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

July 5, 2009

Neuromonitoring mishap for ACDIF

A female patient with neck pain radiating to her arms comes for a two level anterior decompression and instrumentation for fusion of C5-6 C6-7. She has a history of Asthma for which she has been hospitalized in the recent past. She has no other relevant PMH and has taken several puffs from her inhaler prior to proceeding to the operating room. Induction is smooth and intubation without incident. Neuromonitoring utilizing somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) will be used for the case to ensure that the anterior and posterior tracts of the spinal cord are not compromised. Anesthesia is maintained with desflurane at 5%, fentanyl with intermittent boluses, and an infusion of dexmedotomidine (Precedex) is begun at a rate of 0.4 mcg/kg/hr. No paralysis is used. The patient's vital signs remained stable throughout case.

After the instrumention is placed and the surgeon is ready to close, the technicion notifies the surgeon that while the SSEPs remain at baseline, the MEPs have declined dramatically, although still present and otherwise normal in appearance. Based on this information from the neuromonitoring tech, the surgeon removes the some of the hardware. This action provides no improvement in the MEPs. Within 30 minutes, MEPS improve back toward baseline. At the time MEPs decreased desflurane was decreased to aproximately 3%, and vital signs were carefully monitored.

Currently, motor evoked potentials (MEPs) and somatosensory evoked potentials (SSEPs) have become routine for some types of spinal surgery. When used together, they have been shown to provide more sensitivity in predicting negative post operative neurologic outcomes. The corticospinal tract is located anteriorly in the spinal cord which is served by the anterior spinal artery, while the dorsal columns relay sensory information to the brain and are served by two posterior spinal arteries. Because SSEPs only monitor the posterior half of the spinal cord, they are less sensitive, and as a result, negative neurologic outcomes have occurred despite no changes in SSEPs intraoperatively.

In monitoring MEPs amplitude and latency are both visualized. Ischemia and general anesthetics principally effect the measured amplitude, whereas hypothermia tends to have a greater affect on latency. In addition to anesthetics, hypoxia, severe anemia (Hct around 15%), decreased blood flow (systemic hypotension, distraction from instrumentation, severe hypocarbia, increased ICP etc.) will also dampen the measured voltage (amplitude) of MEPs. Furthermore, in some cases dramatic metabolic conditions like hypoglycemia, and marked hyper/hyponatremia or kalemia can affect the amplitude as well. Thus, changes associated from a hypothermic patient can be easily distinguished in most cases from those occuring from other causes (i.e. inhalational anesthetics, ischemia).

In clinical practice, motor evoked potentials can be evoked by either direct stimulation of the motor cortex via electrodes placed in the scalp (most common) or by magnetic stimulation. Because magnetic stimulation is difficult in the OR and is far more susceptible to general anesthetics, it is rarely used. Furthermore, stimulation of the motor cortex can be done by a single pulse, or can be accomplished by multiple pusles which have been shown to overcome the inhibitory effects of anesthetics at the synaptic clefts by creating a summation of excitatory postsynaptic potentials (EPSPs). Presently, a train of 3 to 6 pulses, with an interstimulus interval of 2 ms (500 hz) is recommended for use for transcranial electrical stimulation under GA. Stimulus intensity is typically between 100 to 800 V. Upon stimulating the motor cortex via the anode (positive) electrode a direct (or D) wave is elicited which is nearly entirely resistant to anesthetics since it has not passed through any synapses. As the cortical neurons stimulate in turn various subcortical internuncial neurons, indirect (or I) waves are generated which then summate at the alpha motor neuron for elicitation of a motor response. It is these 'I' waves that are decreased in amplitude by the general anesthetics. In the surgical setting, myogenic responses are most commonly measured since they capture information about the entire corticospinsal tract and the anterior horn neurons leading to the motor neuron and neuromuscular junction. Furthermore, myogenic responses can be measured on each side giving information about which side of the patient is depressed. Lastly, myogenic responses (in contrast to responses measured in the epidural space) require relatively noninvasive placement of electrodes into the various muscle groups (usually tibialis anterior, abductor hallucis, flexar carpi radialis, abductor pollicus, etc.).

While the gold standard in the measurement of MEPs is considered to be a TIVA technique using propofol (+/-) nitrous oxide + remifentanil; this is certainly not the only method available. While it is true that propofol as a constant infusion causes less inhibition of motor evoked potentials in most studies, it still is inhibitory and boluses can cause severe and lasting reductions of the measured amplitudes as shown by Kalkman et al. Latency does not seem to be affected by the general anesthetics. A common cited study to support the use of propofol was done by Pelosi et al. comparing a regimen using a propofol infusion + nitrous oxide to isoflurane (0.78%) + nitrous oxide. MEPs were obtained in 97% of those in the propofol group vs. only 61% in the isoflurance group. Furthermore, it was found that the isoflurane group had smaller amplitudes and more variability of the baseline. Variability is indeed one of the buggaboos of MEP. This is a result of a myriad of factors affecting the internal milieu in which the many neurons and synapses are operating. This is a critical principal to understand. Pathologic decrements tend to overestimate the degreee of corticospinal system compromise, therefore, only disappearance or marked attenuation amounting to virtual desappearance of a previously consistent muscle MEP is genereally accepted as significant. In the above presented case, the MEP was still measurable, and in fact, did not have low volatages. For this reason, cause for concern should have been lessened and an alternative source should have been the primary consideration.

At present, most centers utilizing motor evoked potentials in addition to SSEPs, utilize a multi pulsed direct electrical stimulation method of the motor cortex. Consequently, an inhalational technique is often successful in allowing MEPs to be measured. Of the inhalational anesthetics, desflurane is best suited because it allows rapid changes in anesthetic depth if MEP amplitude should be attenuated during the case. Using multipulsed transcranial stimulation, Lo et al. showed that desflurane at 3.4% + nitrous 66% was not worse than a TIVA technique using propofol and fentanyl. Given that nitrous reduces MEPs in a dose dependent fashion, as shown by Pechstein U et al. avoiding nitrous would improve the results found above by Lo YL et al. Avoiding nitrous oxide allows one to utilize higher desflurane concentrations. This is beneficial in clinical practice because nitrous oxide has large effects on SSEPs.

There are two intravenous anesthetics that do not cause any decrement (and perhaps a slight increase) in amplitude: Etomidate and Ketamine. Therefore, in patients that have pre existing neurologic deficits where the measurment of MEPs is anticipated to be difficult, utilizing etomidate and ketamine may be useful.

Because most MEPs are measuring the compound action potential at a target muscle, neuromuscular blockade must be done with care. Some surgeons prefer a degree of neuromuscular blockade to avoid patient movement during surgery. The downside to this is a proportionate decrement in the response measured. Studies and experience suggest that if neuromuscular blockade is going to be undertaken, maitaining a constant blockade at T1 at between 5 to 20% of baseline is required. This corresponds to a TOF of two twitches out of four being present. Sloan reports in his review on MEPs that at a T1 of 20% of baseline results in a measured MEP reduction of 50 to 60%.

So how does one proceed when a patient presents who is going to undergo a surgical procedure on the spine where MEPs are going to be measured. First, it should be noted that SSEPs are also going to be measured. This must be considered as well. SSEPs are very sensitive to nitrous oxide and when nitrous oxide is added to halogenated agents, the suppression of SSEPs is additive. Therefore, avoidance of nitrous in order to enhance SSEPs is likely beneficial.

A patient coming to surgery as this patient for a cervical decompression and instrumentation for stabilization who does not have ongoing weakness and is otherwise neurologically intact who will be monitored with MEPs and SSEPs, probably would benefit from an inhalational technique using desflurane and fentanyl + ketamine as small bolus (subanesthetic) doses Q 30 min during surgery with minimal neuromuscular blocking agents as an infusion. Maintenance of at least 2 twitches is necessary if neuromuscular blockade is used and an infusion is recommended.

Why not TIVA?

TIVA is certainly an acceptable option but does have some negative aspects that make it an alternative regimen. First, propofol, the typical maintenance anesthetic for TIVA does reduce MEPs, although slightly less than inhalational agents. Second, for a prolonged case such as this, using a propofol infusion will increases costs in comparison to low flow (closed circuit) desflurane at around 3.5 to 4%. Third, for a two level fusion this surgery lasted between 2 to 3 hours, and consequently, a delayed wake up is a possibility unless BIS monitoring is utilized which increases cost even more. Furthermore, the MACawake for potent inhalational agents is about 0.3 to 0.4 MAC whereas it is 0.2 MAC for propofol. This means that in order for patients to respond after a propofol anesthetic, it must be cleared to a far greater degree from the body before the patient will respond. This, in theory, could delay any neurologic exam attempted immediately after surgery. Fourth, patients are far more likely to move unintentionally during a propofol infusion for anesthesia compared to those receiving a potent inhalational agent (40% movment w/ propofol vs <10%).>

Why fentanyl and not remifentanil?
First, remifentanil is more costly than fentanyl. Secondly, there is added effort and time required for set up of an additional infusion pump and tubing, plus preparation. Thirdly, remifentanil (more than other opioids) has been associated with acute opioid tolerance/hyperalgesia.(2,3, 4,5).
Why not utilize nitrous oxide?
First, Nitrous oxide is associated with PONV in high risk patients. (6,7) In this case, the modified Apfel score is 3 (out of a total of 4 possible), giving her a post operative risk of PONV of 60% according to Apfel, which I would consider to be high risk. Nitrous is best avoided for this reason alone. Second, many investigators have demonstrated that nitrous in addition to attenuating SSEPs significantly attenuates MEPs. Kunisawa used a TCES technique utiziling a train-of-five stimulus to elicit myogenic responses in patients given a propofol infusion alone or with 50% nitrous or 66% nitrous. The patients given either 50% or 66% nitrous had equally attenuated MEP amplitude (from 4 mV down to 1 mV). (8) Thirdly, Nitrous is not known to effectively produce effective preconditioning as has desflurane. In these cases where the spinal cord is at sufficient risk that MEPs have been deemed necessary to prevent a deficit which is ischemic in nature, avoiding nitrous and adding an inhalational agent in its place (MACS are additive), could make sense.
Why add ketamine?
Ketamine is your friend when it comes to both SSEPs and MEPs. In multiple studies ketmaine has been shown to not have an effect on MEPs at all. In fact, Kalkman et al. (9) showed that using magnetic MEPs 1 mg/kg of ketamine did not cause significant alterations in volunteers. This significant in that MEPs are reduced to virtually zero in the presence of inhalational or propofol when using a magnet as the source of stimulation. Ketamine is an NMDA inhibitor. This is important in that the NMDA receptor in the spinal column has been shown to mediate post surgical chronic pain syndromes, wind up, post surgical allondynia, and post surgical hyperalgesia. Furthermore, Mao in a review of the NMDA receptor and opioids notes that opioids can induce tolerance and hyperalgesia by themselves and that this is mediated by the NMDA receptor. Ketamine, however, can result in significant psychological affects (i.e. hallucinations) which is more common in the elderly or in those with organic brain disease. By utiziling doses of less than 0.5 mg/kg every 30 min. these side effects are minimized while preserving ketamines beneficial attributes.
Does dexmedetomidine have a role when monitoring motor evoked potentials?
Dexmedetomidine can be very useful in many patients by inhibiting sympathetic outflow from the CNS which is almost always desirable in healthy patients undergoing routine surgery. Furthermore, it has a limited inhibitory effect on myogenic motor evoked potentials per recent studies. (10) Titrating dexmedetomidine to blood pressure is being utilized more frequently intraoperatively in many types of cases as it is known that alpha one receptors modulate hyperalgesia, and as dexmedetomidine can reduce MAC for inhalational agents. Unfortunately, this is an expensive agent. Nevertheless, in cases where MEP measurements are necessary and a quick wakeup is important, dexmedetomidine is an ideal adjuvant in that it does not affect MEPs at dosages of 0.4mcg/kg/hr as shown in the study cited above, it allows a rapid patient wake up at the end of the case, and provides additional analgesia reducing the dosage of narcotics necessary potentially preventing acute opioid induced hyperalgesia.
In conclusion, the approach to any patient who will require neuromonitoring should be balanced against the patient's medical status and the needs of the neuromonitoring technician. In most patients who have no preoperative neurological deficits, a standard anesthetic (desflurane + short acting narcotic + ketamine) is ideal. However, a back up plan should always be available in case there is difficulty in measuring MEPs. In this case, decreasing the inhalational agent and using a low dose propofol infusion + dexmedotomidine and ketamine will be beneficial.

1. Tang J, white PF, Wender RH et al. Fast-Track office-based anesthesia: A comparison of propofol vs. desflurane with antiemetic prophylaxis in spontaneously breathing patients. Anesth Analg 2001;92:95-9.

2. Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 2000; 93: 409–17.

3. Vinik HR, Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg 1998; 86: 1307–11.

4. Luginbuhl M, Gerber A, Schnider T, Petersen S, Arendt-Nielsen, and Curatolo. Modulation of Remifentanil-induced Analgesia, Hyperalgesia, and Tolerance by small-Dose Ketamine in humans. Anesth Analg 2003;96:726-32.

5. Joly V, Richebe P, Guignard B, Fletcher D, et al. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology 2005 Jul; 103: 147-55.

7. Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N. A factorial Trial of six interventions for the prevention of postoperative Nauesea and vomiting. NEJM 350:2441.

8. Kunisawa T, Nagata O, et al. A comparison of the absolute amplitude of motor evoked potentials among groups of patients with various concentrations of nitrous oxide. J Anesthesia 2004:18:181-4.

9. Kalkman CJ, Drummond JC, Patel PM, Sano T, Chesnut RM. Effects of dreoperidol, pentobarbital, and ketamine on myogenic trancransial magnetic motor-evoked responses in humans. Neruosurgery 1994;35:1066-71.

10. Motor and Somatosensory Evoked Potentials Are Well Maintained in Patients Given Dexmedetomidine During Spine Surgery. Survey of Anesthesiology: June 2009;53:136-7.

11. Bala E, Sessler D, Nair D, McLain R, Dalton JE, Farag E. Motor and Sensory evoked potentials are well maintained in patients given dexmedetomidine during spine surgery. Anesthesiology 2008; 109:417.

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