PoCUS Guided Fluids to Prevent Post-induction Hypotension
Condition: Hypotension on Induction
MeSH terms: Hypotension
Study type: Interventional

Summary: 
      Hypotension is a common side-effect of general anesthesia induction, and is related to
      adverse outcomes, including a significantly increased risk of one-year mortality. Hypovolemia
      is a significant risk factor, and optimized fluid therapy remains the cornerstone of its
      treatment. Ultrasound measurements of inferior vena cava (IVC) diameter with respiration have
      been recommended as rapid and noninvasive methods for estimating volume status. Several
      recent studies reported that preoperative IVC ultrasound has a reliable predicting ability of
      arterial hypotension after the induction of general anesthesia. The practical effect of
      optimizing fluid status before surgery using this ability has not been studied. Our
      hypothesis is that preoperative ultrasound-guided intravenous fluid bolus administration may
      reduce the incidence of hypotension after the induction of general anesthesia in adults
      presenting for elective non-cardiac, non-obstetric surgery
    

Detailed description: 
      Background: Hypotension is a common side-effect of general anesthesia induction, and is
      related to adverse outcomes, including significantly increasing risk of one-year mortality
      (intraoperative systolic hypotension increased mortality risk by 3.6% per minute below 80 mm
      Hg). Even short durations of intraoperative hypotension have been associated with acute
      kidney injury (AKI) and myocardial injury.

      The feasibility of POCUS in directing fluid management to prevent hypotension has been
      demonstrated after the induction of spinal anesthesia but not general anesthesia.

      Design: This will be a randomized controlled trial. All participating patients will undergo a
      bed-side ultrasound scan and assessment of the IVC-CI. Patients with collapsible IVC, defined
      as a CI equal or greater than 43%, will be randomized 1:1 to either receive a fluid bolus or
      not. We will test the potential efficacy of an ultrasound directed fluid bolus in reducing
      the hypotension associated with the induction of general anesthesia. This will be a single
      blinded study with the attending anesthesiologist unaware to patient group allocation and
      POCUS data.

      The primary objective is to determine the efficacy of preoperative POCUS-guided intravenous
      fluid bolus administration in reducing the incidence of hypotension after the induction of
      general anesthesia in adults presenting for elective non-cardiac, non-obstetric surgery.

      While in the preoperative area, patients who fulfil the eligibility criteria will be
      approached for recruitment, informed consent, and voluntary participation. Written informed
      consent will be obtained from all patients. Upon informed consent, baseline characteristics
      will be collected which include demographic information, past medical history including
      medical therapy, and the type of scheduled surgery. Thereafter the assessment of preoperative
      IVC-CI will be performed, with patients with an IVC-CI ≥ 43% randomized into the intervention
      and control groups.

      Randomization: Patients who fulfil the eligibility criteria, provide informed consent, and
      are found to have an IVC-CI ≥ 43% according to a POCUS assessment, will be randomized prior
      to surgery while in the preoperative area. The allocation sequence will be created by a
      statistician through a computer-generated random table, and concealed in sequentially
      numbered, opaque, sealed envelopes, with a 1:1 allocation ratio and random block sizes of 4,
      6, and 8 participants. Attending clinicians involved in the care of the patient will be
      blinded to the allocation and intervention.

      Data collected in the preoperative area will include patient demographics [gender, age,
      height, weight, past medical history including coronary artery disease, heart failure,
      diabetes, smoking, peripheral vascular disease, hypertension, current treatment with
      beta-blockers, ACE-I or ARBs, and diuretics, type of surgery (coded as lower limb or upper
      limb orthopedic surgery, lower abdominal surgery, vascular, gynecology (non-obstetric) and
      urology), and the preoperative fasting duration.

      In addition to the IVC measurements obtained by the POCUS scan, we will also document the
      duration of the POCUS scan and the fluid bolus administration, as well as the baseline
      perfusion index (PI), which estimates the pulsatility of blood in the extremities, calculated
      using infrared spectrum as part of plethysmography waveform processing, and has been shown to
      predict hypotension following propofol induction.

      Once in the operating room, the information from the induction of the general anesthesia will
      be collected through the routine electronic chart including blood pressure and heart rate
      (before the induction of anesthesia), drugs administered during and after induction, and
      blood pressure over 20 minutes from the start of induction. In case of an arterial line
      inserted before induction to measure blood pressure invasively and continuously, which is
      indicated according to the discretion of the treating anesthesiologist, it will be used to
      collect the blood pressure and heart rate information.

      A previously reported IVC-CI threshold of 43% had a positive predicting value (PPV) of 86% in
      predicting post-induction hypotension. As our sample will only include patients with a
      collapsible IVC (IVC-CI ≥ 43%), for the sample size calculation we will assume a 85%
      incidence of post-induction hypotension in the FB- group. Since no prior studies have
      assessed the effect of IVC-CI guided fluid bolus within the general anesthesia population, we
      will choose a relative risk reduction (RRR) of 50% with POCUS directed fluid optimization as
      clinically significant. Thus, assuming post-induction hypotension incidence of 85% and 42.5%
      in the FB- and FB+ groups, respectively, a sample size of 19 patients per group (95%
      confidence level) is required to reject the null-hypothesis with a risk of 0.05 and a power
      of 0.8.

      Statistical analysis will follow the trial completion. No other interim analysis will occur
      during this trial. Data collected during the study will be compiled using Excel spreadsheets
      (Microsoft, USA). The lowest MAP recorded during the twenty minutes after the start of
      induction, defined as the first administration of an anesthetic agent at an anesthetic
      dosage, will be used to calculate the percentage decrease from baseline in each patient.
      Baseline will be defined as the first blood pressure measurement in the preoperative area or
      from the pre-anesthesia clinic visit. Descriptive data will be presented as means ± standard
      deviation (SD) for continuous variables and as absolute numbers and percentages for
      categorical variables. This data will include patient demographics, IVC-CI, the incidence of
      hypotension and its total duration, the total amount of fluids and vasopressors administered,
      the mean duration of the POCUS scan, and the incidence of surgical delays. For our primary
      outcome, the reduction in the incidence of post-induction hypotension between FB+ and FB-
      groups, we will use a χ2 test. Student's t test will be used for parametric data null
      hypothesis testing, while two-tailed Manne Whitney U test will be used to evaluate
      significance in non-normally distributed parameters.

      In all cases a p value < 0.05 will be considered as statistically significant. Statistical
      analysis will be performed using SPSS version 20 (IBM, Chicago, IL, USA).
    

Intervention name(s): Ringer's Lactate; IV line
Intervention type(s): Drug; Other
Intervention description(s): 500 ml of Ringer's Lactate; Placing of an IV line before surgery
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Based on the IVC PoCUS exam, volume responsive patients will be randomized into two equal groups: half will receive a fluid bolus (FB+) and half will not (FB-). Patients in the FB+ group will receive a single bolus of 500 ml of Ringer's Lactate over 5-10 minutes with an additional IVC scan at the end of the infusion to record the change in IVC-CI.
Masking: Single (Care Provider)
Primary purpose: Prevention
Keywords: point of care ultrasound; general anesthesia