Spine surgery may induce more intense pain than other surgical procedures because of its multiple factors. First is the incisional pain, which activates peripheral receptors that transmit the information via spinal cord to the brain where it is modulated.1 Incisional pain can be severe in spine surgery patients as it may extend over several dermatomes. Second, damage to structures such as bone, ligaments, muscle, intervertebral discs, and facet joints causes musculoskeletal pain. Among these, periosteal pain is believed to be the most severe as the periosteum has the lowest pain threshold nerve fibers of the deep somatic structures.2 Moreover, periarticular tissues are richly innervated and this gives rise to continuous deep somatic pain and bouts of severe reflex spasms of muscles supplied by the same or adjacent spinal cord segment. These spasms may result in severe or excruciating pain that may last for long duration.3 Though spine surgery could also cause irritation and damage to spinal nerve roots and the cord, this article will not address postoperative analgesic management of pain resulting from such causes.
Over the past several years, advances in surgery have made it possible to perform minimally invasive surgery (MIS) procedures with smaller incisions and decreased muscle trauma. These procedures have grown in numbers over the last 10 years with continued advancements being made. MIS surgery leads to decreased tissue damage and therefore less surgical inflammatory response (inflammatory mediators such as interleukins [IL], cytokines, and prostaglandins) than conventional surgery.4 Decreased surgical inflammatory response has been demonstrated to lead to decreased morbidity in patients.5 Increased levels of IL-6 after surgery has been linked to postoperative morbidity.6 It has been clearly demonstrated that the release of inflammatory mediators such as the neurotransmitters and ILs (IL-6, IL-1) increases with the magnitude of the surgical trauma. The more extensive the surgical trauma, the higher the IL-6 levels in the blood.7,8 The local surgical inflammatory mediator prostaglandin (prostaglandin E2 being the most important for pain) plays a critical role in postoperative pain and rehabilitation after orthopedic surgery.9 Smaller incision, shorter length of hospital stay, and earlier return to daily activities are all benefits of this new era of MIS, which requires the surgeons and anesthesiologists to work together to improve patient care. This collaborative effort between anesthesiologist and surgeons has led to tremendous success in establishing fast-track protocols,10 which have led patients to be discharged home the same day after major joint surgery.11 This article will discuss the various anesthetic and analgesic options for preoperative (Table 1) and postoperative management (Figure 1) of patients undergoing MIS of the spine.
Among the various surgical procedures, the collaboration between the surgeon and anesthesiologist is perhaps closest in MIS where optimizing rapid recovery and long-term outcome are the main objectives. The anesthesiologist involvement often starts in the spine surgeon's office at the time of scheduling surgery. It is indeed at this stage that the patient is evaluated, educated to help set expectations, and a multimodal approach to the perioperative management of pain is initiated.12 It is at this time that the other medical disciplines that are going to be involved with the MIS patient in the postoperative period need to educate the patient.
Patients presenting for spine surgery with low back pain tend to be prescribed various types of medications, including opioids. Patients taking opioids for a period greater than 4 weeks often develop tolerance and opioid-induced hyperalgesia (OIH), though there can be significant patient to patient variability.13 Patients with preexisting chronic back or neck pain and narcotic tolerance and dependency present a unique challenge for postoperative analgesic management. It is imperative that these patients be recognized before surgery so that they can be managed appropriately in the postoperative period. When recognized before surgery, these patients should be sent for a pain management consultation in an attempt to wean off the narcotics or to find a combination therapy without opioids to provide relief for the chronic pain.14 In addition, prospective cohort studies in patients undergoing spine surgery have shown that greater than 50% of the patients are either obese or morbidly obese.15 The incidence of obstructive sleep apnea is often underdiagnosed in these obese and morbidly obese spine surgery patients.16 The recently developed17 screening questionnaire (STOP: Snoring, Tiredness during daytime, Observed apnea, and High blood pressure), which has been validated, should be used on all patients in the spine surgeon's office and lead to appropriate consultations.18 The presence of obstructive sleep apnea presents a challenge not only in the intraoperative period but also for postoperative analgesic opioid therapy, where high dose narcotics in such patients can lead to adverse respiratory events. Identification of these patients before surgery will ensure that these patients will not be on the fast-track perioperative protocol if accepted for MIS of the spine. In addition to medical preoperative preparation and patient education by the health care providers, preoperative physical therapy education has been demonstrated to be beneficial in the fast-track joint replacement programs;19,20 these should be considered and implemented for a successful MIS spine fast-track program.
A multimodal approach to perioperative pain management should be considered for MIS of the spine.21 It is based on a combination of a nonsteroidal anti-inflammatory drug (NSAID) or celecoxib oral (Celebrex), (only cyclooxygenase-2 inhibitor [COX-2]) with sustained release opioids. Celecoxib is usually administered at a dose of 200 mg orally twice a day and could be started 2 to 3 days before surgery. The half life of celecoxib ranges from 6 to 12 hours. The goal of initiating multimodal therapy before surgery is to allow medications to accumulate before the surgical trauma and consequently minimize the stimulation of the inflammation cascade that was discussed earlier in the text.22 Such an accumulation of medication has been demonstrated to suppress the prostaglandin pathway (prostaglandin E2)9 in the cerebrospinal fluid and to result in decreased postoperative pain after orthopedic surgery. On the morning of surgery, the patient receives celecoxib 400 mg orally. This is followed by 200 mg BID for at least 2 weeks after surgery. For lumbar spine surgery (excluding fusion), the addition of NSAIDs to opioids has been demonstrated to be superior to opioids alone in a meta-analysis.23 There is significant controversy24–26 over the use of NSAIDs and COX-2 inhibitors for patients undergoing spinal fusion surgery. The recent conclusion from a meta-analysis of 5 retrospective comparative studies (n = 1403 participants) was that short-time (<14 days) exposure to normal-dose NSAIDs was safe after spinal fusion, whereas short-time (<14 days) exposure to high-dose ketorolac increased the risk of nonunion, which means that the effect of perioperative NSAIDs on spinal fusion might be dose-dependent. However, further studies are needed to find out whether long-time exposure to normal-dose NSAIDs can also increase the risk of nonunion and which type of NSAIDs are likely to have an adverse effect on spinal fusion surgery.27 As such, on the basis of current information, patients undergoing MIS spine fusion should not receive celecoxib or NSAIDs until further large prospective randomized clinical studies are completed with long-term outcome. Contraindications to NSAIDs and celecoxib include allergy to aspirin and for celecoxib sulfonamide allergy. The dose of NSAIDs including celecoxib should be reduced by half in patients with borderline renal failure and in those older than 70 years. The role of orally administered 1000 mg acetaminophen before surgery should also be considered as the mechanism of analgesia for this drug is believed to be at the central nervous system (brain) unlike the NSAIDs.28
The NSAIDs or COX-2 regime should be combined with a sustained release opioid such as oxycodone (OxyContin) at a dose of 10 to 20 mg to have the entire benefit of the multimodal therapy. Sustained release oxycodone 20 mg administered before surgery and continued into the postoperative period has been demonstrated in randomized controlled trials to improve outcomes (earlier recovery of bowel function and higher patient satisfaction) compared to oral placebo with intravenous morphine in patients undergoing spine surgery.29
Recently, gabapentin or pregabalin (Lyrica) has been used by several spine surgeons with good success. Most of the clinical trials have used oral 600 mg of gabapentin before surgery (1 hour before surgery) and continued (gabapentin at 600 mg 2 or 3 times a day) for the next 5 to 14 days depending on the extent of surgical trauma.30 Pregabalin at a dose of 100 to 150 mg before surgery and continued in the postoperative period at a dose of 75 mg twice a day has been used in multiple joint replacement surgical patients and resulted in decreased acute and chronic pain in randomized controlled designs.31 However, at this point, the exact dosing and duration need to be properly established to avoid the sedative side effects of gabapentinoids. Sedation is a side effect that may significantly delay the ability of the patient to start physical therapy and therefore delay early discharge from the hospital, especially in elderly patients.32 Pregabalin/gabapentin acts via the α2-delta subunit of the calcium channel resulting in decreased release of various neurotransmitters, thus providing analgesia.33 Gabapentin (Neurontin) works via the modulation or binding to the α2δ subunit of the presynaptic voltage-dependent calcium channel (VDCC). It has been demonstrated experimentally that there is an up-regulation of the α2δ subunit at the VDCC in the dorsal root ganglions and spinal cord after peripheral nerve injury (surgical trauma). Gabapentin is thought to act at these VDCCs by inhibiting calcium influx and subsequently the release of excitatory neurotransmitters involved in nociception. Gabapentin has a half life of 5 to 7 hours. Common side effects include dizziness, somnolence, ataxia, and fatigue. Pregabalin has greater solubility than gabapentin and therefore crosses the blood–brain barrier rapidly with predictable pharmacokinetics. The half life of pregabalin is approximately 6.3 hours. Common side effects include somnolence, dizziness, ataxia, diplopia, and weight gain. For MIS of the spine, a dose of 600 mg of gabapentin or 100 mg of pregabalin should be administered before surgery (1 hour before surgery). A dose of 600 mg twice a day or pregabalin 75 mg twice a day can be continued in the postoperative period for 5 to 10 days depending on the extent of surgical trauma (the greater the degree of surgical trauma and inflammatory response, the postoperative regime should be continued for 14 days).
On arrival in the preoperative holding area, patients should receive liberal intravenous fluid therapy. Preoperative hydration (20 mL/kg) of patients has been shown to decrease the incidence of adverse outcomes such as postoperative nausea, dizziness, and drowsiness,34 especially if fast-track MIS spine protocols are to be implemented; however, the presence of cardiac or renal failure necessitates changes to this approach. Postoperative nausea and vomiting (PONV) is another major challenge and requires prophylactic measures for MIS of the spine patients. In the preoperative holding area, patients are screened for risk of developing PONV using the current guidelines.35 PONV can be effectively prevented by the use of a transdermal scopolamine patch (1.5 mg), but as it is associated with sedation, it is important to verify that there are no contraindications.36 The most common pharmacological approach is based on the use of HT3 blockers alone or in combination with other drugs depending on the patient's risk factors for PONV.37 Recently, a new substance P inhibitor, Aprepitant,38,39 alone or in combination with an HT3 blocker has been used in high-risk patients identified before surgery for PONV, including patients undergoing MIS of the spine.
General anesthesia, using propofol for induction with a short-acting muscle relaxant and using an endotracheal tube (GETA) is the usual procedure adopted for MIS spine surgery. Since MIS procedures are performed with the patient mostly in the prone position (though lateral and supine positions can also be used depending on the surgical approach), the ability to secure the airway of the anesthetized patient is of utmost importance. As mentioned earlier, the ability to recognize a patient with a difficult airway is critical. Once GETA is established, there are 2 options for maintenance of anesthesia as follows: one is the use of inhalational agents such as sevoflurane or desflurane and the other is the use of intravenous opioid agents such as sufentanil or remifentanil infusions. The benefit of using intravenous (IV) opioid maintenance anesthetic is that it provides a constant steady state of anesthesia and analgesia while maintaining hemodynamic stability.
Neurophysiological Monitoring and Anesthesia
The commonly used neurophysiologic monitoring methods used are somatosensory-evoked potentials (SSEP), motor-evoked potentials, and electromyography. Inhalational agents are known to decrease the amplitude and increase the latency of MEP SSEP signals, which may be misconstrued as an injury to a spinal nerve.40 The appropriate anesthetic of choice for patients having neurophysiological monitoring is yet an area of controversy.41 Continuous infusion of intravenous opioid therapy may be beneficial from a neurophysiologic viewpoint (minimal changes in the signals), but it may make fast-track MIS spine surgery challenging from the opioid-induced adverse events. The use of short-acting, low-dose opioid infusions such as remifentanil may be advantageous in these MIS patients undergoing spine procedures.42 Another choice to consider is intravenous ketamine, which has been shown to have minimal suppression of SSEP signals.43 The use of low-dose intraoperative intravenous ketamine infusion has been demonstrated recently in a randomized controlled trial of opioid tolerant patients undergoing spine surgery to decrease the postoperative narcotic requirements.44 However, when large doses of intravenous opioids are used, they are associated with PONV. A newer class of analgesic such as dexmedetomidine infusion can be used during the maintenance of anesthesia, as it does not have a significant effect on SSEP.45 It is important to realize that when SSEP signals are monitored it is the changes from the baseline that are monitored during the intraoperative period. As such administration of oral analgesics before surgery (multimodal therapy discussed above) and obtaining steady state plasma level of the analgesic before the surgical procedure (before baseline measurements are made for SSEP) will avoid the anesthesiologist from administering a bolus of medications, which can result in SSEP signal changes.
Role of Surgeon in Perioperative Analgesia
Liberal use of local anesthetic (lidocaine 1% with epinephrine: 20–30 mL) should be a standard practice before any surgical incision is made.46 The use of a local anesthetic will not only decrease the surgical hormonal response but also lessen the requirement of analgesics (intravenous) by the anesthesiologist, and therefore decrease PONV. Further, the deeper tissues should be infiltrated with bupivacaine 0.25%, ropivacaine 0.2% (safer in terms of cardiotoxicity) or levobupivacaine 40 to 50 mL at the time of tissue dissection before commencing the surgery on the spine for the pathology.47 After the surgical procedure has been completed liberal use should be made of long-acting local anesthetics, taking care that the drug does not spread to the nerve roots (as it may obscure neurologic assessments made during the immediate postoperative period). However, there are reports of infiltration of bupivacaine 0.5%, 2 mL onto the nerve root sheath (at the level of disc surgery) before disc surgery, resulting in decreased postoperative analgesic requirement.48 Randomized controlled clinical trials have demonstrated decreased postoperative opioid consumption and pain scores when ropivacaine 0.5% (40 mL) was injected and a catheter placed to deliver ropivacaine 0.2% over the next 24 to 48 hours.49 This procedure using ropivacaine (ropivacaine infiltration of 0.5% 40 mL with a catheter for 24 hours infusion of ropivacaine 0.2%) may be useful for MIS spinal fusion patients as they are not suitable for the complete multimodal analgesia (NSAID or COX-2 inhibitors excluded) procedure as discussed earlier.
There are reports of lumbar spine surgery being performed under spinal or epidural anesthesia. The reported benefits of this type of anesthesia are decreased blood loss, improved hemodynamic stability, and reduction of postoperative pain leading to a decrease in opioid use and thereby a decreased incidence of PONV.50 Lumbar spine surgery under spinal anesthesia requires the full understanding and cooperation of the surgeon, anesthesiologist, and the patient. Typically, a single-level procedure should take between 30 and 90 minutes, depending on the size of the patient and adhesion or scar tissue that may complicate the surgery. It should also be noted that some procedures, such as percutaneous discectomy, can be performed under monitored anesthesia care with liberal local anesthetic infiltration.
Video-assisted thoracoscopic surgery to the anterior thoracic spine requires 1 lung ventilation. Though it is anticipated that the duration of 1-lung ventilation using the double lumen tube will be kept to a minimum for fast-track MIS spine protocol, care should be taken to ensure that adequate pulmonary toileting is performed before extubation. In addition, maintenance of deep muscle relaxation and neurophysiological monitoring can present a challenge in these patients. Some of these problems could be minimized by the liberal use of local anesthetics by the spine surgeon and use of short-acting opioid infusions and intravenous ketamine as described earlier in the text.51 Though video-assisted thoracoscopic surgery is known to have decreased postoperative pain in the immediate and long-term period compared to open thoracotomy, there could still be irritation of the intercostals nerves, leading to chronic neuralgia.52 The incidence of chronic pain after surgery can be reduced by the use of multimodal analgesia described earlier in this article.
Prevention of Hypothermia
To prevent patient hypothermia, it is necessary to avoid excessive cooling of the operating room. It is also important to routinely use a forced warming device and to use a fluid warmer for all intravenous fluid administration in the operating room. Mild hypothermia has been shown to increase blood loss and transfusion requirements during major orthopedic surgery.53 In addition, maintenance of normothermia has been associated with reduced incidence of postoperative wound infection.54
Whatever anesthetic protocol is followed, intraoperative anesthetic drugs and management should focus on ambulation of the patient, and therefore measures for prevention of PONV are crucial. To reduce the risk of PONV and optimize rapid recovery, it is important to (i) minimize the use of intravenous opioids during surgery, (ii) avoid or minimize the use of neuromuscular blockade reversal agents, and (iii) minimize hypotension by optimizing the dose of anesthetics and providing appropriate fluid replacement and vasopressor therapy as needed. During the intraoperative period, patients who undergo this type of surgery also receive preventively PONV medications. Common approaches for prophylaxis of PONV include the use of HT3 blockers such as ondansetron 4 mg IV administered 15 minutes before the end of surgery, 25 to 50 mg of dolesatron IV after the induction of surgery, or granisetron 0.3 to 1 mg administered before the induction of anesthesia alone or in combination with dexamethasone 6 to 10 mg IV administered after the induction of anesthesia. An appropriate volume of fluid is essential to facilitate the appropriate recovery of the patient and to minimize the frequency of orthostatic episodes. The total volume of fluid administered depends on the patient's medical history and the blood loss associated with surgery.
Postoperative pain is the most common cause for delayed discharge, and the main reason for unanticipated hospital admission.55 Inadequate pain control will result in patient dissatisfaction; this can result in a cascade of events such as increased cytokine release, acute-phase reactant release, increase in stress hormones, activation of the renin-angiotensin-aldosterone system, coagulopathy, and altered immune response. These can all lead to spinal cord sensitization and may result in chronic pain after surgery. Spinal cord sensitization is believed to occur due to the barrage of inflammatory mediators released during the perioperative period in the general circulation leading to up-regulation of inflammatory mediators in the spinal cord. These increased inflammatory and microglia activities in the spinal cord from surgery trauma can lead to spinal cord sensitization.56 The multimodal therapy commenced before surgery should be continued into the postoperative period so that the fast-track MIS spine patients can rehabilitate and be discharged home early.57
NSAIDs and COX-2 Inhibitors
As stated above, the NSAID or COX-2 inhibitor commenced before surgery should be continued for 5 to 14 days depending on the extent of surgical trauma induced, except for spinal fusion surgery patients (discussed earlier in the text).
Muscle spasms are a common complaint in patients with chronic back pain and in those who have recently undergone spine surgery. Traditionally, patients are prescribed diazepam (Valium) but some of these patients later develop tolerance, dependency, and experience other benzodiazepine-related adverse side effects. Presently, a wide variety of medications classified as muscle relaxants are available, which provide relief for muscle spasms and avoid the side effects of benzodiazepines. Two commonly used muscle relaxants are tizanidine and baclofen. Tizanidine (Zanaflex) is believed to act by binding to central α-2 adrenergic receptors, thus increasing presynaptic motor neuron inhibition and reducing spasticity. Its half-life is 2 to 4 hours and it undergoes extensive liver metabolism. Typically, tizanidine is given as 3 daily doses of 4 mg each. Common side effects include somnolence, dry mouth, bradycardia, and hypotension. Baclofen is thought to inhibit monosynaptic and polysynaptic spinal reflexes (centrally acting muscle relaxant), although the exact mechanism of action is not known. Its half-life is approximately 5.5 hours. Baclofen is usually started at 5 mg orally 3 times a day and increased incrementally to a maximum dose of 40 mg/d. Common side effects are drowsiness, dizziness, weakness, nausea, and confusion.
Opioids have been the mainstay of postoperative pain management, but these medications also present unwanted side effects that could possibly compromise the outcome of MIS spine patients. The use of opioids in the immediate postoperative period is an important step in providing adequate pain control—although it must be remembered that all opioids have effects that can seriously limit the patient's ability to function during the day. There is a wide variety of opioids and derivates available and the choice varies among physicians. In general, prescribing opioids to an opioid-naïve patient begins with a less potent medication such as Hydrocodone/acetaminophen (Vicodin/Norco) or Oxycodone/Acetaminophen (Percocet). If absolutely no pain relief is obtained, then the next appropriate step is to switch to another medication, which would be oxycodone IR (Oxy IR) or morphine sulfate IR. These medications are also given in controlled release preparations to provide a steady state of analgesia. To achieve adequate pain control, these medications are usually supplemented with COX-2 inhibitors, gabapentinoids, and muscle relaxants, unless otherwise contraindicated. Side effects of opioids include nausea, vomiting, constipation, ileus, confusion, sedation, urinary retention, delirium, pruritus, headache, respiratory depression, and other effects due to histamine release such as hypotension. OIH is a phenomenon described initially in animal models and recently in human volunteers and surgical patients. These studies indicate that even short-term use of high-dose opioids can result in OIH and tolerance.58 OIH is thought to be a sustained sensitization of the nervous system in which excitatory amino acid neurotransmitter systems play a critical role. Persistence of the excitatory neurotransmitter system is now considered to be a contributor to the development of chronic pain after surgery.59 The multimodal approach has been advocated as a method to best treat pain in the perioperative period. Adjuvant medication provides the benefit of using less opioids and addressing pain by other mechanisms.
In conclusion, MIS techniques will continue to change the practice of traditional anesthesia care. The anesthesiologist has to adapt to the changing strategies of the surgical procedures, considering these patients as ambulatory surgical patients and practice a multimodal analgesic protocol to provide improved outcomes.
- Providing optimal anesthesia and analgesia is important to accomplish the ultimate goals of minimally invasive spine surgery.
- It is important to implement the multimodal analgesic therapy during the patient's preoperative visits.
- It is also important to use a fast-track anesthetic protocol, and to continue the multimodal analgesia after surgery.
1.Reichling DB, Levine JD. Critical role of nociceptor plasticity in chronic pain. Trends Neurosci
2.Gronblad M, Liesi P, Korkala O, et al. Innervations of the human bone periosteum by peptidergic nerves. Anat Rec
3.Bodguk N. The innervations of the lumbar spine. Spine
4.Huang TJ, Li YY, Weng YJ, et al. Interleukin-6 protein expression is more important than interleukin-6 mRNA levels in assessing surgical invasiveness. J Surg Res
5.Sulter M, Martinet O, Spertini F. Reduced acute phase response after laparoscopic total extraperitoneal bilateral hernia repair compared to open repair with Stoppa procedure. Surg Endosc
6.Oka Y, Murata A, Nishijima J, et al. Circulating interleukin 6 as a useful marker for predicting postoperative complications. Cytokine
7.Kim KT, Lee SH, Suk KS, et al. The quantitative analysis of tissue injury markers after mini-open lumbar fusion. Spine
8.Chao Z, Yue Z, Tong-wei C, et al. Microendoscopic discectomy, a less traumatic procedure for lumbar disk herniation. Chin J Traumatol
9.Buvanendran A, Kroin JS, Berger RA, et al. Up regulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiology
10.Buvanendran A, Tuman KJ, McCoy DD, et al. Anesthetic techniques for minimally invasive total knee arthroplasty. J Knee Surg
11.Berger RA, Sanders SA, Thill ES, et al. Newer anesthesia and rehabilitation protocols enable outpatient hip replacement in selected patients. Clin Orthop Relat Res
12.Buvanendran A, Kroin JS. Multimodal analgesia
for controlling acute postoperative pain. Curr Opin Anaesthesiol
13.Chu LF, Clark DJ, Angst MS. Opioid tolerance and hyperalgesia in chronic pain patients after 1 month of oral morphine therapy: a preliminary prospective study. J Pain
14.Kroenke K, Krebs EE, Bair MJ. Pharmcotherapy of chronic pain: a synthesis of recommendations from systematic review. Gen Hosp Psychiatry
15.Yadla S, Malone J, Campbell PG, et al. Obesity and spine surgery: reassessment based on a prospective evaluation of perioperative complications in elective degenerative thoracolumbar procedures. Spine J
16.Pelosi P, Gregoretti C. Perioperative management of obese patients. Best Pract Clin Anaesthesiol
17.Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology
18.Chung SA, Yuan H, Chung F. A systemic review of obstructive sleep apnea and its implications for anesthesiologists. Anesth Analg
19.Coudeyre E, Jardin C, Givron P, et al. Could preoperative rehabilitation modify postoperative outcomes after total hip and knee arthroplasty? Elaboration of French clinical practice guidelines. Ann Readapt Med Phys
20.Pour AE, Parvizi J, Sharkey PF, et al. Minimally invasive hip arthroplasty: what role does patient preconditioning play? J Bone Joint Surg Br
21.Buvanendran A, Kroin JS. Useful adjuvants for postoperative pain management. Best Pract Res Clin Anaesthesiol
22.Buvanendran A, Kroin JS, Tuman KJ, et al. Cerebrospinal fluid and plasma pharmacokinetics of the cyclooxygenase-2 inhibitor rofecoxib in humans: single and multiple oral drug administration. Anesth Analg
23.Jirarattanaphochai K, Jung S. Nonsteroidal anti-inflammatory drugs for postoperative pain management after lumbar spine surgery: a meta-analysis of randomized controlled trials. J Neurosurg Spine
24.O'Connor JP, Lysz T. Celecoxib, NSAIDs and the skeleton. Drugs Today (Barc)
25.Pradhan BB, Tatsumi RL, Galina J, et al. Ketorolac and spinal fusion: does the perioperative use of ketorolac really inhibit spinal fusion? Spine
26.Lumawig JM, Yamazaki A, Watanabe K. Dose-dependent inhibition of diclofenac sodium on posterior lumbar interbody fusion rates. Spine J
27.Li Q, Zhang Z, Cai Z. High-dose ketorolac affects adult spinal fusion: a meta-analysis of the effect of perioperative nonsteroidal anti-inflammatory drugs on spinal fusion. Spine
28.Flood J. The role of acetaminophen in the treatment of osteoarthrits. Am J Manag Care
29.Blumenthal S, Min K, Marquardt M, et al. Postoperative intravenous morphine consumption and side effects with perioperative oral controlled-release oxycodone after lumbar discectomy. Anesth Analg
30.Rajpal S, Gordon DB, Pellino TA, et al. Comparison of perioperative oral multimodal analgesia
versus IV PCA for spine surgery. J Spinal Disord Tech
31.Buvanendran A, Kroin JS, Della Valle CJ, et al. Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg
32.Gajraj NM. Pregabalin: its pharmacology and use in pain management. Anesth Analg
33.Gilron I. Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions. Curr Opin Anesthesiol
34.Yogendran S, Asokumar B, Cheng DC, et al. A prospective randomized double-blinded study of the effect of intravenous fluid therapy on adverse outcomes on outpatient surgery. Anesth Analg
35.Gan TJ, Meyer TA, Apfel CC, et al. Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesth Analg
36.White PF, Tang J, Song D, et al. Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms. Anesth Analg
37.Apfel CC, Korttila K, Abdalla M, et al; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med
38.Gan TJ, Apfel CC, Kovac A, et al. A randomized double blind comparison of the NK-1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Analg
39.Diemunsch P, Gan TJ, Philip BK, et al. Single-dose aprepitant versus ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind Phase III trial in patients undergoing open abdominal surgery. Br J Anaesth
40.Deiner S. Highlights of anesthetic considerations for intraoperative neuromonitoring. Semin Cardiothorac Vasc Anesth
41.Chandanwale AS, Ramteke AA, Barhate S. Intraoperative somatosensory-evoked potential monitoring. J Orthop Surg
44.Asouhidou I, Katsaridis V, Vaidis G, et al. Somatosensory evoked potentials suppression due to remifentanil during spinal operations: a prospective clinical study. Scoliosis
43.Agarwal R, Roitman KJ, Stokes M. Improvement of intraoperative somatosensory evoked potentials by ketamine. Paediatr Anaesth
44.Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology
45.Anschel DJ, Aherne A, Soto RG, et al. Successful intraoperative spinal cord monitoring during scoliosis surgery using a total intravenous anesthetic regimen including dexmedetomidine. J Clin Neurophysiol
46.Pobereskin LH, Sneyd JR. Wound infiltration with bupivacaine after surgery to the cervical spine using a posterior approach. Br J Anaesth
47.Gurbet A, Bekar A, Bilgin H, et al. Pre-emptive infiltration of levobupivacaine is superior to at-closure administration in lumbar laminectomy patients. Eur Spine J
48.Mordeniz C, Torun F, Soran AF, et al. The effect of pre-emptive analgesia
with bupivacaine on acute post-laminectomy pain. Arch Orthop Truma Surg
49.Bianconi M, Ferraro L, Ricci R, et al. The pharmacokinetics and efficacy of ropivacaine continuous would installation after spine fusion surgery. Anesth Analg
50.Jellish WS, Shea J. Spinal anaesthesia for spinal surgery. Clin Anaesthesiol
51.Schubert A, Deogaonkar A, Lotto M, et al. Anesthesia for minimally invasive cranial and spinal surgery. J Neurosurg Anesthesiol
52.McAfee PC, Regan JJ, Zdeblick T, et al. The incidence of complications in endoscopic spinal reconstructive surgery. A prospective multicenter study comprising the first l00 consecutive cases. Spine
53.Schmied H, Reiter A, Kurz A, et al. Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty. Lancet
54.Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical wound infection and shorten hospitalization. N Engl J Med
55.McGrath B, Elgendy H, Chung F, et al. Thirty percent of patients have moderate to severe pain 24hr after ambulatory surgery: a survey of 5703 patients. Can J Anaesth
56.Melzack R, Coderre TJ, Katz J. Central neuroplasticity and pathological pain. Ann N Y Acad Sci
57.Harrington JF, French P. Open versus minimally invasive lumbar microdiscectomy: comparison of operative times, length of hospital stay, narcotic use and complications. Minim Invasive Neurosurg
58.Angst MS, Clark JD. Opioid-Induced Hyperalgesia: a qualitative systematic review. Anesthesiology
59.Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet