The neuromonitoring Technician: Friend or Foe?

A couple of days ago I took over a posterior lumbar interbody fusion from L2 to S1.  The case had started at 7:45 am that morning, and I came into the room at 3pm.  The report I received from the CRNA was that the patient had been stable for the entire case until just recently when the blood pressure began to sag.  The CRNA had already checked a Hgb and ordered two units of blood which were on there way.  It was clear from a brief glance at the surgical field that this case had a ways to go and there was continual bleeding from the field.  A cell saver machine was working and the patient had received about 300 mL from the cell saver machine already.  I checked the UO and it was low and appeared to be concentrated.  The patient was being maintained on Desflurane at 4% with a dexmedetomidine infusion at about 0.15 mcg/kg/hr which had been discontinued due to low blood pressure.  The patient had a history of COPD and was 68 years old, but other wise had no significant medical history that would impact his anesthetic.  Neuromonitoring consisted of SSEPS, MEPS and running EMGS.  No paralysis was being used. 

The patient had already received 4.5 L of crystalloid and 1 L of Hespan.  Due to the prolonged case and the prone position, this patient was at some risk for perioperative visual loss (POVL).  An ASA task force on perioperative blindness (consisting of 12 ASA members) recently published guidelines to help clinicians better deal with this potential outcome.  The task force culled the most recent literature to make recommendations.  They identified several preoperative risk factors which include: hypertension, glaucoma, carotid artery disease, smoking, obesity and diabetes.  This patient was mildly obese and had a prolonged smoking history having ceased just 6 weeks prior to surgery.  The task force also identified surgery lasting longer than 6.5 hours, preoperative anemia, large volume blood loss (i.e. 44% of blood volume) and also prolonged procedures combined with large blood loss cases.  The task force also identified several intraoperative events that are linked to POVL.  These included intraoperative hypotension, anemia, hypovolemia, hypoxia, hemodilution, edem of face and use of vasopressors, infusion of large amounts of fluid, pressure on the eyes, prone positioning (or head down), and increased venous pressure. This case included several of the above risk factors including long duration procedure with large volume fluid ressuscitation, intraoperative and preoperative anemia.  There was ongoing blood loss and it wasn't clear the total volume that would ultimately be lost during the procedure.

At this point all clinical indicators were that the patient was hypovolemic due to blood loss.  I focused on giving blood and volume while attempting to avoid phenylephrine as much as possible. During this time the Neuromonitor technician notified the surgeon that MEPs on the left lower leg had decreased significantly.  The blood pressure was low (MAP of 60s) at this time so I continued to work on increasing this with rapid blood transfusion (3 units) and crystalloid. (2L).  After this volume the blood pressure improved slightly but began sagging again.  It was clear that the patient was still hypovolemic.  I drew more labs and started pumping in more fluid.  During this time the neuromonitoring technician told the surgeon that we needed to put the patient on 3% Desflurane and start a propofol infusion.  I immediately told the neuromonitoring tech I would not be starting a propofol infusion under any circumstances at this point.

He disagreed with me and began telling me why I was wrong to believe that we shouldn't do as he suggested.  He indicated that I was derelict in my duties because I was not following the established protocol for neuromonitoring and that if he should decide, he could write me up and bring me before peer review for my refusal to follow the protocol.

A brief discussion of the current recommendations for anesthetic technique during neuromonitoring is warranted.  Also, I would recommend looking over previous posts on this topic. 1) MEPs with dexmedetomidine and 2) MEPS in AIDCF.

In a review article on intraoperative monitoring (IOM), it states, "These findings support the current position of propofol being the standard anesthetic approach for IOM recording of MEPs." [1].  "These findings" in the above quote refers to a study done in 1998 by Pechstein et al.[2].  In fact, this study is the  basis for the recommendations made and thus serves as the basis for propofol being the automatic "go to" anesthetic for IOM with MEPS during spine surgery.  It should be noted that in the study by Pechstein et al. there were two study groups of 17 (group A) and 13 (group B) patients.  Group A received TIVA (total intravenous anesthesia) with propofol and alfentanil.  In Group B, patients received Nitrous oxide (66%), isoflurane and fentanyl.  MEPS could be recorded in 88% vs. 8% of group A patients vs. Group B patients.  Therefore, this small study was able to show that mixing nitrous oxide with isoflurane is likely to make it difficult to record MEPs.  It certainly does not allow us to conclude that propofol is the gold standard anesthetic for IOM.  It has been well demonstrated that nitrous oxide can also suppress completely MEPs when given with propofol as well [4]. Another study found that both 50% nitrous or doubling the propofol dose both could decrease the amplitude of tc MEP [5].  Zentner [6] found that using 66% nitrous oxide reduced the recorded MEPS to 6% of baseline.  Todd Sloan, in a review of motor evoked potential monitoring stated, "when compared at equipotent anesthetic concentrations, nitrous oxide produces more profound changes in myogenic tcMEP than any other inhalational anesthetic agent.
 On the other hand, more recent work, has found that desflurane can be utilized effectively when IOM is required. Lo et al. successfully measured MEPS in 9/10 patients undergoing scoliosis surgery with Desflurane (mean 3.3%) + 60% nitrous oxide [3].   In fact, Desflurane + nitrous oxide was compared to a propofol narcotic technique when measuring MEPS [7].  They compared 20 consecutive patients randomly  assigned to one of the two groups (10 in each group).  The Desflurane group received a mean ET concentration of 3.4% + 66% nitrous oxide.  MEPS were adequate in all 20 cases. In fact, prior to instrumentation, amplitudes were higher in the Desflurane group (85 mV vs. 59.1 mV).    These studies (done with nitrous) combined with the evidence that nitrous oxide is a potent inhibitor of MEPS recording, supports the technique of using Desflurane without nitrous oxide with minor effect on MEPS.
Published results suggest that to accomplish the 1 MAC equivalent with propofol, it is required to achieve plasma levels of 6 mcg/mL.  This requires an infusion of approximately 200 mcg/kg/min.  Other authors have already shown that MEPS are reduced when propofol is given at much lower dosages than this. Therefore, on a dose equivalent basis, propofol's advantage over Desflurane is likely very small.  Additionally, most studies using propofol for MEPS recording used infusion rates of around 100 mcg/kg/min.
       Propofol does indeed provide for easy recording of MEPS, and in particular, with pulti pulse stimulation, seems to allow very good signals.  However, when dealing with a hypovolemic patient with multiple risk factors for POVL, adding propofol to the equation in to improve MEPS is risky.  Furthermore, as propofol will likely worsen MAP, in reality, the signals are likely not to improve or worsen as low MAP is particularly inhibitory to the recording of MEPS.
       In reality, the key is to obtain good baseline readings, and then maintain a steady anesthetic state.  Whether propofol or desflurane is used is less important than keeping the baseline anesthetic stable. If during a procedure, attenuation of the signal occurs in one part of the body, it is important to find the source of this inhibition.  Any changes to the anesthetic would be important to note. However, anesthetics will result in global signal reduction, not focal.  Other causes of global signal reduction include, severe anemia, hypotension, and hypoxia.  Focal reduction of signal is most likely related to focal ischemia or mechanical trauma..  If this can be ruled out, then lead placement or other mechanical issues related to the measuring process such as impedance should be ruled out first.  In the above presented case, the patient had significant ongoing bleeding with decreased blood pressure.  He had significant anemia (nadir of about 7 gm/dL) and his blood pressure was suppressed (MAP of 58 to 62 mmHg).   I was running desflurane at a steady concentration of 4% which had not changed during the case.  Dexmedetomine was being titrated to effect and had been decreased due to the patients decreased blood pressure.  The technician's request to switch to 3% desflurane + a propofol infusion was not logical for a number of reasons.  First, as mentioned, a stable anesthetic level will aid in the intepretation of MEPS.  Decreasing the desflurane and adding propofol (he didn't specify what dose he wanted) would disrupt this.   Propofol also suppresses the MEPS to a degree not much less than desflurane if you consider the dose equivalent amount.  Another important factor is the risk for sudden patient movement.   As referenced in a previous post, patients are far more likely to move suddenly during propofol anesthesia than when receiving volatile anesthetics.  Of all the potent inhaled anesthetics, some evidence suggests Desflurane is the most effective in the prevention of patient movement [8].  Therefore, despite that propofol is the best from a neuromonitoring stand point, it is not that much better than desflurane and has the disadvantages of not effectively inhibiting patient movement, inability to monitor real time plasma concentration levels, and causing profound hypotension in anemic hypovolemic patients.  There is one other major disadvantage of propofol.  In the setting of spinal surgery with instrumentation, the whole goal with neuromonitoring is to avoid causing injury to the spinal cord or roots.  The injury is often ischemic in nature although mechanical trauma is also a possibility.  The potent inhalational agents have the beneficial property of anesthetic preconditioning which protects organs against ischemic reperfusion damage. This would be pertinent not only for spinal cord/nerve root ischemic protection, but also, retinal  ischemic protection.

So, if propofol is a poor choice in this setting, what are some other options.  Todd Sloan reports in his review on MEPS that in addition to use a mulit pulse technique, the interstimulus interval (ISI) made need to be varied until the optimal response is found.  For example, he states that at low concentrations of Isoflurane (i.e. 0.2%) a wide ISI  (i.e. 2-5 ms).  However, at higher concentrations (i.e. 0.4-0.6%), a wider ISI is better (i.e. 4-5 ms). At even higher concentrations (1%), the most effective ISI was 1 ms.  In short, its likely best to optimize the ISI to the concentration early on in the case.  Other considerations when its difficult to record MEPS are other anesthetics.  Ketamine and Etomidate are both ideal in that do not effect MEPS to any appreciable degree and also increase SSEP recordings.  Both of these also have positive hemodynamic profiles. Unfortunately, etomidate as an infusion suppresses adrenal function and, therefore, has fallen out of favor.  Ketamine at appropriate dosages (0.25 mg/kg/hr to 0.5 mg/kg/hr), is less likely to cause the negative psychological side effects (hallucinations). Several studies have found ketamine to have a protective analgesia effect in general surgical cases and one study in particular found that intraoperative ketamine reduces post operative morphine consumption in patients on chronic opioid pain therapy undergoing spinal surgery [9].  Todd Sloan reports in a review of IOM that in patients where MEPS are "very sensitive" to inhalational agents and neuromuscular blockers, he uses propofol and then adds ketamine if this isn't sufficient.  His typical protocol calls for:  Mix ketamine into propofol 50 cc's at 2mg ketamine to 1 cc (10mg/cc) Propofol.  He then titrates down on the ketamine concentration for each subsequent 50 cc syringe infused over the duration of the case; i.e. 1st syringe 2mg Ketamine/cc Propofol, 2nd syrine 1.5 mg Ketamine/cc Propofol, 3rd syringe; 1mg Ketamine/cc Propofol infused. etc.  The lasty syringe contains only Propofol.  Of course, Propofol can be avoided altogether in many cases.

In conclusion; IOM is becoming very prevalent and in particular, Motor Evoked Potentials are ever more common.  The anesthesiologist needs to be aware of those things that will affect the IOM and how to adjust the anesthetic so that IOM can be successful while considering the other important aspects of the anesthetic: Immobility, Anesthesia, and Amnesia.





1. Pajewski TN, Arlet V, Phillips LH.  Current approach on spinal cord monitoring: the point of view of the neurologist, the anesthesiologist and the spine surgeon.  Eur Spine J. 2007:18. 115-129.

2.  Pechstein U et al.  Isoflurane plus nitrous oxide vs. propofol for recording of motor evoked potentials after high frequency repetitive electrical stimulation.  Electroencephalogr Clin Neurophysiol. 1998: 108(2): 175-81.

3. Lo YL, Dan YF et al.  Intraoperative monitoring in scoliosis surgery with multi-pulse cortical stimuli and desflurane anesthesia.  Spinal Cord. 2004;42: 342-5.

4.  Kunisawa T et al.  A comparison of the absolute amplitude of motor evoked potentials among groups of patients with various concentrations of nitrous oxide.  J Anesth. 2004;18:181-4.
5.  van Dongen EP. et al.  The influence of nitrous oxide to supplement fentanyl/low-dose propofol anesthesia on trancranial myogenic motor-evoked potentials during thoracic aortic surgery.  J cardiothorac Vasc Anesth.  1999; 13:30-4.
6.  Zentner J et al. Influence of anesthetics-nitrous oxide in particular-on electromyogrphaic response by tc electrical stimulation of the cortex.  Neurosurgery. 1989; 24:253-6.
7.  Lo YL et al. Intraoperative motor-evoked potential monitoring in scoliosis surgery: comparison of desflurane/nitrous oxide with propofol total intraenous anesthetic regimens.  J Neurosurg Anesthesiol. 2006; 18:211-4.
8.  Wulf H. et al. Neuromuscular blocking effects of rocuronium during desflurane, isoflurane, and sevoflurane anaesthesia.  Can J Anaesth. 1998;45: 526-32.
9. Loftus R et al.  Intraoperative Ketamine reduces Perioperative Opiate Consumption in Opiate-Dependent Patients with Chronic Back Pain Undergoing Back Surgery. Anesthesiology. 2010;113: 639-46.

Ketamine in chronic pain patients

The September edition of Anesthesiology reports that in patient's who are chronically taken opioids for pain, using ketamine intraoperatively may be useful to decrease morphine consumption after spinal surgery. The authors randomized pt who were taking preoperative opioids to either 0.5 mg/kg ketamine preop plus 10 mcg/kg/min infusion until wound closure vs. placebo. Many previous studies looking at ketamine have studied it in opioid naive patients and have run the ketamine infusion into the post operative period for up to 72 hrs. This study stopped the infusion at the end of surgery which I believe is important for the practicing anesthesiologist, since most hospital policies will not allow a ketamine infusion on the floor without having a locked pump which adds to logistical constraints and increases costs. Lavand homme et al. have already shown that adding ketamine to an epidural for abdominal surgery can reduce chronic pain up to 6 months later. This study looked at patients having spinal surgery. The results: decreased morphine consumption at 24 hr by 30%, at 48 hrs a 37% decrease. In the PACU, VAS was decreased by 26.7%. This is admittedly modest. However, once again, in this study, ketamine was able to decrease pain scores at a 6 week follow up visit (by 26.2%). This seems like a predictable reaction as we know that ketamine inhibits NMDA which is important in producing secondary hyperalgesia which is thought to be a physical manifestation of wind up (central sensitization) at the spinal cord. It is thought that this is responsible for the development of persistent post surgical pain (chronic pain). As a side note, the authors also reported that patients who received ketamine also reported a decreased use of antidepressants at their 6 week follow up (10% in placebo vs. 0% in the ketamine group). Previous authors have also reported that ketamine has significant antidepressant effects. Also important to note; ketamine was much more effective in decreasing morphine use in patients who were using 40 mg per day or more of oral morphine (or its equivalent). In these patients, morphine use was decreased by 52% at 48 hours, whereas, there was no difference in patients taking less than this equivalent amount preoperatively.

The authors conclude that ketamine probably has a role in patients undergoing moderately painful surgery in reducing opioid consumption. Unfortunately, morphine related side effects were not different between groups.

Ketamine for the reduction of both acute and chronic post operative pain

A 54 year old female comes to the OR for an open hemicolectomy. The patient is offered a thoracic epidural for post op pain control. Is there another medication that might be considered to reduce her acute post operative pain scores? Is there any merit to aggressive treatment of her post op pain in hopes of reducing her chance of developing chronic post surgical pain?

After major abdominal and thoracic surgery, it is now well accepted that aggressive treatment of acute post operative pain is important and may enhance recovery to some degree. What is less well recognized and even less well understood is the relationship of acute post op pain to the development of chronic post surgical pain. The incidence of the development of chronic post surgical pain is unclear and varies from surgery to surgery. What is clear however is that multimodal analgesia is preferred in the acute setting and may be beneficial in reducing chronic pain as well.
Major abdominal surgery, like thoracic surgery, can result in significant post operative pain in the first 3 to 4 days after surgery. In a small subset of patients, there is a risk of developing a chronic post surgical pain syndrome resembling in some ways neuropathic pain. Although there are no criteria that can allow easy prediction of those patients who will go on to develop chronic post surgical pain, it has been demonstrated that those patients who have a greater degree of primary and secondary hyperalgesia after surgery are at higher risk. In a paper on the epidemiology of chronic pain, Visser EJ noted that wound hyperalgesia (which suggests central sensitization) correlated better with chronic pain after 6 months than did acute post operative pain (R=0.81)[1] In other types of surgeries, (mastectomy, thoracotomy and inguinal hernia repair), there is tight correlation between acute and chronic pain. In either case, it is likely that central sensitzation plays a critical role in the development of chronic post surgical pain. Neuronal blockade with local anesthetics are one very effective way to mitigate the development of central sensitzation; but for many patients this is not an option. Ketamine, on the other hand, is inexpensive, readily available in most operating room settings, and in low doses, can be given with relatively few side effects. So is there any benefit in administering ketamine to our patients? In theory, it should. It is known that ketamine acts as an NMDA antagonist, and the NMDA receptor is a major player in central sensitization. In fact, Ilkjaer S et al. demonstrated in a clinical trial with 19 volunteers that ketamine does in fact reduce hyperaglesia (marker for central sensitization) when given in a dosage of 0.3 mg/kg with minimal side effects[2]. There are numerous studies in animal models in which ketamine has also demonstrated the prevention and even reversal of both injury induced hyperalgesia and opioid induced hyperalgesia. In clinical trials with pain as an outcome, ketamine has demonstrated good effect although to a lesser degree than would be expected based on animal models. Likely reasons for this include the fact that ketamine binds to many other receptors (opioid, cholinergic, Na channels and voltage sensitive Ca2+ channels). Furthermore, the NMDA receptor is not the only mediator of central sensitization and chronic pain. Other receptors/pathways include Cox-2, Alpha 2 delta subunit of Ca2+ channels, AMPA receptors, NOS, dynorphin and hemoxygenase.
Neverthless there are several important RCTs that have demonstrated that even at low dosages, ketamine can play a small role in the reduction of chronic and acute pain. One of the most striking studies was done by Marc De Kock, Patricia Lavand'homme and Hilde Waterloos[3]. They had 5 groups of patients in which each group underwent major abdominal surgery for rectal adenocarcinoma and all patients were giving an epidural with bupivacaine, clonidine and sufenta for pain control. Group 1 was placebo, Group 2 was given a bolus of ketamine of 0.25mg/kg and then an infusion for the duration of surgery of 0.125 mg/kg/hr. Group 3 was given double the dose of group 2 and groups 4 and 5 were given respectively the same ketamine doses as groups 2 and 3, but the ketamine was administered epidurally. Pain scores at rest and during mobilization were not statistically different for the first 48 hours after surgery, although, morphine use was statically less in group 3 (IV ketamine at 0.5 mg/kg + 0.25mg/kg/hr infusion) at 48 hours. The authors also measure the area of hyperalgesia around the wound as an indicator of the degree of central sensitization suffered by the patients which correlates with the development of chronic post surgical pain. They found that the area of central sensitization was statiscally significant only in group 3 (ketamine IV at 0.5 mg/kg bolus + 0.25 mg/kg/hr infusion). the authors then followed up with the patients in each group to measure residual pain at 2 weeks, 1 month and 6 months. Once again the number of patients with residual pain was statistically less only in group 3. The take home message from this RCT is that ketamine should be given IV (not neuraxially) and at the appropriate dosage to realize the benefits of reduced chronic post surgical pain. More importantly, ketamine was shown to be effective despite that patients were given epidurals for post op pain control. Stubhaug A et al. also found that ketamine can decrease the degree of central sensitization after abdominal surgery[4]. They performed a DB RCT with 20 living kidney donors. Once group received ketamine as a bolus prior to incision of 0.5 mg/kg (same as the De Kock study) followed by an infusion of 0.12 mg/kg/hr x 24 hr, then reduced to 0.06 mg/kg/hr x 48 hr. They found that the area of hyperalgesia was less on days 1, 3, and 7 after surgery in those patients given ketamine. Unfortunately they did not follow up patients at later time periods in order to measure the incidence of chronic post surgical pain.

Ketamine also can play a role in thoracic surgery whether patients are treated with an epidural or not. Perkins and colleagues did an analysis of the incidence of chronic pain after thoracotomy and found that an outstanding 47% had chronic pain. In their analysis, they did find that acute pain after surgery did predict those that went on to develop chronic pain. Neuraxial analgesia in the perioperative period has been shown to reduce the incidence of both acute and chronic pain [5,6]. However, despite the use of epidural analgesia for post thoracotomy pain, there are individuals who do have problematic acute pain and chronic pain. In other instances, thoracic epidural analgesia is contraindicated. Therefore, Ketamine can be a useful adjuvant for the anesthesiologist who gives priority to reducing the incidence of chronic post surgical pain. Evidence for this comes to us from a few studies. Chow and colleagues [7] found in a DB, RCT of 14 patients undergoing thoracotomy that patients receiving ketamine vs. morphine only had lower VAS scores at 6, 24, and 48 hrs as well as upto 56% less morphine requirements. Furthermore, at 2 months the patients who had received ketamine had less symptoms of chronic pain on the McGill Pain Questionnaire and decreased hyperalgesia indicating suppression of central sensitization. The ketamine dose was 0.15 mg/kg/hr for 3 days. Increased side effects were not found in the ketamine group to be statistically significant. In another study published in Anesthesiology [8] in 2006 found that ketamine added to patients already receiving epidural anesthesia for open thoracotomy was beneficial. Ketamine was titrated to maintain plasma concentrations of only 20 ng/mL over a 3 day period. The initial dose was 0.05 mg/kg/hr (very small). Patients who received ketamine in addition to thoracic epidural reported lower pain scores at 48 hrs, 1 week, 1 month and 3 months after surgery.

It seems that there is reasonable evidence that it might be prudent to utilized ketamine in small dosages in certain patients (probably those not suffering from dementia or at risk of acute delirium in the hospital) to prevent the development of chronic post surgical pain. Major open abdominal surgery, reconstructive breast surgery and thoracic surgery are most likely to result in chronic pain syndrome. However, the utilization of ketamine to prevent or mitigate acute post operative pain may also be helpful. Three large reviews/meta analyses [9,10, 11]have been published on ketamine. They included a large number of studies and comprised a variety of different surgeries. The first, a large systematic reivew by Subramaniam K et al. concluded that ketamine was a safe and useful adjuvant to standard practice opioid analgesia. The second, another systematic review of 24 articles looking for evidence of preventive analgesia (i.e. Pain control lasting longer than expected based on the pharmakokinetics of the medication) concluded: Ketamine provided additive pain control immediately and beyond the expected clinical action of the drug. The authors theorized that ketamines preventive analgesic characteristics resulted from its ability to prevent central sensitization. Thirdly, Himmeslseher S et al. published a meta analysis on ketamine. They concluded that subanesthetic ketamine used during GA provides pain prevention in the post op period and made the following recommendations:
1) Major surgery: give bolus prior to incision of 0.5 mg/kg followed by infusion of 0.5 mg/kg/hr during surgery and then reduce to 0.12 mg/kg/hr x 24 hrs after surgery.
2) Minor surgery: bolus of 0.25 mg/kg then 0.25 mg/kg/hr during surgery.

In conclusion, I consider ketamine for all major abdominal, thoracic and even orthopedic surgeries where I expect pain to be severe. I consider ketamine to be a one modality of pain control in a large possible reperatoire of interventions (NSAIDs, local anesthetics, opioids, Alpha 2 agonists). I avoid or use smaller doses of ketamine in elderly patients ~70 and up, or in any patient with significant psychiatric disease. I also discontinue ketamine use within 45 min of the end of surgery or even 1 to 2 hours for prolonged surgical cases (4 to 6 hours). Anesthesiologists often don't follow their patients for 1 year after surgery to see whether they develop chronic pain, and therefore often do not consider possible interventions to mitigate this risk. Nevertheless, in a small subset of patients, the modalities of pain control we utilize will potentially effect outcomes up to a year in the future. Therefore, it is incumbent upon us to be abreast of the literature on post op pain control, chronic post surgical pain syndromes and the possible preventive measures available to us.


[1] Visser EJ. Chronic post-surgical pain: Epidemiology and clinical implications for acute pain management. Acute Pain; 8(2) 2006: 73-81.

[2] Ilkjaer S et al. Effect of systemic NMDA receptor antagonist (ketamine) on primary and secondary hyperaglesia in humans. BJA. 1996; 76: 829.

[3] De Kock M, Lavand'homme P, Waterloos H. Balanced analgesia in the perioperative period: is there a place for ketamine? Pain 92(2001) 373-380.

[4] stubhaug A, Breivik H, Eide PK,Kreunen M and Foss A. Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization to pain following surgery. Acta Anaesthesiol Scand 1997; 41: 1124-1132.

[5] Obata H, Saito S, Fujita N, et al. Epidural block with mepivacaine before surgery reduces long-term post thoracotomy pain. Can J Anaesth 1999;46:1127-32.

[6] sentruk M, Ozcan PE, talu GK, Kiyan E, Camci E, Ozyalcin S, Dilgege S, Pembeci K: the effects of three different analgesia techniques on long-term postthoracotomy pain. Anesth Analg 2002;94:11-5.

[7] Chow TKF, Goodchild CS, Shanahan EA, O'Flaherty M, NMcNeil JJ. Adding ketamine to morphine reduces acute and chronic post-thoracotomy pain. Anaesth Intens Care 2002; 30:692-3.

[8] Suzuki M, Haraquiti S, Sugimoto K, Kikutani T, shimada Y, Sakamoto A. Low dose intravenous ketamine potentiates epidural analgesia after thoracotomy. Anesthesiology. 2006 Jul: 105(1): 111-9.

[9] Subramaniam K, Subramaniam b, Steinbrook RA. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic reivew. Anesth Analg 2004;99:482-95.

[10] McCartney CJ, Sinha A, Katz J. A Qualitative systematic Review of the role of NMDA receptor antagonists in Preventive Analgesia. Anesth Analg. 2004; 98: 1385-400.

[11] Himmeslseher S, durieux ME. Ketamine for perioperative Pain Management. Anesthesiology. 2005; (102):211-20.