Is Permissive Hypotension Truly Harmless? Early Biomarker Evidence of Subclinical Kidney Injury in Rhinologic Surgery

Relationship Between Permissive Hypotension and Acute Kidney Injury in Rhinologic Surgeries: Evaluation With Serum NGAL and Cystatin C Levels

This study aims to investigate the effects of permissive hypotension, which is routinely used in rhinologic surgeries such as rhinoplasty, septoplasty, and functional endoscopic sinus surgery (FESS), on renal function. Although permissive hypotension has been widely practiced to improve surgical field visibility and reduce intraoperative blood loss, its specific definition is not standardized in the literature. In most studies, maintaining mean arterial pressure (MAP) within the range of 50-65 mmHg is considered permissive hypotension. MAP values below 60 mmHg have been associated with increased risk of cardiac and renal complications. However, in otherwise healthy patients, such episodes are frequently tolerated without clinically apparent renal dysfunction.

The kidneys have a strong compensatory reserve capacity, and early tubular injury may not be detected by conventional renal function tests such as serum creatinine. Therefore, the use of more sensitive biomarkers is necessary to detect potential subclinical injury.

In this prospective observational study, serum NGAL and cystatin C levels will be measured from routine preoperative and postoperative (12-24 hours) blood samples obtained from adult patients undergoing rhinologic procedures. A ≥25% increase in these biomarkers from baseline will be considered indicative of subclinical acute kidney injury.

Additionally, intraoperative hemodynamic data will be monitored, and the duration of MAP <60 mmHg and MAP <65 mmHg will be recorded. At the end of the procedure, surgical field conditions will be evaluated using the Boezaart Surgical Field Score. The relationship between these parameters and biomarker changes will be analyzed.

The goal of this study is to determine whether early, clinically silent renal injury may occur during permissive hypotension and to provide insight into its potential implications for future renal function. All interventions and blood samplings are part of routine care, and no additional procedures will be performed for research purposes.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury; Hypotension

Detailed Description

Permissive hypotension is a commonly used anesthetic technique in rhinologic surgeries to optimize surgical conditions by reducing bleeding and improving visualization. Although widely applied, a standardized definition is lacking in the literature. Many studies define permissive hypotension as maintaining mean arterial pressure (MAP) between 50-65 mmHg. MAP values lower than 60 mmHg may compromise tissue perfusion and oxygenation, particularly in the renal medulla, possibly predisposing patients to ischemic stress. Despite this, in patients without significant comorbidities, these controlled reductions typically do not result in clinically evident kidney dysfunction, which supports the continued use of this technique in suitable cases.

However, due to the high renal reserve, subclinical kidney injury may still occur without notable changes in serum creatinine or urine output. The early detection of renal injury may be possible through biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, which are more sensitive to structural renal injury. This study is designed to evaluate such potential biomarker changes during permissive hypotension applied for rhinologic surgery.

Study Design and Methods: This is a prospective observational, single-center study including 35 adult patients aged 18-65 years who are scheduled to undergo elective rhinoplasty, septoplasty, or FESS. Patients with a history of chronic kidney disease, uncontrolled hypertension or diabetes mellitus, or contraindications to hypotensive anesthesia will be excluded. Informed consent will be obtained preoperatively. All blood sampling and hemodynamic monitoring will be performed as part of routine clinical care, and no additional intervention will be introduced.

Data Collection and Measurements: Preoperative routine blood samples will be analyzed for renal biomarkers including serum NGAL and cystatin C, in addition to standard biochemistry profiles. Serum NGAL levels will be measured using a validated ELISA method (Elabscience, USA), and serum cystatin C levels will be analyzed using the Siemens Atellica Neph 630 analyzer with a nephelometric method.

Intraoperative hemodynamic variables will be recorded every 5 minutes throughout anesthesia, and total durations of MAP <60 mmHg and MAP <65 mmHg will be calculated. Postoperatively, between 12 and 24 hours, routine blood sampling will again be performed, and NGAL and cystatin C levels will be re-evaluated. At the end of surgery, surgical field visibility will be assessed by the otorhinolaryngology surgical team using the Boezaart Surgical Field Score.

Outcome Measures: The primary outcome of this study is the presence of subclinical renal injury, defined as a ≥25% increase in plasma NGAL and/or cystatin C from preoperative baseline to the postoperative 12-24-hour measurement. Secondary outcomes include the association between biomarker changes and intraoperative hypotension exposure (duration of MAP <60 mmHg and MAP <65 mmHg), as well as the relationship between hypotension and surgical field quality assessed with the Boezaart Score.

Safety and Adverse Event Monitoring: All procedures are routine clinical practices and carry no additional risk to participants. In the event of postoperative impairment of renal function, standard clinical management will be followed, including fluid optimization and nephrology consultation when appropriate.

Data Confidentiality: All collected data will be de-identified and stored securely with restricted access limited to the research team.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Yenimahalle
    • Ankara, Yenimahalle, Turkey (Türkiye), 06500
      • Gazi University Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients aged 18-65 years undergoing elective rhinologic surgery under controlled hypotension anesthesia at a single tertiary care center will be enrolled. The study population consists of otherwise healthy individuals (ASA I-II) without known kidney disease and without major comorbidities that could independently affect renal function.

Description

Inclusion Criteria:

• Adults aged 18-65 years
• Scheduled for elective rhinologic surgery (rhinoplasty, septoplasty, or functional endoscopic sinus surgery)
• ASA physical status I-II
• Able to provide written informed consent
• Undergoing controlled hypotension anesthesia as part of routine clinical management

Exclusion Criteria:

• Known chronic kidney disease (baseline creatinine above normal range or documented CKD)
• Uncontrolled hypertension or uncontrolled diabetes mellitus
• Contraindications to controlled hypotensive anesthesia
• Pregnant or breastfeeding women
• History of major cardiovascular disease affecting renal perfusion (e.g., severe heart failure)
• Use of nephrotoxic medications preoperatively that may interfere with renal biomarker interpretation
• Perioperative complications requiring deviation from routine anesthetic management (e.g., major bleeding or hemodynamic instability)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum NGAL and cystatin C concentrations indicating biomarker-defined subclinical renal stress	Serum NGAL concentration (ng/mL) measured by ELISA assay and serum cystatin C concentration (mg/L) measured by automated nephelometric assay will be assessed preoperatively and at postoperative 12-24 hours. A relative increase of ≥25% from baseline will be used as an interpretive biomarker threshold, primarily for NGAL and more cautiously for cystatin C.	Preoperative baseline to postoperative 12-24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mean arterial pressure below 60 mmHg during anesthesia	The total duration (minutes) of intraoperative mean arterial pressure (MAP) <60 mmHg recorded at 5-minute intervals from standard anesthesia monitoring.	Intraoperative period
Duration of mean arterial pressure below 65 mmHg during anesthesia	The total duration (minutes) of intraoperative mean arterial pressure (MAP) <65 mmHg recorded at 5-minute intervals from standard anesthesia monitoring.	Intraoperative period
Correlation between surgical field quality and intraoperative hypotension	Correlation between Boezaart Surgical Field Score (0-5 scale) and cumulative duration of MAP <60 mmHg and <65 mmHg (minutes).	End of surgery
Correlation between intraoperative hypotension duration and renal biomarker changes	Correlation between cumulative duration of MAP <60 mmHg and <65 mmHg (minutes) and percentage change in serum NGAL (ng/mL) and cystatin C (mg/L) concentrations from baseline.	Intraoperative period to postoperative 12-24 hours

Collaborators and Investigators

• Sponsor: Gazi University
• Investigators: Study Director: Hasan K Pampal, M.D., Gazi University Faculty of Medicine, Department of Anesthesiology and Reanimation

Publications and helpful links

General Publications

• Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2017 Jan;126(1):47-65. doi: 10.1097/ALN.0000000000001432.
• Sessler DI, Bloomstone JA, Aronson S, Berry C, Gan TJ, Kellum JA, Plumb J, Mythen MG, Grocott MPW, Edwards MR, Miller TE; Perioperative Quality Initiative-3 workgroup; POQI chairs; Miller TE, Mythen MG, Grocott MP, Edwards MR; Physiology group; Preoperative blood pressure group; Intraoperative blood pressure group; Postoperative blood pressure group. Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery. Br J Anaesth. 2019 May;122(5):563-574. doi: 10.1016/j.bja.2019.01.013. Epub 2019 Feb 27.
• Petrova I, Alexandrov A, Vladimirov G, Mateev H, Bogov I, Paskaleva I, Gotcheva N. NGAL as Biomarker of Clinical and Subclinical Damage of Kidney Function after Coronary Angiography. Diagnostics (Basel). 2023 Mar 20;13(6):1180. doi: 10.3390/diagnostics13061180.
• Ostermann M, Legrand M, Meersch M, Srisawat N, Zarbock A, Kellum JA. Biomarkers in acute kidney injury. Ann Intensive Care. 2024 Sep 15;14(1):145. doi: 10.1186/s13613-024-01360-9.
• Khetpal S, Elias A, Alford J, et al. Anesthesia for rhinoplasty: a summary of clinical considerations, therapeutic modalities, outcomes, and future directions. JCA Adv. 2024;1:100040. doi:10.1016/j.jcadva.2024.100040.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Actual): May 30, 2025
• Study Completion (Actual): July 30, 2025

Study Registration Dates

• First Submitted: December 25, 2025
• First Submitted That Met QC Criteria: December 25, 2025
• First Posted (Actual): January 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: NGAL; Cystatin C; Permissive Hypotension; Subclinical Kidney Injury; Rhinologic Surgery; Surgical Field Visibility; Boezaart Score
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury; Hypotension
• Other Study ID Numbers: PerHypGU0820125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. Only de-identified, aggregated study results will be made available through scientific publications and presentations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No