Body mass index and microcirculatory behavior in patients undergoing cardiac surgery with cardiopulmonary bypass

The prevalence of overweight and obesity as defined by a body mass index (BMI)
of more than 25 kg/m2 or 30 kg/m2, respectively, has reached epidemic
proportions. In the Netherlands 46.5% of men and 41.1% of women were overweight
or obese in 2014 (source: CBS). Obese patients are at risk for conditions that
increase their likelihood to undergo surgery, such as cardiovascular
procedures, but also malignancies, osteoarthritis and gallstones. It is
therefore expected that an increasing proportion of the surgical population
will be categorized as overweight or obese in the near future. While overweight
or mildly obese patients may have better outcomes after surgery, patients with
a BMI above 30 kg/m2, patients with central obesity (abdominal fat
accumulation) as well as patients with the metabolic syndrome are at higher
risk of perioperative complications when compared to lean patients.

The respiratory and cardiovascular physiology of overweight patients is adapted
to the altered tissue demands. Due to decreased functional residual capacity,
the total lung capacity of overweight patients is impaired, leading to a higher
risk for arterial hypoxemia and a higher tendency for desaturation and impaired
oxygenation in the perioperative period. In order to maintain an adequate
balance in tissue oxygen delivery and demand in overweight patients, an
increase in intravascular volume and stroke volume are required. This increases
ventricular load, which may lead to left ventricular hypertrophy. Left
ventricular hypertrophy may eventually contribute to the development of heart
failure, which in itself may increase perioperative risk. The increased
activity of the sympathetic nervous system and RAAS-activation further
contribute to obesity-related cardiomyopathy. Moreover, increased pulmonary
resistance associated with the obstructive sleep apnea syndrome (OSAS) may
cause right ventricular strain and failure, eventually leading to biventricular
dysfunction. Furthermore, coronary flow reserve is impaired in obese patients
with a cardiovascular risk profile,9 which may implicate that during periods of
stress, such as the perioperative period, myocardial perfusion and thus cardiac
function may fall short with respect to myocardial demands. In conclusion,
obesity leads to macrocirculatory changes that may contribute to the
development of myocardial dysfunction and increased pulmonary vascular
resistance.

Perfusion pressure and microvascular oxygenation serve to maintain adequate
vital organ tissue perfusion. Optimization of nutrient and oxygen supply takes
place on a microvascular level, and adequate perfusion is vital to maintain
organ function. In addition, the microcirculation largely determines vascular
resistance and afterload, as in these small arterioles (<150 m in diameter) the
largest hydrostatic drop in pressure occurs. Microvascular dysfunction is a
characteristic of obesity, which not only alters tissue perfusion but also
contributes to the development of hypertension and insulin resistance. Impaired
endothelium-dependent vasodilatation has been demonstrated in obese subjects in
response to several vasodilators, such as acetylcholine and insulin. Obese
subjects also demonstrate a reduction in the number of arterioles and
capillaries.14 Both of these characteristics of obesity can contribute to
impaired tissue perfusion. In conclusion, obesity is associated with vascular
alterations that may lead to hypertension and microvascular dysfunction.

While a substantial part of the surgical population is overweight, the number
of studies focusing on macro- and microcirculatory alterations in the
perioperative period in these patients is highly limited. Early studies
demonstrated a significantly greater depression in cardiac index and stroke
work in morbidly obese patients undergoing surgery when compared to lean
controls. Moreover, most studies focusing on intraoperative hemodynamics have
mainly been performed in morbidly obese patients undergoing bariatric surgery,
with specific emphasis on the effect of pneumoperitoneum on system
hemodynamics. In one study, morbidly obese patients retained stable blood
pressure and cardiac output during the different phases of laparoscopic gastric
bypass surgery. In contrast, a later study in morbidly obese patients showed
systolic as well as diastolic dysfunction, decreased stroke volume and
decreased cardiac output hemodynamics upon insufflation of pneumoperitoneum. In
agreement with this, a decrease in cardiac output was observed in obese
patients during insufflation of pneumoperitoneum, which was worse in morbidly
(average BMI of 45 kg/m2) versus slightly (average BMI of 28 kg/m2) obese
patients.

We previously showed that microcirculatory perfusion is disturbed in patients
undergoing cardiac surgery with cardiopulmonary bypass, and these alterations
continues until 3 days following surgery. Interestingly, this observed decrease
in microcirculatory perfusion in was not related to systemic hemodynamic
parameters, including mean arterial pressure or cardiac output. The
dissociation between cardiac output and microvascular perfusion was further
confirmed in patients undergoing abdominal study.

Since obesity is associated with alterations in system hemodynamics as well as
microcirculatory perfusion disturbances, the association between macro- and
microvascular behavior may be different when compared to lean subjects.
Moreover, there is little known about the effects of anesthesia and cardiac
surgery with cardiopulmonary bypass on microcirculatory perfusion in these
patients.

In this study we aim to investigate whether microcirculatory behavior differs
between obese and lean subjects at a resting state before surgery and after
surgical stress. Moreover, the relation between systemic hemodynamics and
microcirculatory perfusion in obese patients undergoing cardiac surgery with
cardiopulmonary bypass will be evaluated, and compared to those in lean
patients. In particular, as pathophysiological processes as present during
obesity may alter this relation, we hypothesize that obesity is associated with
impaired microcirculatory perfusion when compared to lean subjects, and this
difference is even enlarged after surgery.

Primary objective: Is there a difference in the change in perfused vessel
density between obese and lean subjects after cardiac surgery with
cardiopulmonary bypass?

Secondary Objectives
* Is there a difference in baseline perfused vessel density between obese and
lean subjects?
* Is there a difference in perfused vessel density after cardiopulmonary bypass
between obese and lean subjects?
* Is there a different relation between mean arterial blood pressure and
microcirculatory perfusion between obese and lean subjects?
* What is the relation between perfusion surrogates such as lactate levels and
sublingual microcirculation in lean and obese patients?

* Single center, prospective observational study.
* Patients with severe obesity (BMI * 32 kg/m2) and lean subjects (BMI < 25
kg/m2) undergoing cardiac surgery with cardiopulmonary bypass.
* Sublingual microcirculation perfusion measurements take place before and
during surgery.
* Preoperative HbA1c determination in a blood drop from a finger prick.
* Routine glucose and arterial gas measurements during surgery
* Blood sampling to determine glycocalyx parameters (20 ml).
* The measurements start on the day of surgery and end when patients are
admitted to the intensive care unit.

There is no advantage for patients to participate in this study. Preoperative
HbA1c level will be determined in a blood drop from a finger prick, which may
cause discomfort and pain. A total of 20 ml of extra blood will be drawn from
an existing intra-arterial line, and this line will also be used for blood
pressure measurements. The intra-arterial line is part of routine clinical care
in cardiac surgery, and will therefore not add up to patient discomfort in the
present study. Microscopic imaging of the microvasculature by means of the
GlycoCheck is a noninvasive measurement, and three out of four measurements
will be performed while the patient is under anesthesia.