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Page 2 of 10 Sahulee et al. Vessel Plus 2022;6:5 https://dx.doi.org/10.20517/2574-1209.2021.94

is an imbalance of oxygen delivery and oxygen consumption at the cellular level that may lead to oxygen
debt and organ dysfunction. If unrecognized or untreated, this condition can result in significant morbidity
[1]
and mortality .

Along with considerable advances in cardiac surgery and CPB over the past decades, the prevention and
management of LCOS have evolved to include a vast array of pharmacologic and non-pharmacologic
strategies to restore the balance between oxygen delivery and demand. Pharmacologic therapies for LCOS
have generally included catecholamine inotropes, inodilators, and systemic vasodilators. In addition,
various other medications have been used to manage LCOS in the postoperative period but are less
commonly used. Finally, for medically refractory LCOS, mechanical circulatory support can be deployed. In
this review for Vessel Plus, we hope to summarize high-level evidence (randomized control trials, meta-
analyses, systematic reviews) supporting the use of these pharmacologic therapies to manage LCOS and to
utilize extensive surveys and registry reviews to describe current trends in their use.

Pathophysiology
The LCOS is the result of multiple pathophysiologic processes that complicate cardiac surgery requiring
CPB. Individual patient characteristics, pre-operative state, intraoperative management, residual anatomic
lesions, abnormalities in rhythm, and the inherent inflammatory nature of CPB all contribute to the
derangements in systemic and pulmonary vascular resistances, cardiac output, oxygen delivery, and
alterations in oxygen demand and metabolism [Figure 1].

Pathologic alterations in cardiac loading conditions are the physiologic basis leading to the low cardiac
output state. According to the Frank-Starling mechanism, diminished preload from hypovolemia,
inflammation, or elevated filling pressures lead to reduced stroke volume. Respiratory abnormalities from
pleural effusions, pneumothorax, or elevated airway pressure from mechanical ventilation have a deleterious
effect on ventricular filling. Associated elevations in right ventricular afterload can complicate post-
operative patient management, especially in those with right ventricular hypertrophy or dysfunction.
Changes in pulmonary vascular resistance (PVR), systemic vascular resistance (SVR) after CPB, and
specifically systemic hypertension, can decrease cardiac output after surgery. Furthermore, CPB stimulates
vasopressin release, which increases SVR and can be deleterious to a dysfunctional systemic ventricle all
leading to LCOS.

The exposure of blood to foreign antigens during CPB, along with hypothermia, myocardial ischemia, and
[2,3]
reperfusion injury, can cause profound systemic inflammation . Specifically, there are elevations in pro-
[4]
inflammatory cytokines and activation of complement . These are all associated with LCOS, increased
ventilator time, and adverse neurologic outcomes . In addition, there is also a hypermetabolic and
[5,6]
catabolic state after surgery driving increased oxygen demand. Detailed reviews of the pathophysiology of
LCOS have recently been well described by Epting et al. and Bautista-Hernandez et al. .
[8]
[7]
Incidence
Parr and colleagues first described LCOS in 1975 when they observed patients with a cardiac index less than
2
[9]
2L/min/m in approximately 25% of patients after congenital heart surgery requiring CPB . In the decades
to follow, similar estimates of LCOS incidence in children were obtained by Wernovsky et al. and
[10]
[12]
Hoffman et al. . However, a more recent study by Du et al. found a LCOS incidence of ~10% with a
[11]
contemporary cohort of 8660 children treated at a single center. In this study, independent risk factors for
LCOS development included age, CPB time, residual shunts, outflow tract obstruction for either the left
ventricle (LV) or right ventricle (RV), and tricuspid and mitral regurgitation. These risk factors and other
clinical parameters have been used to develop LCOS scoring systems to assess LCOS severity . Therefore,
[13]