Clinical trial NCT05424510: PoCUS Guided Fluids to Prevent Post-induction Hypotension
Official title: Prevention of Hypotension After Induction of General Anesthesia Using POint-of-care Ultrasound to Guide Fluid Management: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypotension on Induction
Keywords: point of care ultrasound
general anesthesia
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
First posted: 2022-06-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

Brief 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).

Eligibility criteria: Inclusion Criteria:

* Age 18-70 years
* Elective surgery
* IVC-CI ≥ 43% on their preoperative POCUS scan.

Exclusion Criteria:

* Hypotension, defined as MAP below 65 mmhg, prior to the induction of general anesthesia.
* Treated with angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) on the day of surgery.
* Patients with heart failure with ejection fraction (EF) \< 40%.
* Patients with documented acute or chronic renal failure.
* Patients with neuraxial blockade (epidural or spinal) performed before induction of general anesthesia.

Primary outcomes:
measure: Difference in the incidence of hypotension after induction of general anesthesia
timeFrame: 20 minutes from the induction of general anesthesia
Secondary outcomes:
measure: The incidence of surgical delays
timeFrame: Patient consent until the beginning of the operation
measure: The duration of post-induction hypotension
timeFrame: 20 minutes after induction
measure: Adverse events
timeFrame: 20 minutes after induction
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: James S Khan, MD
role: PRINCIPAL_INVESTIGATOR
References: