Anesthetic Induced Middle Ear Pressure Changes And Nausea And Vomiting In Children Undergoing Adenotonsillectomy (Research Paper)

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1 Original article Anesthetic Induced Middle Ear Pressure Changes And Nausea And Vomiting In Children Undergoing Adenotonsillectomy (Research Paper) Mustafa ARSLAN 1, Berrin IŞIK 1, Yusuf KIZIL 2, Özgür ÖZSOYLAR 1, Erdem DİNÇ 2, Mehmet AKÇABAY 1, Yusuf KEMALOĞLU 2 1 Gazi University Faculty of Medicine Department of Anesthesiology and Reanimation, ANKARA 2 Gazi University Faculty of Medicine Department of ENT, Head and Neck Surgery, ANKARA N 2 O, widespreadly used in anesthesia, increases space volumes because of its high rate of diffusion and it increases pressure in non-compliant tissues such as middle ear cavity. Increase in middle ear pressure is an undesirable condition because of its potential complications. The aim of this cross-sectional randomized study is to compare effects of N 2 O plus desflurane or sevoflurane and remifentanil plus desflurane or sevoflurane on middle ear pressure and postoperative nausea and vomiting. Patients in American Society of Anesthesiologists (ASA) group I-II aged between 5-18 years undergoing tonsillectomy or adenotonsillectomy were randomized into groups according to anesthesia we performed as desflurane plus N 2 O group (Group DN, n=), sevoflurane plus N 2 O group (Group SN, n=), desflurane plus remifentanil group (Group DR, n=) and sevoflurane plus remifentanil group (Group SR, n=). Mean arterial pressure (MAP), heart rate (HR) monitorization of cases and preoperative (T 0 ), after intubation (T 1 ), before extubation (T 2 ), after extubation (T 3 ), 30 minutes after extubation (T 4 ) middle ear pressures (MEP) were measured. Finally, MEP values and ABSTRACT postoperative nausea vomiting (PONV) frequencies among groups were compared. T 0 measurements of MEP were not different between groups, but T 1 measurements were higher in N 2 O used groups than remifentanil used groups. Similar rise in MEP was observed in remifentanil used groups parallel to prolonged anesthesia duration. No difference observed among groups with respect to side effects. There was MEP difference between two ears in 17 cases with nausea and vomiting. When left and right MEP values of 17 patients with nausea and vomiting at T 3 were compared, the average of higher cases was 8.9±97.2 and it was -6.8±107.8 for lower cases. The difference was statistically significant (p<0.0001). In middle ear surgery, remifentanil plus sevoflurane or desflurane is a better alternative than N 2 O for brief surgical interventions. Major factor in PONV seems to be the pressure difference between right and left ear independent of the anesthetic agent used, although future studies on this subject are required. Key Words: Middle ear pressure, desflurane, sevoflurane, N 2 O, remifentanil, PONV INTRODUCTION Increase in middle ear pressure (MEP) may cause complications such as ear pain, transient or permanent hearing loss, hemotympanium, disarticulation of stapes, tympanic membrane rupture, serous otitis media, displacement of tympanic membrane graft and postoperative nausea vomiting. These complications increase costs besides being a disturbing factor for the patient 1 7. It is well known that nitrous oxide (N 2 O), which is frequently used for anesthesia, causes volume changes in air filled cavities and increases pressure in noncompliant spaces such as middle ear cavity 1 3,5. Some studies reported that MEP is considerably increased when N 2 O is used with inhalation anesthetics like halothane and isoflurane or intravenous anesthetics like propofol and ketamine 1,8. Thomsen et al. 9 reported that MEP increased to 340 mmh 2 O within 30 minutes after inhalation of 80% N 2 O; to 220 mmh 2 O within 38 minutes after inhalation of 60% N 2 O and to 290 mmh 2 O within 66 minutes after inhalation of 40% N 2 O. Perreault et al. 10 reported that MEP was increased to 400 mmh 2 O 30 minutes after inhalation of 66%-70% N 2 O and 0.5%-1.0% halothane. There is also a case report about spontaneous tympanic membrane rupture after N 2 O use for anesthesia 3. On the other hand it is reported that in total intravenous anesthesia (TIVA) anesthesia practice with propofol, fentanyl and ketamine MEP was also increased but not as much as in N 2 O used group 8, and N 2 O addition to halothane anesthesia had no effect on MEP

2 Our search of literature about effects of N 2 O and remifentanil used with desflurane or sevoflurane on MEP and postoperative nausea and vomiting (PONV), revealed no publication. For that reason we aimed to study effects of N 2 O and remifentanil combined with desflurane or sevoflurane on MEP and rate of PONV during tonsillectomy and adenotonsillectomy. MATERIAL AND METHOD This double-blind, randomized study was conducted by Anesthesiology and Reanimation Department and Ear, Nose and Throat & Head and Neck Surgery Department at Gazi University School of Medicine. The study was confirmed by the commitee of ethics. The sample consisted of 60 tonsillectomy or adenotonsillectomy indicated, ASA (American Society of Anesthesiologist) I-II group cases, aged 5 18 years. Exclusion criteria were presence of hepatic, renal, cardiovascular disorders, drug allergy, asthma, chronic obstructive pulmonary disease, haematological disorders, acute or chronic otitis media, current opioid and anticoagulant usage, history of previous middle ear surgery and motion sickness. Subjects were divided into 4 groups each consisting of patients according to the randomization list. In the first group desflurane and remifentanil was used (Group DR, n=), in the second group sevoflurane and remifentanil was used (Group SR, n=), in the third group desflurane and N 2 O was used (Group DN, n=), in the fourth group sevoflurane and N 2 O was used (Group SN, n=). Patients were orally restricted for 6-8 hours before operation and premedicated with 0.1 mg/kg midazolam (Dormicum ) intramuscularly 30 minutes before operation. In the operating room intravenous (iv) line obtained through hand dorsum with G cannula and infusion began with 5 ml/kg Izoleks-P with 5% Dekstroz (Biosel Turkey). Continuous monitorization of heart rate (HR) with electrocardiogram (ECG), noninvasive monitorization of systolic (SAP), diastolic (DAP) and mean arterial pressures (MAP), oxygen saturation (SpO 2 ) were performed (Odam Physiogard SM France ). Tympanometric measurements were obtained with a portable tympanometer (Interacoustics A/S, Assens DK- 5610, MT10 Audiometer, Denmark ) from left and right ears before anesthesia and recorded as baseline value (T 0 ). Anesthesia induction was standardized in all groups as 2 minutes preoxygenation followed with intravenous 2 mg/kg propofol (Propofol Fresenius 1% ) and 0.5 mg/kg atracurium (Tracrium ). After anesthesia induction, iv 0.1 μg/kg/min remifentanil infusion with infusion pump (IVAC 780, San Diego, CA ) and 2 6% concentration of desflurane (Suprane ) inhalation inside 4L/min 50% O 2 /air for patients in group DR, iv 0.1 μg/kg/ min remifentanil infusion and % 1 2 concentration of sevoflurane (Sevorane ) inhalation inside 4 L/min 50% O 2 /air for patients in group SR, 2 6% concentration of desflurane inhalation inside 4 L/min 50% O 2 /N 2 O for patients in group DN, 1 2% concentration of sevoflurane inhalation inside 4 L/min 50% O 2 /N 2 O for patients in group SN. After adequate muscle relaxation patients were intubated orotracheally and gastric suction performed after intubation. In all groups, controlled ventilation started by setting tidal volume as 7 ml/kg, frequency as and PAW as cmh 2 O after tube fixation. During operation, in order to keep HR and MAP within ± 20 % limits of measurements before anesthesia induction, which were baseline values, desflurane and sevoflurane concentrations were set to 2 6% and 1 2% respectively. In case of bradycardia 0.0 mg/kg atropine administration was planned. At the end of operation after bleeding control, gastric suction was performed, inhalation anesthetics were stopped and 4L/min 100% O 2 was inhalated. Surgery completion time and anesthetic agent cessation time were recorded. Manual respiration with 100% O 2 in 4 L/min fresh flow circuit was maintained until spontaneous respiration was restored. After beginning of regular respiration, muscle relaxation was antagonized by iv administration of 0.0 mg/kg atropine and 0.05 mg/kg neostigmine. With restoration of adequate spontaneous respiration, patients were extubated and transferred to the recovery room. Heart rate (HR), MAP, SpO 2 datas were recorded before and after induction and every 5 minutes until the end of the operation. MEP measurements repeated just after induction (T 1 ), before extubation (T 2 ), after extubation (T 3 ) and 30 minutes after extubation (T 4 ). PONV was evaluated at T 3 T 4 intervals. Investigators evaluating PONV and MEP were blinded to the anesthetics used and investigators performing anesthesia practice were blinded to the MEP measurements and PONV. In recovery room HR, MAP, SpO 2 were also monitorized and MEP was measured 30 minutes after extubation. In case of nausea or vomiting iv metochlopramide 0. mg/kg (Metpamid ) was administered for antiemesis. Obtained data were analized by a computer based statistical programme. Statistical analysis of variance (ANOVA) and Student-Newman- Keul multiple 218

3 comparison test were applied to determine the significant differences among the groups. Bonferroni adjustment was used in the comparisons of intragroup values of MEP, MAP and HR in which the time factor was identified as important through repeated measures of variance analysis. Chi-square and Fisher s exact test compared gender and postoperative side effects of the groups. P values <0.05 accepted as statistically significant. RESULTS There was no significant difference in demographic features among groups (Table 1). MAP changes in time are given in Figure 1. When changes in MAP averages of groups in time were compared, no difference identified among groups. If changes within groups were compared with control values, none of the recorded MAP values were significantly different. Mean Arterial Pressure (mmhg) Group DR Group SR Control Induction Entubation Time (min) Figure 1. Mean arterial pressure values Group DN Group SN Before extubation Extubation 30 Change in mean HR values with time are given in Figure 2. There was no significant difference identified among groups. If changes within groups were compared with the control values, none of the recorded HR values after anesthesia induction and during operation were significantly different. Preoperative MEP values which were assigned as baseline values (T 0 ) was not significantly different among groups. T 1 measurements of right MEP in group DN and group SN were significantly higher than in group DR and they were significantly lower in group SR than in group DN (p=0.002, p=0.026, p=0.009, respectively). T 3 and T 4 measurements of right MEP in group DN and in group SN were significantly lower than in group DR (T 3 p<0.0001, p<0.001; T 4 p<0.0001, p=0.026, respectively) and in group SR (T 3 p<0.009, p<0.026; T 4 p=0.001, p=0.026, respectively), (Table 2). H e a rt R a te Control Induction E n tu b a tio n 5 Figure 2. Heart Rate values Group DR Group SR Time (min) Group DN Group SN Before e x tu b a tio n E x tu b a tio n When right MEP changes within groups were compared, there was a significant increase in group DN and group SN at T 1 and T 2 measurements and a significant decrease at T 4. In group DR there was significant increase of right MEP values at T 2 and a significant decrease at T 4. In group SR a significant increase in right MEP values was observed at T 2 (Table 2). When baseline-t 0 left MEP values were compared, there was no significant difference among groups. At T 1, T 3 and T 4 left MEP in group DR was significantly lower than left MEP values in group DN (p=0.003, p=0.0001, p=0.0001, respectively) and group SN (p=0.034, p=0.009, p=0.016, respectively). When MEP values in group SR were compared to grup DN; they were significantly different at all measurements except T 0 (p=0.012, p=0.003, p=0.029, p=0.026, respectively), (Table 3). When left MEP changes within groups were compared, there was a significant increase in group DN and group SN at T 1 and T 2 measurements and a significant decrease at T 4. In group DR and group SR there was a significant increase at T 2 and a significant decrease at T 4 (p<0.05), (Table 3). Nausea and vomiting were the only side effect encountered. There was no statistically significant difference among groups when frequency of nausea and vomiting were compared (Table 4). When left and right MEP values of 17 patients with PONV at T 3 were compared, the average of higher cases was 8.9±97.2 and it was -6.8±107.8 for lower cases. The difference was statistically significant (p<0.0001), (Table 5). 219

4 Table 1. Demographic Datas (Mean± SD, n) Characteristics Group DR Group SR Group DN Group SN (n=) (n=) (n=) (n=) Age (yr) 8.4± ± ± ±3.1 Gender (female/male) 6/9 5/10 7/8 6/9 Weight (kg) 29.8± ± ± ±10.5 Height (cm) 129.0± ± ± ±16.3 Duration of anesthesia (min) 77.3± ± ± ±13.4 Duration of surgery (min) 65.9± ± ± ±.4 Table 2. Right ear MEP measurements (Mean±SD) MEP Group DR (n=) Group SR (n=) Group DN (n=) Group SN (n=) T ± ± ± ±85.2 T ± ± ±101.1*, 22.4±144.5*, T ± ± ±102.9, 127.7±129.8 T ± ± ±121.0*, ±106.3*, T 4-1.2± ± ±62.0*,, ±57.1*,, P<0.05, * Group DR, Group SR Compared to the values of the other groups, Compared to the values T 0 preoperative (T 0 ), after intubation (T 1 ), before extubation (T 2 ), after extubation (T 3 ), 30 minutes after extubation (T 4 ), MEP: Middle ear pressure Table 3. Left ear MEP measurements (Mean±SD) MEP Group DR (n=) Group SR (n=) Group DN (n=) Group SN (n=) T ± ± ± ±77.1 T ± ± ±126.4*,, 24.3±122.5*, T ± ± ±1.6, 104.6±109.1 T ± ± ±95.2*, -4.8±95.8*, T 4-6.5± ± ±33.6*,, ±53.2*, P<0.05, * Group DR, Group SR Compared to the values of the other groups, Compared to the values T 0 preoperative (T 0 ), after intubation (T 1 ), before extubation (T 2 ), after extubation (T 3 ), 30 minutes after extubation (T 4 ) MEP: Middle ear pressure Table 4. Nausea and vomiting findings [n (%)] Parameters Group DR (n=) Group SR (n=) Group DN (n=) Group SN (n=) Nausea 5 (33.3) 4 (26.7) 6 (40) 5 (33.3) Vomiting 4 (26.7) 4 (26.7) 4 (26.7) 5 (33.3) Table 5. Right and left ear pressure measurements of vomiting patients Patients with PONV Group DR Group SR Group DN Group SN right left right left right left right left DISCUSSION In our study there was an increase in MEP values in both remifentanil and N 2 O used groups, while the latter resulted in an earlier increase. PONV frequency was similar among groups although there was a significant difference in mean right and left MEP values between patients with PONV. Armstrong et al. 6 stated a relation between positive middle ear pressure and ear symptoms. An increase in MEP values from 40.8 to 68 mmh 2 O resulted with ear fullness and hearing loss in most of the cases. Pressures between mmh 2 O caused restlessness and tinnitus even pain and vertigo, while pressures above 408 mmh 2 O caused severe pain, tinnitus and vertigo. N 2 O which is widely used in inhalation anesthesia, rapidly diffuses into spaces causing volumetric increase in flexible tissues and pressure increase in unflexible tissues like middle ear due to high blood gas partition coefficient 1-3,7,8. Thomsen et al. 9 showed that MEP values changed according to 220

5 N 2 O inhalation time and concentration. Chinn et al. 12 evaluated MEP change ratios in 138 cases aged between 6 months and 9 years by taking measures in every 5 minutes during anesthesia starting before anesthesia. MEP change ratio was found as 46% in only halothane used group, while it was 38% in halothane and N 2 O used group. Kubota et al. 8 determined that MEP values reached maximum 60 minutes after TIVA with propofol, fentanyl and ketamine. On the other hand, Gates and Cooper 13 informed that N 2 O use had no significant effect other than halothane use only. In our study, N 2 O resulted in an earlier increase in MEP values, while remifentanil also caused a similar but gradual increase in MEP values. N 2 O use is not the only factor acting on MEP values in operations under general anesthesia. Physiological differences between individuals are important for passive opening of eustachian tube during positive pressure administration. Elam et al. 14 showed a correlation between middle ear positive pressure regulation and mastoid bone dimensions during N 2 O anesthesia. In case of eustachian dysfunction such as inflammation, infection or scar contracture, there is no change in MEP 13. It is reported that during spontaneous respiration, N 2 O administered with mask or by intubation has no effect on severity of effusion and ventilation technique used during anesthesia does not change MEP values. Koivinen et al. 7 reported that N 2 O increased middle ear pressure but had no effect on effusion. Another factor affecting tympanometric measurements is the position of the patient. In our study, in randomly assigned groups MEP values before anesthesia were similar, effusion was not present and similar ventilation technique was used. In all patients, tympanometric measurements were made in supine position which impeded significant differences among groups. Several studies showed that duration of N 2 O administration had influence on MEP values. Kubota et al. 8 reported that although MEP values were increased in TIVA administered cases with propofol, fentanyl, ketamine when 60% N 2 O added MEP was increased significantly just after induction of anesthesia and reached to its upper limit 36 minutes later. In our study, in desflurane or sevoflurane plus N 2 O used groups MEP values in early period (T 1 ) were higher than in desflurane or sevoflurane plus remifentanil used groups, while after anesthesia MEP values (T 4 ) showed greater decrease. Operation durations were similar in different groups but with increase in operation duration MEP values were also increased in both remifentanil and N 2 O used groups. Eustachian tube blockage during anesthesia recovery causes negative pressure. It is shown that negative pressure remained up to 48 hours after anesthesia in a case report who had tympanic membrane rupture after anesthesia with 66 70% N 2 O/34 30% O 7 2. Blackstock et al. 16 reported that first day after administration of 66% N 2 O for minutes (mean 47 mins) with halothane or isoflurane, negative middle ear pressure arised in one ear or both ears of all cases. Chinn et al. 17 found that single use of halothane or halothane with N 2 O made no significant difference in MEP values. In another study, Chinn et al. 12 reported that barometric effects of N 2 O became obvious immediately after induction of anesthesia. In our cases, MEP values increased more rapidly in N 2 O used groups and decrease was greater after anesthesia. Since MEP values were measured until 30 minutes after extubation, exact time of return to baseline values was not clear. Recent studies report that PONV is a major problem with a 30% occurance rate if antiemetic medication was not administered. Frequency of PONV depends on many factors such as age, gender, body weight, presence of motion sickness history, gastric fullness, operation site, concomitant pathologies, duration of anesthesia, method of anesthesia and anesthetic agents 4,5. Gastric distention, severe postoperative pain and narcotic analgesic use are factors adversely affecting nausea and vomiting during anesthesia practice. Middle ear surgery is one of the operations with high rate of PONV 5. Cases with preoperative remifentanil infusion has % rate of PONV 18. N 2 O used in anesthesia also increases rate of PONV by causing barometric changes 5,11. In a meta-analysis Tramer et al. 11 reviewed 24 studies including 2478 patients and reported that removing N 2 O during general anesthesia decreases PONV incidence in high risk patients. Gastric distention during N 2 O use is an important factor increasing nausea and vomiting besides its central effects 5. In our study demographic features such as age and gender were similar in all groups. By standardization of surgery and anesthesia techniques and excluding risk factors increasing nausea and vomiting, we aimed to control the confounding effects. We suggest that gastric suction in all groups after intubation and before extubation prevented nausea and vomiting caused by gastric distention. In our study, there was a similar rate of PONV both in remifentanil and N 2 O used groups. 221

6 The mechanism of nausea and vomiting due to middle ear pressure changes is not exactly known. But rapid changes in middle ear pressure may play a role in PONV by rapid pressure reflection to labyrinth and vestibule via round window 1. In our series right and left middle ear pressure values were significantly different in cases with nausea and vomiting that s why we concluded that difference in middle ear pressures of right and left ear causes nausea and vomiting. As a result, N 2 O use seems to be inappropriate for brief operations because it inceases MEP. However, in long term operations N 2 O used with remifentanil has no effect on MEP as well as on nausea and vomiting. Difference between right and left MEP values is an important factor increasing nausea and vomiting frequency and this should be further supported by future studies with larger sample size. REFERENCES 1. Simpson G, Reedy RL. Middle ear pressure changes after nitrous oxide anesthesia and its effect on postoperative nausea and vomiting. Laryngoscope 2004;114: Perreault L, Normandin N, Plamondon L. Tympanic membrane rupture after anesthesia with nitrous oxide. Anesthesiology 1982;57: White PF. Spontaneous rupture of tympanic membrane occurring in the absence of middle ear disease. Anesthesiology 1983; 59: Golembiewski J, Chernin E, Chopra T. Prevention and treatment of postoperative nausea and vomiting. American Journal of Health-System Pharmacy 2005; 62: Palazzo MGA, Strunin L. Anaesthesia and emesis. I: Etiology. Can Anaesth Soc J 1984; 31: Armstrong HG, Heim JW. The effect of flight on the middle ear. JAMA 1937;109: Koivunen P, Alho OP, Uhari M, Partanen A, Luotonen J. General anesthesia with and without nitrous oxide (N 2 O) and the weight of middle ear effusion in children undergoing adenoidectomy and tympanostomy. Laryngoscope 1996; 106: Kubota T, Kazuyoshi H, Noriaki O et al. Middle-ear pressure variations during total intravenous anesthesia with propofol, fentanyl, and ketamine. J Anesth 1998;12: Thomsen KA, Terkildsen K, Arnfred I. Middle ear pressure variations during anesthesia. Arch Otolaryngol 1965;82: Perreault L, Rousseau P, Garneau JF, Forget G. Gas diffusion in the middle ear during anesthesia for tympanoplasty. Can Anaesth Soc J 1981;28: Tramer M, Moore A, McQuay H. Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperative awareness and postoperative emesis in randomized controlled trials. Br J Anaesth 1996;76: Chinn K, Brown OE, Manning SC. Effects of inhalant anesthesia on the middle ear as measured by tympanometry. Arch Otolaryngol Head Neck Surg 1993;119: Gates GA, Cooper JC Jr. Effect of anesthetic gases on middle ear pressure in the presence of effusion. Ann Otol Rhinol Laryngol Suppl 1980;89: Elam M, Harell M, Luntz M, Fuchs C, Sade J. Middle ear pressure variations during 50% N2O anesthesia as a function of mastoid pneumatization. Am J Otol 1998;19: Drake-Lee AB, Casey WF. Anaesthesia and tympanometry. Int J Pediatr Otorhinolaryngol 1983;6: Blackstock D, Gettes MA. Negative pressure in the middle ear in children after nitrous oxide anaesthesia. Can Anaesth Soc J 1986;33: Chinn K, Brown OE, Manning SC, Crandell CC. Middle ear pressure variation: effect of Nitrous oxide. The Laryngoscope 1997;107: Scott LJ, Perry CM. Remifentanil: a review of its use during the induction and maintenance of general anaesthesia. Drugs 2005;65: Correspondence: Mustafa ARSLAN M.D. Gazi University Faculty of Medicine, Beşevler-Ankara marslan36@yahoo.com Arriva date : Acceptance date :