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

NOACs in Surgery

This a video from the European Society of Intensive  Care Medicine on monitoring , time of holding and restarting of NOACs in relation to surgery and treatment/reversal  with various degrees of bleeding. A couple of important points:

1) Apixaban does not affect coagulation parameters, as all other NOAC's do to a variable extend (but never correlate with degree of anticoagulant effect) . dTT and PT/PTT will only tell you if there is treatment effect if elevated, but it says nothing about the actual levels of the drug . A normal PT/PPT and TT in a patient taking an unknown NOAC , can have significant elevated drug levels and be coagulopathic when the drug was apixaban.
2) There is no role for a FFP during bleeding with any of these drugs ....you will have to give liters and liters and deplete the bloodbank in the process
3) Thromboelastograms will become more and more important, especially now that rivaroxiban is approved in conjunction with DAPT in ACS
4) Be very careful with NOACs in Stage D HFrEF patients, as they often have wide swings in renal function and a large number of them have cardio-renal syndrome class II. I still prefer VKA as drug of choice. Moreover, these patients were not studied in the various trials
5) Although not mentioned in this Webinar: NOAC's are contraindicated in patients with mechanical valves ( until further trials available)  !

Attached is also an article from JACC on the relation of NOAC's and coagulation parameters.

Laboratory Measurement of the Anticoagulant Activity of the Non–Vitamin K Oral Anticoagulants