Blog with interesting cases and/or problems related to anesthesia with discussion based on best evidence in the literature.

June 20, 2010

Follow up on MEPs and Dexmedetomidine

comment on recent article in Anesthesiology:
Mahmoud M, Sadhasivam S, Salisbury S, Nick TG, Schnell B, Sestokas AK, Wiggins C, Sauels P, Kabalin T and McAuliffe J. Susceptibility of TceMEP to varying Targeted Blood Levels of Dexmedetomidine during Spine Surgery. ANESTHESIOLOGY 2010;112:1364.

In the June 2010 issue of Anesthesiology an article was published looking at the effects of dexmedetomidine on the ability to measure MEPs. This post is a follow up on a previous post on a case report involving a decrement of MEPs intraoperatively.
The study protocol consisted of inducing anesthesia with propofol and then after this getting a baseline measurement of MEPs. SSEPs were also measured. A propofol infusion was utilized in all patients at 110 mcg/kg/min. They looked at 5 groups of patients with a combination of low dose dexmedetomidine (dex) and low dose propofol, high dose dex + low prop, low dex + high propofol, high dex + high prop, and lastly intermediate dex + intermediate propofol. In summary they found that the high dose dex group did show a significant decrease in measured MEPs.

Some caveats should be considered. First, the study had planned to recruit 72 patients, but only 40 patients completed the study. The study actually had to be terminated early because a change occurred of surgical technique during the study period. The group utilized a pharmacokinetic model from Petroz et al. [1] to estimate target based plasma dexmedetomidine levels. The study the authors based their infusion rates on by Petroz et al. was created in pediatric patients aged 2 yr to 12 yr. The age group in the present study ranged from 10 yr to 25 yr. As pharmacokinetics may differ in a two year old from that of a 25 year old, the question arises as to how reliable the target plasma levels of dexmedetomidine were in the present study. Furthermore, the Petroz study only had 36 patients, far from a robust study to given reliable plasma drugs levels based on a predetermine infusion rate. The plasma levels chosen were 0.4 ng/ml and 0.8 ng/ml for the low and high dex groups respectively. They did the same for propofol. They do not provide us good insight as to what infusion rates were utilized to acheive the target plasma levels cited in the study (i.e. 0.4 ng/ml and 0.8 ng/ml). Although the authors did randomly take plasma samples to verify that the pharmacokinetic model they were using was accurate, there is a small chance that some patients deviated from the target plasma drug level of dex. The small number of patients creates further risk of varying plasma levels disrupting an statistical analysis.

Their study did seem to match the results of two previous studies looking on the effect of dexmedetomidine in neuromonitoring in that SSEPs were not affected at all even at higher dexmedetomidine dosages.[2,3] The previous studies, however, concluded that dexmedetomidine did not effect MEPs in a clinically relevant matter. One of the studies (Bala et al.) utilized two target plasma levels for dex (0.3 ng/ml and 0.6 ng/ml). Once again, one can only wonder if the actual plasma levels of dex in the present study were as claimed. The authors of the current study claim to confirm the results of the other study listed [3], but then state, "...Whereas the other eight patients do not fit into any of our experimental groups as the computed propofol effect site concentration is less than that targeted in our group 2." Tobias looked at 9 patients who received a propofol infusion w/ BIS monitoring. Dexmedetomidine was loaded with a dosage of 1 mcg/kg over 20 minutes. This would provide a plasma concentration per the authors of the present study of 0.84 ng/ml (the same as their high dex group). The first patient in the protocol had a BIS decrement from 58 to 31 indicating overdosage of anesthesia. The protocol in Tobias et al. was then modified to decrease the propofol infusion to maintain a stable BIS as dexmedetomidine was added. Although the MEPs did decrease in the first patient, it was likely a result of very deep anesthesia, and the next eight patients in the Tobias study did not experience a significant decrement in MEPs with dexmedetomidine. The other patients had their BIS maintained at about 50.
The take home message is probably that dexmedetomidine, like many other anesthetics, decreases MEPs more than it decreases the ability to measure SSEPs. However, the overall depth of anesthesia is likely more important. Propofol, while effective at maintaining MEPs, is not a panacea. Propofol and dexmedetomidine infusions are useful when measuring MEPs, but they add cost and difficulty to the case. Furthermore, propofol continues to experience shortages in some areas of the United States. Dexmedetomidine is expensive (although tremendously effective when utilized correctly).
Given the current evidence, my practice is still to use desflurance, fentanyl + or - ketamine in most patients where MEPs are measured. I tend to avoid nitrous oxide (effects both MEPs and SSEPs). I will add dexmedetomidine in cases when I suspect the patient is opioid tolerant (a large percentage of the spinal fusions and neck fusions), or where baseline signals are poor with an inhalational agent. Remifentanil is a fantastic drug, but requires another infusion device, has been associated with acute opioid induced hyperalgesia, and is more costly than fentanyl. In the end, you are measuring the MEPs, and you can titrate to that end. You can make any changes necessary to acheive that end.

1. Petroz GC, Sikich N, James M, Van Dyk H, Shafer SL, Schily M, Lerman J: A phase I, two -center study of the pharmacokinetics and pharmacodynamics of dexmedetomidine in children. Anesthesiology 2006; 105: 1098-110.
2. Bala E, Sessler DI, Nair DR, McLain R, Dalton JE, Farag E: Motor and SSEP are well maintained in patients given dexmedetomidine during spine surgery. Anesthesiology 2008; 109:417.
3. Tobias JDS, Goble TJ, Bates G, Anderson JT, Hoernschemeyer DG: Effects of dexmedetomidine on intraoperative motror and SSEPs during spinal surgery in adolescents. Paediatr Anaesth 2008; 18:1082.

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