ECCO2R in patients with acute respiratory failure

Carbon dioxide (CO2) which is twenty times more diffusible and has different physiological features compared to oxygen, still continues to occupy one of the most important physiological parameters in intensive care practice and can often act like double-edged sword. Hypercapnia may have deleterious effects on cardiac, brain and lung function. In contrast, it has also been shown that acidosis secondary to CO2 elevation may have an anti-inflammatory effect and consequently permissive hypercapnia may prevent progression of lung injury. However, this immunosuppressive effect can increase the tendency for bacterial super-infection (1).

Over last decade, artificial support systems called Extracorporeal Carbon Dioxide Removal or ECCO2R have increasingly become popular devices used to control CO2 levels. Indications include not only optimisation of lung protection in acute respiratory distress syndrome (ARDS) management, but also for type 2 respiratory failure induced by exacerbations of severe asthma and chronic obstructive pulmonary disease (COPD) or temporarisation as a bridge to lung transplantation (2-5). The main characteristics that separate ECCO2R from other extra-corporeal life support (ECLS) techniques, is the need for significantly reduced calibre of cannulae required for vascular access (due to the low blood flow requirement through the extra-corporeal gas exchange membrane to remove CO2).

This recent article by Morelli et al (6) in the journal Intensive Care Medicine highlights that there is a lack of current evidence (small, single centre studies) for the general application of ECCO2R to daily practice. The main clinical indications at present are in ARDS and COPD.

Initially the use of ECCO2R was introduced into ARDS through the need to prevent excessive hypercapnia as a result of low tidal volume lung protective strategies. Zapol et al. introduced the concept of applying ECMO in order to prevent ventilator induced lung injury (VILI) (7). Further evidence came from the Xtravent study by Bein et al. where ultraprotective ventilation strategies, specifically with the use of ECCO2R suggested a trend towards improved survival (8). As a result, there are two large ongoing prospective multicentre randomised control studies (SUPERNOVA and REST) in France and the UK examining the safety and feasibility of such a strategy. It is expected that, within the next five years, the results of these studies will provide valuable guidance regarding the evidence based application of the combination of ultra protective ventilation and ECCO2R in acute respiratory failure.

The other use of ECCO2R is in the support and prevention of invasive mechanical ventilation (IMV) in patients with acute type 2 respiratory failure. It does not only avoid endotracheal intubation in these patients, but also reduces respiratory work, the need for sedation and as a result, further CO2 production. In a similar fashion, ECCO2R may be also be a supportive strategy as a bridge to lung transplantation  in the maintenance of respiratory muscle strength. In addition, ECCO2R may improve pulmonary hypertension and right heart function and improve myocardial efficiency (9).

However it should be emphasised clearly that, even if ECCO2R helps intensivists in the situations described above, there could be some inevitable drawbacks for patients related to utilising these devices. The expense of lowering CO2 can sometimes increase hypoxaemia, as a result of atelectasis with low tidal volume associated low airway pressures and ventilation-perfusion mismatch and there may be recourse to ECMO in some patients treated with ECCO2R. Furthermore, due to the low blood flows used through the extracorporeal circuit, there is increased risk of thrombosis within the catheter and gas exchange membrane (10).

To conclude, due to observational designs, low patient numbers, controversial results and some disadvantages such as hypoxemia, current studies do not demonstrate  the efficiency and applicability of ECCO2R. More robust studies are needed to determine its efficacy in daily practice with these patients.

This article review was submitted by EJRC members Dr Burcin Halacli and Dr Brijesh Patel (Royal Brompton Hospital), on behalf of the NEXT committee.

References
1.     Ismaiel NM, Henzler D (2011) Effects of hypercapnia and hypercapnic acidosis on attenuation of ventilator-associated lung injury. Minerva Anestesiol 77:723–733
2.     Gattinoni L, Agostoni A, Pesenti A et al (1980) Treatment of acute respiratory failure with low-frequency positive-pressure ventilation and extracorporeal removal of CO2. Lancet 2:292–294
3.     Tajimi K, Kasai T, Nakatani T, Kobayashi K (1988) Extracorporeal lung assist
for patient with hypercapnia due to status asthmaticus. Intensive Care
Med 14:588–589
4.     Sklar MC, Beloncle F, Katsios CM et al (2015) Extracorporeal carbon dioxide removal in patients with chronic obstructive pulmonary disease: a systematic review. Intensive Care Med 41:1752–1762
5.     Schellongowski P, Riss K, Staudinger T et al (2015) Extracorporeal CO2 removal as bridge to lung transplantation in lifethreatening hypercapnia.
Transpl Int 28:297–304
6.     Morelli A, Del Sorbo L, Pesenti A, Ranieri VM, Fan E. Extracorporeal carbon dioxide removal (ECCO2R) in patients with acute respiratory failure. Intensive Care Med. 2017 Apr;43(4):519-530.
7.     Zapol WM, Snider MT, Hill JD et al (1979) Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective
study. JAMA 242:2193–2196
8.     Bein T, Weber-Carstens S, Goldmann A et al (2013) Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus “conventional” protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Med 39:847–856.
9.     Karagiannidis C, Strassmann S, Philipp A, Müller T, Windisch W (2015) Veno-venous extracorporeal CO2 removal improves pulmonary hypertension in acute exacerbation of severe COPD. Intensive Care Med 41:1509–1510
10.     Fanelli V, Ranieri MV, Mancebo J et al (2016) Feasibility and safety of
low-flow extracorporeal carbon dioxide removal to facilitate ultraprotective
ventilation in patients with moderate acute respiratory distress
syndrome. Crit Care 20:36

What’s new in refractory status epilepticus?

Refractory status epilepticus (RSE) is defined by persistent seizures, resistant to first-line (benzodiazepines) and second-line (“classic” anticonvulsant therapy, suchas valproate, phenytoin/fosphenytoin or levetiracetam), usually requiring general anesthesia and continuous electroencephalogram (EEG) monitoring . This is of particular importance since up to 43  % of patients with status epileptics will progress to RSE. Rossetti and Bleck recently proposed an update on the management of status epilepticus .

This article reviews the recent literature on convulsive RSE in adults, aiming to summarize advantages/disadvantages and comparative studies of “standard” intravenous anesthetics (propofol, midazolam, barbiturates) and describe the emerging use of the alternative anesthetic agent, ketamine. An algorithm is p[roposed for the management of RSE in the ICU.

Note the option and role of ketamine.

Hemodynamic Monitoring:what is new in 2017

Here is a  link to the audio of the entire (Non- Invasive) Hemodynamic Montoring in perioperative setting and in the ICU in critically ill intubated and non- intubated patients at ISICEM  37th Meeting Brussels , Belgium . It's somewhat of an exhaustive review.I will publish the slides later, as I am sending this ad hoc from the Starbucks at Brussels Central train Station. 

At the end, I felt somewhat let down as I could not pinpoint either Xavier Monnet or Ivor Douglas what single test to use on on critically ill septic patients to asses PLR, particularly in intubated patients without arrhythmia's, sedated and not over- breathing the ventilator (either on VCV- AC and PC- AC).

Both speakers also had a significant conflicts of interest. Xavier Monnet with Precision Medical and Ivor Douglas with Cheetah Medical, both heavily sponsored for there research in the field. 
Nevertheless, I think you will take away clinical useful information from most of the talks. 

Keep in mind that the latest and newest drug or test often doesn't stand the test of time.  An important article from the New Yorker ,  highlights the point I am trying to make here .Will NICOM or etCO2  as CO ( cardiac output ) surrogate measurement technique to assess FLR  fall prey to " regression to the mean ",  as happens for most clinical interventions and diagnostic tests?  Bioimpedance is a noteworthy example in this category. I am afraid the answer will be eventually ...yes. 

(More thoughts of the decline effect, New Yorker) 

A few pratical and clinical helpful messages can be taken away form this session: 

1) Provided you believe the results, act accordingly to what the device tells you (consistency). Unfortunately, I have not found the +LR and -LR ratios for either etCO2 and NICOM. I asked the question, neither researchers could give me an answer.

2) Probably, the most useful result you can get, applied to the current "slow data-point collection" NICOM device is a negative result ( I supect NICOm has a good NPV but I cannot prove this based on the literature). This is important because further aggressive fluid administration will avoid  further damage to the glycocalyx and capillary leak  

3) Repeated fluid boluses guided by a positive result on NICOM ( assuming an unrealistic 100% accuracy - probably more in the 60- to 70% range), may still cause an overshoot. 
Is the infliction point for CO on the Frank-Starling (FS) curve the end- point  for optimal tissue perfusion and oxygenation?
What is the ideal CO for an individual patient ? (something these devices cannot tell us ). We are already high on the FS ("flat part") curve once the test becomes negative. Do we need to go this far ?  

4) Maintenance fluids after initial volume resuscitation (this is  after the usual 30 ml/kg in the hypotensive septic patient and +/- pressor use initially) should be abandoned in favor of clinical assessment and FLR.Either etCO2 ( but specific conditions will need to be met and thsi will be a topic of another blog entry) or NICOM maybe a useful CO surrogate marker, although PPV/SVV techniques can still  be used in the right clinical context. 
Unchecked/unmonitored use of maintenance fluids is associated with increased mortality.

5) "Rapid NICOM" (not clinically available yet ) may be the most single useful test in the near future for FLR ( flid responsiveness).

6) Because of the well studied variable accuracy ( >30-40%) of various noninvasive hemodynamic monitoring techniques, trending results does not necessarily improve clinical decision making. Accuracy is not independent of interpretation of trending results.   

Programme Hemodynamic Non- Invasive Montoring 37th Symposium 2017, Brussels, Belgium 

Norepinephrine Shortage and Mortality

This  important study, presented yesterday in Brussels at the 37th ISICEM and same time publication in JAMA,  raises  the concern that national drug shortages could be placing potentially large numbers of patients in jeopardy, such as an increased risk of death from septic shock.


Potential pitfalls of the study are addressed in the Editorial.  

Driving Pressure: An Important Parameter to Prevent ARDS/VILI

I will write more about this in the next blog, but the concept of driving pressure ( Pdr = Vt/Crs- Vt;  tidal volume, Crs; compliance respiratory system ) is important in VILI and is and independent risk factor. Just ventilating at 6 ml/kg does not assure decreased risk of VILI if done with Pdr> 12. This is an important bedside concept we will need to incorporate in our clinical thinking.

The following presentation is a nice and simple introduction:

Driving Pressure in ARDS

Capnography during Cardiac Arrest

Here is some useful info on etCO2 during cardiac arrest as well as some references pointing out benefits and limitations of the technique, as well as use in practice. etCO2 during CPR is certainly a useful​ adjunct.

The AHA Guidelines only label this as a Class  IIB recommendation and needs to be used with additional clinical parameters . Also, be able to troubleshoot the device as other factors can be involved giving an inaccurate reading .

Here are some references with additional info:

Heradstveit BE, Sunde K, Sunde GA, Wentzel-Larsen T, Heltne JK. Factors complicating interpretation of capnography during advanced life support in cardiac arrest–a clinical retrospective study in 575 patients. Resuscitation. 2012 Jul;83(7):813-8. doi: 10.1016/j.resuscitation.2012.02.021. Epub 2012 Feb 25. PubMed PMID: 22370007.

Kolar M, Krizmaric M, Klemen P, Grmec S. Partial pressure of end-tidal carbon  dioxide successful predicts cardiopulmonary resuscitation in the field: a prospective observational study. Crit Care. 2008;12(5):R115. doi: 10.1186/cc7009. Epub 2008 Sep 11. PubMed PMID: 18786260; PubMed Central PMCID: PMC2592743.

Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med. 1997 Jul 31;337(5):301-6. PubMed PMID: 9233867. [Free Full Text]

Comparative Effectiveness of Vancomycin and Metronidazole

Among patients with severe disease, 30-day all-cause mortality was significantly lower for those who were treated with oral vancomycin than for those who were treated with metronidazole (15% vs. 20%); 30-day mortality did not differ significantly among patients with mild-to-moderate disease. Also, CDI relapse rates did not differ between treatment groups in either stratum of disease severity.

Comparative Effectiveness of Vancomycin and Metronidazole for the Prevention of Recurrence and Death in Patients With Clostridium difficile Infection


Real life data show that metronidazole is still given frequently in patients with severe disease.


Here is a risk calculator for moderate- severe disease requiring oral vancomycin