Bryan Hayes has a great post on ALIEM on proper dosing of vancomycin.
We are very bad at this in the ED
Proper Vancomycin Dosing
- 15-20 mg/kg every 8-12 hours in patients with normal renal function 
- In seriously ill patients (eg, sepsis, meningitis, infective endocarditis) with suspected MRSA infection, a loading dose of 25-30 mg/kg may be considered 
- Actual body weight should be used
- IDSA recommends a max dose of 2 gm
- In adults, we round to the nearest 250 mg increment
See the post for more and all of the references
If you hadn’t already read John (Last Name Not Given), go immediately to this post and read it.
The comment was in response to the two podcasts on Dr. Paul Marik’s Fluids in Sepsis Talk
The Role of the Lymphatics
In the light of our ‘improved’ understanding of the capillary fluid dynamics of which lymphatics play a significant part (I know, I am sounding like a broken record when it comes to the role of lymphatics!), a few points need to be addressed…..
Optimal fluid resuscitation involves the maintenance of adequate microcirculatory flow coupled with prevention of development of interstitial edema. Edema develops when the capillary hydrostatic pressure increases, coupled with a reduction in removal of interstitial fluid. There is always a normal extravasation of fluid from the intracapillary space to the extracapillary (interstitial) space, otherwise the cells would starve. This extravasation happens along the entire length of the non-fenestrated, non-sinusoidal capillaries and not just at the arteriolar end, as previously thought ( Tom W’s fantastic article!!).
A normally functioning lymphatic system is crucial for returning this fluid back to the central circulation, otherwise edema would ensue.
Normal Lymphatic Function
Let us have a very brief outline of the normal lymphatic structure in this context. I find it useful to think about the arrangement as a kind of a bronchial tree in reverse ….
Initial lymphatics, rich in numbers and deeply embedded in tissue parenchyma, consist of pure endothelial channels without perivascular cells (e.g., pericytes) and smooth muscle cells. They have overlapping cell junctions forming primary valves in addition to traditional secondary lymph valves, and they rely on surrounding tissue motions to achieve periodic lymph channel expansion and compression for collection of interstitial fluid and fluid transport inside the lymphatics.
By contrast, the contractile lymphatics, (calcium dependant) are equipped with rows of bileaflet valves and contract by a specialized smooth muscle phenotype unique to the lymphatics to carry fluid from the initial lymphatics to the lymph nodes. Each pair of upstream and downstream valves in contractile lymphatics forms a lymphangion, facilitating unidirectional lymph fluid during periodic contraction. Contractile lymphatics have many of the vascular control mechanisms present in the arterioles, from classical myogenic contraction to neurogenic, purinergic, and endothelial-dependent and -independent controls.
The microenvironment surrounding collecting lymphatic vessels is a determinant of lymphatic function. Under physiological conditions, NO produced by eNOS in endothelial cells is required for periodic contraction and lymph flow; removing NO caused a reduction in contraction strength. Under inflammatory conditions, iNOS overproduces NO, overwhelms the subtle flow-dependent NO production from eNOS, and prevents contraction. At least in mouse models, higher levels of NO production stimulated by ACh evoked dilation, decreased tone, slowed contraction frequency and reduced fractional pump flow. The situation facilitates lymph edema, reduces antigen delivery into lymph nodes, and consequently, reduces antigen-presenting cells and T-cell activation. It is interesting to note that the effect of nitric oxide and therefore Nitroglycerin are completely different in normal circumstances and in inflammation!
Suppression of lymphatic function by CD11b-positive myeloid cells is a mechanism of self-protection from autoreactive responses during on-going inflammation. To initiate an immune response, antigen and antigen-presenting cells arrive in lymph nodes within hours on antigen encounter. Myeloid cells may accumulate at an inflammatory site and inhibit collecting lymphatic function, suppressing additional immune response to self-antigen by reducing antigen transport into the lymph node.
Some good references on this point are ..
- Liao S, et al. Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci USA. 2011;108:18784–18789.
- Schmid-Schönbein GW. The second valve system in lymphatics. Lymphat Res Biol. 2003;1:25–29.
- Lynch PM, Delano FA, Schmid-Schönbein GW. The primary valves in the initial lymphatics during inflammation. Lymphat Res Biol. 2007;5:3–10.
Now, on to the aspect of glycocalyx protection,
Injudicious fluid administration in resuscitation practices can cause edema to develop by a variety of mechanisms.
A rapid fluid bolus can cause significant shear stress on the delicate glycocalyx, disrupting it and breaking down the barriers to extravasation.
Colloids and hyperoncotic stuff can themselves cause dessication and compaction of the glycocalyx, by sucking up its water content.
Hypervolemia itself can cause atrial stretch, causing the release of ANP and BNP (evil twins of volume overload.) The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin–angiotensin–aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. They have a rather differential action on the lymphatics, interms of altering either the permeability or the contractility. Notably, ANP abolishes spontaneous contraction amplitude while BNP augments both parameters by ?2-fold . In aggregate, the consensus is that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion. The works of Joshua P. Scallan, Michael J. Davis and Virginia H. Huxley, in this regard are noteworthy.
One can see the possible pitfalls of using Nitroglycerine at a micro-circulatory level….
One, by causing vasodilatation, it can aggravate edema..(increased capillary hydrostatic pressure)
Two, by knocking off lymphatics, (through the NO synthase mechanisms) it might perpetuate interstitial fluid retention.
Hope this helps.
“Semi retired critical care doc”.
It does indeed help, but…!
Now, an alternative view is to go to the actual clinical data (albeit preliminary), for instance
Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002 Nov 2;360(9343):1395-6.
His letter of response to questions also has additional references for the mode of action that may be beneficial
These two fantastic review articles on microcirculatory resuscitation are must reads:
- Intensive Care Med 2002;28:1208
- Critical Care 2006;10:221
What do you think?
John (I think he wants to remain somewhat anonymous) is a clinically-retired, still actively teaching intensivist in India. He left the following comment on my Marik Response Post:
In the last 5 years or so, we have had a better understanding of capillary fluid dynamics, particularly in conjunction with an appreciation of the glycocalyx. We now know that the glycocalyx normally ‘traps’ about a litre and half of plasma water in it (due to its hydrophilic chemical composition!) and that normally in the capillaries, there is a central moving layer of plasma and a relatively immobile layer closer to the endothelium….the bit that is bound to the glycocalyx. This explains the differences in measured capillary and venous hematocrit values, and also why Crystalloid : Colloid equivalence is 1.3 : 1 rather than 4: 1 as previously thought.
We have also acquired a better understanding of the mechanisms of edema formation in critical illness and more importantly, the magical phenomenon of improved diuresis that we have all marvelled at, during the recovery phase.
In short, we have kinda debunked the original Starling theory of fluid dynamics in the capillary.
We now know that the colloid osmotic pressure in the intravascular space will only oppose the outward movement of water, and increasing the colloid osmotic pressure by synthetic colloids will not reverse the flow and draw fluid from the interstitial to the intravascular space. ( Multiple trials , starting with the SAFE trial have proved the futility of using synthetic colloids !) What they end up doing is, probably drawing water from the glycocalyx in the intravascular space itself and dehydrating and then disintegrating this vital layer. As a result you will find a transient improvement in blood pressures, but afterwards, a lot of this fluid will track into the extravascular space. Any hyperosmolar solution can do this including Soda Bicarb….we have all seen the very transient increase in blood pressure after bicarb which has always been incorrectly attributed to ‘reversal of acidosis’…bah!!
Extravasation of fluid from the capillaries is predominantly dependant on capillary hydrostatic pressure and not on decreased intravascular colloid osmotic pressure— because we have realised that interstitial and intravascular colloid osmotic pressures are very close to each other.
The way to prevent overloading and thus extravasation would be to minimise rapid increases in capillary hydrostatic pressure. How can we do that? – By small volume crystalloid boluses and early use of alpha1 agonists—the latter work by afferent arteriolar constriction and thus minimising huge increases in capillary hydrostaic pressures. This is where Marik’s argument takes a strong foothold.
Albumin is needed for the integrity of glycocalyx, — explaining why albumin is making a comeback into our fluid armamentarium.
The lymphatics have assumed a pivotal role in the normal mechanisms that prevent edema formation. We have realised that they are a very active conduit to return of interstitial fluid to the central circulation, and they they have contractile collecting ducts and passages that are calcium dependant. They are inhibited by the terrible twins ANP and BNP—therefore shutting down in active sepsis, where the twins tend to dominate. (This also partly explains the peripheral edema commonly seen with Ca channel blockers when they are used as antihypertensives). Once the sepsis resolves, ANP and BNP levels drop and the lymphatics recover their contractile elements. All the interstitial fluid can now be returned to the central circulation causing an improved diuresis.
In any case, fluids should only be used as any other drug should be— only if needed. We need to realise that fluid requirement and fluid responsiveness are two completely different things and focus on appropriate fluid balance rather than branding it as either restrictive or liberal.
What do you think? One question that I had is are we not doing the same thing with pressors if their true first action is to add to stressed venous volume?
Gosh, you must be just sick about this IVC Crap
We have discussed it a bunch here on the podcast:
Then I debated Stone at Castlefest 2013
Then the French Canadians did an incredible podcast on the Ultrasound Podcast.
These folks were even brave enough to integrate Guyton curves and still keep it interesting.
A Review Article in Critical Care
- Bodson and Vieillard-Baron Critical Care 2012, 16:181
Mayo Reveals New Evidence is Pending
My friend Paul Mayo dropped an enticing hint of things to come at a recent sepsis meeting. He told us that a French gent is about to release a study showing IVC ultrasound does indeed assess fluid status quite well. More to come…
SMACC Back from Justin Bowra
SMACC Back #2 was on Justin Bowra’s excellent SMACC 2013 lecture on the myth of the use of IVC for fluid assessment. If you haven’t heard Justin’s talk or the SMACC Back, none of the below will make sense so go listen to both of them.
Thanks very much to Scott for his enjoyable and even painful ‘SMACC back’. Consider me SMACCed!
But seriously folks… I’m not sure his arguments make that much difference overall.
Here’s a summary of the issues so far:
- Scott says we agree on 90% of the topic, so in that context our differences (outlined below) are probably not that important.
- All you can really say is that IVC is probably only useful at extremes (fat and full versus flat and collapsing). I don’t think there’s any point in trying to be more accurate using this tool… pending the result of better studies (Scott’s suggestion, which I agree with).
- Scott believes that IVC collapsibility index (IVCCI) is a great test of fluid responsiveness. [Editor: Never said this. Said it is a great test of fluid tolerance, maybe a decent test for fluid responsiveness based on the evidence we have so far] However, the studies he quotes (by Lanspa and Muller) suggest that IVCCI is promising at best.
- Two other studies he quoted (by Blehar & Miller) are actually of patients with heart failure, who were sitting up at 45 degrees. It’s not a great idea to use them as surrogate evidence to support a 15% IVCCI cutoff in supine patients (a different population).
- He wrapped up by mentioning LVOT VTI assessment of cardiac output as a gold standard. This is a complex issue, which is worth discussing in depth (see below).
Let’s look at the issues one by one:
Q. In the spontaneously breathing patient, is IVC useful as a marker of fluid status, fluid responsiveness & fluid tolerance? Are there any numbers we can use?
My original SMACC answer was that based on the available evidence, the best one can say is that IVC is probably only useful at extremes (fat and full versus flat and collapsing). The best numbers I could find were:
- Maximum IVC diameter (IVCD) <0.9cm = emptyish. IVCD >2cm maybe fullish.
- IVC collapsibility index (IVCCI) >40% = emptyish (72% of the time). IVCCI <15% = fullish.
- Serial IVC measurements seem useful.
Scott’s SMACC back went as follows (I’ll put his comments in italics):
‘A quick look at size and collapsibility gives huge amounts of information’
JB: I AGREE. As I noted in my talk, IVC assessment helps with the diagnosis of obstructive shock, and helps at the extremes. But that’s all.
Scott then noted that the receiver ROC curves in the Lanspa & Muller studies both had points on which the IVCCI didn’t miss any fluid responders.
JB: I DISAGREE. There are 2 studies here: one by Lanspa et al, and the other by Muller et al. Both looked at IVCCI as a marker of fluid responsiveness. Both used LVOT VTI [obtained in the A5C view] as a gold standard. Both found similar results.
Yet the authors reached completely opposite conclusions.
- Lanspa et al (14 patients) asserted a ‘good diagnostic accuracy’ for IVCCI, based on an area under the curve [AUC] of 0.83 (95% confidence interval, 0.58 – 1.00).
- Muller et al (40 patients) asserted the opposite, based on an AUC for IVCCI of 0.77 (95% CI 0.60 – 0.88)
- Scott says that AUC is the wrong thing to look at, and in fact each curve had a point (about 20-30% IVCCI) where no fluid responders were missed.
So who’s correct?
Well, it’s tricky. I’m not too experienced with ROC, so I asked my friendly hospital statistician and she replied ‘The confidence interval on the (Lanspa) study is too wide to be drawing definite conclusions.’
I’ve also been doing some reading of my own. See my analysis at the end of this document for the details if you’re into that sort of thing, but the summary is:
- It’s true that Lanspa’s AUC of 0.83 is pretty good.
- However, with only 14 patients, Lanspa’s results include a very wide 95% confidence interval (CI) of 0.58 – 1.00. This means that the test may have an AUC as low as 0.58- and there’s also a 5% chance that the true AUC may be even lower.
- Muller’s larger study (40 patients) achieved an AUC for IVCCI was 0.77 (95% CI 0.60, 0.88). Recognizing that the true AUC may have been as low as 0.60, the authors concluded that IVCCI ‘cannot reliably predict fluid responsiveness in spontaneously breathing patients with ACF.’
- Therefore the Lanspa and Muller studies suggest that IVCCI is promising at best, but needs larger studies to determine its accuracy. To quote Lanspa: It appears that either very large or very small values of VCCI may have some utility in predicting response to VE, although VCCI may have a wide range where it is clinically indeterminate in the spontaneously breathing patient.
So let’s get back to Scott’s SMACC Back.
Scott states that ‘IVCCI 15% had good accuracy (92% sens/84% spec) for CHF (Blehar et al. The American Journal of Emergency Medicine 2009;27(1):71)… and similar results in the 2012 Miller study.’
JB: I DISAGREE. Although it’s true that both these studies had good accuracy for the diagnosis of acute decompensated heart failure, it’s quite another thing to say that they can be applied to supine shocked patients. Both these studies measured IVCCI in breathless patients, to answer the Q ‘CCF or not?’ (Which certainly is not a bad surrogate for fluid tolerance.)
HOWEVER, Blehar 2009 measured with the patients up at 45 degrees. If lying flat, it’s likely they would have had a lower IVCCI, so the 15% cutoff in this study probably doesn’t apply to supine patients. Put simply, they are two different populations: lying down very probably makes the IVC ‘fill up’.
Same goes for Miller 2012: this study measured patients at 30 degrees. Using an IVCCI index of15% as a cutoff yielded a 37% sensitivity (ie you’ll only ID 37% of the Ps who are probably fluid intolerant, or in fact 22-55% when you look at the 95% CI) but 96% specificity (the ones you ID had better not get any fluid loading from you).
To me, this means that:
- 15% cutoff only works if sitting up- this figure likely lower in supine
- Even in those sitting up, Miller’s study suggests that this cutoff will incorrectly reassure you that a fluid challenge is ‘safe’ in 63% of patients in whom it’s likely to be dangerous.
Scott then said: ‘Go for gold: look for a 15% increase in SVi with a REAL cardiac output monitor or skilled evaluation of LV VTI.’
JB: LVOT VTI estimation by US can be bloody tricky. It’s worth digging into this issue, because LVOT VTI has been used as the gold standard in a number of the above studies, and is increasingly popular in critical care.
So… Just how valid is LVOT VTI (using TTE in spontaneously ventilated patients) as a marker of cardiac output?
Here’s my summary:
- LVOT VTI is fiddly, time consuming & inaccurate except in the hands of experts.
- There are also plenty of patients you can’t really use it on: eg those with AF, valvular disease or marked respiratory distress.
- It’s probably too inaccurate to use as a standalone measure of absolute cardiac output.
- But it is probably OK if you limit its use to what Scott describes: when you’re looking for a change in cardiac output after an intervention (e.g. a fluid bolus).
See below (A LOOK AT LVOT VTI) for details.
Final question: Just how accurate do I need to be when I measure the IVC?
This is important. Do I need to measure the IVC down to the nearest millimetre, or can I be 10-20% out?
My gut says that it’s OK to be 10-20% out because probably none of these measurements (not even LVOT VTI) are any better than that. This is one reason that I prefer a ‘Goldilocks Algorithm’ of ‘obviously full, obviously empty, or somewhere in between’.
BUT if we are talking about applying ‘hard’ numbers such as a cutoff of 15% IVC collapse for ‘wet versus dry’, then it becomes very important indeed. If I measure IVCCI as 10% but someone else measures it as 20% in the same patient, then we might draw very different conclusions about the same patient.
The problem is that until all the big studies are done, no-one knows the answer to this question. IVCCI might well be accurate enough to use hard numbers… but it might not.
In the spontaneously breathing patient:
Q.Is IVC useful? Undoubtedly. It helps with the diagnosis of obstructive shock and fluid status, taken as part of the overall clinical context.
- What IVC numbers predict ‘empty patient’?
- IVCD <0.9cm, probably.
- IVC collapsibility index >40%, probably.
Q. What IVC numbers predict ‘full patient’?
- First make sure you’ve excluded all the other stuff that causes a large IVC (obstructive shock, right heart disease). That leaves…
- IVCD >2cm probably = ‘full’ (Certainly 2.5cm predicts it in mechanically ventilated patients, and they have bigger IVCs overall.)
- IVC collapsibility index for ‘fullness’ is tricky.
- <35% is suggested by some, but as a predictor of high RA pressure (by Brennan) rather than ‘won’t tolerate fluids’
- Scott’s quoted studies of seated patients use 15% as a cutoff for ‘fullish’, which suggests that <10% = probably fullish if supine
- In other words, IVC is probably better at predicting ‘empty’ than ‘full’ (there are too many other conditions that lead to a big IVC)
- None of these numbers have been validated in good studies of supine patients. For example, some come from patients sitting up.
- Serial IVC measurements seem useful.
- Go for gold by all means… but for most of us (weekend warriors and part-time cardiac sonologists who certainly don’t use LVOT VTI every day), ‘gold’ is clinical assessment plus whatever tests you have to hand, including bedside US.
…But as they say, that’s just one man’s opinion. What do others think?
Cheers from Justin Bowra in Sunny Sydney
NOW FOR THE ANALYSIS OF THE ROC CURVES IN THE LANSPA & MULLER STUDIES
I had a big long think about these two studies and why they seemed to come up with opposing conclusions despite similar results. Using the references above and with sage advice from Jill the hospital statistician, here’s what I’ve come up with:
As Scott pointed out in his SMACC Back, it looks like there’s a spot on Lanspa’s curve where not a single fluid responder was missed. And it’s also true that Lanspa’s AUC of 0.83 is pretty good. Roughly speaking, looking at the AUC is a way of assessing how good a test is at predicting the outcome of a binary variable. A handy guideline is the following:
- AUC 0.5 = no better than a random guess (flipping a coin)
- 0.6– 0.7 = not great
- 0.7-0.8 = fair (still not that good)
- 0.8-0.9 = good
- >0.9 = excellent
- 1.00 = perfect
Therefore a result of 0.83 is not bad at all.
However, with only 14 patients (which is reflected in the shape of their ROC) Lanspa’s results include a very wide 95% confidence interval (CI) of 0.58 – 1.00. This means that the test may not be that good at all- in fact it may be have an AUC as low as 0.58- and there’s also a 5% chance that the true AUC may be even lower. It also means that the numbers simply aren’t high enough to draw any firm conclusions. Lanspa didn’t miss any fluid responders at a 20-30% IVCCI cutoff… but that might’ve been just a chance finding after all.
Muller’s study was larger, with 40 patients, reflected in its narrower CI and smoother ROC. Their AUC for IVCCI was 0.77 (95% CI 0.60, 0.88). Recognizing that 0.77 is fair rather than great, and that there’s a 95% chance the true AUC was as low as 0.60, the authors concluded that IVCCI ‘cannot reliably predict fluid responsiveness in spontaneously breathing patients with ACF.’
Similarly, Muller’s ROC curve missed a couple more fluid responders than Lanspa at the 20-30% IVCCI cutoff, and this might be because IVCCI just isn’t as good as we’d like it to be, and the higher numbers in this study made this more apparent.
So how many numbers do we need before we can say with confidence that an IVCCI cutoff of 20-30% will pick up all the fluid responders? Well, I don’t know. But we probably need more than the numbers in these two studies.
I’ve also come across a couple of sites that question the utility of ROC analysis, but that level of analysis is beyond me.
Therefore the Lanspa and Muller studies suggest that IVCCI is promising at best, but needs larger studies to determine its accuracy. To quote Lanspa: It appears that either very large or very small values of VCCI may have some utility in predicting response to VE, although VCCI may have a wide range where it is clinically indeterminate in the spontaneously breathing patient.
…but we knew that already.
NOW A LOOK AT LVOT VTI:
- My 1st point here is a mea culpa: I’m no expert. I’ve done a search (helped greatly by ace cardiac sonographer Sharon Kay) and I’ve picked the brains of Drs Chris Choong, Jason Sharp and Greg Nelson (cardiologists at my hospitals who perform LVOT VTI regularly) and Dr Adrian Goudie FACEM DDU (who certainly does more cardiac US, and at a higher level, than yours truly).
- But I may have missed something important. So please let me know if that’s the case.
- LVOT VTI is used as a noninvasive surrogate marker for cardiac output. It looks like a great idea: using a view such as the PLAX, measure the LVOT diameter at the AV annulus immediately proximal to valve leaflets (the best site seems to differ among the studies and guidelines). Use this diameter to derive the cross-sectional area at that spot (this assumes the annulus is round). Then using A5C view, measure the flow through that same spot. Derive the velocity time integral (VTI) and multiply by the cross-sectional area and you’ll get the stroke volume (SV) (i.e. how far that column of blood travelled through that LVOT). Multiply the SV by the heart rate and you’ll get the cardiac output. Nice.
- There are potential problems with this technique, however. To summarise what I’ve found from the literature:
- The first problem is that the technique may not be reliable enough as a standalone measure of cardiac output. Coats’ review suggests that this technique ‘has a 95% chance of lying within ± 28% or or 1 -41 min~’ of the standard.’ Note that this is not the same thing as simply looking for a change in CO- see below.
- The next problem is the exclusions: arrhythmia eg AF, aortic valve disease or prosthetic aortic valve. Huntsman et al estimated that Doppler estimation of CO could be performed in only 85% of patients in their study. Coats also listed COPD patients as difficult.
- It’s fiddly and time-consuming in practice: in PLAX, Lewis et al averaged AV diameter measured across 5-10 cardiac cycles; in A5C, Lewis averaged VTI across average of 5-10 cycles. Bouchard averaged across 3 cycles in NSR patients, and across 10 cycles if ‘rhythm or haemodynamic disturbance’. Sharon Kay tells me you need to average across at least 3 beats.
- Inter-observer variability can be a issue:
- i. In Lewis et al’s study, this wasn’t so bad: only 6.8% +5%
- ii. In Bouchard’s study, slightly worse: 9-11%
- Patient position: patient needs to be in left lateral position- Lewis- or in ‘steep left lateral’- Bouchard. But also the patient position should remain constant, to make it easier to obtain the same angle of probe position / insonation. This isn’t so hard in ventilated patients in ICU, but a good deal harder in the critically ill patient who’s spontaneously breathing.
- Patient respiratory variation can also be an issue: eg a large respiratory effort (such as in our unstable patients pre ventilation) can also alter beat-to-beat measurements, both real (by altering the actual stroke volume) and by altering angles. (Thanks to Adrian Goudie for pointing this out.)
- However, there are advantages as well:
- Repeating the same measurement, at the same site, in the same patient (who’s in the same position) from the same window should eliminate variables due to measurement of LVOT area and hopefully angle of insonation
- If the same operator performs pre- and post-scans, this should also eliminate inter-observer variability.
- If the two measurements are performed just before and after an intervention such as a fluid bolus, then this should also improve accuracy.
- Coats’ review article states that LVOT VTI assessment from the A5C window ‘probably’ has a 90% chance of picking up a 7% difference in CO… therefore it should be even more likely to pick up a 15% change.
- Here are the validation studies I’ve been able to find:
- Coats AJ. (1990) According to this review article, Doppler methods of cardiac output estimation show accuracies varying from 10 to 22%. The A5C estimation of LVOT VTI is the best, but even that ‘has a 95% chance of lying within ± 28% or or 1 -41 min~’ of the standard.’
- Huntsman (1983): used CW Doppler at the suprasternal notch compared to thermodilution, rather than A5C. So it may not be relevant, unless plenty of people are using suprasternal window instead of A5C.
- Ihlen H (1984): This study showed very good correlation between Doppler VTI estimation of CO and invasive estimation of CO. However, it looks like they obtained Doppler measurements from suprasternal window, not apical. So I’m not sure if this study applies to the technique of using the A5C window.
- Lewis et al (1984): a great study: the gold standard was thermodilution performed within minutes of the TTE. Good result with interobserver variability only 6.8% +5%
- Bouchard (1987): another good result using thermodilution. However, used CW Doppler, not PW Doppler. Also, used 3 different locations including suprasternal notch. And in 28 of the 43 patients, the gold standard was performed within 24h.
- There are plenty of papers on the USCOM device, but I don’t think this is being used much so I didn’t include them.
- From my reading, it looks like LVOT VTI is fiddly, time consuming & requires skills beyond the reach of non-experts. It doesn’t look like it has the accuracy to measure absolute cardiac output.
- But that’s quite a different question from asking if it can be used to measure a 15% change in cardiac output. If the same operator performs the measurement at the same site and angle in the same patient who’s lying in the same position, and if that operator is an expert and not just a weekend warrior, then yes.
NOW FOR THE REFERENCES (a couple of others weren’t listed here but appear at the end of my SMACC talk)
- Lanspa MJ, Grissom CK et al. Applying dynamic parameters to predict hemodynamic response to volume expansion in spontaneously breathing patients with septic shock. Shock 2013. 39(2). pp. 155-160
- Muller L et al. Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use. Critical Care 2012, 16:R188
- Blehar DJ, Dickman E, Gaspari R. Identification of congestive heart failure via respiratory variation of inferior vena cava. Am J Em Med 2009;27:71–5.
- Miller et al. Inferior vena cava assessment in the bedside diagnosis of acute heart failure. Am J Emerg Med 2012;30:778-83
- Coats AJ. Doppler ultrasonic measurement of cardiac output: reproducibility and validation. Eur Heart J (1990) 11 (suppl I): 49-61
- Huntsman LL, Stewart DK, Barnes SR, Franklin SB, Colocousis JS, Hessel EA. Noninvasive Doppler determination of cardiac output in man: clinical validation. Circulation 1983;67:593-602.
- Ihlen H et al. Determination of cardiac output by Doppler echocardiography. Br Heart J 1984; 51: 54-60
- Lewis JF, Kuo LC, Nelson JG, Limacher MC, Quiñones MA. Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window. Circulation 1984;70:425-31.
- Bouchard A et al. Measurement of left ventricular stroke volume using continuous wave Doppler echocardiography of the ascending aorta and M-mode echocardiography of the aortic valve. JACC 1987;9:75-83
Cliff Reid at Resus.me has a great post on the failure of the intra-aortic balloon pump to show benefit for empirical operations and for cardiogenic shock getting immediate intervention:
- Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial The Lancet, Volume 382, Issue 9905, Pages 1638 – 1645 ? Abstract
- A Randomized Controlled Trial of Preoperative Intra-Aortic Balloon Pump in Coronary Patients With Poor Left Ventricular Function Undergoing Coronary Artery Bypass Surgery Crit Care Med. 2013 Nov;41(11):2476-83 ? Abstract
- Is the intra-aortic balloon pump leaking? Lancet 2013;382:1616-7
photo credit: urbancitylife
I have previously blogged about a study demonstrating that there are ED patients being intubated and then not sedated or pain-controlled.
So it was no surprise to see a new study showing the same thing:
Watt et al. Effect of paralytic type on time to post-intubation sedative use in the emergency department (Emerg Med J 2013;30:893-895)
If the patient received sux, they got their sedatives started at the 15 minute mark (still sucks), but if they got rocuronium (they won’t be flailing about and alarming the vent) it took a mean of 27 minutes.
We can do better.
I had Paul Marik on the show a while back to discuss his Seven Mares debunking of CVP for predicting fluid responsiveness. He just published an updated meta-analysis adding further nails in CVP’s coffin. Too bad the Surviving Sepsis Campaign doesn’t read his stuff.
Does the Central Venous Pressure Predict Fluid Responsiveness? An Updated Meta-Analysis and a Plea for Some Common Sense*
Paul E. Marik, MD, FCCM; Rodrigo Cavallazzi, MD
(Crit Care Med 2013; 41:1774–1781)
Background: Despite a previous meta-analysis that concluded that central venous pressure should not be used to make clinical decisions regarding fluid management, central venous pressure continues to be recommended for this purpose. Aim: To perform an updated meta-analysis incorporating recent studies that investigated indices predictive of fluid responsiveness. A priori subgroup analysis was planned according to the location where the study was performed (ICU or operating room). Data Sources: MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. Study Selection: Clinical trials that reported the correlation coefficient or area under the receiver operating characteristic curve (AUC) between the central venous pressure and change in cardiac performance following an intervention that altered cardiac preload. From 191 articles screened, 43 studies met our inclusion criteria and were included for data extraction. The studies included human adult subjects, and included healthy controls (n = 1) and ICU (n = 22) and operating room (n = 20) patients. Data Extraction: Data were abstracted on study characteristics, patient population, baseline central venous pressure, the correlation coefficient, and/or the AUC between central venous pressure and change in stroke volume index/cardiac index and the percentage of fluid responders. Meta-analytic techniques were used to summarize the data. Data Synthesis: Overall 57% ± 13% of patients were fluid responders. The summary AUC was 0.56 (95% CI, 0.54–0.58) with no heterogenicity between studies. The summary AUC was 0.56 (95% CI, 0.52–0.60) for those studies done in the ICU and 0.56 (95% CI, 0.54–0.58) for those done in the operating room. The summary correlation coefficient between the baseline central venous pressure and change in stroke volume index/cardiac index was 0.18 (95% CI, 0.1–0.25), being 0.28 (95% CI, 0.16–0.40) in the ICU patients, and 0.11 (95% CI, 0.02–0.21) in the operating room patients. Conclusions: There are no data to support the widespread practice of using central venous pressure to guide fluid therapy. This approach to fluid resuscitation should be abandoned.
A listener, Brian Katan, wrote to suggest adding ondansetron to the awake intubation procedure. Now this is interesting, because I don’t want the patient to vomit from ramming things into the back of her throat, but the mechanism is not nausea–it is the gag reflex. So, the question is: does ondansetron affect the gag reflex? Turns out it does…
Evaluation of the efficacy of oral ondansetron on gag reflex in soft palate and palatine tonsil areas
So now, ondansetron 4 mg IVP has been added to the airway checklist. Thanks Brian!
My friend Chris Bond runs a blog called SOCMOB (see below for an explanation).
Like all Canadians, Chris likes to have a nice meal, drink a glass of wine, and then go to the parking lot, break a beer bottle and stab people with it. In Canada, they call this bottling. When not bottling, Chris posts on emergency medicine topics; he put together a video on how to build a cheap and dirty cric trainer. Take a look…
Here is the original SOBMOB post.
The trainer is based on this article: (Anaesthesia 2004; 59:1012–15).
A recent letter to the editor takes the model even further: (Anaesthesia, 2009, 64, pages 687–697).
Seth Trueger turned me on to this other, superior (though more complicated) version of the surgical cricothyrotomy training device:
It is from:
St. George Hospital; Sydney, Australia
SOCMOB Chris is also the creator of the, “Diagnosis Wenckebach” video:
What is SOCMOB?
SOCMOB = Standing on the corner, minding my own business. For any of you who work in emergency departments, you’ve likely heard this history before. Most likely the presenting complaint was trauma