Vasopressors for the cardiac surgical patient

The defense of blood pressure with vasopressors is an important part of the "management encompassing resuscitation, initial and ongoing monitoring and supportive treatment" for "Cardiac surgery: including sternotomy for bypass grafting, valve surgery and aortic surgery", a Level 1 topic from Section 2.1.18 in the second edition of the CICM Syllabus for the Second Part Examination. This appeared in Question 7 from the first paper of 2013, where the candidates were expected to reason throughtfully about the advantages and disadvantages of using a α-1 agonist specifically in the management of a post-bypass patient. The summary below, therefore, relates only to this specific use of noradrenaline. A more detailed general overview of noradrenaline is available, where its many virtues are gleefully explored. The generic approach to the haemodynamically unstable cardiac surgical patient  is also discussed elsewhere; noradrenaline forms a small part of the overall approach.

In summary:

Vasoactive agents to manage post-bypass vasoplegia

Post-bypass hypotension is often the consequence of vasodilation due to systemic inflammation, referred to as "vasoplegia" and defined by Levin et al (2009) as 

"a state of low systemic arterial pressure despite high cardiac output and adequate fluid resuscitation characterized by markedly low systemic vascular resistance"

The term "vasoplegia", suggesting that the vessels are paralysed, has been in use for a weirdly long time, appearing in such unusually corners as the British Journal of Dermatology and Syphilis (1926), when it was mostly used to describe the loss of the tone of blood vessels, whether pathologically or when the anaesthetist administers a ganglionic blocker. The natural response to this phenomenon would obviously be a vasopressor of some sort, and considering we have several options and still always resort to noradrenaline even though there is minimal evidence, it would be surprising to find something different in cardiac surgery. The best we have is Guarracino et al (2021), the consensus report of a 22-expert panel, an excellent reference and bibliography for this subject and a cracking read for other reasons, not the least of which are the frequent hilarious dissenting statements from one expert in the panel (thank you for you input, Uwe Schirmer from Bochum).  This makes life much easier for the CICM exam candidate, as the near-total lack of evidence make memorising trial outcomes less of a priority. The real questions for them to focus on are therefore:

• When to choose another vasopressor agent?
• When to add another agent?
• And which other agent do we choose?

In general it is often unnecessary to entirely replace the noradrenaline with another drug, as the other drug may be either too long acting to titrate conveniently, or have some limitations to its use (eg. metaraminol which may have unpredictable pharmacodynamics or methylene blue which can produce unspeakable toxicity). The answers to the question "when would you need to do that" are very scenario-specific.

• HOCM and LVOTO. Noradrenaline, given in sufficient doses, will increase the contractility of a big meaty ventricle by a β1 effect, and the conventional teaching is to avoid it in these patients. Zakynthinos et al (2024) recommend phenylephrine or vasopressin instead.
• Takotsubo calls for noncatecholamine pressors for a similar reason (and in general can be regarded as LVOTO with extra steps). Sattar et al (2020) recommend aiming for either a pure α agonist effect or something entirely noncatecholamine, like vasopressin.
• Severe pulmonary hypertension and right heart failure. Noradrenaline is a pulmonary vasoconstrictor, and in right heart failure there is a real possibility of rapidly and pointlessly escalating the doses of this agent.  Adie et al (2022) noted that its role in the maintenance of MAP is preserved (the RV will love the extra coronary perfusion) but the addition of another agent (ideally something like vasopressin) is recommended earlier rather than later, to avoid increasing RV afterload unnecessarily.
• ​​​​​Where the avoidance of AF is for some reason the focus: for example, where there is severe MR, but the patient's atria have not remodelled into huge useless sacks, making the goal of maintaining sinus rhythm a plausible one. Still, it takes a fair amount of noradrenaline to cause this problem (doses in excess of 0.5 μg/kg/min were required for this in Schmittinger et al, 2012).  Okamoto et al (2015) determined that adding vasopressin empirically reduces the risk of AF.
• When the patient is profoundly vasoplegic, i.e. where the noradrenaline dose alone would be preposterously high,  and one is facing escalating toxicity with escalating doses. It will surprise nobody to learn that there is no widely-accepted threshold for when one should be thinking about this. Schmittinger et al as well as various others point to various vaguely unpleasant consequences of using high dose catecholamines (hyperglycemia! lactate! Intestinal ischaemia!) but the range of noradrenaline doses at which a second agent is introduced ranges from 0.1 μg/kg/min and 0.7 μg/kg/min among the clinical trials. 

What other agent?

• Vasopressin is the only sane choice. In contemplating a second agent, one needs to take into account that most of the authors listed above mention vasopressin as their next choice for an adjunct, in basically all of the abovementioned scenarios. If one reflects on the question, one will conclude that there are very few reasons to reach for a non-vasopressin pressor as the second agent. It is widely available (unlike angiotensin), has little effect on the pulmonary circulation (unlike phenylephrine), has predictable linear dose-response behaviour (unlike metaraminol), is more titratable than terlipressin, and has no real complications related to its use beyond the harmful extension of its vasoconstrictor effects (unlike methylene blue, a nighmarish coal tar derivative that inhibits MAO, undermines your pulse oximetry and disables your haemoglobin). Moreover we can borrow from our extensive experience with using it in sepsis. 

What's normal, a junior doctor with the eyes of a baby deer might ask on their first night shift in the cardiothoracic ICU. Well, noradrenaline is normal. Some noradrenaline, in fact, is to be expected, and its absence is the deviation. Assuming the four French ICUs surveyed by Guinot et al (2023) were representative of the wider community, about 60% of cardiac surgical patients require noradrenaline postoperatively, and of these, the majority stay below 0.10 μcg/kg/min, or 10-12 ml/hr of the standard dilution. It is also normal for it to dissipate over the first day of ICU stay, with the median duration of around 10 hours, i.e. soon after the ceased sedation hands their autonomic system back to them, the patient will be able to generate enough of their own catecholamines to maintain a normal blood pressure. A departure from this normal progression is to be regarded with suspicion, and raises questions about the patient's postoperative contractility.