xuzhou, China) [17 (link)]. The drug dosage was calculated according to the lean body weight (LBM), and the drugs were continuously administered during the procedure until wound irrigation. The parameters were recorded even after the operation was completed.
During inhalation of air, side effects such as hypotension (SBP < 90 mmHg or DBP < 60 mmHg), bradycardia (HR < 55 bpm) and hypoxemia (SpO₂ level < 93%) were observed and noted. An SpO₂ level of < 93% was treated with 2–4 l min⁻¹ oxygen administration. Hypotension was treated with 6 mg of intravenous ephedrine administration. Further, sinus bradycardia was treated with 0.5 mg of intravenous atropine administration. These side effects were reported by the anaesthesiologist who was blinded to the study protocol.

60 people received one cc of normal saline (1 ml) as a placebo two minutes before changing from lithotomy to supine position.
Each ephedrine syringe contained 50 mg of ephedrine diluted with 9 ml of distilled water in 10 cc syringes, each cc containing 5 mg of ephedrine. The placebo syringes were in the form of 10 cc syringes containing distilled water, and two minutes before changing the lithotomy position to the supine position, one cc of each was randomly injected intravenously into the patients in the study groups. The patients, surgeons, and anesthesiologists were blinded to the allocation of the patients to the studied groups. All aseptic precautions were conducted before performing the spinal anesthesia. Spinal anesthesia was performed with a #25 needle (SPINAL ANESTHESIA NEEDLE, Dr.J brand, made in Japan, Quincke type) in the sitting position from the third and fourth intervertebral space (midline approach) and by injecting 12.5 mg hyperbaric bupivacaine in the subarachnoid space. Then, the patients were placed in the supine position and received 4 liters of oxygen per minute during the operation through a simple face oxygen mask. Sensory levels were determined by the pinprick test after block (every 15–20 seconds for 3 minutes), and the motor blockade was evaluated using Bromage's criteria until the level of spinal anesthesia was raised to the T8 level.
Cystoscopy was performed in lithotomy position, a ureteric catheter was entered into the upper ureter or renal pelvis and fixed with tape to the indwelling Foley catheter, and patients were placed in the supine position. The patient's supine position changed to the prone position, and renal access was conducted in the prone position under fluoroscopic guidance; superior and inferior bolsters were placed at the xiphoid process cartilage to support the lower rib cage, and at the symphysis pubis, vertical bolsters were put in the standard manner along the lateral sides of the chest.
All vital parameters, including HR and NIBP, were recorded perioperatively the time before spinal anesthesia performing (T0), immediately after spinal anesthesia induction (T1), after the lithotomy position (T2), when lithotomy position changed to the supine position (T3), and then when the patient was placed in the prone position (T4). Afterward, vital signs were documented every 3 minutes for 60 minutes (T5–T25) and finally at the end of surgery time (Tf).
If the systolic blood pressure was under 100 mmHg or less than 20% from the baseline, it was treated with 5 mg ephedrine and increased crystalloid speed. If the heart rate (HR) was under 50 beats/minute, it was treated with 0.75 mg of atropine. The incidence of hypotension, bradycardia, nausea, vomiting, shivering, and other complications were recorded.

60 people received 5 mg ephedrine (1 ml) two minutes before changing from lithotomy to a supine position.