Review of anesthesia for middle ear surgery

R e v i e w o f A n e s t h e s i af o r M i d d l e E a r S u r g e r y Sharon Liang, BSc, Michael G. Irwin, MB, ChB, MD, FRCA KEYWORDS Anesthesia for middle ear surgery  Controlled hypotension The middle ear refers to an air-filled space between the tympanic membrane and theoval window. It is connected to the nasopharynx by the eustachian tube and is in closeproximity to the temporal lobe, cerebellum, jugular bulb, and the labyrinth of the innerear. The middle ear contains three ossicles—the malleus, incus and stapes—whichare responsible for transmission of sound vibration from the eardrum to the cochlea.
This air-filled cavity is traversed by the facial nerve before it exits the skull via the sty-lomastoid foramen.The facial nerve provides motor innervation to the muscles offacial expression.
Middle ear disease affects patients of all ages. Common middle ear pathologic condi-tions requiring surgery in adults include tympanoplasty (reconstructive surgery for thetympanic membrane, or eardrum), stapedectomy or ossiculoplasty for otosclerosis,mastoidectomy for removal of infected air cells within the mastoid bone, and removalof cholesteoma.Common middle ear surgery in children includes tympanoplasty,mastoidectomy, myringotomy, grommet insertion. and cochlear Some of these procedures can be performed under local anesthesia, although obvi-ously, all surgery can be performed under general anesthesia if necessitated bypatient or surgical factors ANESTHETIC CONSIDERATIONS IN MIDDLE EAR SURGERY Given the unique location, size, and delicate content of the middle ear, great care mustbe taken during the perioperative period. Special considerations include: provision ofa bloodless surgical field, attention to patient’s head positioning, airway management, a Department of Anaesthesiology, Queen Mary Hospital, Main Block, Room 43, 2/F, 102 Pokfu-lam Road, Hong Kongb Department of Anaesthesiology, University of Hong Kong, K424, Queen Mary Hospital,Pokfulam Road, Hong Kong* Corresponding author.
E-mail address: Anesthesiology Clin 28 (2010) 519–528doi:10.1016/j.anclin.2010.07.009 1932-2275/10/$ – see front matter Ó 2010 Elsevier Inc. All rights reserved.
Box 1Common procedures in middle ear surgery  Insertion of grommet Myringoplasty Tympanoplasty Stapedotomy Stapedectomy Ossiculoplasty (IOFNM) Mastoidectomy (IOFNM) Cholesteoma surgery via intact ear canal (IOFNM)  Adult Patient must be able to understand, cooperate, hear and communicate  Cochlear implantation Long operations Complicated surgery (eg, extensive scar tissue in middle ear)  Children Mentally unstable, uncooperative patients Patients who request general anesthesia Abbreviation: IOFNM, intraoperative facial nerve monitoring.
facial nerve monitoring, the effect of nitrous oxide on the middle ear, a smooth andcalm recovery, and prevention of postoperative nausea and vomiting A bloodless surgical field is ideal, as even small amounts of blood will obscure the surgeon’s view in microsurgery. A combination of physical and pharmacologic tech-niques is used to minimize bleeding. Attention to patient’s head positioning is impor-tant to avoid venous obstruction and congestion. In addition, extreme hyperextensionor torsion can cause injury to the brachial plexus and the cervical In patientswith carotid atherosclerosis, carotid blood flow may be compromised or plaqueemboli dislodged, and it is worth auscultating for carotid bruit before surgery. Duringgeneral anesthesia, the airway can be maintained with a laryngeal mask airway (LMA)or endotracheal intubation; intubation may be more appropriate if extreme neck exten-sion or rotation is required. LMA, however, is a suitable alternative for most middle earsurgery, and a wide range of devices are now available. A well-documented potentialcomplication of otologic surgery is facial nerve paralysis, and a nerve stimulator isoften employed for intraoperative monitoring of evoked facial nerve electromyo-graphic activity to aid preservation of the facial nerve. Muscle relaxants should beavoided in this circumstance or, if neuromuscular block is needed to facilitate smooth Review of Anesthesia for Middle Ear Surgery intubation, choose a dose and an agent (eg, mivacurium no longer manufactured in theUnited States) that ensures the return of function before the need for neuromuscularmonitoring arises.It also should be borne in mind that sudden unexpected patientmovement may jeopardize the success of surgery, and depth of anesthesia monitoringmay be useful. The use of nitrous oxide in middle ear surgery is controversial. Asmooth recovery without coughing or straining is important, especially in patientswho have undergone reconstructive middle ear surgery to prevent prosthesisdisplacement. PONV is a common problem after middle ear surgery that can be mini-mized by appropriate choice of anesthetic technique and antiemetic prophylaxis.Most middle ear procedures can be performed as outpatient surgery; thus rapidrecovery, good analgesia, and avoidance of nausea and vomiting are essential.
For adults, simple middle ear surgery can be performed under local or general anes-thesia, although complicated or long procedures should be performed under generalanesthesia. Patients who are able to understand the procedure, and to communicateand cooperate throughout the procedure, are suitable candidates for local anesthesiawith or for foregoing sedation.Patients undergoing middle ear surgery often sufferfrom extensive hearing loss, thus hindering their ability to cooperate, and in this situ-ation, surgery might be better performed under general anesthesia. Leaving thehearing aid in situ in the nonsurgical ear before induction and replacement beforeemergence may help to minimize anxiety and ease communication. Oral anxiolysispremedication with benzodiazepines can be considered or standard sedation regi-mens used intraoperatively. A history of cardiovascular disease, hypovolemia, andanemia will limit the degree of hypotension possible. In pediatric patients, in additionto the usual components of preoperative assessment, it is important to check forcoexisting syndromes and recent upper respiratory tract Four nerves provide innervation to the ear. The auriculotemporal nerve supplies theouter auditory meatus; the great auricular nerve supplies the medial and lower aspectof the auricle and part of the external auditory meatus. The auricular branch of thevagus nerve supplies the concha and the external auditory meatus, and the tympanicnerves supply the tympanic cavity.
General or local anesthesia has advantages and disadvantages. Uncomplicated middle ear surgery can be performed under local anesthesia. In a study on localanesthesia in middle ear surgery by Caner and patients were pre-medicated with meperidine and atropine intramuscularly 30 minutes before beingtaken to surgery, and 5 mg to 10 mg diazepam was given intravenously if thepatient was still agitated in the operating room. Two percent lidocaine with1:10,000 epinephrine was used for infiltration and auriculotemporal/auricular nerveblocks. Seventy-three of the 100 patients said they would prefer local anesthesiafor a similar operation in the future. In a similar survey, found the mostcommon discomforts reported were noise during surgery and anxiety, followedby dizziness, backache, claustrophobia, and earache. Despite these discomforts,however, 89% of patients said they would prefer local anesthesia for similar oper-ations in the future. Pain was felt mainly at the beginning of surgery when multipleinjections of local anesthetic were given, and perhaps the preoperative applicationof lidocaine and prilocaine (EMLA) could have assisted in this. For the surgeons,the main advantage of performing middle ear surgery under local anesthesia is the ability to test hearing during surgery, and they also report less bleeding. Themain concerns of not performing middle ear surgery under local anesthesia arethat patients may not tolerate the discomfort and the possibility of sudden move-ment. Another drawback is potential toxicity, as near-toxic plasma levels of localanesthetic have been reported in the first 5 minutes following infiltration for tym-The head may be obscured by drapes during surgery, and extra vigi-lance is required for possible respiratory depression or airway obstruction.
Supplementary oxygen can be provided with nasal cannulae, and it is alsopossible to use capnometry or a precordial stethoscope to monitor breathing.
Clear plastic drapes may reduce feelings of claustrophobia, and a forced airdevice can be used to provide some room air ventilation.
Thus, with careful patient selection, adequate preoperative explanation, and appro- priate use of sedation, middle ear surgery can be successfully performed under localanesthesia, with high patient and operator satisfaction and acceptance. Benedik andcompared safety and efficacy of propofol versus midazolam for conscioussedation in middle ear surgery. The study demonstrated that propofol was associatedwith significantly shorter recovery time and better patient and surgeon satisfactioncompared with midazolam. Adverse effects of propofol and midazolam, such as respi-ratory depression, hypotension, and sudden intraoperative movements, are obviousdrawbacks.
Alpha-2 agonists such as clonidine or, more recently, dexmedetomidine, may have some advantages, as they produce arousable sedation, analgesia, and a modestreduction in heart rate and blood pressure without respiratory depression, particularlyimportant when the head is obscured by surgical Dexmedetomidine hasbeen used successfully as the primary sedative with supplementary low-dose propo-fol and midazolam for monitored anesthesia care during awake thyroplasty, a proce-dure that requires the patient to verbalize when asked and otherwise remainimmobile.Surgeons reported satisfactory operating conditions, and patients hadno recall of the procedure and no It also has a role in awake craniotomy.Thus, dexmedetomidine could be used in a similar way for middle ear surgery buthas not been widely reported in the literature.
In summary, the advantages of performing middle ear surgery under local anes- thesia and conscious sedation include less bleeding, reduced pain in the immediatepostoperative period, early mobilization, cost-effectiveness, and the ability to testhearing restoration during surgery.
Despite these advantages, however, and the special concerns of general anesthesia for middle ear surgery outlined earlier, most middle ear surgery is still performed undergeneral anesthesia.
Total intravenous anesthesia (TIVA) versus volatile-based anesthesia for middle ear surgery long has been a subject of debate. Mukherjee and colleaguescompared PONV, pain, and conditions for surgery in patients who had undergonemiddle ear surgery under TIVA using remifentanil and propofol, with technique usingfentanyl, propofol, and isoflurane maintenance. More patients in the inhalation groupsuffered from PONV (25%) versus the TIVA group (8%) in the recovery room. In theearly postoperative period, the TIVA group reported higher pain scores and requiredmore morphine in the recovery room, but there was no significant difference at 2, 4,6, 8, 12, and 18 hours. Conditions for surgery in the TIVA group were reported to besuperior. In another study comparing propofol-based anesthesia with inhalationanesthetic techniques in terms of recovery profile and incidence of PONV for middleear surgery, TIVA was associated with more rapid emergence and less nausea and Review of Anesthesia for Middle Ear Surgery The use of nitrous oxide in anesthetic practice has declined in recent years as a result of concerns over both physical and metabolic effect.The use of nitrousoxide in middle ear surgery is particularly controversial. Nitrous oxide is more solublethan nitrogen in blood and in high concentrations enters the middle ear cavity morerapidly than nitrogen leaves, causing a raise in middle ear pressure if the eustachiantube is During tympanoplasty, the middle ear is open to the atmo-sphere; thus there is no build-up of pressure, but once a tympanic membrane graftis placed the continued use of nitrous oxide might cause displacement of graft. Atthe end of surgery, when it is discontinued, nitrous oxide is rapidly absorbed, whichmay then result in negative pressure also possibly resulting in graft dislodgement,serous otitis media, disarticulation of the stapes, or impaired hearing.Thus, theuse of nitrous oxide is not recommended in tympanoplasty. Furthermore, a well knownadverse effect of nitrous oxide is PONV, and consequently, its use in middle earsurgery may further increase the incidence of PONV above that already associatedwith this type surgery.
Endotracheal intubation and laryngoscopy during general anesthesia is associated with many potential complications such as sore throat, cough, dental injury, difficultemergence, and use of muscle relaxants for tube In comparison, theLMA is free from such complications, and a smooth recovery can be attained easily.
It also offers advantages of intravenous sedation with less risk of over sedation andobstructive apnea.Safety and efficacy of the LMA were compared with endotra-cheal intubation in patients who underwent otologic surgery in a retrospective chartreview study conducted at a military tertiary care teaching hospital. No major airwaycomplication was reported in either group; a significant decrease in the use of neuro-muscular blockers was noted in the LMA group, and total anesthetic time was alsoshorter in this group. There was no difference in the incidence of PONV or durationof postanesthesia care unit The use of the LMA for head and neck proceduresis reviewed in the article by Mandel elsewhere in this issue for further exploration ofthis topic.
A bloodless operative field is essential, because even a few drops of blood can obscure the surgical field. Physical and pharmacologic techniques are used: a head-up tilt 15 to 20, avoidance of venous obstruction, normocapnia, and controlled hypo-tension. Controlled hypotension is defined as a reduction of systolic blood pressure to80 mm Hg90 mmHg, a reduction of mean arterial pressure to 50 mm Hg to 65 mm Hg inpatients without hypertension, or a reduction of 30% of baseline mean arterial pressurein patients with hypertension.A slightly elevated position of the head reduces arterialand venous pressures in areas above the heart; however, it increases the risk of airembolism. In the presence of hypotension, elevating the head will further compromiseperfusion of the head and neck region. Pharmacologic agents used for controlledhypotension in ear, nose, and throat surgery include: inhalation anesthetics (eg, isoflur-ane and sevoflurane), vasodilators (eg, sodium nitroprusside and nitroglycerin), betaadrenoceptor antagonists (labetalol and esmolol), alpha-2 adrenergic agonists (cloni-dine and dexmedetomidine), opioids (remifentanil),and more recently magnesiumHowever, controlled hypotension is not without risk; in addition to theadverse effects of certain pharmacologic agents, it can cause tissue hypoxia byreducing microcirculatory autoregulation of vital organs.
In moderate concentrations, isoflurane lowers blood pressure via a vasodilating effect while preserving cerebral autoregulation. However, at higher concentrations,it causes an increase in intracranial pressure due to increased cerebral blood flowand impairment of cerebral Sevoflurane produces its hypotensiveeffect by direct vasodilatation without modifying cochlear blood In addition, it has a low blood gas solubility and low airway irritability, making it a good agent forgas induction in pediatric patient, although its use is commonly associated with emer-gence agitation and negative postoperative behavioral changes in this group.In highconcentrations, inhalation anesthetics interfere with the measurement of evokedpotentials use for facial nerve monitoring.
The vasodilators sodium nitroprusside and nitroglycerin have become less popular because of adverse effects and the availability of better agents. Sodium nitroprussideis very potent and has a fast onset and offset, but it has several serious adverse effectsincluding tachyphylaxis, rebound hypertension, organ ischemia, and cyanidetoxicity.Sodium nitroprusside employed as an adjunct to sevoflurane anesthesiain children improved surgical field visibility but provoked lactic acidosis and increasedhypercapnia.Nitroglycerin is a short acting nonspecific direct vasodilator of venousand arterial vessels, which does not produce toxic metabolites. Compared withsodium nitroprusside, nitroglycerin is less effective in inducing hypotension anddoes so more slowly.Both agents require close blood pressure monitoring, prefer-ably with an arterial line.
Labetalol is a competitive antagonist at beta and alpha receptors with a ratio of 7:1.
Beta adrenoceptor blockade decreases myocardial contractility and heart rate, whilealpha blockade produces vasodilatation.Adverse effects include bronchospasm,prolonged hypotension, and conduction blockade. Esmolol is a short-acting beta-1adrenoceptor antagonist, which has an onset time of about 3 minutes and durationof action of approximately 10 minutes. It decreases blood pressure by lowering heartrate and reducing renin activity and catecholamine levels.Compared with sodiumnitroprusside, beta adrenoceptor antagonists lower blood pressure and reduce bloodflow to the middle ear and improve surgical field without metabolic complications.
The alpha-2 adrenoceptor agonists, clonidine and dexmedetomidine, have been discussed earlier in relation to their sedative and analgesic properties. They also mark-edly reduce catecholamine secretion, are anesthetic sparing, and produce moderatebradycardia and A randomized study investigating the effective-ness of dexmedetomidine in reducing bleeding during septoplasty and tympanoplastyoperations demonstrated dexmedetomidine significantly reduced bleeding and fen-tanyl requirement in septoplasty and reduced fentanyl requirement in tympanoplastyoperations, but the decrease in bleeding was not Durmus andcolleaguesused dexmedetomidine to improve the quality of surgical field in bothtympanoplasty and septoplasty, and concluded that dexmedetomidine is a usefuladjuvant to decrease bleeding.
Remifentanil is an ultrashort-acting mu receptor agonist. It is able to decrease systemic blood pressure, reduce blood flow to the middle ear, and produce better visi-bility in the operative field without impairing autoregulation of the middle ear microcir-The proposed mechanism of action is via central sympathetic blockade.
Degoute and colleaguesreported that remifentanil combined with sevoflurane inchildren enabled controlled hypotension, reduced middle ear blood flow, andprovided a good surgical field for middle ear surgery with no additional need for otherhypotensive agents. Furthermore, remifentanil reduced sevoflurane requirement andhelped avoid the use of muscle relaxants. There is some evidence that intraoperativeinfusion of high doses of remifentanil can cause postoperative hyperalgesia,increasing the postoperative analgesic requirement but this is controversial.
Magnesium sulfate is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with antinociceptive effects, and it inhibits entry of calcium ions into cells.
Magnesium sulfate is used as a vasodilator for controlled hypotension. Ryu andcolleaguescompared remifentanil and magnesium sulfate for middle ear surgery Review of Anesthesia for Middle Ear Surgery in terms of hemodynamic effects and postoperative pain when combined with sevo-flurane. They reported no significant difference over time in mean arterial pressureor heart rate between the drugs. Patients in the magnesium sulfate group had a lowersevoflurane requirement than those receiving remifentanil. Overall, magnesium sulfatewas associated with more stable perioperative hemodynamics and produced betteranalgesia and less PONV compared with remifentanil.
Otologic surgical procedures are associated with facial nerve paralysis, and thus facial nerve protection is an important consideration. Preservation of the facial nervecan be easily confirmed if the patient is not paralyzed,but use of muscle relaxantscompromises the interpretation of evoked facial electromyographic activity. Sinceany sudden movement could jeopardize surgery, it has been suggested that partialneuromuscular blockade as determined by train-of-four peripheral nerve stimulationbe Middle ear surgery is associated with a high incidence of PONV. In the absence of antiemetic treatment, 62% to 80% of patients will be afflicted.The etiology of PONVis multifactorial and depends on various factors, including patient demographics,history of PONV, anesthetic technique, use of nitrous oxide, duration of anesthesiaand operation, and even surgical experience.TIVA reduces PONV comparedwith using volatile agents.Use of nitrous oxide is associated with a higher incidenceof PONV. Patients operated on by residents required more aggressive prophylaxis forPONV than those operated on by specialists.Prophylactic administration of anti-emetic medication also decreases the incidence of PONV. Usmani and colleaguescompared the efficacy of ondansetron (0.1 mg/kg), dexamethasone (0.15 mg/kg)and a combination of ondansetron (0.1 mg/kg) and dexamethasone (0.15 mg/kg) forprevention of PONV in a randomized double-blind study involving 90 American Societyof Anesthesiologists (ASA) I and II patients. They concluded that prophylactic therapywith ondansetron together with dexamethasone is superior to either drug alone.
Another study comparing the efficacy of combining granisetron and dexamethasoneto either drug alone yielded similar results.This also holds true in pediatricpatients.Thus, the combination of a selective 5-hydroxy tryptamine type 3receptor antagonist together with dexamethasone is more effective in preventingPONV than either drug alone. Yeo and compared the antiemetic efficacyof dexamethasone combined with midazolam and concluded that the addition of mid-azolam did not significantly reduce the overall incidence of PONV compared withdexamethasone alone. However, the addition of midazolam did lower the incidenceof vomiting and the need for rescue antiemetic.
Patients who underwent middle ear surgery under local anesthesia experienced less immediate postoperative pain than those under general anesthesia. A multimodalanalgesic approach combining opioids, nonsteroidal anti-inflammatory drugs/COX-2selective inhibitors, and acetaminophen is generally appropriate. A recent study foundblockade of the auricular branch of the vagus nerve with 0.2 mL of 0.25% bupivacaineto be more effective than intranasal fentanyl (2 mg/kg) in management of postoperativepain in infants and children undergoing myringotomy and tube placement.
In conclusion, with careful patient selection, local anesthesia with sedation is a good alternative to general anesthesia for simple middle ear surgery. Generalanesthesia with TIVA provides a better recovery profile and less nausea and vomit-ing compared with inhalational anesthesia, and nitrous oxide should be avoided.
Remifentanil is a good drug for controlled hypotension and for avoidance of musclerelaxants. If required, partial neuromuscular blockade can still allow facial nervemonitoring during surgery. Combination PONV prophylaxis is more effective thansingle drug treatment.
1. Moore KL, Dalley AF. Clinically orientated anatomy. 4th edition. Philadelphia: Lippinocott Williams and Wilkins; 1999.
2. Dhillon RS, Eas CA. Ear, nose, throat, and head and neck surgery: an illustrated colored text. 2nd edition. Edinburgh (UK): Churchill Livingstone; 1999.
3. Deacock AR. Aspects of anaesthesia for middle ear surgery and blood loss during stapedectomy. Proc R Soc Med 1971;64(12):1226–8.
4. Miller RD. Miller’s anesthesia, vol. 2. 6th edition. Hershey (PA): Elsevier Churchill 5. Morgan EG, Mikhail MS, Murray MJ. Clinical anesthesiology. 4th edition.
New York: Lange Medical Books/McGraw-Hill; 2006.
6. Bailey CR. Management of outpatient ear, nose and throat surgery. Curr Opin 7. Yung MW. Local anaesthesia in middle ear surgery: survey of patients and surgeons. Clin Otolaryngol Allied Sci 1996;21(5):404–8.
8. Caner G, Olgun L, Gultekin G, et al. Local anesthesia for middle ear surgery.
Otolaryngol Head Neck Surg 2005;133(2):295–7.
9. Bachmann B, Biscoping J, Adams HA, et al. Plasma concentrations of lidocaine and prilocaine following infiltration anesthesia in otorhinolaryngologic surgery.
Laryngol Rhinol Otol (Stuttg) 1988;67(7):335–9.
10. Benedik J, Manohin A. Sedation for middle ear surgery: prospective clinical trail comparing propofol and midazolam. Cent Eur J Med 2008;3(4):487–93.
11. Yuen VM. Dexmedetomidine: perioperative applications in children. Paediatr 12. Busick T, Kussman M, Scheidt T, et al. Preliminary experience with dexmedetomi- dine for monitored anesthesia care during ENT surgical procedures. Am J Ther2008;15(6):520–7.
13. Poon CC, Irwin MG. Anaesthesia for deep brain stimulation and in patients with implanted neurostimulator devices. Br J Anaesth 2009;103(2):152–65.
14. Mukherjee K, Seavell C, Rawlings E, et al. A comparison of total intravenous with balanced anaesthesia for middle ear surgery: effects on postoperativenausea and vomiting, pain, and conditions of surgery. Anaesthesia 2003;58(2):176–80.
15. Jellish WS, Leonetti JP, Murdoch JR, et al. Propofol-based anesthesia as compared with standard anesthetic techniques for middle ear surgery. J ClinAnesth 1995;7(4):292–6.
16. Jellish WS, Leonetti JP, Fahey K, et al. Comparison of 3 different anesthetic tech- niques on 24-hour recovery after otologic surgical procedures. Otolaryngol HeadNeck Surg 1999;120(3):406–11.
17. Irwin MG, Trinh T, Yao CL. Occupational exposure to anaesthetic gases: a role for TIVA. Expert Opin Drug Saf 2009;8(4):473–83.
18. Sanders RD, Weimann J, Maze M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology 2008;109(4):707–22.
19. Taheri A, Hajimohamadi F, Soltanghoraee H, et al. Complications of using laryn- geal mask airway during anaesthesia in patients undergoing major ear surgery.
Acta Otorhinolaryngol Ital 2009;29(3):151–5.
20. Duff BE. Use of the laryngeal mask airway in otologic surgery. Laryngoscope 21. Ayala MA, Sanderson A, Marks R, et al. Laryngeal mask airway use in otologic surgery. Otol Neurotol 2009;30(5):599–601.
Review of Anesthesia for Middle Ear Surgery 22. Degoute CS, Ray MJ, Manchon M, et al. Remifentanil and controlled hypotension; comparison with nitroprusside or esmolol during tympanoplasty. Can J Anaesth2001;48(1):20–7.
23. Degoute CS. Controlled hypotension: a guide to drug choice. Drugs 2007;67(7): 24. Ryu JH, Sohn IS, Do SH. Controlled hypotension for middle ear surgery: a comparison between remifentanil and magnesium sulphate. Br J Anaesth2009;103(4):490–5.
25. Albera R, Ferrero V, Canale A, et al. Cochlear blood flow modifications induced by anaesthetic drugs in middle ear surgery: comparison between sevofluraneand propofol. Acta Otolaryngol 2003;123(7):812–6.
26. Kuratani N, Oi Y. Greater incidence of emergence agitation in children after sevo- flurane anesthesia as compared with halothane: a meta-analysis of randomizedcontrolled trials. Anesthesiology 2008;109(2):225–32.
27. Ebert TJ, Hall JE, Barney JA, et al. The effects of increasing plasma concentra- tions of dexmedetomidine in humans. Anesthesiology 2000;93(2):382–94.
28. Ornstein E, Young WL, Ostapkovich N, et al. Are all effects of esmolol equally rapid in onset? Anesth Analg 1995;81(2):297–300.
29. Talke P, Richardson CA, Scheinin M, et al. Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine. Anesth Analg 1997;85(5):1136–42.
30. Ayoglu H, Yapakci O, Ugur MB, et al. Effectiveness of dexmedetomidine in reducing bleeding during septoplasty and tympanoplasty operations. J ClinAnesth 2008;20(6):437–41.
31. Durmus M, But AK, Dogan Z, et al. Effect of dexmedetomidine on bleeding during tympanoplasty or septorhinoplasty. Eur J Anaesthesiol 2007;24(5):447–53.
32. Degoute CS, Ray MJ, Gueugniaud PY, et al. Remifentanil induces consistent and sustained controlled hypotension in children during middle ear surgery. Can JAnaesth 2003;50(3):270–6.
33. Richa F, Yazigi A, Sleilaty G, et al. Comparison between dexmedetomidine and remifentanil for controlled hypotension during tympanoplasty. Eur J Anaesthesiol2008;25(5):369–74.
34. Lee LH, Irwin MG, Lui SK. Intraoperative remifentanil infusion does not increase postoperative opioid consumption compared with 70% nitrous oxide. Anesthesi-ology 2005;102(2):398–402.
35. Cai YR, Xu J, Chen LH, et al. Electromyographic monitoring of facial nerve under different levels of neuromuscular blockade during middle ear microsurgery. ChinMed J (Engl) 2009;122(3):311–4.
36. Honkavaara P, Saarnivaara L, Klemola UM. Prevention of nausea and vomiting with transdermal hyoscine in adults after middle ear surgery during generalanaesthesia. Br J Anaesth 1994;73(6):763–6.
37. Usmani H, Siddiqui RA, Sharma SC, et al. Ondansetron and dexamethasone in middle ear procedures. Indian J Otolaryngol 2003;55(2):97–100.
38. Honkavaara P. Effect of ondansetron on nausea and vomiting after middle ear surgery during general anaesthesia. Br J Anaesth 1996;76(2):316–8.
39. Honkavaara P, Pyykko I. Surgeon’s experience as a factor for emetic sequelae after middle ear surgery. Acta Anaesthesiol Scand 1998;42(9):1033–7.
40. Fujii Y, Toyooka H, Tanaka H. Prophylactic antiemetic therapy with a combination of granisetron and dexamethasone in patients undergoing middle ear surgery. BrJ Anaesth 1998;81(5):754–6.
41. Fujii Y, Saitoh Y, Tanaka H, et al. Prophylactic therapy with combined granisetron and dexamethasone for the prevention of post-operative vomiting in children. EurJ Anaesthesiol 1999;16(6):376–9.
42. Gombar S, Kaur J, Kumar Gombar K, et al. Superior anti-emetic efficacy of gra- nisetron-dexamethasone combination in children undergoing middle ear surgery.
Acta Anaesthesiol Scand 2007;51(5):621–4.
43. Yeo J, Jung J, Ryu T, et al. Antiemetic efficacy of dexamethasone combined with midazolam after middle ear surgery. Otolaryngol Head Neck Surg 2009;141(6):684–8.
44. Voronov P, Tobin MJ, Billings K, et al. Postoperative pain relief in infants under- going myringotomy and tube placement: comparison of a novel regional anes-thetic block to intranasal fentanyl–a pilot analysis. Paediatr Anaesth 2008;18(12):1196–201.

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