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P responsed to Blood volume prior to and following treatment of acute cardiogenic pulmonary edema with the following –
Could you elaborate a little bit on why you included this study? Was it just to point out that Lasix does not work the way many in EMS think it does?
There are two reasons I chose this study.[1] It provides evidence that the reason for giving furosemide (Lasix – frusemide in Commonwealth countries) to the unstable CHF/ADHF (Congestive Heart Failure/Acute Decompensated Heart Failure) patient is not valid.
The other reason is the age of the article. We have a long history of ignoring the evidence that the problem is not too much fluid in the patients, but a problem of the fluid being in the wrong places.
Or rather, that in EMS we are taught an incorrect mechanism for Lasix.
I did not really address the possible mechanisms by which furosemide might work, but I will in looking at other research.
Chronic CHF and acute CHF are not the same condition, even though they share many features.
I don’t think furosemide works for patients with acute CHF.
I think furosemide makes things worse for patients with acute CHF.
I will write more about this using other articles, many of which have been around for decades, but have been ignored because too many of us just know it works.
I understand why Lasix has largely fallen out of favor for the treatment of acute CHF, but reading through the actual study it seems like this supports the use of Lasix.
You ask an excellent question.
The study does give the impression that furosemide improved outcomes, but it was never designed as a study of whether furosemide is helpful, or even just not harmful. Other than oxygen, morphine, and furosemide (apparently in that order) we do not know much about the treatment of this small group of patients. Even pulmonary suction is listed as a treatment, but there are no suggestions that treatments are even limited to those listed. (PE = Pulmonary Edema in this case, not Pulmonary Embolism)
Studies were performed in 21 patients, 11 men and 10 women, ranging from 44 to 83 (median 67) years in age. In 16 of the patients, PE was observed at the time of admission to the Center for the Critically Ill and in five patients, PE appeared during the course of in-patient care.[2]
Previous history of acute pulmonary edema was elicited in nine of the 21 patients; 11 patients had been treated with diuretics prior to the occurrence of acute pulmonary edema; and six patients had evidence of peripheral edema on admission.[2]
The initial set of measurements were obtained immediately after referral to the Center for the Critically Ill from either the emergency department or general medical services following onset of acute PE. Oxygen was the only agent administered prior to the initial set of measurements.[2]
This is something I did not pay attention to when writing the first post. These appear to be ICU (Intensive Care Unit) patients. I had mistakenly assumed these were ED (Emergency Department) patients. This also weakens the conclusions I was drawing from the study. I had been reading the Center for the Critically Ill as a fancy name for the ED.
11/21 patients. These patients had a very high rate of the pink, frothy sputum we were told to expect from CHF.
In 11 patients, there was expectoration of frothy fluid.[2]
Whatever treatment was given to the patients in the ED does not appear to have helped, but we have no idea what the denominator is.
Treatment included oxygen administered by rebreathing mask, ventimask, or nasal prongs in oxygen concentrations ranging from 28 to 60 (mean 40) %. After an initial set of measurements had been obtained, morphine sulfate was injected intravenously in bolus doses ranging from 2 to 5 mg with total dose ranging from 5 to 15 mg until acute anxiety was relieved.[2]
This is prior to any furosemide (maybe not the total doses of morphine, but the initial doses). If we wanted to see the effects of furosemide, there would be some control of any differences in treatment. There would be more documentation of differences.
Bilateral moist rales and radiographic signs of grade 3 or 4 pulmonary edema, according to the criteria of Turner, Lau, and Jacobson,10 were documented in each instance.[2]
This suggests that there is good objective evidence that these patients really did have CHF, which is an important point.
Furosemide was administered by intravenous bolus injection in amounts of 40 or 80 mg. Additional doses of 40 or 80 mg of furosemide were administered after 1 hour in the absence of a diuretic response. The total dose of furosemide during the initial 24 hours of management ranged from 40-160 (mean 71.4) mg.[2]
How many patients did not have a diuretic response (make urine) in the first hour after receiving furosemide?
We do not know, and the mean of 71.4 mg, with an initial dose of 40 or 80 mg and 40 or 80 mg increments, leaves a lot of room for speculation.
Is that what happened? Did half of the patients receive repeat doses?[3]
As I stated, I am only speculating, but I could come up with a variety of dose combinations that would produce a similar total mean dose. The point is that this information is not helpful for evaluating the possible effect of furosemide.
Why would patients not have a diuretic response for over an hour after furosemide?
Isn’t furosemide supposed to act like Kryptonite (is there yellow Kryptonite?[4]) to the fluid retention of CHF?
Aren’t we supposed to keep urinals and bedpans ready for these patients?
If the patient is shunting blood away from the less critical organs, during times of critical illness, how is the furosemide supposed to get to the kidneys quickly?
In patients with chronic heart failure and especially in the presence of generalized edema, prior investigations have demonstrated either increases in intravascular volume17-19 or no consistent changes.20 During acute cardiogenic pulmonary edema, however, blood volume is more frequently reduced.[2]
If the patient is stable, drawing off this excess water seems to help to prevent fluid from leaking into the lungs. Should we assume that furosemide preferentially removes fluid from the lungs in patients who are already intravascularly volume depleted?
Accordingly, plasma water had been removed from the intravascular compartment. The evidence points to extravasation of fluid from the intravascular compartment that is low in colloid content. The likelihood that this represents, at least in part, fluid which is extravasated into the lung is consistent with observations on the protein content and colloid osmotic pressure of pulmonary edema fluid.[2]
If the solution were removal of the patients’ already low intravascular volume and furosemide could be shown to have a rapid diuretic effect, furosemide would probably be useful.
Can these patients really wait more than an hour to breathe?
If furosemide could be shown to produce some sort of vasodilation, furosemide would probably be useful, even if the diuresis were not the method.
At another time, I will write about the way furosemide causes vasoconstriction – which is the opposite of the effect we are told furosemide produces.
For evaluating the efficacy of furosemide, this study has too many unknowns. The authors never intended to study the efficacy of furosemide, so that is not a problem of poor study design. Their study was designed to find out something else.
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Footnotes:
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[1] Blood volume prior to and following treatment of acute cardiogenic pulmonary edema.
Figueras J, Weil MH.
Circulation. 1978 Feb;57(2):349-55.
PMID: 618625 [PubMed – indexed for MEDLINE]
Free Full Text Download from Circulation in PDF format
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[2] Blood volume prior to and following treatment of acute cardiogenic pulmonary edema.
The same study as above.
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[3] Speculation on possible dosage combinations –
We do not know, and the mean of 71.4 mg, with an initial dose of 40 or 80 mg and 40 or 80 mg increments, leaves a lot of room for speculation.
I am putting some speculation down here, since it does take up a lot of room and may not be of interest to many people.
We do not know how many had an initial dose of 40 mg. If 20 of the patients received 40 mg and one patient received 80 mg, then the mean initial dose would be 41.9 mg.
If 20 of the patients received 40 mg and one patient received 80 mg, and every patient received one repeat of their initial dose (20 x 40 mg and 1 x 80 mg), then the mean total dose would be 83.8 mg. Most of the patients could have received repeat doses after an hour of no diuresis.
On the other hand, if one patient received 40 mg and 20 of the patients received 80 mg, then the mean initial dose would be 78.1 mg. Each initial 40 mg dose would make the total mean dose almost 2 mg higher.
What if 5/21 received 80 mg initially and no further doses; 11/21 received 40 mg and each received a second 40 mg dose; and 5/21 received only a 40 mg initial dose?
This would produce a total mean dose of 70.5 mg, which is close to the actual total mean dose of 71.4 mg.
Is that what happened? Did half of the patients receive repeat doses? As I stated, I am only speculating, but I could come up with a variety of dose combinations that would produce a similar total mean dose. The point is that this information is not helpful for evaluating the possible effect of the medication.
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[4] Kryptonite
Wikipedia
Variations
Article
More than I ever wanted to know about Kryptonite. There is a gold Kryptonite. There is even a yellow hoax Kryptonite. Could either of these be made of furosemide? 🙄
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Figueras J, & Weil MH (1978). Blood volume prior to and following treatment of acute cardiogenic pulmonary edema. Circulation, 57 (2), 349-55 PMID: 618625
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Edited 12-27-2018 to correct link to what I am responding to and because this does constitute a correction of a misreading of the original paper. I added the following to what I am responding to.
These appear to be ICU (Intensive Care Unit) patients. I had mistakenly assumed these were ED (Emergency Department) patients. This also weakens the conclusions I was drawing from the study. I had been misreading the Center for the Critically Ill as a fancy name for the ED (A&E in Commonwealth countries).
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Furosemide may cause a brief lowering of blood pressure, but overall it increases BP through augmentation of the renin-angiotensin-aldosterone system.
This is not a good thing in the hypertensive APE patient.
Of course, you probably get a pretty pronounced period of hypotension if you slam the Lasix in, but apparently that rate of administration is harmful on their ears.
You’re gonna love my From Classroom To Street article in EMS World Magazine next month. 😉
Gah frusemide is just modern blood letting to rid the patient of cardiogenic bad humours aka “fluid on the lungs”
The patient is not volume overloaded, the fluid is in the wrong place, up to a litre has come from the circulation and is now in the lungs, so giving bloody frusemide is only going to make him more hypovolaemic and pee out electrolytes
I once read a study about Paramedics in Los Angeles (unsure if it was LAFD or LACoFD, I think the latter) where they studied the ability of the Ambulance Officers to diagnose CHF; the most bizzare case I remember from said study was them giving frusemide for leg pain? Must be the bad humours right?
Correction to the above – it was low back pain not leg pain that was the ultimate diagnosis, see
Hoffman, J.R. and Reynolds, S. (1987) Comparison of nitroglycerin, morphine and furosemide in treatment of presumed pre-hospital pulmonary edema. Chest October 1987 92(4) 586-593; doi:10.1378/chest.92.4.586
I’m still unsure if the Paramedics concerned were from LAFD or LACoFD as it refers to “Los Angeles County” and presumably (as is the case now) LA County EMSA covers both the City and County Paramedics.
Two very interesting points from the study are (1) the Paramedics in question RESISTED a randomised control trial and (2) they were PROHIBITED from “diagnosing”. WTF?
NB I am no relation to the study author (I wish I was!)