Hey all!

It’s been awhile since I’ve written anything and I’m sorry for that.  I’ve been ridiculously busy, even by my standards and I haven’t had time to sit down and write in any meaningful way.  I prefer not to throw something together for the sake of doing it, so here’s my attempt at a mediocre quality product!  For my first research-based article I wanted to discuss prehospital Nitroglycerin usage, specifically in the presence of ACS.  I’ll start with our protocol and get into some pitfalls and problems that can happen.  I’ll also touch on how recent research feels about Nitroglycerin and where it may be going in the future.   This won’t be a comprehensive study project, but more of a light review.  My disclaimer applies heavily here – follow your local protocols and don’t use my blog as medical direction.  I always attempt to be accurate in my writing and my education, but I welcome any and all feedback that contradicts what I’m writing today.

Nitroglycerin is a staple ACS treatment in the EMS world.  In most systems it is a BLS and an ALS drug and is used primarily in the treatment of angina pectoris, although it has some other usages as well that I won’t be getting into.  In Maryland we administer Nitroglycerin sublingually at a dose of .4mg.  Some systems are using spray and some are using tablets.  I haven’t been able to find much substantial difference between the two in research or in clinical practice, although I find the spray to be a touch easier to work with.  We have a 3 dose limit and each dose should be spaced apart about 3-5 minutes.  Most EMS protocols have the obvious contraindications of sexual enhancement drugs as well as pulmonary hypertension drugs.  In addition, most have precautions against low heart rates and precipitous drops in blood pressure.  These are in place in effort to stave off a hypotensive shock situation which results from too much vasodilation.

Overall Nitroglycerin is considered by most authorities to be a very safe drug.  My review of the literature found approximately 10-25% of patients experienced a significant drop in systolic blood pressure (SBP) of around 30mmHg or more1.  In addition to this being reflected by this cohort, I would say about 25% seems accurate to my own clinical experience in regards to a significant drop in SBP.  Another study of approximately 300 patients found some significant events involving apnea and even asystole in approximately 1.4% of their patients2.  There is no surprise that most of the adverse effects are all centered around uncontrolled or significant vasodilation and resulting hypotensive shock.  In the cases I reviewed I could not find any that did not result in recovery of the patient.

So the big question on my mind has always been does Nitroglycerin work?  Despite its positive safety record, any adverse events are too many if there isn’t solid science and evidence behind its usage.  Unfortunately, as with much of medicine, there isn’t clear data here.  Nitroglycerin has been shown to increase blood flow to the heart in the presence of ACS and thus reduce mortality/morbidity3.  What remains unclear is the dosing structure and how much of Nitroglycerin is a good thing.  Despite my review of today’s literature, I could not find any solid information on how we came about our dosing structure for prehospital usage.  I’m not sure where the 3 dose limit comes from or even where the .4mg dosing came from.  I do know that my own clinical practice in critical care medicine would suggest that IV/titrated Nitroglycerin would be far more likely to be therapeutic due to the ability to finely control the dosing.  When I was studying for my flight paramedic, the instructor drew the following diagram up on the board:

In this diagram the top X would represent the clinical efficacy of the Nitroglycerin immediately after administering in pill/spray form.  The bottom x would then conversely represent the effect after the drug has been utilized.  In the middle we see therapeutic window, which is when the effects of the medication are truly clinically effective.  The challenge with prehospital Nitroglycerin is that, unlike IV Nitroglycerin, we cannot stay in that therapeutic window for long, and truthfully we aren’t equipped to monitor the effects that closely anyway in the prehospital world.  Ok Scott, so you have a pretty picture onboard and what you’re saying makes sense, but does that therapeutic window even matter?  I mean, if Nitroglycerin has been shown to help, has any research shown that it has an upper limit?  Well interestingly enough, it has indeed.  Current research has shown that too much Nitroglycerin can result in a chain of events that will ultimately reduce coronary perfusion4.  To quote that particular study:

“ALDH2 metabolizes nitroglycerin, leading to generation of the vasodilator, nitric oxide. Yet, prolonged treatment with nitroglycerin decreases ALDH2 activity (5, 11). We reasoned that if ALDH2 activity is critical for cardioprotection from ischemic damage, prolonged treatment with nitroglycerin should inhibit εPKC-dependent preconditioning.  As expected, a 30-minute treatment of nitroglycerin (GTN; 2μM) in the ex vivomyocardial infarction model in rodents greatly inhibited ALDH2 activity and abolished ethanol- and εPKC-induced activation of ALDH2″

The translation of this is that over time, Nitroglycerin has been shown to reduce coronary perfusion.

So what does all this mean?  Well as I said in the beginning, we are bound by protocols and we must follow them.  The advantage to having a good background knowledge is that we can better apply clinical judgement and clinical priority to our practice.  We should be performing the best interventions for our patients in the best order, and it is my opinion that we will be seeing prehospital Nitroglycerin get lower and lower on that list.  The challenge with literature and studies is that they don’t always pan out the way they start out.  For example, many of the test subjects on the studies I referenced were rodents and haven’t yet been applied to humans.  That said, if we are to be proficient clinical providers we must keep abreast of what is next and be the driving forces of change in our field.  We must always remember the basics of pharmacology and apply them to our daily practice: right patient, right drug, right time, right dose, right route, aaaand right documentation (the hidden sixth).  If the intervention isn’t the right time or the right patient then it isn’t the right intervention.  Until next time boys and girls, everyone stay safe!

References

• http://www.ncbi.nlm.nih.gov/pubmed/26024432
• http://www.ncbi.nlm.nih.gov/pubmed/8273955
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527093/
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741612/