Yes, but it should also be based on patient-age, ASA classification and kind of anesthetic agents used.

Yes, but it will take much re-education.

Thank you Hugo Vereecke for this very interesting question. I agree with Andre De Wolf. It takes time and effort to change behavior, and this is not necessarily a bad thing. It is how we operate. Change will happen eventually in hand with better models, validated by better sensors (ways to meassure the impact of hypnotics and analgesics) and also better effectors (i.e. hypnotics and opioids with more accurate titration profiles).

At our institution since the introduction of BIS (A type of sensors that should get better with time) I have seen a reduction in CAM (Des and Sev) and Cp for Propofol, and a trend to use a higher opioid dose. Change wasn't complete throughout our entire staff, and it started with younger anesthesiologists and senior residents.

Hugo, I think the short answer is yes. This is one of the issues I would like to see adressed at www.navat.org.

Yes, I think this would be very valuable. However, acceptance of this will require time and education.

It continues to be mind boggling to me that our colleagues do not embrace this more. Maybe it also has to do with the fact that our drugs are so short acting?

There are already monitors available commercially that attempt to measure nociception by indices such as heart rate variability. Whether they are accurate enough to predict analgesic doses yet is a debatable point!

BIS is a good indicator to measure doses of hyp.notics

Yes, I think it's possible, it's necessary a good use of opioid medications and education on the concept of a nociceptive stimulus and pain, a more appropiate monitoring and a gradual education of behavior.

The idea is great. It is sort of happening already if you use propofol/remifentanil induction on TCI basis and titrate both agents really carefully observing patient's response at least clinically. But obviously having an additional tool would help.

Thanks to all responders. Personally, I find it cumbersum to experience that so much data is already availlable on this topic, but so little application of this knowledge is seen in current clinical practice. I guess it has something to do with how quality in anesthesia is defined. Currently, speed of turn-over between operations remains the number one quality parameter for anesthesia. I pleed for more patient related quality endpoints to validate anesthesia practice. Only then it will become clear that this emerging technology is a major aid to the anesthesiologist for achieving the Required "patient related" quality goals. Examples of this could be: absense of hang-over, low risk for PONV, no unnecessary use of inotropics to compensate for overdosing, etc... Even if this new technology requires a minimal increase in induction and/or recovery times, small organisational changes in the OR may easily compensate for this potential consequence of optimising drug titration according to the pharmacological evidence. In the end, benefits are inevitable if we succeed to do a fine job with less drug. The lower the required dose, the lower the probability of side-effects.

Well, I would. But even though we have the SmartPilot available, many colleagues do not bother to use it (read: do NOT adjust her/his dosing strategy according to this evidence based concept). Why is that? Is this a technique that is ahead of its time? Or does it not give enough "added value" in clinical practice? [I don't have the answer].

Very interesting topic. Since the routine intraoperative BIS use it has been widely observed a reduction in the MAC requeriments specially when a potent analgesic like remifentanil infusion is used. This practice implies a special caution to prevent postoperative pain because no opioid drug amount is left after 10 minutes of disrupting the continous infusion. ANI (analgesic nociception index monitor) has been recently present in our institution and I expect it will help us to improve the adecuate level of intraoperative analgesic requirements.

The problem is that I don't care what the probability of response is for any patient other than the one I'm caring for at the moment. While the variability of volatile agents is relatively low, for propofol it is much higher, and the opioids higher still. Thus, we tend to target 90% or 95% response probability, not 50%. What we want is to find the sensitivity of the individual patient and target that. This is the point of our paper "The Variability of Response to Propofol Is Reduced When a Clinical Observation Is Incorporated in the Control: A Simulation Study", A&A, June 2012.

"We currently have the ability to predict the probability of response to a standardized noxious stimulation like laryngoscopy throughout an anesthetic case." Do we? Which index are you referring to?

" My question is: Would a clinical anesthesiologist be prepared to adjust his dosing strategy according to this evidence based concept.......?"

Firstly...I'm not aware of a predictive methodology to customize the dose that one could use prior to the administration of induction agents/opiates. After the event it is easy to judge!

However, the responsiveness of a patient can be assessed; not by BIS which is not an 'analgesiometer' and is dependent on drugs used.

We have been working on a Evidence-Based-Monitoring system that can detect sympathetic responses to stimuli and it has been shown to have a graded response to different effect site concentrations of remifentanil. See www.custos.co.nz

Would anaesthetists use it? As a previous writer has said - it takes education and time - there are always people who are either quick or slow to take up new ideas. The present day trainees are possibly more likely to see the advantages - especially now that it is hypothesized that 'deep' anaesthesia may be associated with greater postoperative morbidity.

The SmartPilot e.g. does allow the clinician to add where the INDIVIDUAL patient becomes unresponsive to shake and shout e.g. That is an attempt to try to figure out on which isobole that particular patient lies.

I think I would prefer to respond to a physiological change than to a PK/PD model. 'Surgical noise' - i.e. blood loss, IVC compression changing cardiac output, traction on viscera, re-application of retractors all have an effect on the patient at random points in time.

Michael hits the nail on the head . . . it is currently impossible to model all the variables that can (and do) alter patient responses during surgery. It has proven to be quite difficult to measure anesthetic depth, even with sophisticated EEG monitors.

We must always identify and adjust doses according to clinical response that we observe. The great biological variability from being categorical in doses. The clinical observation should always be the parameter that tells us if we increase or decrease the dose

Dosing the anesthetic according to the physiologic response of the patient is a set-up for underdosing the agent, and therefore for patient recall. In "sick" patients (= hemodynamically unstable patients), there is no inherent relationship between hemodynamics and depth of anesthesia, and therefore we will most certainly fail in providing the most important aspect of general anesthesia: assuring unconsciousness. Since we don't have a reliable monitor of depth of anesthesia, we have to make sure that we give enough anesthetic, and the only way to do that is to rely on pharmacokinetics/pharmacodynamics. Of course the PK/PD models should take into account the condition of the patient (e.g., low CO). Whether we achieve our goal (= unconsciousness) through inhaled agents or intravenous agents is irrelevant in this context.

I agree with Andre De Wolf. Reaching a safe dose to provide unconsciousness and surgical analgesia often puts our patients in an unstable hemodynamic situation. Most often this represents an augment in venous capacity due to simpatholysis and our response is administering vasoactive drugs (or IV fluids) or establishing a lighter plane of anaesthesia. The first one requires a precise knowledge of our patients hemodynamic situation because neither intervention is without a cost, the second one (letting our patients regulate their one hemodynamic situation through autonomic reflexes) may put them at risk of recall. This comes as a very simplistic explanation, but until we have absolute cetainty we are providing adequate hypnosis with lighter anathesia planes I ll be choosing deeper levels and sustain normal hemodynamics with fluids and/or vasoactive drugs.

Dear Vereecke, The question is interesting, but my opinion is, the anesthesiologist works on his/her mentally generated MAAC (minimum altered alveolar concentration???) since even we use constant rate infusions of different agents, and not much bothering about the actual MAC of the agent, pain relief with balancing agent(short acting agents) can modulate the respiratory effect , probably a lower sympathetic stimuli, hence aculally the MAC is being modulated for surgical anesthesia, all working anesthesiologists are flexible enough to handle this situation, even where you have no set up to monitor anesthesia through MAC readings and all.

Actually, I think that as anesthesiologists, we are already adding opioid interaction in our evaluation of the MAC... who would ask the surgeon to wait until the patient's MAC reaches 2.0 for the Sevoflurane before starting surgery? No one, because we are already integrating the effects of all the drugs (opioids but also benzodiazepines or ketamine) that we previously administered to the patient.

Of course finding a monitor of anesthesia depth that could take into account all the drugs administered and all the patients' responses could be useful but it will probably remains a "Grail" for a few years. Since even the BIS has several limits, particularly when using anything else than propofol (see Whitlock et al. Anesthesiology 2011) we should be very careful in our use of any anesthesia depth predictor.

It took me some time before getting back to this page... and wow: Thank you all for this vivid discussion on the topic.

@ Dr. Harrison and others: Here is my update and personal opinion on this question:

The Noxious Stimulation Response Index (NSRI) is currently being developed as a measure of potency of "general anesthesia" including all interactions between opiates (Fentanyl, sufentanyl, remifentanil and alfentanil|), propofol, sevoflurane, isoflurane, desflurane and N2O. It is a number between 100 and 0 derived from the probability of "tolerance to laryngoscopy", observed in several studies that focussed on the interaction between the major groups of anesthetic drugs.

A NSRI number of 100 correlates with a maximal probability that your patient will respond (motorically and/or with a 15-20% increase in BP or HR) after a laryngoscopy. A NSRI number of 20 correlates with a 90% probability of tolerance to laryngoscopy in the population. As this correlation is valid both during intravenous as well as during inhaled anesthesia conditions, NSRI also opens innovative possabilities to compare the potency of each technique versus a population reference. As such NSRI has the potential to become a "MAC extended" and I see many more application possabilities in that view.

However: Limitations are:

(1) Accuracy is dependent of the accurate documentation of the dose and timing of all anesthesia drugs. (pumps and vaporisers are detected automatically, manual bolusses and demographics of the patient need to be entered manually)

(2) The population on which the observations were performed were relatively healthy (ASA1-2), although a relatively wide age range was included

(3) Morfine, ketamine, dexmedetomidine, benzodiazepines are not included in the total potency calculation because no accurately performed interaction studies on these drugs are availlable. As such when one of these drugs is administered, the anesthesiologist still needs to extrapolate the total effect in an experienced based (empirically learned) way. At that point, NSRI may not be very much different from the (population) estimation of MAC.

(4) By using predicted effect-site concentrations for each drug as an input for the TOL calculation, the time differences between dose and effect in individuals (each with their own demographic features) is maximally compensated for. However, these effect-site concentration predictions remain population averages and some individual uncertainty of the prediction will always remain. All population models are (by definition) wrong for the individual BUT the application of such an imperfect model may nevertheless prove usefull as it allows maximal reproducability of the interaction study findings in different parts of the world.

(5) Clinical experience and prospective validation with NSRI is still mandatory to determin the optimal NSRI ranges needed for several surgical or diagnostic procedures.

(6) observations are done in "steady state" anesthetic conditions (=steady effect-site concentration). As such during induction and when sudden and large changes in dose are applied, the predictions may have a larger uncertainty. The NSRI is meant for targetting maintenance of anesthesia (and avoiding excessive accumulation of drugs), rather than for setting induction goals.

Despite these limitations, NSRI may well be the next best thing to quantify and compare anesthetic potencies in an reproducible, evidence based and objective way. Anesthetic practice (how potent is your anesthesia?) between several hospitals can soon be studied even if one uses mostly TIVA and the other inhaled anesthetics. It has large potential to teach young trainees not to exagerate outside certain bounderies of dosing. A "reference population dose versus effect range" can now be set at the bedside of the patient.

The NSRI version on TIVA anesthesia was already published some years ago (Luginbuehl et al...) in "Anesthesiology". Based on data of Bouillon et al.

Expected publication date for the "all in" NSRI will be 2014. First results of performance seem promissing but need confirmation (cfr abstract laureate best abstract runner up competition, (second price) ESA Barcelona 2013:

Drug interaction models are better predictors of tolerance/response to noxious stimuli compared to individual measured parameters

Hannivoort L.N., Proost J.H., Eleveld D.J., Struys M.M.R.F., Luginbühl M., Vereecke H.E.M.

I agree with many of the responders to this question that clinical observation and adjusting dose according to individually observed responses will remain mandatory for anesthesia. But maybe the initial dose setting for maintenance can become more "according to a documented normal population" improving some quality features of anesthesia outcome.

To be continued... :-)

While it may not be possible to measure anesthetic depth now, remember:

“It always seems impossible until its done.” - Nelson Mandela