Nitroglycerin - Old and New: Pt 1

The modern medic gets to use a lot of fancy technology. She interprets capnographic waveforms, reads 12-lead (and 13- and 15-lead) ECGs, places ET tubes, LMAs , and CPAP masks, uses portable lactate analyzers, and even knows how to spell "sphygmomanometer."

Let's face it - compared with all that, nitroglycerin is not a "sexy" EMS tool. 

Unlike this little beauty. You know, I think I've seen this before...

Nitro has been used for angina since 1879, and was also used for "spasms," headaches, and even toothaches. After 133 years of clinical experience, it seems we would have nothing new to say. For example, we take for granted 2 things about NTG:

• The dose is one tab (or spray), every 5 minutes, to a maximum of 3 doses; and
• You should to do an ECG to check for an inferior MI before giving it.

I'll talk about using "high-dose" nitro tablets for CHF in Part 1 today, and discuss the evidence-based concerns about using NTG during an inferior or right-sided MI in Part 2.

Increasing the dose - 1, 2, or 3 tabs sublingual
In case you haven't heard, Lasix is old-fashioned, at least for EMS. It's not a good drug for acute hypertensive congestive heart failure, for any number of reasons, and the modern EMS system uses CPAP and nitro instead.

So how do I usually give NTG for CHF? Once the patient gets to the hospital, I'll use a starting dose of IV NTG at 200 - 400 µg/minute.For the first 20 minutes I'll be adjusting the dose up & down pretty frequently, until the patient's breathing gets better, and the BP has come down.

However, the sublingal NTG dosing used by EMS for CHF is usually the same small dose used for angina pectoris, 0.4 mg every 5 minutes. That's about 80 µg/minute, if you assume that it's absorbed over that 5 minutes. 

Let me point out some basic math:

80 µg < 400 µg

As an emergency doctor, I can get around this problem easily: if I don't have IV NTG available, I give several NTG tabs at once. While the nurses are scrambling to get a second IV and program the IV pump, and the respiratory tech is setting up the CPAP, I'm practically dumping the bottle of NTG under their tongue. The higher their blood pressure is, the more I can give. And I don't stop at 3 doses either; I keep giving it every 5 minutes until the IV juice is flowing.

So, this strategy makes sense pharmacokinetically, and some paramedics having been doing this for years, albeit "off-protocol". For one example, read Peter Canning's excellent blog post NTG and The Hero Medic, about a medic who, evidently, felt comfortable with pretty aggressive NTG doses.

So it's good to read about an EMS system that decided to act rationally, and then study it. In an abstract in the most recent Prehospital Emergency Care, EMS researchers in Buffalo discuss their experience with changing the EMS protocol to allow multiple simultaneous doses of nitro for CHF with hypertension, depending on the BP. I copied the entire article below, but the protocol was simply:

• SBP < 160 mmHg --> 1 tab (0.4 mg)
• SBP > 160 mmHg --> 2 tabs
• SBP > 200 mmHg --> 3 tabs
• Repeat as needed, no maximum # doses

So were patients dropping like flies from this crazy dosing? 

Not so much. Out of 95 patients who got the high-dose NTG, only 3 patients dropped their BP. Which could have been concerning, except that the breathing of those patients was better (which is the whole point), while the hypotension was transient, resolving on the next BP measurement. 

The Bottom Line
Nitroglycerin is an old drug, but we are still learning about how to best use it. Our old habit of "1 q 5', to a max of 3" is perhaps just that, an old habit!

The SHCGB Guidelines, on the other hand, do not set a limit on the maximum number of doses that can be given, and allow the medic to aggressively treat CHF. If the blood pressure is severely elevated during an episode of likely CHF, you can give up to 4 tablets at a time.

Unfortunately, some paramedics may have ingrained patterns of behavior, and there may be doctors who haven't heard about developments in nitro use since 1880. Time to drag them into the 21st century, with all our fancy "new" medications and medical devices!

As for the "sexy" airway tool that looked so familiar above...

Found it!

PREHOSPITAL ADMINISTRATION OF MULTIPLE SIMULTANEOUS NITROGLYCERINE SUBLINGUAL TABS RARELY CAUSES HYPOTENSION
Brian Clemency, Gina Tundo, Jeffrey Thompson, Heather Lindstrom, University at Buffalo, State University of New York
  Background. High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional emergency medical services (EMS) protocol was introduced allowing advanced providers to treat CHF with oral nitroglycerin. Patients were treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mmHg or three sublingual tabs (1.2 mg) when SBP was >200 mmHg every 5 minutes as needed. To assess the protocol’s safety, we studied the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers. 
Methods. A retrospective case review of records from a single commercial EMS agency over a six-month period (January–June 2012). Cases with at least one administration of MSN were reviewed. For each administration, the first documented vital signs before and after administration were compared. Administrations were excluded if they were missing pre- or post-administration vital signs. Blood pressure was measured in mmHg.  
 Results. One hundred cases had at least one MSN administration by an advanced provider during the study period. Twenty-five cases were excluded because of incomplete vital signs. Seventy-five cases with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was –14.7 (standard deviation 30.7; range +59 to –132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50, and 66/47 mmHg). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100 mmHg. The incidence of hypotension following MSN administration was 3.2%.  
 Conclusion. Hypotension was rare and self-limited in this sample of prehospital patients receiving MSN.