Taking a look again, I’m relatively stunned I by no means revealed a First10 strategy to sympathetic crashing pulmonary edema. I assume it by no means felt essential, because it used to be the primary ever EMCrit submit, and due to this fact felt neatly lined within the FOAMed neighborhood. Alternatively, a complete 15 years after that first EMCrit podcast (congrats at the decade and a part of FOAMed Scott), I nonetheless come across many clinicians (nurses and medical doctors alike) who’re uncomfortable with suitable doses of IV nitroglycerin. To be honest, till now, the proof has most commonly been observational and retrospective. Alternatively, we’ve an RCT that displays beautiful exceptional growth with prime dose intravenous nitroglycerin, so possibly follow will begin to exchange.
The Accompanying YouTube Video
The paper
Siddiqua N, Mathew R, Sahu AK, Jamshed N, Bhaskararayuni J, Aggarwal P, Kumar A, Khan MA. Top-dose as opposed to low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised managed trial. Emerg Med J. 2024 Jan 22;41(2):96-102. doi: 10.1136/emermed-2023-213285. PMID: 38050078
The Strategies
That is an open-label, unmarried middle, pragmatic randomized managed trial from India.
Sufferers
Grownup sufferers with acute onset (lower than 6 hours of signs) dyspnea, high blood pressure, tachypnea, hypoxia, and bilateral crackles.
Explicit standards have been systolic force >159 and diastolic force >100 (or MAP >120), RR >30, sats <90%.
Exclusions: acute MI, allergy to GTN, sildenafil inside 24 hours, tadalafil inside 48 hours, average to serious aortic stenosis, hypertrophic cardiomyopathy, sufferers requiring rapid intubation.
Intervention
Top dose intravenous nitroglycerine: 600–1000 mcg bolus adopted via an infusion beginning at 100 mcg/min and due to this fact titrated via scientific reaction.
Comparability
Low dose intravenous nitroglycerine: no bolus and an infusion beginning at 20–40 mcg/min. Dose used to be titrated via the doctor, however used to be now not allowed to exceed 250 mcg/min.
Commonplace same old procedures
Each teams got BIPAP give a boost to with an preliminary inspiratory sure airway force of 12 mm Hg and expiratory sure airway force of 6 mm Hg.
Result
They used ‘co-primary results’ of answer of signs at 6 and 12 hours. (Subjective growth on a 7 level Likert scale, plus a minimum of 2 purpose markers of growth: answer of tachypnea, answer of hypoxia, answer of high blood pressure.)
The Effects
They enrolled 52 sufferers out of 169 to begin with screened. The imply age used to be within the mid 40s with a few 50/50 male/feminine cut up. This used to be a quite unwell cohort, regardless of being so younger. 70% of the sufferers had persistent kidney illness and necessarily they all had baseline high blood pressure. Vitals indicators at presentation integrated a mean respiration price within the prime 30s, oxygen saturation of 80-85%, and blood force of about 200/125.
Top dose nitroglycerin used to be significantly better than low dose. At 6 hours, 65% of the prime dose staff had answer in their signs as in comparison to simplest 12% of the low dose staff (p<0.001). The variation used to be nonetheless massive at 12 hours, with 89% answer as in comparison to 19% (p<0.001). (Those numbers are all unusually low to me, as I am getting with regards to 100% answer of SCAPE inside the first hour or two with prime dose GTN and BiPAP.)
Mainly all results have been worse within the low dose staff. Intubation used to be 19% vs 4% (despite the fact that now not statistically vital). (I’ve now not intubated this kind of sufferers in my occupation, so this staff turns out means sicker, or other in any other means, than what I’m seeing in Canada.) Admission charges, medical institution duration of keep, and MACE have been all upper with low dose nitroglycerin.
In the event you care about track based totally results, the essential indicators additionally stepped forward extra within the prime dose staff:
When it comes to adversarial occasions, no sufferers advanced hypotension in both staff. 11 sufferers within the low dose staff and three within the prime dose staff advanced a headache.
My ideas
That is a very powerful find out about, however it’s clearly a long way from a really perfect find out about. This can be a small unmarried middle find out about, with a inhabitants that turns out very other from what I’m used to in North The united states. (Sources and control methods may also be other, however I don’t know.) Opaque envelopes aren’t the most productive allocation concealment process. It’s dishonest to make a choice co-primary results, particularly if you end up simply the use of other time frames that aren’t in reality clinically other. The calculated pattern measurement is in response to an anticipated 54% absolute distinction between the teams. Even supposing I’m a reasonably large supporter of prime dose nitroglycerin, that turns out ridiculously over-optimistic to me.
The most important particular person methodologic factor with this find out about is that it used to be now not blinded. Even if you end up measuring quite purpose scientific results, a loss of blinding introduces a prime chance of bias. Vitals indicators will have to be purpose, however we’ve all rechecked vitals after they don’t fit what we think. Affected person studies of growth will also be influenced via the way in which questions are requested. (“You have got been at the easiest dose for a couple of hours now. You should be feeling higher, proper?”) The diversities on this trial appear too dramatic to be completely in response to bias, however we can not have a prime degree of walk in the park till we see prime quality, multi-center, blinded trials.
I do surprise about generalizability. Those sufferers are more youthful and sicker than my moderate affected person. That may give an explanation for the results, however I haven’t noticed a SCAPE affected person that required intubation, or who wasn’t higher inside 6 hours, in my complete occupation. The truth that our sufferers are much less unwell could be why such a lot of other people have got away with the use of miniscule doses of nitroglycerin in North The united states.
Clearly, a unmarried middle find out about of simplest 52 sufferers isn’t sufficient to in reality touch upon adversarial occasions. Alternatively, we already robotically give prime doses of nitroglycerin at all times (2 sprays of sublingual GTN is 800mcg as a bolus, about part of which is absorbed). Moreover, should you rely all adversarial occasions, together with hypoxia and intubation, and don’t simply center of attention on hypotension, It’s not that i am certain you even be expecting prime dose treatment to be ‘riskier’.
There are a selection of alternative publications that recommend prime dose nitroglycerin is quite protected (and almost definitely efficient). Wilson (2016) revealed an observational cohort by which they used 2 mg IV (2,000 mcg) push doses of nitroglycerin, and it used to be related to much less ICU use. The prevalence of hypotension used to be simplest 2%. Some other small find out about of 25 sufferers used bolus doses between 600 and 1000 mcg (moderate 872 mcg) relying at the presenting blood force, without a headaches. (Matthew 2021) Houseman et al (2023) describe a cohort of 67 sufferers who had nitroglycerin infusions >100mcg/min, with a hypotension price of four%. (After all, a large number of hypotension is brief lived and clinically beside the point, being controlled via merely preventing or lowering the infusion.)
I’m steadily vital of follow exchange in response to small unblinded research. I believe it’s cheap to be wary, and we for sure want extra research on this space. Alternatively, any other idea that I persistently emphasize is the vital of pretest chance in proof based totally medication. We’re used to the use of prime dose nitroglycerin safely sublingually. There may be observational information suggesting that is the suitable means. Thus, in comparison to the common small unblinded RCT, I believe the conlclusions of this trial are much more likely to be proper. The possible receive advantages for sufferers seems massive, with minimum chance, so I believe this is sufficient to exchange follow whilst looking forward to larger research.
Final analysis
I’ve been suggesting prime dose nitroglycerin (blended with BiPAP) for SCAPE for a few years. This RCT, despite the fact that a long way from highest, demonstrates considerably stepped forward results with upper doses of nitroglycerin, and will have to be sufficient to switch follow for other people recently the use of decrease doses.
Different FOAMed
Top dose nitroglycerin lined in Articles of the month Oct 2016,
The first actual EMCrit Episode: Sympathetic Crashing Acute Pulmonary Edema (SCAPE)
Crucial care infusion drug dosing cheat sheet
Proof based totally medication is simple
The EBM bibliography
Proof based totally medication sources
EBM deep dives
References
Houseman BS, Martinelli AN, Oliver WD, Devabhakthuni S, Mattu A. Top-dose nitroglycerin infusion description of protection and efficacy in sympathetic crashing acute pulmonary edema: The HI-DOSE SCAPE find out about. Am J Emerg Med. 2023 Jan;63:74-78. doi: 10.1016/j.ajem.2022.10.018. Epub 2022 Oct 18. PMID: 36327753
Mathew R, Kumar A, Sahu A, Wali S, Aggarwal P. Top-Dose Nitroglycerin Bolus for Sympathetic Crashing Acute Pulmonary Edema: A Potential Observational Pilot Find out about. J Emerg Med. 2021 Sep;61(3):271-277. doi: 10.1016/j.jemermed.2021.05.011. Epub 2021 Jun 30. PMID: 34215472
Siddiqua N, Mathew R, Sahu AK, Jamshed N, Bhaskararayuni J, Aggarwal P, Kumar A, Khan MA. Top-dose as opposed to low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised managed trial. Emerg Med J. 2024 Jan 22;41(2):96-102. doi: 10.1136/emermed-2023-213285. PMID: 38050078
Wilson SS, Kwiatkowski GM, Millis SR, Purakal JD, Mahajan AP, Levy PD. Use of Nitroglycerin via Bolus Prevents ICU Admission in Sufferers with Acute Hypertensive Center Failure. The American Magazine of Emergency Drugs. 2016. article PMID: 27825693
