Association Between Intraoperative Mean Arterial Pressure Variability and Postoperative Fatigue in Patients Undergoing Laparoscopic Abdominal Surgery
Conditions: Fatigue Symptom, Blood Pressure Variability
Sponsor: The First People's Hospital of Lianyungang

Official Title: Association Between Intraoperative Mean Arterial
Pressure Variability and Postoperative Fatigue in Patients
Undergoing Laparoscopic Abdominal Surgery
NCT Number: Pending
Document Date: 2025-10-15
Document Type: Study Protocol
Research
Institution:
The
First
People's
Hospital
of
Lianyungang
Principal
Investigator:
XiaoBao
Zhang,
Department
of
Anesthesiology
Confidentiality Statement:
This document is intended solely for research purposes. It does
not contain any personally identifiable information of study
participants.

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1. Background
With the global demand for surgical procedures increasing significantly1,
laparoscopic surgery has become the preferred technique for major
abdominal operations due to its minimally invasive nature, lower
complication rates, and faster postoperative recovery2,3.
Postoperative fatigue syndrome (POFS) is one of the common
complications after abdominal surgery. Clinical manifestations include
fatigue, muscle weakness, sleep disturbances, and impaired attention4,
which can significantly hinder the implementation of enhanced recovery
after surgery (ERAS) protocols5,6. POFS can prolong postoperative bed
rest and delay early functional exercises. Most evidence on postoperative
outcomes is collected within the first 7 days after surgery, but without
early interventions, POFS may persist longer, sometimes up to 12 months
postoperatively. Additionally, POFS may lead to secondary complications,
extended hospital stay, and impaired social function6,7. Therefore, with the
increasing adoption of ERAS, the prevention and management of POFS
warrant greater attention.
The pathophysiology of POFS is complex. While some mechanisms have
been elucidated, no single therapy has been proven to significantly
improve POFS8. Studies suggest that esketamine may reduce POFS by
increasing cerebral blood flow and facilitating the clearance of metabolic
waste. Other research has shown that acupoint massage promoting blood

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circulation can also reduce POFS incidence9. These findings indicate that
hemodynamic stability may be closely associated with POFS
improvement.
Blood pressure variability (BPV) is an important indicator of
hemodynamic stability10. In healthy individuals, the compensatory
mechanisms of the sympathetic and parasympathetic nervous systems
ensure that blood pressure and cerebral perfusion respond adequately to
environmental, physical, and emotional stimuli. The magnitude and
pattern of these BP changes constitute BPV11.
Perioperative BPV is similarly important. Increased BPV has been linked
to adverse postoperative outcomes, including myocardial injury, renal
injury, stroke, and delirium12,13. Recent studies on cardiac and non-cardiac
surgeries indicate a significant association between postoperative adverse
events and both reduced mean arterial pressure (MAP) and increased
MAP fluctuations14-16.
BPV partly reflects autonomic nervous system function. Moderate
fluctuations are physiologically normal and indicate dynamic
cardiovascular balance. However, persistently abnormal BP—either too
high or too low—may signal potential perfusion issues, fluid imbalance,
or other pathological conditions, requiring attention and further
assessment.
Currently, BPV assessment lacks standardized methods. Standard

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deviation (SD) is commonly used17,18. Hansen et al. proposed Average
Real Variability (ARV)19 to evaluate short-term BP fluctuations,
calculated as the sum of absolute BP differences between consecutive
readings multiplied by the measurement intervals and divided by total
time. ARV is more reliable than SD for time-series variability but only
applies to equally spaced measurements; unequal intervals may
overestimate sharp fluctuations20. To address this, Mascha et al.
introduced Generalized ARV (G-ARV), which does not require equally
spaced data, providing more accurate representation of dynamic
changes20.
In summary, we hypothesize that intraoperative BPV is associated with
POFS. This study aims to explore the relationship between hemodynamic
stability and postoperative fatigue in elderly patients undergoing
laparoscopic abdominal surgery, providing scientific guidance for optimal
intraoperative blood pressure management.

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2. Study Objectives
To record intraoperative blood pressure data and postoperative
Christensen fatigue scores, analyze the relationship between
intraoperative BPV and postoperative fatigue, and investigate the
predictive value of intraoperative MAP variability for POFS. The study
aims to guide clinical management of intraoperative BP and postoperative
fatigue, improving anesthesia care and recovery for patients.
3. Study Type
Prospective cohort study: preplanned and real-time collection of exposure
(MAP variability) and outcome (POFS) data, with follow-up to track
occurrence of POFS.
4. Research Personnel
Preoperative Team: Screening and baseline data collection.
Intraoperative Team: Distribution of study drugs, data collection during
surgery, coordination of procedures. Anesthesiologists administer drugs
according to protocol.
Postoperative Team: Outcome assessment and data collection.
All personnel are trained independently and do not share patient-specific
information.

5
Data analysis will be conducted independently by a designated
statistician.
5. Inclusion Criteria
Age ≥18 years;
ASA physical status I–III;
Scheduled for elective laparoscopic abdominal surgery under general
anesthesia
6. Exclusion Criteria
Severe cardiac, hepatic, or renal insufficiency, or major
neurological/psychiatric disorders;
Known drug allergies during the study period;
Participation in other clinical trials within the past 3 months;
Unable to complete required questionnaires or assessments;
Surgery duration < 60 minutes
7. Withdrawal Criteria
Severe perioperative complications;

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Insufficient BP readings (artifacts lasting >5 minutes
1 or readings
spaced >5 minutes)
20;
Patient or proxy requests withdrawal
8. Study Procedures
Preoperative visit: 16:00–20:00 on the day before surgery; collect basic
information, baseline BP, medications, and history; informed consent
signed
Monitoring & Anesthesia: Noninvasive BP, radial artery catheter for
invasive BP, ECG, SpO2, temperature, BIS
Induction: Sufentanil, propofol, rocuronium IV
Maintenance: Remifentanil 0.1–0.5 μg/kg/min, rocuronium as needed,
sevoflurane 1–3%, propofol infusion, BIS 40–60
Postoperative analgesia: PCIA with sufentanil citrate; rescue doses
allowed as per protocol
Follow-up: Pre- and postoperative data collection per appendices
1 Artifact Removal Criteria: Recorded artifacts; Out-of-range readings: SBP ≥300
mmHg or ≤20 mmHg; SBP ≤DBP + 5 mmHg; DBP ≤5 mmHg or ≥225 mmHg;
Sudden changes: SBP change ≥80 mmHg in any direction within 1 minute, or ≥40
mmHg in both directions within 1 minute

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9. Exposure Variable
This study plans to enroll patients at Lianyungang First People’s Hospital
who meet the inclusion criteria.
Based on a pilot study including 90 subjects, with an effect size of f=0.25,
a significance level of α=0.01, and a statistical power of 0.90, it was
calculated that 94 subjects are required per group. Considering a 20%
dropout rate, the total sample size is at least 353 subjects.
10. Outcomes
Primary Outcome:
Postoperative fatigue (Christensen score, postoperative days 1, 3, 7)
Secondary Outcomes:
Intraoperative vasoactive drug use
Postoperative recovery quality (QoR-15, days 1, 3, 7)
Postoperative opioid consumption
11. Adverse Events
Tachycardia, bradycardia, hypotension, hypertension, intraoperative
awareness
Serious events: death, life-threatening, prolonged hospitalization,
permanent disability
All events recorded, treated, and reported per protocol

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12. Statistical Analysis
Continuous variables will be presented as mean ± standard deviation
(SD) or median (minimum, maximum; or interquartile range), and
categorical variables will be expressed as number (percentage).
All statistical analyses will be two-sided, and a p-value < 0.05 will be
considered statistically significant.
The generalized average real variability (G-ARV) of intraoperative blood
pressure (BP) will be calculated using the following formula:
Generalized ARV = 1
�
�=1
�−1
 
෍BP�+1 −BP�mmHg/min
where T is the total time from the first to the last BP measurement, and
N is the total number of BP readings.
The G-ARV values will be ranked in ascending order, and P33 (33rd
percentile) and P67 (67th percentile) will be calculated. Postoperative
fatigue data will be categorized into three groups:
Low Variability (LV): G-ARV ≤P33
Medium Variability (MV): P33 < G-ARV ≤P67
High Variability (HV): G-ARV > P67
Bonferroni tests will be used to compare postoperative fatigue among
groups. Analysis of covariance (ANCOVA) will be applied to adjust for
covariates and to account for imbalanced confounding factors between
groups (e.g., baseline fatigue score, age, surgery duration, and anesthesia

9
time).
10. Quality Control
Research Personnel: Training, accurate data recording, calibration of
monitors, rigorous statistical analysis.
Patients: Clear explanation, informed consent, right to withdraw, trial
halted if study-related deaths occur.
11. Ethics
The study protocol must be approved by the ethics committee before the
research can commence.
For each potential participant, the investigator is responsible for fully
explaining the purpose of the study, procedures, and possible risks in
writing.
Each participant must be informed that he or she has the right to
withdraw consent and discontinue participation at any time during the
study.
A written informed consent form must be provided to each participant.
Each participant or authorized proxy must sign the consent form prior to
participation, and the written informed consent will be kept as part of the
clinical trial documentation.

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