Correlation Between Circulating Biomarkers of Organs Damage and Intraoperative Hypotension Management
Condition: Hypotension; Brain Injuries; Renal Failure; Endothelial Dysfunction
MeSH terms: Brain Injuries; Hypotension
Study type: Interventional

Summary: 
      Intraoperative hypotension (defined as mean arterial pressure below 65 mmHg) is associated
      with increased organs dysfunction and mortality. Even short durations of reduced arterial
      blood pressure episodes significantly increased the risk of myocardial injury, neurological
      deficits, renal failure, and mortality. Hypotension rate during surgery is quite common and
      recent studies showed an incidence up to 60% of patients endured hypotension during
      anesthesia for an average of 10% of surgical time.

      Nowadays hypotension seems to be preventable even if current management of the hypotensive
      episodes is predominantly reactive and rather occurs with some delay.

      The investigators hypothesize that the prevention of hypotension by means Edwards
      Lifesciences new technology (HPI software) can improve patients outcome after surgery.

      The present pilot randomized clinical trial is aimed at investigating various biomarkers
      involved in organ dysfunction and how they correlate with different intraoperative
      hypotension management strategies (Invasive blood pressure monitored by a normal arterial
      line vs Invasive blood pressure monitored by Edwards FloTracIQ system with HPI software).
    

Detailed description: 
      The primary objective of this pilot study is to investigate if an early treatment of
      intraoperative hypotension driven by an Edwards Lifesciences new technology (Hypotension
      Probability Index - HPI software) and integrated hemodynamic variables is able to determine a
      modification of the blood levels of several specific biomarkers of tissue and organ damage
      compared to a traditional management of hypotension. It will also be evaluated if the
      management strategy of patient hemodynamics based on the Hypotension Probability Index (HPI)
      is associated with a lower incidence of hypotensive events and / or a shorter overall
      duration of intraoperative hypotension.

      In the study will be enrolled forty adult patients requiring an arterial line (at discretion
      of treating physician) undergoing non-cardiac non-day surgery (with an expected duration of
      more than 2 hours and an aimed medium arterial pressure - MAP of 65 mmHg) at the Universitary
      Hospital of Catania.

      The patients will be randomly (1:1) assigned to one of the subsequent two groups: a group
      monitored with FloTracIQ with HPI software (Treatment Group) and a group with standard
      invasive blood pressure monitoring (Control Group).

      In the Control Group, all hypotensive episodes during surgery will be treated according to
      standard of care.

      Patients randomized to the Treatment Group will receive monitoring with integration of HPI
      index and hemodynamic parameters visible on the EV1000 platform; these informations will be
      used to guide the investigator in the choice of the more appropriate treatment to be carried
      out. The value of HPI is updated every 20 seconds and expresses in percentage the probability
      of occurrence of a hypotensive event. The cut-off value of HPI is equal to 85%. Values above
      the cut-off are related to a higher probability of hypotension. A specific visual and sound
      "ALERT" will indicate to the investigator if the threshold value is reached / exceeded. Any
      treatment strategy will be based on integrated analysis of clinical and instrumental data
      showed on the screen of the EV1000 platform [MAP, cardiac output (CO), systemic vascular
      resistance (SVR), stroke volume (SV), stroke volume variation (SVV), intra-ventricular
      pressure rate of rise (dP/dt), dynamic arterial elastance (Eadyn)].

      In both groups different blood samplings will be performed in order to assess biomarkers of
      specific organ dysfunction: T0 (baseline, before starting operating procedures); T1 (2 hours
      after starting anesthesia); T2 (at the end of surgical procedures). The following biomarkers
      will be assessed: neuron specific enolase and S100B (for brain monitoring); high sensitive
      cardiac troponin T (for heart monitoring); Neutrophil Gelatinase-Associated Lipocalin (NGAL,
      for kidney monitoring); circulating endothelial cells counting and cytofluorimetric analysis
      (for endothelial monitoring). There will also be determined the systemic effect of
      intraoperative hypotension as measured by inflammatory cytokines [Interleukin (IL)-6, IL-1
      beta and Tumor necrosis factor (TNF)-alfa], oxidative stress (reduced glutathione, lipid
      hydroperoxides) and markers of hypoxia (HIF1alpha, lactate, acetylCoA, CoA).

      Various clinical informations will be collected at the same time: glomerular filtration rate,
      plasma electrolytes, creatinine, aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), blood gasses analysis, anion gap.

      A telephone interview will be performed one month after surgery, in order to investigate
      general health condition and any re-admission to hospital.

      Sample size calculation:

      Given the pilot nature of the study, no formal justification of sample size has been made.

      Statistical analysis:

      For a test of normal distribution, the Kolmogorov-Smirnov test will be used. Continuous data
      with normal distribution will be tested with paired or unpaired t tests, non-normally
      distributed data using Mann-Whitney U test and Wilcoxon rank-sum test for unpaired and paired
      results, respectively.

      Changes in biomarkers over time will be tested using analysis of variance (ANOVA) on repeated
      measurements. Categorical data will be tested using Chi-square test and Chi-square test for
      trend. Data will be presented as mean ± standard deviation when normally distributed and as
      median [interquartile ranges] in case of abnormal distribution. A p < 0.05 will be considered
      statistically significant for all tests.
    

Intervention name(s): Flo TracIQ with HPI software
Intervention type(s): Device
Intervention description(s): Patients will be monitored intraoperatively with Flo TracIQ with HPI software in order to predict hypotensive events. Blood sample will be obtained in order to evaluate ealy organ dysfunction.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Biomarkers; Hypotension; Organ Protection; Intraoperative