Conventional Fluid Management Versus Plethysmography Variability Index-based Goal-directed Fluid Management in Patients Undergoing Transurethral Resection of the Prostate-a Randomized Controlled Trial (TURP)

Transurethral resection of the prostate (TURP) is a widely performed surgical procedure for the management of benign prostatic hyperplasia, which affects a significant number of elderly men . TURP involves the removal of prostate tissue via the urethra and is associated with potential fluid shifts, blood loss, and hemodynamic instability. Effective fluid management during the procedure is crucial to ensure optimal patient outcomes, minimizing complications such as hypotension, acute kidney injury, and electrolyte imbalances .

Because of the constant and frequently undetectable fluid exchange through the open prostatic venous sinuses, it is difficult to determine the precise amount of irrigating fluid absorbed after TURP surgery. Unpredictable intravascular volume changes may result from this. While over-resuscitation raises the risk of fluid overload, pulmonary edema, and cardiac events, under-resuscitation in older individuals can lead to hypotension and decreased organ perfusion Fluid management in TURP has always depended on traditional techniques that employ clinical evaluations like blood pressure and heart rate monitoring or fixed-volume infusion procedures. Although the goal of these methods is hemodynamic stability, they might not be accurate in dynamically adapting to the specific requirements of each patient, especially when there are large fluid shifts. Furthermore, these approaches frequently overlook the fluctuations in patients' hemodynamic state in real time, which may result in either excessive or insufficient resuscitation By using advanced technologies, goal-directed fluid therapy (GDFT) methods continually monitor and evaluate a patient's physiological status in real time, modifying fluid dosage as necessary. A dynamic method for determining volume status, the plethysmography variability index (PVI) has been studied in numerous clinical settings and has proven reliable in predicting fluid responsiveness and acting as a fluid resuscitation guide .

The PVI has been shown to perform similarly to more invasive and expensive dynamic fluid assessment technologies (such as pulse pressure variation and stroke volume variation) . A small-sized randomized controlled trial (RCT) showed that PVI-directed fluid management reduced the lactate concentrations and improved fluid management in abdominal surgery recipients .

Nevertheless, the clinical outcomes of conventional fluid management with PVI-based GDFT were investigated in previous studies like colorectal surgeries and spine surgeries; we did not find a previous study investigating this strategy in elderly patients undergoing TURP surgery .

This randomized controlled trial (RCT) aims to compare the clinical outcomes of conventional fluid management with PVI-based GDFT in patients undergoing TURP. We hypothesize that PVI-guided fluid management will result in better intraoperative hemodynamic stability, a reduction in postoperative complications, and an overall improvement in patient recovery.

1. Inclusion criteria

   • Male patients aged from 50 to 80 years Scheduled for elective TURP.
   • ASA Ⅰ, Ⅱ.

2. Exclusion criteria

   • Cardiac arrhythmias (e.g., atrial fibrillation)
   • Left ventricular ejection fraction <40%
   • Chronic kidney disease (stage ≥ 3)
   • Hepatic dysfunction
   • Peripheral vascular disease
   • Prolonged procedures more than 2 hours or complicated procedures with severe bleeding affecting management (Severe bleeding will be defined as any of the following: a drop in hemoglobin of ≥ 2 g/dl, hemodynamic instability due to blood loss that requires blood transfusion).
   • Patients refuse to share in this study.

V. Study Procedures

1. Randomization (in RCT only)

   Participants will be randomly assigned into two groups using a computer-generated randomization sequence:

   • Group Conventional: Conventional fluid therapy
   • Group PVI: PVI-guided goal-directed fluid therapy A double-blinded randomization technique will be employed, in which both the patient and the primary anesthesiologist responsible for routine intraoperative monitoring will be blinded to study. A study anaesthesiologist who will receive the randomization assignment and apply the allocated strategy (conventional fluid management or PVI-guided goal-directed therapy) will be present only to implement the fluid protocol and will not participate in data collection intraoperative, postoperative patient care, data collection, or outcome assessment.
2. Study Protocol After history taking and examination of the labs (complete blood count, coagulation profile, blood chemistry including creatinine level , Alanine Aminotransferase (ALT) aspartate aminotransferase (AST), Na and K levels ) and airway of the patient, a written informed consent will be obtained, and all patients will fast for 8 hours.

Upon arrival to the operating room, an intravenous wide-bore 18 G venous cannula will be placed, premedication with 2 mg midazolam will be given, and standard monitoring (ECG, oxygen saturation, and non-invasive blood pressure) will be applied. A Masimo SET (Mighty-Sat 9900, Masimo Corporation, Irvine, CA, USA) will be connected to the index finger of the hand in each patient in both groups contralateral to that used for intravenous access and blood pressure and will be shielded with towels to avoid the effects of ambient light on its signals. The Masimo set will be connected to a smart device via Bluetooth, and the plethysmography waveforms will be recorded. Baseline vitals and PVI will be recorded in both groups and then will be recorded every 5 minutes till the end of the operation.

Skin sterilization will be done with the use of povidone-iodine solution to the lower back. This will be repeated 3 times. The area will be draped with sterile towels to maintain a sterile field. Then local anesthesia will be given after identification of the interspace (L4-L5). About 2-3 ml of 2% lidocaine will be injected along the trajectory of the planned spinal needle. Then wait for 1-2 minutes for the local anesthetic to take effect.

A spinal puncture will be performed at the L4-5 level with the patient in the sitting position. After the cerebrospinal fluid is detected, a standard dose of heavy bupivacaine 0.5% (15 mg) with fentanyl (25 μg) (total volume 3.5 ml) will be injected intrathecal via a 25-G Quinke needle. The sensory block level will be targeted: The T10 dermatome. Patients will be positioned supine with a slight head-up tilt to prevent high block. Moreover, 500 mL of acetated Ringer's solution, at an open co-loaded infusion, will be administered over 10 minutes. Hypotension will be defined as a reduction in MAP to ≤ 75% from baseline. Bradycardia (HR < 50). Rescue medication will be given for hypotension (ephedrine, 6 mg, IV) and bradycardia (atropine, 0.6 mg, IV).

Intraoperative monitoring will be standard monitors: ECG, non-invasive blood pressure (NIBP), and pulse oximetry. PVI monitor for Group P heart rate, mean arterial pressure (MAP), SpO₂, and PVI recorded every 5 minutes.

*Standardization of PVI measurements and handling of lithotomy positioning:-*

• Baseline plethysmographic measurements (PVI and Perfusion Index [PI]) will be recorded with the patient supine prior to spinal anaesthesia and before any leg manipulation.
• After induction of spinal anaesthesia (and after the sensory level is confirmed and hemodynamics have stabilized for 5 minutes), PVI will again be recorded in the supine position.
• Immediately after positioning to lithotomy, PVI and PI will be recorded at 2 minutes and 5 minutes after positioning. For any PVI value used to trigger fluid administration, we will use the average of consecutive PVI readings over a 60-120 second window to reduce beat-to-beat/artifact variability.
• PVI-guided interventions will not be triggered during active leg manipulation or while the surgeon is changing leg position. If leg position is changed during surgery, a 2-minute stabilization period will be observed before taking new PVI values used for decisions (11).

Fluid Management

Group Conventional:

• Maintenance fluid with Ringer's acetate at 1 mL/kg/h all through the operation (12).
• MAP will be measured every 5 min.
• If the MAP is ≥75% of the baseline, 5 ml/kg/hr will be continued.
• If the MAP is ≤75% of the baseline, an additional 250 mL of 0.9% NaCl bolus will be given.
• After a fluid bolus, if the MAP ≥ 75% of the baseline, a 5 ml/kg/hr will be continued.
• If the MAP is still less than 75% of the baseline ephedrine IV bolus (6 mg), repeat every 5 minutes till the MAP is ≥ 75% of baseline.

Group PVI:

• Maintenance fluid with Ringer's acetate at 1 mL/kg/h all through the operation (12).
• The PVI will be measured every 5 min.
• If the PVI ≤ 13%, we will check the MAP; if the MAP ≥ 75% of the baseline, 2 ml/kg/hr will be continued.
• If the MAP is ≤75% of the baseline (and the PVI ≤ 13%), an ephedrine IV bolus (6 mg) will be given and repeated every 5 min till the MAP is ≥ 75% of the baseline.
• If the PVI ≥ 13%, we will check the MAP. If the MAP ≥ 75% of the baseline, a 250 mL bolus of 0.9% NaCl will be given and repeated every 5 min till PVI ≤ 13%.
• If the MAP is less than 75% (and PVI ≥ 13%) of the baseline, a 250 mL bolus of 0.9% NaCl will be given and repeated every 5 min till PVI ≤ 13%, plus an ephedrine IV bolus (6 mg) repeated every 5 min till MAP ≥ 75% of baseline.

Diuretics will not be administered routinely and will be reserved for patients who develop clinical evidence of fluid overload or pulmonary congestion (13). Lung ultrasound will be performed at the end of the procedure. In such cases, an intravenous dose of furosemide 1mg/kg will be administered (14), until lung ultrasound confirms resolution of pulmonary congestion.Lung ultrasound will be performed after 1 hour as the diuretic effect of furosemide is established within 15 minutes and the peak effect occurs within the first half hour (15). These patients will be recorded as a subgroup.