By Tom Heaton

“Just when you thought it was safe to return to your anaesthetic room, the makers of ‘Etomideath: An Anaesthetic Horror Story’, bring you the terrifying sequel - Etomideath 2: The Heartbreaker!! No RSI is exempt, no adrenals are safe, and this time it’s after your heart!”

After our recent look at etomidate and its fall from favour as an induction agent, my eye was caught by this recent study on etomidate in the March 2014 publication of Anesthesiology. It primarily caught my attention as it appeared to be trying to look at some of the questions that we had discussed around the last post; namely where do we stand with etomidate in non-septic patients. The evidence of adrenal suppression seems to be there even if the clinical consequences aren’t clear, but most of this examination of clinical effects seem to be focused on the septic patient needing intubation where perhaps this adrenal suppression could be seen as being more problematic. There seem to be (to me at least) a good selection of other clinical scenarios where having a cardiovascularly gentle induction agent might prove advantageous e.g. a multitrauma patient with head injury where ketamine would definitely raise the ICP (little something for you there John), but even brief peri-induction hypotension is bad. In this paper the authors look at the use of etomidate in another group of patient where it might be advantageous; those undergoing cardiac surgery who probably have knackered hearts to start with. Hopefully this preamble is enough to get your interest stoked too whilst we go in for a closer look at the paper. If you haven’t been able to have a look at it for yourself yet then the link is below.

By John Weeks

Nitrous is a controversial topic, which Tom has already covered. Another one is Ketamine, Traumatic Brain Injury (TBI) and Intracranial Pressure (ICP). The teaching from multiple sources (books, colleges, guidelines etc) is that ketamine may increase the ICP and is therefore contra-indicated in TBI. However, there are strong advocates that ketamine does not cause a rise in ICP. 

Like most of these things my initial opinion was that if there is disagreement there is probably a lack of concrete evidence. Picking the right drug, for the right patient, at the right time (& being able to justify it) can be difficult. This is (partially) why I think this is a particularly interesting article.

Article: The Ketamine Effect on ICP in Traumatic Brain Injury

There are a lot of blogs covering this topic of sedative agents in TBI already so I won't go over old ground here, but links are included at the end for further reading. 

This isn't the first article to look at ketamine & ICP in this context, nor by any means is it to first to question the 'ketamine raises the ICP' story, but it is a systemic review published very recently (Feb 2014) and worth a look.

They did a pretty comprehensive search of a large number of popular (and less popular) databases, as well as looking at proceedings of meetings and conferences etc. They posed a clear question of "In patients with TBI, what is the effect of ketamine on ICP", but also looked at secondary outcome measures including CPP, Mean Arterial Blood Pressure (MAP), patient outcome and adverse effects. Animal and non-English language studies were excluded. 
From 371 citations found they chose 7 articles, all prospective, with data on 156 patients (101 adult and 55 paediatric). 4 of the papers assessed ketamine infusions and 3 looked at bolus ketamine. All patients had severe TBI with a Glasgow Coma Scale (GCS) < or equal to 8, and all were sedated and mechanically ventilated. 
The authors did a lot of work to get access to data not in journals (e.g. presented at conferences etc). 

ICP didn't go up up. 
In the four infusion studies there was either no difference in the ICP or a very slight increase (2 mmHg), described as "statistically...yet not clinically significant". Two studies reported in increase in CPP (by as much as 8 mmHg) and one study reported a decreased vasopressor requirement.
In fact, in three of the studies it fell. In paediatric populations bolus doses of ketamine caused a fall in ICP of almost a third. For CPP, data were lacking in two of the studies but the third showed
There was a lack of quality outcome data (therefore long term effects were difficult to comment on), but the three studies reporting Glasgow Outcome Scale (GOS) reported the ketamine group was "comparable" in one study and "favourable" in another. 

There were no significant adverse events, and only two reports of non-clinically significant tachycardia.
The authors seem to have taken a pretty rigorous approach. Two individuals independently identified articles and then a similar approach was used for extracting data. 
However, inspite of their broad search, the numbers are small (only 156 patients, not enough for a meta-analysis) and there was considerable differences between the methodologies of the trial (heterogeneity). They calculate the strength of evidence against ICP elevation in TBI with ketamine as GRADE C, Oxford 2b.

Interesting question. The use of a sedative drug in TBI which is cardiostable and may potentially have neuroprotective effects (NMDA antagonism resulting in inhibition of glutamate activation and decreased nitric oxide (NO) levels) has a certain attractiveness.
Some of the older studies which reported a rise in the ICP assessed patients spontaneously breathing. The authors of this trial assert that this results in a rise in arterial carbon dioxide, causing cerebral vasodilation and therefore an increase in an ICP. 
We're left with a situation where some of the guidelines and textbooks are giving different advice to what's coming out in some of the literature (nothing new there...) A number of other articles (e.g. Chang et al., Filanovsky et al.)  have challenged the current thinking and perhaps in time opinions will change (after sufficient time for knowledge transfer). 
As is often the case, we're measuring a surrogate marker for 'badness'. Patients probably wouldn't really care if their ICP goes up, down, or stays the same, but rather if the outcome (e.g. neurological status) is improved. 


It would be interesting to see protocols from others regarding the use of ketamine and other sedative agents in TBI and polytrauma in other hospitals. 

The PHARM run by Minh Le Cong ran a series on ketamine mythbusters, which included a podcast on the effects of ketamine on the ICP. There are some good links in the notes.

BestBets is full of great practical evidence advice. A bet done recently found:

Andy Neill's Ketamine thoughts

LITFL on ketamine RSI in head injury

By Tom Heaton

It's a sunny weekday morning and the surgeons are elbow deep in an emergency laparotomy. The anaesthetic jobs are done and the patient is stable, needing only the regular glances at the monitors as input from us. The emergency list has been going well and I have had the chance to further practice my intubation skills. As a fairly new trainee at this point, I seize this lull in the otherwise busy day to make the most of the direct one-to-one consultant teaching available to us.
“Can I ask a bit more about etomidate as an induction agent? I’ve not actually seen it used yet.”
Silence descends upon the operating theatre. A peal of thunder rumbles ominously in the distance (I thought it was sunny!). Even the surgeons look up from the table, eyes widening above their facemasks. Someone drops a scalpel. 

By John Weeks
There has been an explosion of conversation about Targeted Temperature Management (TTM) in post-arrest patients following the publication of the TTM trial by Nielson et al in the NEJM recently. 

Full article - Engl J Med 2013; 369:2197-2206 December 5, 2013



There has been loads of commentary and debate and I won't try to re-invent the wheel here.

Obviously I suggest you read the paper, listen to the podcasts and decide on your own opinion. However, I would probably summarise what I learnt as:
- HypERthermia after a cardiac arrest is probably bad (not contained in this paper but useful background knowledge)
- Controlling the temperature to 36°C may be the same as cooling the patient to 33°C, but we don't know that. We do know that there isn't a large difference.
- Studies to prove similarity between two interventions have to be massive (studies to show no difference can be smaller - MATHS fans)
- Cooling is an intervention and like any other thing we give (e.g. drugs) there is probably a dose-response relationship
- Neuroprognostication is difficult in the context of hypothermia and difficult post-cardiac arrest, and the two combined make things exceptionally tricky.

It may well be that different patients need different temperatures (for example patients with a long down-time and asystole might require longer at a lower temperature) - but clearly more studies are needed before this becomes practice.

Some links:
There's some useful background info on post-arrest hypothermia from Lewis Macken from SMACC 2013. This talk pre-dates the release of this trial but has some really interesting points, esp how small the numbers are in existing RCTs

A very readable summary from The Intensive Care Network

Interview with Nielson, the primary author of the study

St. Emlyn's info on the stats behind the trial

By Tom Heaton

Welcome back to the final part of our emergency surgery trilogy. In this series we have been looking at the ‘Big Three’ of emergency surgery: the ruptured AAA, the laparotomy, and the fractured hip. All three posts are based on the recent Anaesthesia supplement on the big three which you can get to through the link below (if you have managed to avoid it after the last few posts), focusing particularly on the elderly population. We wrap up with a look at those patients who have suffered a fractured hip, and all the problems that these patients encounter.

Welcome back to the second part of our look at the holy trinity of emergency surgery; a look at the three biggest operations and particularly focusing on their impact on the elderly population undergoing them. Today we turn our attention to the laparotomy, the go-to guy for all manner of intra-abdominal problems. As I mentioned in the last post, the basis for this blog post is the recent Anaesthesia supplement looking at ‘The Big Three’ of emergency surgery If you haven’t had a look at it yet check it out via the link below: