About this trial

Hemodynamic change after induction of general anesthesia is usually judged from mean arterial pressure. Pressure, however, is a surrogate for flow, and the two can separate: cardiac output may fall while arterial pressure remains apparently adequate. The interval that follows induction of anesthesia, before surgical stimulation begins and while hemodynamic conditions are determined by anesthetic management alone, has not been characterized in terms of flow. This study is designed to define post-induction low cardiac output (PiLCOs) in patients undergoing coronary artery bypass grafting.

This is a prospective, observational, two-centre cohort study. Consecutive adults undergoing isolated coronary artery bypass grafting with cardiopulmonary bypass at two tertiary cardiovascular surgery centre will be enrolled. No aspect of anesthetic or surgical management will be altered for the purposes of the study. An arterial catheter is sited before induction while the patient is awake, and cardiac index is recorded continuously at 30-second intervals by arterial waveform analysis. Mean arterial pressure, heart rate, stroke volume index and cardiac index are recorded at the same resolution.

The analysis window is the 30 minutes that follow induction of anesthesia. The period of cardiopulmonary bypass is excluded from all analyses, because flow during bypass is generated by the pump rather than by the heart.

The primary outcome has two components, both defined over that window and both referenced to a cardiac index threshold of 2.0 L/min/m2. The first is the total time spent below threshold, in minutes. The second is the cumulative low-output burden, defined as the integral over time of the difference between the threshold and the measured cardiac index, taken only where that difference is positive. Dimensional analysis reduces the unit of burden to L/m2, a body-surface-indexed volume of undelivered flow, which multiplied by body surface area yields an absolute flow deficit in liters. Time below threshold describes how long the exposure lasts and cumulative burden describes how deep it is. The two together define the exposure, and neither alone is sufficient.

Secondary outcomes are the same two measures computed at cardiac index thresholds of 2.2 and 2.5 L/min/m2; the incidence of PiLCOs, defined as at least one measurement below 2.0 L/min/m2 within the window; the time-weighted average depth across the window and the median depth sustained while below threshold; the distribution of cumulative burden across the three consecutive ten-minute segments of the window; and the time from induction to the first measurement below threshold.

Exploratory analyses will examine the association between the presence and the magnitude of PiLCOs and the postoperative course, including acute kidney injury, serum lactate, duration of mechanical ventilation, intensive care unit and hospital length of stay, and mortality. All outcome analyses are treated as exploratory and hypothesis-generating, and no adjustment is made for multiple comparisons.

Sample size was derived from an internal pilot of 30 patients, comprising the first 15 consecutive patients enrolled at each centre. In that pilot the standard deviation of time below threshold was 8.14 min and the incidence of PiLCOs was 70.0%. Setting the half-width of the 95% confidence interval at 1.7 min for mean time below threshold requires 88 patients, and setting it at 9.5 percentage points for incidence requires 90; the larger figure was carried forward and rounded to 90, allocated as 45 patients per centre. Allowing 15% for withdrawal, protocol deviation and unusable recordings gives a planned enrollment of 104 patients. Because the study estimates the frequency and the magnitude of an event that has not previously been characterized, rather than testing a prespecified superiority hypothesis, sample size is based on the precision of estimation rather than on power.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18 years or older.

Scheduled for elective or emergency cardiac or non-cardiac surgery under general anesthesia.

Availability of peri-operative cardiac output monitoring using the MostCare hemodynamic monitoring system, starting before induction of anesthesia and continuing during surgery.

Availability of required baseline preoperative clinical and laboratory data.

Disqualifiers

Age under 18 years

Coronary artery bypass grafting combined with valve or aortic surgery

Preoperative mechanical circulatory support

Preoperative infusion of an inotrope or a vasopressor

Trial population

Adults scheduled for isolated coronary artery bypass grafting with cardiopulmonary bypass at two tertiary cardiovascular surgery centre. Patients are approached before induction of anesthesia and enrolled consecutively. Every eligible patient during the enrollment period enters the cohort and no selection is applied.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

routine clinical monitoring, observed only
Other intervention
routine clinical monitoring, observed only

Treatment groups

103 Participants

are divided into 1 treatment group

Group A: Isolated coronary artery bypass graft surgery with cardiopulmonary bypass1 intervention

Trial outcomes

Primary outcomes

1

Time below threshold: total duration with a cardiac index below 2.0 L/min/m2, in minutes

The total duration for which cardiac index lies below 2.0 L/min/m2 during the analysis window, expressed in minutes. Cardiac index is recorded continuously at 30-second intervals by arterial waveform analysis. Duration is computed between consecutive measurement pairs by the trapezoidal rule with linear interpolation, and threshold crossings are located exactly rather than rounded to the sampling grid. Intervals between consecutive measurements longer than the sampling period are not counted as observed time. The period of cardiopulmonary bypass is excluded.

Time frame