Very interesting article in JAMA: http://jama.jamanetwork.com/article.aspx?articleID=1752246
I’m curious as to whether this has been generating interest in the cc community. I think it is one of those articles that – at least conceptually – shines light in an area we don’t spend much time reflecting on.
I know that as an IM resident, and a CC fellow, my understanding of vasopressor therapy was pretty basic: squeeze the vessels to bring up the pressure, and hope you don’t squeeze so hard the fingers and toes fall off. In truth, no one ever really pointed out that to some degree or other, the same process killing off the fingers is probably happening to a varying degree in all organs. But maybe I just nodded off and missed it.
Since then, however, I’ve had some time to re-examine things, and my practice has slowly been evolving. For one thing, bedside ultrasound allows a really good assessment of inotropy, so I started to ask myself why I was giving b-agonists to patients who clearly didn’t need any help with contractility (e.g. normal, and even more so, hyperdynamic RVs and LVs). After all, I’m putting them at risk for arrhythmias, or at least tachycardia. So whereas levophed (norepinephrine) remains my reflex pressor, I routinely shift to phenylephrine when faced with arrhythmias (most commonly fast atrial fibrillation) or tachycardia (beyond 110-120) once adequate volume resuscitation has been done. Why 110-120? Its an absolute guess. Somewhat educated – or I try to convince myself of that – in figuring that at some point, the increased CO via HR will be offset by decreased filling time, and with the weak but recurring data showing an association between tachycardia over 90-100 and poor outcome.
So this study – counterintuitive as it may sound to some – is really about blunting the potentially unwanted effects of b-agonists. They randomised 336 patients to IV esmolol to a HR <95 vs a control group of standard care. They found a reduced mortality of 60%… Obviously the massive benefit should be taken with a healthy dose of skepticism, but even just the fact that they didn’t make patients worse is very, very significant.
Read the paper. They do a great job of reviewing the concept and it’s worth going over their protocol.
Physiologically, we know that catecholamines can cause stress cardiomyopathy. The question is, when cardiomyopathy is noted, how often do we think this is related to therapy? More often, we figure it’s the disease process – septic cardiomyopathy. At the bedside, this is impossible to differentiate.
The concept of lusitropy – active relaxation – and its contribution to cardiac output – is often overlooked, and can be affected by catecholamines. In fact it can be the most important factor related to preload, despite getting much less attention than volume loading. Remember that preload is not a pressure (especially not a CVP!!!), but a volume, and physiologically it is the degree of myocardial stretch. The ventricle is not passive, and its compliance is highly related to the active relaxation phase. Fluids will not affect this.
In addition, the decreased filling time by tachycardia can also decrease output.
Fantastic study, even if only to open the door. I would have liked (in typical N=1 fashion and as a bedside sonographer) to see a quick echo prior to initiation, and seeing if there would have been an association with baseline RV/LV function and response/outcome to esmolol. Intuitively and physiologically, it would seem that the hyperdynamic RVs and LVs would have benefitted most, since they didn’t need beta agonism to start with – but I can also entertain that those would be unaffected and that the worse ventricles could have been worsened by stress cardiomyopathy… So a critical question in my opinion.
So…bottom line? Is this practice-changing? It might be. For me, I might start looking at RV/LV and opting for a quicker conversion to neosynephrine if I see a hyperdynamic state or lowering my HR threshold to do so…100? 105? – maybe just a shift rather than a change in practice. I’m not sure I’ll start esmolol infusions yet, but it will be at the back of my mind and I might, given the right set of circumstances. What I would like to see is reproducibility, and if it does happen, I would be happy to get HR’s under 95.
Love to hear what anyone else has to say!