Or “Ser’s” as they say in Austria.
My name is Kathleen, or Kass Thomas
And my name is Thomas Hamp
And together we are Team Thomas
T: So today we have one purpose, and one purpose only – to bust, or at least disucss, 5 common myths that are heard escaping from the lips of many an ICU registrar, including both of us in fact.
K: You see, Thomas is the St George/St Vincents Austrian echo fellow extraordinaire – you know, one of those high achievers who is not only becoming and echo guru, but is also an intensivist and an anesthetists. So imagine my shock when I heard a myth come out of his mouth; a myth that many of my fellow registrars had also agreed with; a myth that continues to permeate medical schools across the world.
And so after Kass proved me wrong, I then asked her a question about PEEP, and she recited another, commonly held myth.
So, after much discussion, we thought we would get together and discuss these myths in more detail and try to get to the bottom of them.
And I have to say, it was much more difficult than I expected. None of this is really all that straight forward. But we will try our best bust the myths, or, if nothing else, to inspire some discussion.
Ok, shall we get started?
Myth # 1: oxygen induced hypercarpia
Thomas: Hey Dr Kass, I have just brought a patient up from the a ward with COPD exacerbation. I had to put him onto BIPAP because his pCO2 went up to 110.
Kass: Right. So what caused his pCO2 suddenly to rise?
Thomas: Oh, it’s because he is a CO2 retainer and was put on oxygen on the ward.
Kass: How did the oxygen cause his pCO2 to rise?
Thomas: Don’t you remember from medical school? It because he is CO2 retainer and therefore his respiratory drive is based on his hypoxia. Therefore when the ward gave him oxygen it knocked off his hypoxic respiratory drive so he hypoventilated and caused his pCO2 to rise. Right?
Kass: and here en-lies our first myth: Giving O2 to a CO2 retaining COPD patient, knocks off their hypoxic respiratory drive leading to CO2 retention.
A myth? Really? Prove it to me.
Well lets go on a little journey back in time to how this myth started and what has arisen since.
So sometime between 1940 and 1960, this theory of loss of hypoxic respiratory drive was first published. The simplicity of this explanation was attractive and permeated into medical education. I know that I got taught this theory in medical school (I know you got taught this because I called you out on it one day… right?) and many people who review this topic open their discussion with a very similar clinical vignette.
1980 was the first time this theory was challenged Aubier and his collegueas. Aubier et al did a prospective study looking at minute ventilation and pCO2 in patients with acute exacerbation of COPD vs control while breathing room air, then breathing 100% O2. ****They found that there was an initital drop in minute ventilation which correlated to an initial rise in pCO2. However, the minute ventilation then recovered almost to baseline within 15 minutes on O2 therapy. Despite the recovery of minute ventilation, the pCO2 continued to rise. I am not exactly sure how they measured this, but they concluded that the rise in pCO2 was out of proportion to the decrease in minute ventilation and therefore there must be another, or an additional mechanism to explain this rise in pCO2.
A further study by Aubier and co looked at the respiratory drive by measuring mouth occlusion pressure in the first 100ms (P0.1) in both chronic and acute COPD exacerbations compared to controls. They found that when giving O2, there was (1) a marginal decrease in minute ventilation, and (2) reduced mouth occlusion pressure, however this was still 3 times that of control patient, suggesting a high respiratory drive. They demonstrated that the observed increase in pCO2 again did not correlate to the decrease in minute ventilation, and that there was makedkly increased respiratory drive in patient during an exacerbation of COPD even with O2 therapy. ***They concluded that a reduction in respiratory drive is not a major contributor to oxygen induced hypercapnia in these patients.
So why did they think pCO2 was rising?
So a few theories were put on the table which have lead to the ongoing research in this area. There are 2 major theories:
- Loss of hypoxic vasoconstriction causing areas of increased shunt and increased alveolar dead space
- The Haldane effect
Oh wow, I am having flashbacks to the primary exam. Can you take me through these two theories.
****Hypoxic pulmonary vasoconstriction is the physiological compensatory mechanism which aims to optomise the balance between perfusion and ventilation with the lung units. So when an alveoli is underventilated and hence hypoxic, the low pO2 induces vasoconstriction, minimises the blood flow to that alveoli so that you don’t have alveoli which are underventilated and overperfused. In patients with COPD, it is thought that the this mechanism is extremely important in optimisating V/Q in their severely diseased lungs.
So the theory is that when you give high O2 to COPD patients, the pO2 in those lung units which are poorly ventilated will rise, cause the vasodilation of the surrounding capillary bed and hence increase the blood flow to those units. This will cause areas of the lung which are poorly ventilated to have increased perfusion (and hence increasing shunt). But in doing this, it also means that blood is pulled away from the alveoli with better ventilation and hence it increases the alveolar dead space.
While increasing shunt does not have a major effect on CO2 removal, increasing alveolar dead space does reduce CO2 removal and hence will increase PCO2.
The Haldane effect states that deoxygenated Hb binds to and therefore carries CO2 with more affinity then oxygenated Hb. O2 therapy increases pO2, hence reducing the amount of deoxygenated Hb and hence carriage of CO2, therefore shifting the CO2 dissociation curve to the right and increased the pCO2.
So is there any evidence for these two theories?
So Aubier et al proposed that 25% of the PCO2 rise they saw in their patients was caused by the Haldane effect.
****In 1996, Hanson et al. used a computer model which simulated gas exchange and pulmonary hemodynamics in multiple lung units to see if the theory of V/Q mismatch was plausible. Using the data extracted from Aubier’s work, they found that changes in alveolar deadspace in combination with the Haldane effect are sufficient to account for the hypercapnia developed by patients with acute exacerbations of COPD when treated with supplemental oxygen.
****In 2000, Robinson et used a multiple inert gas elimination technique in combination with CO monitoring to study more closely the theory of loss of hypoxic vasoconstriction causing CO2 retention. Specifically they wanted to compare CO2 retainers and non retainers which had not been compared in the past. They studied 22 patients hospitalised with acute exacerbation of COPD. In the retainer group, they found that minute ventilation fell by about 20% (similar to what was found by Aubier). But, they did not find any change in minute ventilation in the non retainer group. They did see a change in the V/Q matching secondary to loss of hypoxic vasoconstriction, however the change was noted in both the retainers and the non retainers. The distribution of the change, however was different, and in the retainer group, they found a 24% increase in the area of the lung with higher V/Q ratio (ie increased alveolar dead space). Interestingly, despite the observed increase in alveolar dead space in the retainer group, Robinson et al concluded that it was the reduction in ventilation was responsible for CO2 retention. They then proposed that the increased alveolar dead space was not causative, but instead a response to a rising pCO2, perhaps related to bronchodilation.
The most recent study I could find was published in 2015 by Rialp et al and looked at the role of respiratory drive in hyperoxia in 14 ready-to-wean patients on PSV ventilators recovering from COPD exacerbation.
They found a small but statistically INSIGNIFICANT decrease in minute ventilation which did not correlate to the rise in pCO2. Importantly, the central drive remained (measured again by mouth occlusion pressure or P0.1) unaltered with hyperoxia. They concluded that a damped respiratory drive or a reduction in minute ventilation does not seem to be the major mechanism responsible for hyperoxia-induced hypercapnia and suggested instead that it depends more on increased dead space, worsening ventilation-perfusion distribution, or the Haldane effect.
So from what you are telling me; you wanted to bust that myth that the rise in CO2 is caused by loss of hypoxic drive. But to be honest, all these studies about the V/Q mismatch have significant limitations. I mean non of them has more than 30 patients included!
Yes but there really aren’t any studies that prove the theory of hypoxic respiratory drive.
So what do we conclude? Busted or not?
To me it’s busted. I think what is clear, is that the theory of loss of hypoxic respiratory drive is certainly an oversimplification and while there may be a component of decreased minute ventilation, or blunted central respiratory control, it is certainly not adequate to explain completely the rise in CO2. The most likely contributing factors include an increase in alveolar dead space likely secondary to loss of hypoxic vasoconstriction and subsequent V/Q mismatch, in combination with the Haldane effect.
Myth #2: PEEP
Imagine we are doing the morning handover and after the first three patients Kass starts questioning my ventilator settings.
Kass: Thomas, I saw that you ventilate all of our patients differently. There is this young guy with asthma….you put him on 0 PEEP. Than there is this big lady with peritonitis and ARDS that you put on 20 PEEP. And then there is this other patient with pneumonia and you put her on a PEEP of 8. Don´t we usually ventilate our intubated patients with a PEEP of 5?
You see Kass, the thing about PEEP is that it is more complex. Let´s talk about PEEP a bit more in detail. So why do you think we apply PEEP to intubated patients?
Kass: Oh I heard several reasons for that.
1st we need PEEP because this overcomes the resistance of the tube and therefore reduces the work of breathing.
2nd we lose our physiologic PEEP once intubated.
And 3rd usually we breath with negative pressures and positive pressure ventilation causes alveolar collapse.
Thomas: You know what Kass, I think all these explanations are myths… so let me bust them.
Lets start with the first myth: PEEP helps to overcome the resistance of the endotracheal tube.
This could easily be busted with one sentence only but for you I will explain it slowly.
What is the definition of resistance?
Kass: Resistance is pressure difference divided by flow. Or in other words, resistance is the pressure needed to force a certain volume in a certain time through a tube.
Thomas: Absolutely correct.
So in order to have resistance you need flow, right?
Or in other words, if there is no flow, there is no resistance…
Kass: that´s right. So what?
Thomas: So what is the definition of PEEP?
Kass: PEEP is defined as positive end expiratory pressure.
Thomas: Absolutely correct. So the end of expiration is when all the air has come out of the lung and flow ceases before inspiration starts. And we measure the PEEP when there is no flow right?
Kass: Yes. Ok ok I can see where this leads to. No flow means no resistance and PEEP is defined at the pressure at end of expiration where there is no flow, therefore it has nothing to do with resistance.
Thomas: Yes! You see, myth busted!
Kass: So why do we say PEEP reduces the work of breathing then?
Thomas: well the application of PEEP can reduce the work of breathing in many ways. If PEEP recruits alveoli, the compliance of the lung improves and work of breathing is reduced due to the improved compliance. And if the patient has significant intrinsic PEEP – which is a positive pressure in the alveoli and the end of expiration caused by small airway obstruction – the application of PEEP reduces the work of breathing.
Kass: So how does that work?
Thomas: If you breath spontaneously without being connected to some ventilator and you have intrinsic PEEP, you have to lower your transpulmonary pressure until the pressure in the alveoli drops below 0 in order to create airflow into your lungs. But if you apply external PEEP you have to lower the transpulmonary pressure only below the external PEEP in order to create airflow into your lungs.
Kass: Aaaaaaahhhh right. And is this the same reason why COPD patients do this weird things with their lips?
Thomas: This is not exactly the same but this maneuver also reduces their work of breathing. So what they do is, they limit the flow during expiration. This somehow reduces the hyperinflation of the chest and therefore reduces the intrinsic PEEP, which in turn reduces the amount of pressure drop they have to create to start airflow into the lungs. There are several theories out there how this works. Some say the small airways are splinted, some say it is because the slow flow is more laminar. I never really understood how it works. But anyway, because they are not connected to a device that applies PEEP, the pressure in the alveoli still has to drop below 0. You see the application of PEEP with a device works different to how the so called auto PEEP created by their lips works.
Kass: Alright, accepted. Now what about the physiologic PEEP?
Thomas: What the fuck is physiologic PEEP?
Kass: Isn’t it that thing where the vocal cords close at the end of expiration and stop airflow out of the lungs so that there is still PEEP left? And if we put a tube through the vocal chords they can’t close anymore? And therefore you lose that physiological PEEP.
Thomas: Yes I know this is what people say, but it never made sense though. Alright, let me bust that myth of a physiologic PEEP!
First, why do we think there is a physiologic PEEP at all? I think this comes from the fact that if we intubate patients, we can see that, alveoli collapse after the intubation and we also know that we can counteract this to some degree with the application of PEEP.
And we all have seen the clips of the mouse lung that is completely collapsed initially and perfectly inflated after PEEP is applied. But keep in mind there was no chest wall of that mouse left. It was only her lung left.
Given this observations, it seems reasonable for us to conclude: under physiologic conditions alveoli are open. After intubation we see collapse of alveoli. PEEP keeps these alveoli open. So thee must be some physiologic PEEP. Right?
Kass: yes, sounds good. But?
Thomas: But let´s get back to the very basics…. So how does air get into our alveoli?
Kass: Ok very basically spoken….Our inspiratory muscles contract and this leads to expansion of the chest.
This chest expansion causes an expansion of the lungs because it is adherent to the chest wall. And this expansion of the lungs sucks air from outside through the nose, pharynx, larynx, trachea, and bronchi into the alveoli.
Thomas: Great I can see you clearly studied medicine, or at least you have been awake at school.
So when does air flow cease?
Kass: Airflow ceases when the pressure in the alveoli is equal to the ambient pressure.
Thomas: Right. So what is the pressure in the alveoli at the end of expiration now?
Kass: Well if the pressure in the alveoli and ambient air is equal, the pressure is 0.
Thomas: So the end expiratory pressure within the alveoli at the end of expiration is 0. Where is the physiologic PEEP now?
Kass: but don´t the vocal chords close at the end of expiration?
Thomas: No. If you have ever seen a nasendoscopy, you know that the vocal chords during normal breathing are open all the time.
You see the myth of a physiologic PEEP is clearly BUSTED!
But why do alveoli collapse after intubation?
Ummmmmmm……. Yeah tell me the answer
Alveoli collapse because we lose our physiologic functional residual capacity.
Why does FRC decrease?
Well this is because we sedate plus minus paralyse patients for the intubation.
If I would intubate you while you are completely awake, your FRC would not drop.
But because we put patients in a bed and anaesthetise them, the FRC gets smaller.
Putting you into bed would reduce your FRC by roughly 25%.
In addition, sedation causes loss of muscle tone, the diaphragm comes up, the intercostal muscles relax and the actual chest volume decreases until there is again an equilibrium between the retracting forces of the lung and the expanding forces of the chest wall.
And this reduction in FRC decreases the size of alveoli because the lung is made of alveoli.
This decrease in size leads – according to La place´s law – to an increase in surface tension. And this increase in surface tension leads to the collapse of the alveoli.
And all of this happens in “normal” lungs and in “sick” lungs which are oedematous, their compliance is reduced and where surfactant is reduced, this effect is certainly pronounced.
So by the application of PEEP, we just keep additional volume in the lungs during expiration which increase the FRC again, which then increases the size of the alveoli, reduces surface tension and keeps the alveoli open.
Ok wrap it up for me Thomas
Ok, after intubation, because we put patients into a bed, we sedate and paralyse them, their FRC decreases. This causes an increase in surface tension which leads to alveolar collapse.
We try to counteract these mechanisms by increasing the FRC which can only be achieved by keeping air in the lungs. And we do this with the application of PEEP which works like a force against the recoil forces of the relaxed chest wall.
Kass: Ok I think I got it. So we usually apply a PEEP of 5 to our ventilated patients because this keeps the alveoli open because we counteract the loss of muscle tone. Why 5? And not 10? Or 20?
Thomas: Well this is actually a very very good question….. What is the optimal PEEP level?
And answering this is almost impossible. There are so many factors we have to consider. But I guess 5 probably does not fit everyone.
I mean people are different. For example, it makes a difference if we ventilate a 45 kg patient or a 145kg patient.
And it already has been shown that increasing BMI causes an exponential drop in FRC in anaesthetised patients. Just because the chest is heavier and the diaphragm gets pushed up by the big tummy.
But not only body habitus plays a role.
If we look at different lung pathologies, the effect of PEEP on FRC, compliance and oxygenation is quite variable.
Bikker et colleagues compared FRC in three different groups of patients. And they also looked at the effect of different PEEP settings on FRC, compliance and oxygenation in these groups.
One group were patients intubated for neurologic problems, with otherwise normal lungs, the second group were patients with ARDS due to pneumonia and the third group were patients with ARDS caused by abdominal sepsis.
And compared to the predicted FRC of a healthy, non ventilated person, the actual sedated and ventilated patients of all groups had a reduced FRC at a PEEP of 5. And this was not only due to putting them into bed.
They then also applied different levels of PEEP – 5, 10 and 15 and looked at the effect. In all groups, the amount of PEEP was correlated with the FRC, meaning that the higher the PEEP, the higher the FRC.
BUT – and this is what makes it really interesting- higher PEEP only increased compliance in patients with ARDS of extrapulmonary origin meaning only in patients with ARDS due to abdominal sepsis.
In patients with healthy lungs and in patients with ARDS of pulmonary origin a higher PEEP despite leading to a higher FRC did not increase compliance.
Why was that?
Well it seems that in healthy lungs, high PEEP does not recruit alveoli, it only distends already open alveoli. And the consolidation in the patients with pneumonia could not be recruited either but the other parts of the lung were over distended.
For me it seems that higher PEEP levels only work if you have a generally wet and sick lung, as these patients with extrapulmonary ARDS do have.
Kass: So does that mean we should ventilate patients with extrapulmonary ARDS with higher PEEP and other patients with lower PEEP?
Thomas: No. I think what this study showed is, that PEEP has different effects on different lung features in different patients.
The problem is that we often mix all kinds of respiratory failure together and do not consider that these are different diseases and the lungs respond differently to our therapeutic actions.
But even if we would consider all these variables, we still would not know what parameter we should actually chase with our PEEP settings.
Is the best PEEP the one that leads to the highest paO2?
Is the best PEEP the one that provides the highest FRC?
Or is the best PEEP the one that leads to the best compliance or the lowest driving pressure?
Maybe it´s we shouldn´t chase any of these parameters. Maybe we should be guided by some -yet unknown- biomarker that represents stress to the lungs caused by ventilation like shear stress, atelectotrauma etc.
Ok. To end this otherwise never ending discussion, I would say:
one size doesn´t fit all. And what size we should actually choose in what setting is not quite clear.
Yes, so I would say the myth that a PEEP of 5 is best for all of our patients is definitely BUSTED, but unfortunately I can´t answer the question what the optimal PEEP for a specific patient really is.
Kass: Alright, busted, lets move on to the next myth.
Myth #3: Autoanticoagulation in liver failure
(on a ward round)
Thomas: So this is Jack Daniels, a 50 year man who was found unconscious secondary to hepatic encephalopathy from decompensated liver disease.
Kass: Should we start some DVT prophylaxis?
Thomas: Well, his INR is 2.5 and his platelets are 100. So he is already “auto anticoagulated.” He doesn’t need VTE thromboprophylaxis. Right?
And this brings us to our third myth. Patients with liver disease who have an increased INR are “auto-anticoagulated” protecting them against venous thromboembolism and therefore we don’t need to give them any VTE prophylaxis.
Please enlighten me
Ok so a quick review of the liver’s role in coagulation. ****So yes, the liver does produce many pro-coagulation factors – 2, 7, 9, 10. Importantly, it also produces some important anti-coagulation factors – protein C, protein S and antithrombin. It also plays an important role in platelet production by release of thrombopoeitin. According to Schaden et al,
Actually it’s Schaden – she’s from my hospital in Vienna.
an additional anti-coagulation product produced by the liver is ADAMTS13 which is a vWBF cleaving enzyme.
****We know that coagulation is all the balance between the pro and the anticoagulation factors. Liver failure results in deficiencies in all of the factors that I just mentioned. In addition, Schaden et al also note a relative increase in some pro-coagulant liver independent factors such as vWBF. The clinical result is therefore dependent on the derangement of the delicate balance between these factors, making it possible to both bleed and to clot or to do both at the same time.
Ok so I accept that liver disease causes a decrease in both pro and anti-coagulant factors. But why then do they have an elevated INR? Doesn’t this suggest that the balance is tipped in favour of bleeding?
Good question. ****So INR only measures pro-coagulant factors. It doesn’t measure the anti-coagulant factors and hence doesn’t reflect the balance of the two and therefore is not necessarily an accurate measurement of the overall invivo haemostasis.
What about other coagulation tests – like thromboelastography or TEG or ROTEM – do they reflect haemostasis more accurately in liver failure?
So there has been a study by ****Stravitz et all which used TEG to assess 51 patients with liver failure assumed to be “autoanticoagulated” based on their INR, which ranged between 1.9-9.6 with a mean INR of 3.4. Despite the deranged INR, they found the majority of their subjects had normal haemostasis parameters
Ok so maybe INR does not reflect a bleeding tendency in liver failure, but is there any evidence that these patients are NOT protected against venous thromboembolism – as in do they actually get DVTs/PE?
Yes there is some evidence. While there are no prospective RCTs, there are quite a few large observational and case control studies. ***There are two recently published systematic reviews, One by Ha and Regal from this year and one by Aggarwal et al in 2014 which pool all these studies. ****While the incidence of VTE in these studies varies, they are all suggestive that cirrhotic patients have a significant VTE risk compared to the both the general population and a similar risk compared to other medical patients. Infact there is even some research to suggest that chirrotic patients may even be at higher risk of VTE than non cirrhotic patients. In some studies that compared the risk of VTE with increasing liver disease severity, they found that there may actually be an increased risk of VTE in those with more severe liver disease.
Ok, I accept that there is a risk of VTE in patients with liver disease, but isn’t there also an increase risk of bleeding?
So again, there hasn’t been any big prospective randomised control trials looking directly at the safety and efficacy of pharmacological prophylaxis of VTE in hospitalised patients with cirrhosis. However, the current body of literature as summarised by the two review articles have not found a significant increased risk of bleeding in cirrhotic patients with VTE prophylaxis. Some studies found that in those who did have bleeding complications, the risk was higher with heparin compared to enoxaparin.
And can I tell you just a little food for thought here?
There has been some evidence to suggest that the hypercoagulation which can occur in liver disease may lead to progression of liver cirrhosis possibly due to hepatic micro thrombi. As a result there has been some research which demonstrates that prophylactic enoxaparin decreases the risk of decompensation in liver disease.
Ok… so should we give VTE prophylaxis in our liver disease ICU patients?
Well… we should at least consider it, especially in patients exposed to high risk VTE conditions. I think there is still a lot more work to be done in this field, particularly in our critically ill patients who probably represent a unique subgroup of cirrhotic patients, however what is for certain is – We can’t judge a cirrhotic patient’s haemostasis based on their INR and there is therefore no such thing as “auto-anticaogulation.” And There is no evidence that liver patients are protected from VTE.
So I think we can confidently say that this myth is busted!
Thomas: Imagine we are again doing a ward round and again – as it happens all the time – Kass starts questioning my therapy. So there is this 120kg lady with abdominal sepsis and ARDS now day 5 in our ICU. She still needs a bit of noradrenaline to maintain her MAP, the peripheries are warm and she is about 10 l positive. My plan would be to start frusemide to get rid of the fluid but then Kass comes into play…
Kass: Wait wait wait Thomas, you can´t start frusemide on this patient, she still is on Norad!
Thomas: Yes, I know that she is still on norad, but there is sooo much literature out there that clearly says a restrictive fluid regime is definitely better. You know the fluid we give ends up in the tissue after a few minutes and causes tissue oedema. The oedema is not only in the soft tissue, it is in EVERY organ. It´s in the kidneys, the liver, the heart, the lungs, the brain, just everywhere. And this impedes the organ perfusion and also increases the distance oxygen has to travel across to get into the mitochondria.
Yeah, yeah, we all know fluid restriction is the way forward, but once the fluid is in, can you get it out while still on vasopressors?
I recently did a little pubmed research to support my argument and found this paper published in 2011. This was a sub analysis of the FACCT trial and they found that A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in patients with acute lung injury; this effect may be mediated by fluid balance.
Kass: Hmmmmm well while you were talking I actually was not listening, but I did my own literature search and found this paper by Mehta et folks published in JAMA who came to the conclusion that:
The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function.
And they also state that the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.
So what do you say now?
Thomas: I would say we need a meta analysis or at least a systematic review to answer this.
And lucky us, this has already been done by Malbrain and colleagues. They published a paper entitled in 2014 which is definitely worth reading.
And if we look at their Forest plot diagram we can clearly see that a restrictive fluid regime is better than a liberal fluid regime with an odds ratio of 0.42 for mortality.
Kass: ok so I will look into that. So a restrictive fluid regime is beneficial and maybe we should try to achieve this with the use of diuretics in our lady here in ICU since she already is 10l positive. But remember the myth was not so much about liberal vs restrictive fluid regime, it was specifically about using frusemide in patients on vasopressors. Is there any evidence that this is safe and works?
Thomas: Ah yes… so I have to admit I wanted to do bust this myth because I am a true believer that you can and should diurese patients to achieve a normal fluid balance as soon as possible even if they are still on vasopressors.
But when I did my literature search to support my believe, I realised that there is not much evidence to support my view.
I think most of use agree that we should try to get rid of fluid once a patient is stable.
This is usually referred to as the “de-resuscitation phase” of critical illness, when you should actively take things out, mobilise the patients and get rid of vasopressors and inotropes.
And many authors recommend to diurese patients in this phase once they are stable.
The difficulty is to quantify “stable”.
Does stable mean the patient doesn´t need further escalation of vasopressors or fluids?
And does this then mean that they are stable even if they are on extreme doses of noradrenaline but the dose was stable for the last 6? 12? 24? whatever hours?
Is a bleeding patient stable whose vital parameters are stable just because we keep filling him up with blood?
Or does stable mean that they are off all vasopressors?
And what if they need only a tiny dose of norad to keep the MAP in a certain range but are otherwise doing totally fine?
I think we all have some idea what “stable means but yeah defining “stable” seems to be quite tricky.
So coming back to my literature search. I found many studies that used diuretics as part of their restrictive fluid regime, but none of them used diuretics in patients on vasopressors. They all waited until they were off vasopressor for a certain amount of time.
But because I am a true believer I went further back and I found 1 study published in 1987 when the measurement of extravascular lung water became a fashion.
In this study they tested fluid management guided by extravascular lung water, compared to standard care at that time.
According to their protocol, they restricted fluids and used vasopressors for hypotension in patients with extravascular lung water > 7ml/kg and diuresed them if they where not hypotensive.
And they really found that patients managed in the restrictive arm actually received vasopressors for a shorter period of time.
So I initially thought : Ha that’s it, myth busted!
But then I tried to find out what they did with patients who were not hypotensive because they were receiving vasopressors.
Did they diurese them or did they wait until they were off vasopressors and then diurese them?
And what happened if they became hypotensive requiring vasopressors after diuresis?
Unfortunately, this was not described in the publication. So it could well be that also in this study they only diuresed them if they were normotensive without vasopressor support.
So…. Bottom line – you are telling me that the myth that you can´t diurese patients while being on vasopressors is still nooot busted.
But I will keep digging – so expect a study about this in the next years!
Myth 5: Peripheral norad
Thomas: G’day. I am one of the GPs from Farfaraway and I am calling you to discuss the patient that we are sending you.
Kass: Oh right. What can I do for you?
Thomas: So we have Mrs Staphauereus, the 50 year old with septic shock. So we have loaded her with fluid and she is still hypotensive.
Kass: how much fluid and how hypotensive?
Thomas: Well we have given her 5L and her SBP is still 75
Kass: Sounds like she needs noradrenalin
Thomas: Well yes, but I can’t put in a central line, and no one else here can either. So noraderenaline is not an option
Kass: That’s ok – you can give it through a peripheral cannula
Thomas: What????? But you can’t run noradrenaline through a peripheral line! Right?!?
Well that brings us to our final myth: you can’t give noradrenliane through a peripheral cannula.
Don’t you think it’s weird that we are happy to run adrenaline through a PVC, but not noradrenaline through a peripheral canula is a no no.
So first for all, what are we afraid of when giving peripheral vasopressors?
****Extravassation causing tissue necrosis, limb ischemia etc.
Yeah that’s right.
But is this really something to be afraid of?
So there was a **** systematic review by Loubani et al of all articles ever published on extravasation and local tissue injury from administration of vasopressors through peripheral IV cannulas and CVC through Jan 2014. There were 325 events reported. The two important points from this review is (1) About 90% of these events occurred in PVC distal to the antecubital or popliteal fossa and ****(2) the vast majority of these events occurred when vasopressors were infused >12 hours, and really > 24 hours. Loubani concluded that while no definitive conclusions could be drawn, they felt that PVC can be performed as a temporising measure until central venous access is obtained.
Ok, so extravasation can happen, but are there any RCTs comparing central lines with PVCs?
Why yes, yes there are
**** Ricard et al published a multicentre RCT in 2013 which looked at 3 French ICUs over 2 years who randomized their patients undergoing adrenaline, noradrenaline dopamine or amiodarone infusion to either initial PVC or CVC . 70% of these patients were on vasopressors, the majority on noradrenaline. There were 128 patients in the PVC and 135 in the CVC arm. Primary outcomes was rate of catheter related complications at 28 days.
What type of complications are you talking about?
Failed insertion of PVC, extravasation, infections, thrombosis etc.
So what did they find?
There was significantly more complications in the PVC group, including 19 extravasation episodes (all of which, according to Scott Weingart who reports speaking to the authors, were managed conservatively with nil necrosis or ischeimia). However when the complications were looked at in terms of severity, most of the complications of minor with nil clinical consequences. With regards to the major complications, there was no significant difference in the complication between the two groups. Worthwhile noting that 46% of the PVC patients were managed throughout their stay with PVC only, the remainder had to be crossed over to CVC.
Ricard et al concluded that both CVC and PVC seemed safe and certainly starting with PVC may allow appreciable gain of time in some critically ill patients needing urgent treatment.
So are you convinced?
Ok and now for the money shot?
But the one that just takes it home for personally is the most recent American study published in the Journal of Hospital Medicine in May 2015 by Cardenas-Garcia et al. So this was a single centre, single arm consecutive patient study which looked at 953 patients over about 2 years in an 18 bed medical ICU who were receiving either noradrenaline, dopamine or phenylephrine. Essentially these guys changed standard from central lines to peripheral lines. The primary outcome was rate of local tissue injury resulting from use of vasopressors via peripheral cannula.
In this study, they had a strict protocol for insertion, maintenance and trouble shooting of the peripheral cannulas; so they used either 18 or 20g cannulas that were inserted either in the basilic or cephalic veins that needed to be > 4mm measured with USS and position confirmed on USS. Once inserted, the cannula needed to be checked every 2 hours by diligent nurses and in place for a maximum of 72 hours.
In the case of extravasation, phentolamine was injected into the site as well as Nitroglycerine paste applied topically.
Of the 953 patients, 783 were maintained with a peripheral line and 170 required a CVC. Those that required a central line got one because either they were unable to get or maintain peripheral access or they needed other central access drugs. Of the 783 with peripheral lines, only 19 (2%) had extravasation, the majority of whom had noradrenaline infusion running at the time. Despite these extravasation, there were no tissue injuries at the site and no subsequent infection.
Their clear conclusion: the delivery of vasopressors via PVC is safe and feasible.
Well I am still bit sceptical of this idea. Don’t you think these results are limited because it is a single centre study and it may not be applicable to my environment.
You could also argue that a particular set of skills, particularly ultrasound guided IVC access is required. Or that because the rate of extravasation was low, the study is underpowered to show incidents of tissue necrosis from extravasation. But for me… I feel pretty convinced.
Ok so break it down for me – conclusion.
Yes, you can give noradrenaline peripherally. But if you are going to do it, use a larger canula as proximal as possible, and check it diligently for signs of extravasation.
So… myth busted? Yes, totally busted.
Alright, so we hope that you do not think we are complete smart asses or totally of the track. But that you got some fresh ideas to think about.
Thanks for listening,
Good bye and Pfiat di! Team Thomas signing off.