Severe pain + 2mg of Morphine = severe pain.

- Rogue Medic

Is Nitroglycerin Bad for Severe Sepsis?

ResearchBlogging.org
 

Yesterday at The Paramedic’s Edge, this was the topic of reactive, reflexive, dogmatic, rejection discussion of a possible use of NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries).

NTG is a vasodilator and sepsis is a vasodialtion problem. There are other problems with sepsis, but vasodilation may be the primary problem.
 

Nitro for severe septic patients. What are your thoughts?[1]

 

Here is a sampling of some of the unfortunately typical responses.
 

The amateur lawyer who thinks that what we do should be guided by fear of law suits approach.
 

Oh to put them out of their misery?! Sounds like a lawsuit waiting to happen

 

The just drive fast, I don’t understand any of this medical mumbo jumbo appraoch.
 

We’re medics not doctors. Best thing we can do is a diesel infusion

 

The most common responses seemed to be of this kind.

The I only know one thing about nitro and that scares me approach.
 

True hemodynamic instability is a contraindication

 

Hmmmm let’s drop their pressure even more…that’s a thought? So my answer…HE’LL NO!!

 

We will probably end up using NTG in the treatment of cardiac arrest – the ultimate low blood pressure state, so how far fetched is using NTG for sepsis?[2],[3],[4],[5],[6],[7]

Why?

NTG can lower blood pressure, but it can also increase cardiac output.

To over-simplify things –

If the CO (Cardiac Output) increases by more than the the vasodilation would decrease the BP (Blood Pressure), the BP will actually be expected to increase.

CO = SV (Stroke Volume) x HR (Heart Rate).

CO MAP (Mean Arterial Pressure)/TPR (Total Peripheral Resistance).

BP = CO x TPR.

Are all cardiac outputs and vascular resistances the same? No, but we simplify things by making that assumption.
 


 

Jean-Charles Preiser and colleagues question the routine use of nitroglycerin because of the risk of hypotension and the possible induction of mitochondrial dysfunction.[8]

 

Many people question the use of NTG and worry about hypotension.
 

Although we observed a temporary drop in blood pressure, blood flow was maintained and, in fact, increased in our patients.[8]

 

We do worry obsess about things that are brief and insignificant (such as ROSC – Return Of Spontaneous Circulation – in treatment of cardiac arrest), while we ignore the things that are more important (such as living long enough to leave the hospital with a brain that works well enough to recognize family members).
 

Space constraints meant that we were not able to include specific haemodynamic results in our Research letter, but mean arterial pressure temporarily dropped by an average of 21 mm Hg (range 13—33 mm Hg) in the eight patients we investigated.[8]

 

A drop in MAP (Mean Arterial Pressure) of 21 mm/Hg is huge!
 

Mean arterial pressure returned to baseline level within 1 min in all patients with concomitant fluid infusion.[8]

 

Less than 1 minute?

Try using that as a pickup line.

I can rock your world for less than 1 minute.

How much alcohol is going to be required to make that sound significant?

We give adenosine to do what?

To completely stop the heart for usually less than one minute.

We cardiovert to do what?

To completely stop the heart for usually less than one minute.

A short-term worsening of vital signs for a long-term improvement in survival is an excellent trade-off.

Does NTG improve long-term survival?

That is not clear, but this does show that we need to abandon more dogma in our search for the best care of our patients.
 

The increase in microvascular blood flow as a result of this procedure confirms our clinical experience that resuscitation efforts should be aimed at optimising blood flow not blood pressure.[8]

 

NTG does improve blood flow.

Too many of us are afraid to use NTG, or afraid to use large doses of NTG, or afraid to use IV bolus NTG, or afraid to use large doses of IV bolus NTG out of too much concern for blood pressure and not enough concern for blood flow.

This quotes are from a response to a letter about research paper looking at NTG for sepsis. This paper is not something that should be summarily dismissed.[9]

The EMS drug of choice, dopamine, may be a bad idea for sepsis.[10],[11]

Think about that – For sepsis dopamine may make things worse and NTG may make things better.

Is it that simple? Maybe. Maybe not. Dopamine may make things better, but just not do as good a job as norepinephrine. Or all catecholamines may be harmful.

Dr. Mervyn Singer makes an excellent case that catecholamines are not helpful, or that they are at least tremendously overused. Go listen to his podcast.[12]

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Footnotes:

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[1] Nitro for severe septic patients. What are your thoughts?
The Paramedic’s Edge
Facebook
Facebook discussion page

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[2] High dose nitroglycerin treatment in a patient with cardiac arrest: a case report.
Guglin M, Postler G.
J Med Case Rep. 2009 Aug 10;3:8782. doi: 10.4076/1752-1947-3-8782.
PMID: 19830240 [PubMed]

Free Full Text from PubMed Central.
 

A possible explanation for the hemodynamic benefit of NTG in our patients is increased cardiac output produced by rapid vasodilatation in a heart operating at the extreme of the Frank-Starling curve. Vasodilators in heart failure with or without acute myocardial infarction have been proven to decrease left ventricular filling pressure and systemic vascular resistance while increasing cardiac index [7]. The more severe the failure, the more beneficial the effect of vasodilators [13].

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[3] Sodium nitroprusside enhanced cardiopulmonary resuscitation improves survival with good neurological function in a porcine model of prolonged cardiac arrest.
Yannopoulos D, Matsuura T, Schultz J, Rudser K, Halperin HR, Lurie KG.
Crit Care Med. 2011 Jun;39(6):1269-74. doi: 10.1097/CCM.0b013e31820ed8a6.
PMID: 21358401 [PubMed - indexed for MEDLINE]

Free Full Text from acoep.org.

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[4] Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models.
Schultz JC, Segal N, Caldwell E, Kolbeck J, McKnite S, Lebedoff N, Zviman M, Aufderheide TP, Yannopoulos D.
Crit Care Med. 2011 Dec;39(12):2705-10. doi: 10.1097/CCM.0b013e31822668ba.
PMID: 21725236 [PubMed - indexed for MEDLINE]

Free Full Text from PubMed Central.

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[5] Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest.
Schultz J, Segal N, Kolbeck J, McKnite S, Caldwell E, Yannopoulos D.
Resuscitation. 2012 Mar;83(3):374-7. doi: 10.1016/j.resuscitation.2011.07.038. Epub 2011 Aug 22.
PMID: 21864483 [PubMed - indexed for MEDLINE]

Free Full Text from PubMed Central.

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[6] Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation.
Schultz J, Segal N, Kolbeck J, Caldwell E, Thorsgard M, McKnite S, Aufderheide TP, Lurie KG, Yannopoulos D.
Resuscitation. 2011 Dec;82 Suppl 2:S35-40. doi: 10.1016/S0300-9572(11)70149-6.
PMID: 22208176 [PubMed - indexed for MEDLINE]

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[7] Controlled pauses at the initiation of sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitate neurological and cardiac recovery after 15 mins of untreated ventricular fibrillation.
Yannopoulos D, Segal N, McKnite S, Aufderheide TP, Lurie KG.
Crit Care Med. 2012 May;40(5):1562-9. doi: 10.1097/CCM.0b013e31823e9f78.
PMID: 22430233 [PubMed - indexed for MEDLINE]

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[8] Nitroglycerin for septic shock.
Preiser JC, De Backer D, Vincent JL.
Lancet. 2003 Mar 8;361(9360):880; author reply 880. No abstract available.
PMID: 12642079 [PubMed - indexed for MEDLINE]

Free Full Text from the Lancet.

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[9] Nitroglycerin in septic shock after intravascular volume resuscitation.
Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF.
Lancet. 2002 Nov 2;360(9343):1395-6.
PMID: 12423989 [PubMed - indexed for MEDLINE]

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[10] Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis*.
De Backer D, Aldecoa C, Njimi H, Vincent JL.
Crit Care Med. 2012 Mar;40(3):725-30. doi: 10.1097/CCM.0b013e31823778ee.
PMID: 22036860 [PubMed - indexed for MEDLINE]

CONCLUSIONS:
In patients with septic shock, dopamine administration is associated with greater mortality and a higher incidence of arrhythmic events compared to norepinephrine administration.

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[11] Norepinephrine or dopamine for septic shock: systematic review of randomized clinical trials.
Vasu TS, Cavallazzi R, Hirani A, Kaplan G, Leiby B, Marik PE.
J Intensive Care Med. 2012 May-Jun;27(3):172-8. doi: 10.1177/0885066610396312. Epub 2011 Mar 24. Review.
PMID: 21436167 [PubMed - indexed for MEDLINE]

CONCLUSIONS:
The analysis of the pooled studies that included a critically ill population with shock predominantly secondary to sepsis showed superiority of norepinephrine over dopamine for in-hospital or 28-day mortality.

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[12] Catecholamines Should Be Banned
Mervyn Singer
2009-04-24-1545
6th Annual Critical Care Symposium
Manchester, UK
Page with link to free mp3 download from Free Emergency Medicine Talks.

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Guglin, M., & Postler, G. (2009). High dose nitroglycerin treatment in a patient with cardiac arrest: a case report Journal of Medical Case Reports, 3 (1) DOI: 10.4076/1752-1947-3-8782

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SPRONK, P., INCE, C., GARDIEN, M., MATHURA, K., & ZANDSTRA, D. (2003). Nitroglycerin for septic shock The Lancet, 361 (9360), 880-880 DOI: 10.1016/S0140-6736(03)12692-X

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Spronk, P., Ince, C., Gardien, M., Mathura, K., Straaten, H., & Zandstra, D. (2002). Nitroglycerin in septic shock after intravascular volume resuscitation The Lancet, 360 (9343), 1395-1396 DOI: 10.1016/S0140-6736(02)11393-6

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