Question 19

College answer

Syllabus topic/section:

2.1.14    Environmental injuries and toxicology: Poisoning and drug intoxication: L1
2.1.4      Cardiovascular Intensive Care: Shock: L1

Discussion: 

A structured answer to shock management which included a tiered response starting with vasopressin and steroids all the way through to methylene blue, addressing arrythmias (options for pacing) and ECMO for example was expected. It was also expected that candidates would include general supportive therapy with dialysis and rationale explained, i.e. normalisation of acid base balance, and electrolytes e.g. calcium, as well as specific therapies for the overdose.
Candidates who did well focussed on vasodilatory shock while considering an overlap with other forms of shock including cardiogenic due to the antihypertensive overdose. They also included antidotes for the common overdoses of these drugs as part of specific management is to treat the underlying cause while addressing the pathophysiology.

Although the question specified vasodilatory shock, given the history, it was important to look for an overlap with other forms of shock, (like cardiogenic from an antihypertensive drug overdose). However, the answer did not require a generic approach to shock nor a confirmation of vasodilatory shock and candidates who spent time on this aspect were less likely to score as highly.
 

Discussion

An excellent mnemonic to add to the already mnemonic-rich environment of toxicology is ABC: Absorb/Abate, Block/Bypass, Control/Cope - to classify the mechanisms of actions of antidotes, mentioned in this excellent paper by Buckley et al (2016). For vasoplegic shock, vasopressors fall into the "control and cope" stage, where they attempt to counteract the vasoplegia by pushing the vessels from the opposing vector direction; this is easy to manage at the bedside, but the "absorb" and "bypass" are much better for the patient because they can reduce the overall exposure to the toxic effects of the aGent, and the focus should be on these primarily. One may therefore benefit from ordering this list in a way that puts the interventions with the greatest downstream benefit at the top.

Remove the removable 

• Use CRRT to rapidly correct the acid base abnormalities while removing any circulating soluble toxins
• unlike in the management of sepsis, to resort to dialysis early is a reasonable option, considering that some portion of even highly protein bound drugs may become available for removal in massive overdose where all the binding sites are saturated).
• Haemoperfusion with charcoal may still have relevance in this area
• Decontaminate in other ways, including gastroscopy colonoscopy or even surgery to remove any bezoar of drug that may be contributing (eg. in body packers, it may even be surrounded by ischaemic gut, contributing to the shock state)
• Intralipid emulsion for highly fat soluble drugs (it's not just for local anaesthetic toxicity!)

Reverse the reversible

• Antidotes could be key to survival. Notably, "block/bypass" activities are favoured in this list:
• High dose insulin for beta blocker toxicity
• Calcium for calcium channel blockers
• Naloxone for clonidine toxicity and ACE-inhibitor overdose (apparently the vasoplegia is at least partially mediated by ACE inhibitors inhibiting the enzyme enkephalinase, which normally degrades endogenous opioids)
• Yohimbine for clonidine overdose

Correct the correctable

• Finish fluid resuscitation. The capacity of the now-dilated circulatory system is larger than you probably expected. 
• Correct metabolic acidosis with sodium bicarbonate
  (added bonus of protecting from sodium channel blocker effects of tricyclic antidepressants and helping ion-trap weak acid drugs in the urine). It does not hurt to note
• Calcium chloride to restore ionised calcium to a normal level (it contributes to pressor responsiveness)
• Esmolol to slow the heart rate and allow more diastolic filling (unless beta blocker overdose is implicated) 
• Pacing if the heart rate being slow is the problem 

Add moar vasopressor

• Vasopressin: restores vascular reactivity and catecholamine responsiveness
• Methylene blue: a nitric oxide synthase inhibitor, which as a bonus also acts as an MAOI, decreasing the breakdown of catecholamines. It may also make things worse by precipitating serotonin syndrome, causing methaemoglobinaemia, and derailing the whole resuscitation if the patient had unrecognised G6PD.
• Hydroxocobalamin, both a nitric oxide synthase inhibitor and a nitric oxide scavenger, may be superior to methylene blue, and could have an additive effect
• Angiotensin II, which may not be available anywhere except for Aoteroa right now, but which is a handy agent (especially if ACEI overdose is implicated)

Explore the possibility that there be more than just one type of shock

• The question specifically says "vasoplegic shock" so we could reasonably limit our discussion to that, but realistically, any situation that calls for four vasopressor classes to be pulled out of the cupboard is a situation that calls for at least a bedside echo assessment.

Prevent further endothelial activation

• Use albumin for resuscitation, unscientifically, just in case it protects the endothelial glycoicalyx. A side benefit may be to increase the binding sites available for protein-bound drugs, decreasing their effect-site bioavailability
• Add steroids to address any real or imagined "relative adrenal insufficiency" and because of the relative safety of these agents
• Cool the patient, because extreme hyperthermia contributes to the vascular endothelial injury (though whether therapeutic hypothermia helps is not clear; it may be better to merely aim to maintain a normal temperature)