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Sahulee et al. Vessel Plus 2022;6:5 https://dx.doi.org/10.20517/2574-1209.2021.94 Page 7 of 10

postulated that T3 repletion could improve patient outcomes after cardiac surgery. In a pilot RCT
[41]
performed by Mackie et al. , continuous T3 infusions were associated with a significant reduction in the
time to negative fluid balance, without significant increases in cardiac index. In the OTICC RCT of 208
patients under three years of age, the incidence of LCOS was lower in those receiving the oral T3 group
compared to placebo . The more comprehensive TRICC RCT included 193 children under two years of
[42]
age undergoing surgery with CPB. Although overall, there was no significant difference in time to
extubation between the T3 replacement and placebo groups, subgroup analysis demonstrated improved
time to extubation and extubation success rate for children less than five months of age receiving T3 .
[43]
Similar improvements with T3 administration in children less than five months of age were found by
[44]
[45]
Marwali et al. . However, in a 2019 meta-analysis by Flores et al. , although there was a significant
reduction in the mean inotropic score for those receiving some form of T3, there was no difference in any
other significant outcomes, including ventilator time, ICU LOS, hospital LOS, or mortality.

Vasopressin and norepinephrine
Vasopressin and norepinephrine have been used in the management of patients with LCOS and vasoplegia.
Although increases in SVR can lead to a decrease in cardiac output, they can be used to maintain adequate
perfusion pressures for vital organs such as the brain and kidneys. The use of arginine vasopressin, the
stimulant of the V1 receptor, has been shown to decrease the need for fluid resuscitation and inotropic
support. However, it has not been found to be associated with significant improvements in major outcomes
[46]
like ICU LOS or duration of mechanical ventilation . Interestingly, for patients undergoing the Fontan
procedure, transpulmonary gradient and chest tube drainage were significantly lower in the vasopressin
group compared to placebo . Norepinephrine has been used for patients with LCOS and low systemic
[47]
vascular resistance, but less commonly than epinephrine and vasopressin . Finally, in a recent review of
[48]
the PHIS database by Loomba and Flores , while the use of catecholaminergic inotropes and vasopressors
[15]
after cardiac surgery have decreased over the past ten years, the use of vasopressin has increased.

Extracorporeal life support
There is, unfortunately, a subpopulation of children who experience prolonged or severe LCOS refractory to
medical management who may require short or long-term mechanical circulatory support (MCS). Early
recognition of the failure of medical management for LCOS is important so that MCS can more safely be
deployed prior to cardiac arrest. Extracorporeal membrane oxygenation is a commonly used and widely
[49]
available therapy for prolonged or medically refractory LCOS . A 2014 analysis of the Society for Thoracic
Surgeons database found that 2.4% of all surgical patients are placed on postoperative MCS, and 95% of the
cases utilized extracorporeal membrane oxygenation as the MCS strategy . Unfortunately for those
[50]
[51]
needing postoperative MCS, the mortality remains dauntingly high, with rates up to ~65% .

CONCLUSION
The management of low cardiac output syndrome after pediatric cardiac surgery is evolving, and new
pharmacologic therapies continue to emerge with ongoing research. At this time, there is insufficient
evidence to support a single pharmacologic agent as the universal best therapy for the prevention or
treatment of low cardiac output syndrome. Database reviews and surveys demonstrate that milrinone,
epinephrine, and dopamine are the most commonly used pharmacologic therapies, but there remains
substantial provider and center variability in the approach towards the management of these patients.
Therefore, rigorous multicenter studies with granular data are needed to help providers tailor specific
pharmacologic therapies to best support each critically ill child.