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The effect of preoperative dexamethasone on early oral intake, vomiting and pain after tonsillectomy
International Journal of Pediatric Otorhinolaryngology (2006) 70, 73—79
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The effect of preoperative dexamethasone on early oral intake, vomiting and pain after tonsillectomy M. Nil Kaan a,*, Onur Odabasi b, Erdal Gezer a, Alper Daldal b a
Adnan Menderes University, School of Medicine, Department of Anesthesiology and Reanimation, 09100 Aydin, Turkey b Adnan Menderes University, School of Medicine, Department of Otolaryngology, 09100 Aydin, Turkey Received 6 April 2005; accepted 8 May 2005
KEYWORDS Tonsillectomy; Dexamethasone; Pediatrics; Postoperative pain; Vomiting; Oral intake
Summary Objective: Postoperative morbidity in patients undergoing tonsillectomy with or without adenoidectomy includes inadequate oral intake, pain, nausea, vomiting and bleeding. The purpose of this study is to evaluate the effect of preoperative 0.5 mg/kg i.v. dexamethasone on postoperative early oral intake, pain, vomiting in patients undergoing adenotonsillectomy while performing standard anesthesia technique and sharp dissection tonsillectomy. Methods: In this prospective, double-blinded, placebo-controlled study 62 children, aged 4—12 years, who underwent tonsillectomy with or without adenoidectomy were randomly assigned to receive single dose of 0.5 mg/kg i.v. dexamethasone preoperatively. Patients started to receive 100 ml of clear fluids 2 h postoperatively, then were offered every hour. When pain score was 3 or above, paracetamol was given for pain control. Tolerating 400 ml of clear fluids, no bleeding and no vomiting were accepted as discharge criteria. The discharge time was also recorded. The incidence of early vomiting, pain scores, amount of oral intake were recorded until the discharge time. Results: Compared with placebo, the patients who received preoperative dexamethasone had significantly less pain score during the first 6 h postoperatively ( p < 0.05), adequate amount of oral intake time was shorter ( p < 0.05) and the discharge time was earlier ( p < 0.05). No difference was found in vomiting incidence in both groups. Conclusion: Preoperative dexamethasone use significantly reduces early posttonsillectomy pain, improves oral intake and facilitates meeting the discharge criteria while using standard anesthesia technique and sharp dissection tonsillectomy without any significant side effects. # 2005 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Tel.: +90 256 444 1 256/358; fax: +90 256 214 6495. E-mail address: [email protected] (M.N. Kaan). 0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.05.013
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1. Introduction Among the morbidities after adenotonsillectomy operations, nausea, vomiting, inadequate oral intake and fever are most commonly encountered. The incidence of vomiting after tonsillectomy with or without adenoidectomy has been reported ranging between 40 and 70% [1—3]. The delay in postoperative oral fluid intake and also inadequate oral feeding because of the nausea, vomiting and pain prolongs the discharge period, and also increases dehydration risk in early or late postoperative period [4,5]. Because of these reasons, it is extremely important in pediatric patients to take pain, nausea and vomiting under control and also to start oral fluid intake in the earliest postoperative (PO) period. The antiemetic effect of dexamethasone has been demonstrated in cancer patients receiving chemotherapy and also after gynecologic and laparoscopic operations [6—9]. There have been studies which show decreasing incidence of vomiting after electrodissection tonsillectomy shortening the first oral intake time and increasing quality of oral intake in pediatric age group [10—16]. However, a few number of published studies, which investigated the effects of preoperative dexamethasone on postoperative morbidities failed to show any beneficial effects of dexamethasone in tonsillectomies using sharp dissection technique [17,18]. Catlin and Grimes [19] noted that to return to a full or semi-full diet in patients with sharp dissection tonsillectomy occurred after 3 days postoperatively, which was significantly sooner in the steroid-treated patients than in the control patients. The aim of our study is to investigate effects of 0.5 mg/kg i.v. dexamethasone given before induction of anesthesia on early oral intake, vomiting and pain in pediatric patients undergoing tonsillectomy with or without adenoidectomy, during the first 8 h of postoperative period while performing standard anesthesia and sharp dissection tonsillectomy.
2. Methods After approval from the institution’s ethical committee and informed consent from the parents, 62 patients, 4—12 years old, ASA physical status I or II and undergoing tonsillectomy with or without adenoidectomy, were enrolled in the study. The study design was prospective, randomized, double-blinded and placebo-controlled. Children who received antiemetics, steroids, antihistaminics, or phychoactive drugs within 24 h before sur-
M.N. Kaan et al.
gery were excluded from the study. Additionally, children in whom i.v. induction was indicated or steroid administration was contraindicated, and patients with diabetes and mental retardation were not included in the study. Oral intake was stopped 8 h and clear fluids were stopped 4 h preoperatively. Premedication with oral midazolam 0.5 mg/kg was administered 20—30 min to the children before taken to operating room. Patients were monitored by EKG (heart rate and rhythm), non-invasive arterial blood pressure and SpO2. Anesthesia was induced with 8% sevoflurane with mixture of 50% O2 and 50%N2O via mask. After eyelash reflex has disappeared, i.v. cannula was inserted. During the operation all patients received 20—30 ml/kg of lactated Ringer’s solution. Endotracheal intubation was facilitated by 0.1 mg/kg vekuronyum, and all children received fentanyl 1 mg/kg before the operation. Anesthesia was maintained with concentration of 1.5—2% sevoflurane and 50% N2O. After endotracheal intubation, all patients received paracetamol 15 mg/kg by rectal route for postoperative pain control. Following anesthesia induction and just before the surgical procedure, the patients were randomized to receive either dexamethasone (dexamethasone group, n = 32) 0.5 mg/kg (maximum 16 mg) or placebo (equivalent volume of saline solution, control group, n = 30) by i.v. route according to the study classification. The program in the www.randomizer.org Internet website was used for the randomization. All procedure was performed in double-blind fashion. The same sharp dissection tonsillectomy technique, and suture ligation for the bleeding control was performed in all patients. If the heart rate and blood pressure values increased more than 25% of the baseline induction values during the operation, they were adjusted with fentanyl 1 mg/kg i.v. Additional fentanyl dosage, if needed, was also recorded. Residual neuromuscular blockade was reversed with 0.015 mg/kg atropin and 0.05 mg/kg neostigmin i.v. Children were transported to postanesthesia care unit when they were all awake, comfortable, stable and responding to verbal stimuli. The patients were closely observed for their vomiting, pain and for possible agitation status in postanesthesia care unit. The patients who met the criteria (stable vital signs, adequate pain control, absence of vomiting) were transferred to floor after 1 h. Pain, vomiting and oral intake were assessed by an independent observer at hourly intervals. Retching or vomiting more than once in 3 min was recorded as ‘‘one vomiting episode’’ and metoclopramide 0.15 mg/kg i.v. was administered. As the children could not express their feeling of nausea
Effect of preoperative dexamethasone after tonsillectomy
exactly, retching and/or vomiting episodes more than once were considered significant in recording vomiting index. If retching and/or vomiting was not under control in the next 20 min, then 0.15 mg/kg ondansetron was administered. Early (just after extubation and in postanesthesia care unit) and late postoperative (at floor) vomiting episodes and antiemetic requirements were also documented. Pain was assessed using a five-point ‘‘faces’’ scale (1 = smiling face: no pain, 5 = crying face: highest pain score). If the pain score was noted above 3 or could not be assessed exactly because of agitation, meperidine 1 mg/kg i.v. was administered in postanesthesia care unit, and paracetamol 15 mg/kg PO in the floor was given and application time was documented. After parents and nurse caring for child were informed about the procedure, oral fluids were offered at second postoperative hour. Children without retching and/or vomiting during the last hour were asked if they could tolerate oral fluids. The amount of water or clear fluid that children were able to drink within hourly periods was recorded. The scale was as follows: 100 ml (full), 50 ml (half), 10—15 ml (little) and none. As soon as they ingested total 150 ml clear fluids, i.v. line was removed. The children were considered to meet the discharge criteria when they were full awake, cooperated, stable, free of tonsillar bleeding, having pain score 1 or 2, and were able to ingest total of 400 ml clear fluid or soft diet. ‘‘Discharge time’’ was recorded as soon as they met the criteria above. Pain, vomiting or oral intake recordings were documented until the discharge time. The patients and parents were instructed to return to ENT clinic in case of bleeding, two or more vomiting episode or inadequate oral intake after discharge. Statistical analysis of the data was performed by ‘‘SPSS 10.0 for Windows’’ (SPSS Inc., Chicago, Illinois). Groups (demographic characteristics, anesthesia and operation time, discharge time)
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were compared using Student’s t-test. In frequency comparison x2 or Fisher’s exact tests; for pain score comparisons Mann—Whitney U-test were used. p < 0.05 was considered significant.
3. Results Demographic and clinical findings, additional intraoperative fentanyl requirements, duration of anesthesia and operation were not significantly different between the two groups (Table 1). There were no significant difference between early and late postoperative vomiting incidence and antiemetic requirements between groups (Table 2). Total vomiting frequency in dexamethasone group was 6 and in control group was 10. None of the patients needed ondansetron in both groups. Meperidine i.v. was administered in PACU for agitation and/or pain control in eight patients in dexamethasone group and 12 in control group (Table 2). The postoperative first hour pain score before transferring to floor were similar between the two groups (Fig. 1). The postoperative first 6 h pain score after transmitting to floor was significantly lower in dexamethasone group than the control ( p < 0.05). Eighth hour scores were also lower, however, statistically not significant (Fig. 1). First postoperative oral paracetamol intake time and need for paracetamol were similar between two groups (Table 2). The number of patients who had ‘‘full’’ oral intake of fluid and soft diet after 2 h postoperatively were more in dexamethasone group compared with the control ( p < 0.05) (Fig. 2). The patients in dexamethasone group reached discharge criteria earlier (5.6 0.9 h) compared to control (7.2 2.0 h) ( p < 0.05). None of the patients in both groups applied to ENT clinic for poor oral intake and was taken to operating room for bleeding control.
Table 1 Patient demographic and clinical data Dexamethasone (n = 32)
Control (n = 30)
Age (years) Weight (kg) Sex (F/M) Intraoperative fentanyl (n) Duration of surgery (min) Duration of anesthesia (min)
7.6 5.1 20.1 7.1 22/10 11 36.6 8.9 51.5 6.3
9.3 7.4 19.5 4.9 20/10 14 40.7 7.3 55.2 7.1
Type of surgery Tonsillectomy (n) Adenotonsillectomy (n)
13 19
12 18
Values are expressed as number (n), or mean (S.D.).
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M.N. Kaan et al.
Table 2 Frequency of retching/vomiting, requirement of antiemetics, analgesics and time to first oral paracetamol postoperatively Dexamethasone (n = 32)
Control (n = 30)
Vomiting (n) PACU Floor Overall
6 0 6
6 4 10
Antiemetic requirement (n) Metoclopramid Ondansetrone
6 0
10 0
Analgesic requirement (n) Meperidine PACU
8
12
6 11 12 3
4 17 7 2
Paracetamol 2h 3h 4h 5h Time to first oral paracetamol (h) (mean S.D.)
3.2 0.8
3.8 0.9
PACU: postanesthesia care unit.
4. Discussion Several studies which investigated the effects of preoperative dexamethasone on postoperative pain, vomiting and quality of oral intake in patients undergoing adenotonsillectomy demonstrated conflicting results, because of limited number of patients, different dose of dexamethasone, different surgical techniques (electrodissection versus sharp dissection) and lack of standardized anesthetic technique [10—20]. In this present study, the administration of preoperative dexamethasone at a dose of 0.5 mg/kg in patients undergoing tonsillectomy with or without adenoidectomy with sharp dissection technique was associated with reduced postoperative pain score and increased oral intake during the hospital stay. Additionally, the dexamethasone group showed
Fig. 1
shorter hospital stay period compared with control group. However, no significant effect of dexamethasone on vomiting incidence was noted. Most common factors that affect the time to first oral intake and its quality are postoperative nausea, vomiting and pain. These factors also delay the discharge period after the operation. Splinter [20] reported that each vomiting episode prolonged the hospital stay approximately 13.2 min. Although some studies fail to show any significant effect of dexamethasone on postoperative vomiting incidence [18,19], there have been a quite number of randomized, placebo-controlled studies revealing a decrease in vomiting incidence [10—16,20]. Aouad et al. [15] found that the vomiting incidence in patients undergoing tonsillectomy or adenotonsillectomy, administered dexamethasone 0.5 mg/kg preoperatively was 10% and in placebo group was
Postoperative ‘‘faces’’ pain score (mean S.D.); *p < 0.05, between two groups.
Effect of preoperative dexamethasone after tonsillectomy
Fig. 2
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Postoperative oral intake amounts; *p < 0.05, between two groups.
30% ( p < 0.05). In a similar study, Elhakim et al. [16] demonstrated that the vomiting incidence was 30 and 56%, respectively ( p < 0.05). Pappas et al. [13] reported that 1 mg/kg dexamethasone given before the surgery showed minimal effects on postoperative morbidity; however, it minimized vomiting incidence in the late postoperative period (24 h after home discharge). These results were attributed to dexamethasone’s biological half-life of 36—48 h [21]. In meta-analysis of eight published studies, Steward et al. [22] reported that in patients undergoing tonsillectomy, preoperative dexamethasone decreased vomiting incidence two times and improved oral intake of clear fluids and soft diet within the first 24 h when compared with placebo group. On the other hand, when pain scores were compared, these studies failed to show any significant difference because of missing of data and differences in evaluation methods. The regression analysis of the antiemetic effect of dexamethasone dose suggests that when dexamethasone dose was increased to 1 mg/kg, the positive antiemetic effect was also increased [22]. Antiemetic action of dexamethasone occurs via prostaglandin antagonism, release of endorphins and tryptophan depletion. But it is not clear whether in this procedure dexamethasone shows its effect by a central or peripheral mechanism [23,24]. In the present study, the patients were closely observed until they reached discharge criteria. During this period, vomiting, pain scores and the amount of oral intake were recorded. During their hospital stay, six postoperative vomiting episodes (18.7%) in dexamethasone group and 10 in placebo group (33.3%) were observed. The difference did not reach significance; however, there was a clear trend toward a better control of vomiting in dexamethasone group. The possible explanation of these results might be the limited number of patients and/or 0.5 mg/kg of dexamethasone dose.
When similar studies were reviewed, patients who received preoperative dexamethasone showed faster first oral fluid intake, earlier sufficient oral intake amount and had better quality of oral intake. In most of the studies electrodissection tonsillectomy was performed. Although the beneficial effect of dexamethasone was clearly seen, there were significant differences in time periods [11—16]. Oral intake quality was recorded similarly in three studies as follows: excellent = child requests, good = child accepts when offered, fair = child accepts it when coaxed and poor = child refuses [13,15,16]. Aouad et al. [15] noted that first oral intake time in dexamethasone group was 5.3 h and in placebo group 10.9 h ( p < 0.05), and also oral intake quality was higher at 24 h postoperatively in dexamethasone group [15]. A similar study by Elhakim et al. [16] demonstrated that first oral intake time in dexamethasone group was 0.4 0.2 h, compared with placebo 1.3 0.7 h ( p < 0.05). Quality of oral intake was better than the control group [16]. Pappas et al. [13] found no significant difference while comparing the pain scores and quality of oral intake within the first 3 h between the two groups postoperatively; however, when examining the 24 h quality of oral intake, the dexamethasone group showed significant improvement. Additionally, the number of patients who returned to hospital due to dehydration and poor oral intake were higher in the placebo group [13]. In the present study, oral feeding was started 2 h after the operation and soft diet/clear fluids were offered hourly. In dexamethasone group, after 2 h postoperatively the amount of oral intake was higher than the control group ( p < 0.05). As our institution is a tertiary referral clinic, the majority of our patients are referred to ENT Clinic from 45—60 min distance. Also, the seasonal temperature averages are higher than in most parts of the country. In addition, a possible postoperative bleeding may cause hypovolemia in this small age
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group easily. Therefore, it is important to be sure that the children have enough oral fluid intake before discharging home. In our study, one of the accepted discharge criteria of tolerating 400 ml of oral fluid was achieved earlier in dexamethasone group (5.6 0.9 h) than the control (7.2 2.0 h). The results were statistically significant ( p < 0.05). Comparing with previous studies, fluid and soft diet were given more frequently (every hour) in the postoperative period. This protocol might have increased the amount of oral intake and shortened the 400 ml of fluid intake time. In the previous published studies that showed the beneficial effect of preoperative dexamethasone in patients undergoing tonsillectomy or adenotonsillectomy, electrodissection tonsillectomy was preferred surgical technique. In a small number of studies sharp dissection technique was used; however, they failed to show the significant effects of dexamethasone in reducing postoperative pain, vomiting and quality of oral intake [17,18]. Only Catlin and Grimes [19] found the ability to return to a full or semi-full diet occurred on the third and fourth postoperative days, significantly sooner in the steroid-treated patients than in the control patients. No significant differences were observed in postoperative pain, nausea, emesis, fever, or in the need for postoperative pain medications [19]. Hanasono et al. [14] compared the effects of 1 mg/kg dexamethasone on postoperative morbidity in both surgical techniques (electrodissection versus sharp dissection). It was concluded that dexamethasone decreased postoperative pain but the patients undergone to sharp dissection tonsillectomy had less pain than electrodissection tonsillectomy. The possible explanation might be the thermal effect associated with electrodissection to the remaining tissues [14]. In both surgical techniques, patients in dexamethasone group showed higher percentage of returning to a full diet compared with placebo group at the end of postoperative day 1 (42.5 and 31.7%, respectively; p < 0.05). In addition, patients undergone sharp dissection technique and received preoperative dexamethasone, showed significant improvement in oral intake and less pain score. However, the assessment was performed 24 h after the operation [14]. Unlike the studies that demonstrate positive effects of dexamethasone on pain in patients undergoing to adenotonsillectomy [11,14,16], some published papers could not reach the same results [10,12,17—19]. Elhakim et al. [16] noted less pain score in patients who received dexamethasone at 30 min, 4, 12 and 24 h postoperatively. They have used both the faces and CHEOPS (Children’s Hospital Eastern Ontario Pain Scale) pain scales in their
M.N. Kaan et al.
evaluation. The results of the two evaluation methods were similar in the early postoperative period [16]. During tonsillectomy, the underlying muscle tissue and surrounding tissues are damaged mechanically, thermally, or both. This results an acute inflammatory response in the surrounding tissues, causing spasm of pharyngeal muscles, irritation of nerve endings and even disruption of the mucosa [25]. This event results in imbalance in the delicate mechanism of swallowing, incoordination, dysphagia and pain. For these reasons, it is important to prevent the tissue damage and help re-establish the normal physiologic mechanisms [26]. Glucocorticoids cause inhibition of the inflammatory response by blocking factors, such as bradykinin, prostaglandin and leukotrienes, which results decrease in degree of inflammation and lessening accompanying signs and symptoms, including pain [26]. In our study, we used five ‘point’ faces scale in order to evaluate postoperative pain. Our results showed that the pain score in the first 6 h of the postoperative period was lower in dexamethasone group, compared with control group ( p < 0.05); on the other hand, no difference was noted in analgesic requirement between groups. These results may be attributed to the anti-inflammatory effect produced by dexamethasone, which may reduce local edema and pain [21]. Additionally, dexamethasone modulates inducible COX-2 [27]. Complications from corticosteroid therapy, such as increased rate of infection, peptic ulceration and adrenal suppression are usually related to its longterm use. The risk of steroid therapy of <24 h is negligible [28]. We have not noticed any of the complications in our patients mentioned above. In conclusion, a prophylactic intraoperative single dose of 0.5 mg/kg dexamethasone in patients undergoing tonsillectomy with or without adenoidectomy decreases postoperative pain, improves oral intake as well as increases quality of oral intake without apparent side effects. None of the patients returned to the hospital because of prolonged recovery. We have not noticed a significant decrease in postoperative vomiting incidence. Frequent offering of small amounts of fluids and soft diet increases the total amount of oral intake, which may facilitate the patients to meet discharge criteria earlier.
References [1] S.R. Furst, A. Rodarte, Prophylactic antiemetic treatment with ondansetron in children undergoing tonsillectomy, Anesthesiology 81 (1994) 799—803.
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[2] R.S. Litman, C.L. WU, F.A. Catanzaro, Ondansetron decreases emesis after tonsillectomy in children, Anesth. Analg. 78 (1994) 478—481. [3] L.R. Ferrari, J.V. Donlon, Metoclopramide reduces the incidence of vomiting after tonsillectomy in children, Anesth. Analg. 75 (1992) 351—354. [4] J.S. Carithers, D.E. Gebhart, J.A. Williams, Postoperative risk of pediatric tonsilloadenoidectomy, Laryngoscope 97 (1987) 422—429. [5] W.S. Crystale, D. Russel, Complication of tonsillectomy and adenoidectomy in 9409 children observed overnight, Can. Med. Assoc. J. 135 (1986) 1139—1142. [6] M.S. Aapro, D.S. Alberts, Dexamethasone as an antiemetic in patients treated with cisplatine, N. Engl. J. Med. 305 (1981) 520 (letter). [7] J.J. Wang, S.T. Ho, Y.H. Liu, S.C. Lee, Y.C. Liu, Y.C. Liao, et al. Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy, Br. J. Anaesth. 83 (1999) 72—75. [8] J.J. Wang, S.T. Ho, H.S. Liu, C.M. Ho, Prophylactic antiemetic effect of dexamethasone in women undergoing ambulatory laparoscopic surgery, Br. J. Anaesth. 84 (2000) 459— 462. [9] K. Liu, C.C. Hsu, Y.Y. Chia, The effective dose of dexamethasone for antiemesis after major gynecological surgery, Anesth. Analg. 89 (1999) 1316—1318. [10] F. Vosdoganis, D.B. Baines, The effect of single-dose intravenous dexamethasone in tonsillectomy in children, Anaesth. Intensive Care 27 (1999) 489—492. [11] Tom LWC, J.J. Templeton, M.E. Thompson, R.R. March, Dexamethasone in adenotonsillectomy, Int. J. Pediatr. Otorhinolaryngol. 37 (1996) 115—120. [12] M.M. April, N.D. Callan, D.M. Nowak, M.A. Hausdorff, The effect of intravenous dexamethasone in pediatric adenotonsillectomy, Arch. Otolaryngol. Head Neck Surg. 122 (1996) 117—120. [13] Pappas ALS, R. Sukhani, A.J. Hotaling, et al. The effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy, Anesth. Analg. 87 (1998) 57—61. [14] M.M. Hanasono, M.L. Lalakea, A.A. Mikulec, K.G. Shepard, V. Wellis, A.H. Messner, Perioperative steroids in tonsillectomy using electrocautery and sharp dissection techniques, Arch. Otolaryngol. Head Neck Surg. 130 (2004) 917—921.
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[15] M.T. Aouad, S.S. Siddik, L.B. Rizk, G.M. Zaytoun, A.S. Baraka, The effect of dexamethasone on postoperative vomiting after tonsillectomy, Anesth. Analg. 92 (2001) 636—640. [16] M. Elhakim, N.M. Ali, I. Rashed, M.K. Riad, M. Refat, Dexamethasone reduces postoperative vomiting and pain after pediatric tonsillectomy, Can. J. Anaesth. 50 (2003) 392— 397. [17] M.S. Volk, P. Martin, L. Brodsky, J.F. Stanievich, M. Ballou, The effects of preoperative steroids on tonsillectomy patients, Otolaryngol. Head Neck Surg. 109 (1993) 26—30. [18] L.A. Ohlms, R.T. Wilder, B. Weston, Use of intraoperative corticosteroids in pediatric tonsillectomy, Arch. Otolaryngol. Head Neck Surg. 121 (1995) 737—742. [19] F.I. Catlin, W.J. Grimes, The effect of steroid therapy on recovery from tonsillectomy in children, Arch. Otolaryngol. Head Neck Surg. 117 (1991) 649—652. [20] W. Splinter, D.J. Roberts, Dexamethasone decreases vomiting by children after tonsillectomy, Anesth. Analg. 83 (1996) 913—916. [21] L.S. Goodman, A. Gilman (Eds.), The Pharmacological Basis of Therapeutics, fifth ed., MacMillan, New York, 1975, p. 1487. [22] D.L. Steward, J.A. Welge, C.M. Myer, Do steroids reduce morbidity of tonsillectomy? Meta-analysis of randomized trials, Laryngoscope 111 (2001) 1712—1718. [23] A.L. Harris, Cytotoxic-therapy-induced vomiting is mediated via enkephalin pathways, Lancet 27 (1) (1982) 714—716. [24] S.M. Sagar, The current role of anti-emetic drugs in oncology: a recent revolution in patient symptom control, Cancer Treat. Rev. 18 (1991) 95—135. [25] J.H. Dempster, Post-tonsillectomy analgesia: the use of benzocaine lozenges, J. Laryngol. Otol. 102 (1988) 813—814. [26] C.E. Palme, P. Tomasevic, D.V. Pohl, Evaluating the effects of oral prednisolone on recovery after tonsillectomy: A prospective, double-blind, randomized trial, Laryngoscope 110 (2000) 2000—2004. [27] S. Honda, K. Migita, Y. Hirai, Y. Ueki, S. Yamasaki, S. Urayama, et al. Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells, Biochem. Biophys. Res. Commun. 268 (2000) 928—931. [28] J.C. Melby, Aldosterone — an independent risk factor in cardiovascular disease, J. Clin. Endocrinol. Metab. 87 (2002) 447.
www.elsevier.com/locate/ijporl
The effect of preoperative dexamethasone on early oral intake, vomiting and pain after tonsillectomy M. Nil Kaan a,*, Onur Odabasi b, Erdal Gezer a, Alper Daldal b a
Adnan Menderes University, School of Medicine, Department of Anesthesiology and Reanimation, 09100 Aydin, Turkey b Adnan Menderes University, School of Medicine, Department of Otolaryngology, 09100 Aydin, Turkey Received 6 April 2005; accepted 8 May 2005
KEYWORDS Tonsillectomy; Dexamethasone; Pediatrics; Postoperative pain; Vomiting; Oral intake
Summary Objective: Postoperative morbidity in patients undergoing tonsillectomy with or without adenoidectomy includes inadequate oral intake, pain, nausea, vomiting and bleeding. The purpose of this study is to evaluate the effect of preoperative 0.5 mg/kg i.v. dexamethasone on postoperative early oral intake, pain, vomiting in patients undergoing adenotonsillectomy while performing standard anesthesia technique and sharp dissection tonsillectomy. Methods: In this prospective, double-blinded, placebo-controlled study 62 children, aged 4—12 years, who underwent tonsillectomy with or without adenoidectomy were randomly assigned to receive single dose of 0.5 mg/kg i.v. dexamethasone preoperatively. Patients started to receive 100 ml of clear fluids 2 h postoperatively, then were offered every hour. When pain score was 3 or above, paracetamol was given for pain control. Tolerating 400 ml of clear fluids, no bleeding and no vomiting were accepted as discharge criteria. The discharge time was also recorded. The incidence of early vomiting, pain scores, amount of oral intake were recorded until the discharge time. Results: Compared with placebo, the patients who received preoperative dexamethasone had significantly less pain score during the first 6 h postoperatively ( p < 0.05), adequate amount of oral intake time was shorter ( p < 0.05) and the discharge time was earlier ( p < 0.05). No difference was found in vomiting incidence in both groups. Conclusion: Preoperative dexamethasone use significantly reduces early posttonsillectomy pain, improves oral intake and facilitates meeting the discharge criteria while using standard anesthesia technique and sharp dissection tonsillectomy without any significant side effects. # 2005 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Tel.: +90 256 444 1 256/358; fax: +90 256 214 6495. E-mail address: [email protected] (M.N. Kaan). 0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.05.013
74
1. Introduction Among the morbidities after adenotonsillectomy operations, nausea, vomiting, inadequate oral intake and fever are most commonly encountered. The incidence of vomiting after tonsillectomy with or without adenoidectomy has been reported ranging between 40 and 70% [1—3]. The delay in postoperative oral fluid intake and also inadequate oral feeding because of the nausea, vomiting and pain prolongs the discharge period, and also increases dehydration risk in early or late postoperative period [4,5]. Because of these reasons, it is extremely important in pediatric patients to take pain, nausea and vomiting under control and also to start oral fluid intake in the earliest postoperative (PO) period. The antiemetic effect of dexamethasone has been demonstrated in cancer patients receiving chemotherapy and also after gynecologic and laparoscopic operations [6—9]. There have been studies which show decreasing incidence of vomiting after electrodissection tonsillectomy shortening the first oral intake time and increasing quality of oral intake in pediatric age group [10—16]. However, a few number of published studies, which investigated the effects of preoperative dexamethasone on postoperative morbidities failed to show any beneficial effects of dexamethasone in tonsillectomies using sharp dissection technique [17,18]. Catlin and Grimes [19] noted that to return to a full or semi-full diet in patients with sharp dissection tonsillectomy occurred after 3 days postoperatively, which was significantly sooner in the steroid-treated patients than in the control patients. The aim of our study is to investigate effects of 0.5 mg/kg i.v. dexamethasone given before induction of anesthesia on early oral intake, vomiting and pain in pediatric patients undergoing tonsillectomy with or without adenoidectomy, during the first 8 h of postoperative period while performing standard anesthesia and sharp dissection tonsillectomy.
2. Methods After approval from the institution’s ethical committee and informed consent from the parents, 62 patients, 4—12 years old, ASA physical status I or II and undergoing tonsillectomy with or without adenoidectomy, were enrolled in the study. The study design was prospective, randomized, double-blinded and placebo-controlled. Children who received antiemetics, steroids, antihistaminics, or phychoactive drugs within 24 h before sur-
M.N. Kaan et al.
gery were excluded from the study. Additionally, children in whom i.v. induction was indicated or steroid administration was contraindicated, and patients with diabetes and mental retardation were not included in the study. Oral intake was stopped 8 h and clear fluids were stopped 4 h preoperatively. Premedication with oral midazolam 0.5 mg/kg was administered 20—30 min to the children before taken to operating room. Patients were monitored by EKG (heart rate and rhythm), non-invasive arterial blood pressure and SpO2. Anesthesia was induced with 8% sevoflurane with mixture of 50% O2 and 50%N2O via mask. After eyelash reflex has disappeared, i.v. cannula was inserted. During the operation all patients received 20—30 ml/kg of lactated Ringer’s solution. Endotracheal intubation was facilitated by 0.1 mg/kg vekuronyum, and all children received fentanyl 1 mg/kg before the operation. Anesthesia was maintained with concentration of 1.5—2% sevoflurane and 50% N2O. After endotracheal intubation, all patients received paracetamol 15 mg/kg by rectal route for postoperative pain control. Following anesthesia induction and just before the surgical procedure, the patients were randomized to receive either dexamethasone (dexamethasone group, n = 32) 0.5 mg/kg (maximum 16 mg) or placebo (equivalent volume of saline solution, control group, n = 30) by i.v. route according to the study classification. The program in the www.randomizer.org Internet website was used for the randomization. All procedure was performed in double-blind fashion. The same sharp dissection tonsillectomy technique, and suture ligation for the bleeding control was performed in all patients. If the heart rate and blood pressure values increased more than 25% of the baseline induction values during the operation, they were adjusted with fentanyl 1 mg/kg i.v. Additional fentanyl dosage, if needed, was also recorded. Residual neuromuscular blockade was reversed with 0.015 mg/kg atropin and 0.05 mg/kg neostigmin i.v. Children were transported to postanesthesia care unit when they were all awake, comfortable, stable and responding to verbal stimuli. The patients were closely observed for their vomiting, pain and for possible agitation status in postanesthesia care unit. The patients who met the criteria (stable vital signs, adequate pain control, absence of vomiting) were transferred to floor after 1 h. Pain, vomiting and oral intake were assessed by an independent observer at hourly intervals. Retching or vomiting more than once in 3 min was recorded as ‘‘one vomiting episode’’ and metoclopramide 0.15 mg/kg i.v. was administered. As the children could not express their feeling of nausea
Effect of preoperative dexamethasone after tonsillectomy
exactly, retching and/or vomiting episodes more than once were considered significant in recording vomiting index. If retching and/or vomiting was not under control in the next 20 min, then 0.15 mg/kg ondansetron was administered. Early (just after extubation and in postanesthesia care unit) and late postoperative (at floor) vomiting episodes and antiemetic requirements were also documented. Pain was assessed using a five-point ‘‘faces’’ scale (1 = smiling face: no pain, 5 = crying face: highest pain score). If the pain score was noted above 3 or could not be assessed exactly because of agitation, meperidine 1 mg/kg i.v. was administered in postanesthesia care unit, and paracetamol 15 mg/kg PO in the floor was given and application time was documented. After parents and nurse caring for child were informed about the procedure, oral fluids were offered at second postoperative hour. Children without retching and/or vomiting during the last hour were asked if they could tolerate oral fluids. The amount of water or clear fluid that children were able to drink within hourly periods was recorded. The scale was as follows: 100 ml (full), 50 ml (half), 10—15 ml (little) and none. As soon as they ingested total 150 ml clear fluids, i.v. line was removed. The children were considered to meet the discharge criteria when they were full awake, cooperated, stable, free of tonsillar bleeding, having pain score 1 or 2, and were able to ingest total of 400 ml clear fluid or soft diet. ‘‘Discharge time’’ was recorded as soon as they met the criteria above. Pain, vomiting or oral intake recordings were documented until the discharge time. The patients and parents were instructed to return to ENT clinic in case of bleeding, two or more vomiting episode or inadequate oral intake after discharge. Statistical analysis of the data was performed by ‘‘SPSS 10.0 for Windows’’ (SPSS Inc., Chicago, Illinois). Groups (demographic characteristics, anesthesia and operation time, discharge time)
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were compared using Student’s t-test. In frequency comparison x2 or Fisher’s exact tests; for pain score comparisons Mann—Whitney U-test were used. p < 0.05 was considered significant.
3. Results Demographic and clinical findings, additional intraoperative fentanyl requirements, duration of anesthesia and operation were not significantly different between the two groups (Table 1). There were no significant difference between early and late postoperative vomiting incidence and antiemetic requirements between groups (Table 2). Total vomiting frequency in dexamethasone group was 6 and in control group was 10. None of the patients needed ondansetron in both groups. Meperidine i.v. was administered in PACU for agitation and/or pain control in eight patients in dexamethasone group and 12 in control group (Table 2). The postoperative first hour pain score before transferring to floor were similar between the two groups (Fig. 1). The postoperative first 6 h pain score after transmitting to floor was significantly lower in dexamethasone group than the control ( p < 0.05). Eighth hour scores were also lower, however, statistically not significant (Fig. 1). First postoperative oral paracetamol intake time and need for paracetamol were similar between two groups (Table 2). The number of patients who had ‘‘full’’ oral intake of fluid and soft diet after 2 h postoperatively were more in dexamethasone group compared with the control ( p < 0.05) (Fig. 2). The patients in dexamethasone group reached discharge criteria earlier (5.6 0.9 h) compared to control (7.2 2.0 h) ( p < 0.05). None of the patients in both groups applied to ENT clinic for poor oral intake and was taken to operating room for bleeding control.
Table 1 Patient demographic and clinical data Dexamethasone (n = 32)
Control (n = 30)
Age (years) Weight (kg) Sex (F/M) Intraoperative fentanyl (n) Duration of surgery (min) Duration of anesthesia (min)
7.6 5.1 20.1 7.1 22/10 11 36.6 8.9 51.5 6.3
9.3 7.4 19.5 4.9 20/10 14 40.7 7.3 55.2 7.1
Type of surgery Tonsillectomy (n) Adenotonsillectomy (n)
13 19
12 18
Values are expressed as number (n), or mean (S.D.).
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Table 2 Frequency of retching/vomiting, requirement of antiemetics, analgesics and time to first oral paracetamol postoperatively Dexamethasone (n = 32)
Control (n = 30)
Vomiting (n) PACU Floor Overall
6 0 6
6 4 10
Antiemetic requirement (n) Metoclopramid Ondansetrone
6 0
10 0
Analgesic requirement (n) Meperidine PACU
8
12
6 11 12 3
4 17 7 2
Paracetamol 2h 3h 4h 5h Time to first oral paracetamol (h) (mean S.D.)
3.2 0.8
3.8 0.9
PACU: postanesthesia care unit.
4. Discussion Several studies which investigated the effects of preoperative dexamethasone on postoperative pain, vomiting and quality of oral intake in patients undergoing adenotonsillectomy demonstrated conflicting results, because of limited number of patients, different dose of dexamethasone, different surgical techniques (electrodissection versus sharp dissection) and lack of standardized anesthetic technique [10—20]. In this present study, the administration of preoperative dexamethasone at a dose of 0.5 mg/kg in patients undergoing tonsillectomy with or without adenoidectomy with sharp dissection technique was associated with reduced postoperative pain score and increased oral intake during the hospital stay. Additionally, the dexamethasone group showed
Fig. 1
shorter hospital stay period compared with control group. However, no significant effect of dexamethasone on vomiting incidence was noted. Most common factors that affect the time to first oral intake and its quality are postoperative nausea, vomiting and pain. These factors also delay the discharge period after the operation. Splinter [20] reported that each vomiting episode prolonged the hospital stay approximately 13.2 min. Although some studies fail to show any significant effect of dexamethasone on postoperative vomiting incidence [18,19], there have been a quite number of randomized, placebo-controlled studies revealing a decrease in vomiting incidence [10—16,20]. Aouad et al. [15] found that the vomiting incidence in patients undergoing tonsillectomy or adenotonsillectomy, administered dexamethasone 0.5 mg/kg preoperatively was 10% and in placebo group was
Postoperative ‘‘faces’’ pain score (mean S.D.); *p < 0.05, between two groups.
Effect of preoperative dexamethasone after tonsillectomy
Fig. 2
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Postoperative oral intake amounts; *p < 0.05, between two groups.
30% ( p < 0.05). In a similar study, Elhakim et al. [16] demonstrated that the vomiting incidence was 30 and 56%, respectively ( p < 0.05). Pappas et al. [13] reported that 1 mg/kg dexamethasone given before the surgery showed minimal effects on postoperative morbidity; however, it minimized vomiting incidence in the late postoperative period (24 h after home discharge). These results were attributed to dexamethasone’s biological half-life of 36—48 h [21]. In meta-analysis of eight published studies, Steward et al. [22] reported that in patients undergoing tonsillectomy, preoperative dexamethasone decreased vomiting incidence two times and improved oral intake of clear fluids and soft diet within the first 24 h when compared with placebo group. On the other hand, when pain scores were compared, these studies failed to show any significant difference because of missing of data and differences in evaluation methods. The regression analysis of the antiemetic effect of dexamethasone dose suggests that when dexamethasone dose was increased to 1 mg/kg, the positive antiemetic effect was also increased [22]. Antiemetic action of dexamethasone occurs via prostaglandin antagonism, release of endorphins and tryptophan depletion. But it is not clear whether in this procedure dexamethasone shows its effect by a central or peripheral mechanism [23,24]. In the present study, the patients were closely observed until they reached discharge criteria. During this period, vomiting, pain scores and the amount of oral intake were recorded. During their hospital stay, six postoperative vomiting episodes (18.7%) in dexamethasone group and 10 in placebo group (33.3%) were observed. The difference did not reach significance; however, there was a clear trend toward a better control of vomiting in dexamethasone group. The possible explanation of these results might be the limited number of patients and/or 0.5 mg/kg of dexamethasone dose.
When similar studies were reviewed, patients who received preoperative dexamethasone showed faster first oral fluid intake, earlier sufficient oral intake amount and had better quality of oral intake. In most of the studies electrodissection tonsillectomy was performed. Although the beneficial effect of dexamethasone was clearly seen, there were significant differences in time periods [11—16]. Oral intake quality was recorded similarly in three studies as follows: excellent = child requests, good = child accepts when offered, fair = child accepts it when coaxed and poor = child refuses [13,15,16]. Aouad et al. [15] noted that first oral intake time in dexamethasone group was 5.3 h and in placebo group 10.9 h ( p < 0.05), and also oral intake quality was higher at 24 h postoperatively in dexamethasone group [15]. A similar study by Elhakim et al. [16] demonstrated that first oral intake time in dexamethasone group was 0.4 0.2 h, compared with placebo 1.3 0.7 h ( p < 0.05). Quality of oral intake was better than the control group [16]. Pappas et al. [13] found no significant difference while comparing the pain scores and quality of oral intake within the first 3 h between the two groups postoperatively; however, when examining the 24 h quality of oral intake, the dexamethasone group showed significant improvement. Additionally, the number of patients who returned to hospital due to dehydration and poor oral intake were higher in the placebo group [13]. In the present study, oral feeding was started 2 h after the operation and soft diet/clear fluids were offered hourly. In dexamethasone group, after 2 h postoperatively the amount of oral intake was higher than the control group ( p < 0.05). As our institution is a tertiary referral clinic, the majority of our patients are referred to ENT Clinic from 45—60 min distance. Also, the seasonal temperature averages are higher than in most parts of the country. In addition, a possible postoperative bleeding may cause hypovolemia in this small age
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group easily. Therefore, it is important to be sure that the children have enough oral fluid intake before discharging home. In our study, one of the accepted discharge criteria of tolerating 400 ml of oral fluid was achieved earlier in dexamethasone group (5.6 0.9 h) than the control (7.2 2.0 h). The results were statistically significant ( p < 0.05). Comparing with previous studies, fluid and soft diet were given more frequently (every hour) in the postoperative period. This protocol might have increased the amount of oral intake and shortened the 400 ml of fluid intake time. In the previous published studies that showed the beneficial effect of preoperative dexamethasone in patients undergoing tonsillectomy or adenotonsillectomy, electrodissection tonsillectomy was preferred surgical technique. In a small number of studies sharp dissection technique was used; however, they failed to show the significant effects of dexamethasone in reducing postoperative pain, vomiting and quality of oral intake [17,18]. Only Catlin and Grimes [19] found the ability to return to a full or semi-full diet occurred on the third and fourth postoperative days, significantly sooner in the steroid-treated patients than in the control patients. No significant differences were observed in postoperative pain, nausea, emesis, fever, or in the need for postoperative pain medications [19]. Hanasono et al. [14] compared the effects of 1 mg/kg dexamethasone on postoperative morbidity in both surgical techniques (electrodissection versus sharp dissection). It was concluded that dexamethasone decreased postoperative pain but the patients undergone to sharp dissection tonsillectomy had less pain than electrodissection tonsillectomy. The possible explanation might be the thermal effect associated with electrodissection to the remaining tissues [14]. In both surgical techniques, patients in dexamethasone group showed higher percentage of returning to a full diet compared with placebo group at the end of postoperative day 1 (42.5 and 31.7%, respectively; p < 0.05). In addition, patients undergone sharp dissection technique and received preoperative dexamethasone, showed significant improvement in oral intake and less pain score. However, the assessment was performed 24 h after the operation [14]. Unlike the studies that demonstrate positive effects of dexamethasone on pain in patients undergoing to adenotonsillectomy [11,14,16], some published papers could not reach the same results [10,12,17—19]. Elhakim et al. [16] noted less pain score in patients who received dexamethasone at 30 min, 4, 12 and 24 h postoperatively. They have used both the faces and CHEOPS (Children’s Hospital Eastern Ontario Pain Scale) pain scales in their
M.N. Kaan et al.
evaluation. The results of the two evaluation methods were similar in the early postoperative period [16]. During tonsillectomy, the underlying muscle tissue and surrounding tissues are damaged mechanically, thermally, or both. This results an acute inflammatory response in the surrounding tissues, causing spasm of pharyngeal muscles, irritation of nerve endings and even disruption of the mucosa [25]. This event results in imbalance in the delicate mechanism of swallowing, incoordination, dysphagia and pain. For these reasons, it is important to prevent the tissue damage and help re-establish the normal physiologic mechanisms [26]. Glucocorticoids cause inhibition of the inflammatory response by blocking factors, such as bradykinin, prostaglandin and leukotrienes, which results decrease in degree of inflammation and lessening accompanying signs and symptoms, including pain [26]. In our study, we used five ‘point’ faces scale in order to evaluate postoperative pain. Our results showed that the pain score in the first 6 h of the postoperative period was lower in dexamethasone group, compared with control group ( p < 0.05); on the other hand, no difference was noted in analgesic requirement between groups. These results may be attributed to the anti-inflammatory effect produced by dexamethasone, which may reduce local edema and pain [21]. Additionally, dexamethasone modulates inducible COX-2 [27]. Complications from corticosteroid therapy, such as increased rate of infection, peptic ulceration and adrenal suppression are usually related to its longterm use. The risk of steroid therapy of <24 h is negligible [28]. We have not noticed any of the complications in our patients mentioned above. In conclusion, a prophylactic intraoperative single dose of 0.5 mg/kg dexamethasone in patients undergoing tonsillectomy with or without adenoidectomy decreases postoperative pain, improves oral intake as well as increases quality of oral intake without apparent side effects. None of the patients returned to the hospital because of prolonged recovery. We have not noticed a significant decrease in postoperative vomiting incidence. Frequent offering of small amounts of fluids and soft diet increases the total amount of oral intake, which may facilitate the patients to meet discharge criteria earlier.
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[2] R.S. Litman, C.L. WU, F.A. Catanzaro, Ondansetron decreases emesis after tonsillectomy in children, Anesth. Analg. 78 (1994) 478—481. [3] L.R. Ferrari, J.V. Donlon, Metoclopramide reduces the incidence of vomiting after tonsillectomy in children, Anesth. Analg. 75 (1992) 351—354. [4] J.S. Carithers, D.E. Gebhart, J.A. Williams, Postoperative risk of pediatric tonsilloadenoidectomy, Laryngoscope 97 (1987) 422—429. [5] W.S. Crystale, D. Russel, Complication of tonsillectomy and adenoidectomy in 9409 children observed overnight, Can. Med. Assoc. J. 135 (1986) 1139—1142. [6] M.S. Aapro, D.S. Alberts, Dexamethasone as an antiemetic in patients treated with cisplatine, N. Engl. J. Med. 305 (1981) 520 (letter). [7] J.J. Wang, S.T. Ho, Y.H. Liu, S.C. Lee, Y.C. Liu, Y.C. Liao, et al. Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy, Br. J. Anaesth. 83 (1999) 72—75. [8] J.J. Wang, S.T. Ho, H.S. Liu, C.M. Ho, Prophylactic antiemetic effect of dexamethasone in women undergoing ambulatory laparoscopic surgery, Br. J. Anaesth. 84 (2000) 459— 462. [9] K. Liu, C.C. Hsu, Y.Y. Chia, The effective dose of dexamethasone for antiemesis after major gynecological surgery, Anesth. Analg. 89 (1999) 1316—1318. [10] F. Vosdoganis, D.B. Baines, The effect of single-dose intravenous dexamethasone in tonsillectomy in children, Anaesth. Intensive Care 27 (1999) 489—492. [11] Tom LWC, J.J. Templeton, M.E. Thompson, R.R. March, Dexamethasone in adenotonsillectomy, Int. J. Pediatr. Otorhinolaryngol. 37 (1996) 115—120. [12] M.M. April, N.D. Callan, D.M. Nowak, M.A. Hausdorff, The effect of intravenous dexamethasone in pediatric adenotonsillectomy, Arch. Otolaryngol. Head Neck Surg. 122 (1996) 117—120. [13] Pappas ALS, R. Sukhani, A.J. Hotaling, et al. The effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy, Anesth. Analg. 87 (1998) 57—61. [14] M.M. Hanasono, M.L. Lalakea, A.A. Mikulec, K.G. Shepard, V. Wellis, A.H. Messner, Perioperative steroids in tonsillectomy using electrocautery and sharp dissection techniques, Arch. Otolaryngol. Head Neck Surg. 130 (2004) 917—921.
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[15] M.T. Aouad, S.S. Siddik, L.B. Rizk, G.M. Zaytoun, A.S. Baraka, The effect of dexamethasone on postoperative vomiting after tonsillectomy, Anesth. Analg. 92 (2001) 636—640. [16] M. Elhakim, N.M. Ali, I. Rashed, M.K. Riad, M. Refat, Dexamethasone reduces postoperative vomiting and pain after pediatric tonsillectomy, Can. J. Anaesth. 50 (2003) 392— 397. [17] M.S. Volk, P. Martin, L. Brodsky, J.F. Stanievich, M. Ballou, The effects of preoperative steroids on tonsillectomy patients, Otolaryngol. Head Neck Surg. 109 (1993) 26—30. [18] L.A. Ohlms, R.T. Wilder, B. Weston, Use of intraoperative corticosteroids in pediatric tonsillectomy, Arch. Otolaryngol. Head Neck Surg. 121 (1995) 737—742. [19] F.I. Catlin, W.J. Grimes, The effect of steroid therapy on recovery from tonsillectomy in children, Arch. Otolaryngol. Head Neck Surg. 117 (1991) 649—652. [20] W. Splinter, D.J. Roberts, Dexamethasone decreases vomiting by children after tonsillectomy, Anesth. Analg. 83 (1996) 913—916. [21] L.S. Goodman, A. Gilman (Eds.), The Pharmacological Basis of Therapeutics, fifth ed., MacMillan, New York, 1975, p. 1487. [22] D.L. Steward, J.A. Welge, C.M. Myer, Do steroids reduce morbidity of tonsillectomy? Meta-analysis of randomized trials, Laryngoscope 111 (2001) 1712—1718. [23] A.L. Harris, Cytotoxic-therapy-induced vomiting is mediated via enkephalin pathways, Lancet 27 (1) (1982) 714—716. [24] S.M. Sagar, The current role of anti-emetic drugs in oncology: a recent revolution in patient symptom control, Cancer Treat. Rev. 18 (1991) 95—135. [25] J.H. Dempster, Post-tonsillectomy analgesia: the use of benzocaine lozenges, J. Laryngol. Otol. 102 (1988) 813—814. [26] C.E. Palme, P. Tomasevic, D.V. Pohl, Evaluating the effects of oral prednisolone on recovery after tonsillectomy: A prospective, double-blind, randomized trial, Laryngoscope 110 (2000) 2000—2004. [27] S. Honda, K. Migita, Y. Hirai, Y. Ueki, S. Yamasaki, S. Urayama, et al. Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells, Biochem. Biophys. Res. Commun. 268 (2000) 928—931. [28] J.C. Melby, Aldosterone — an independent risk factor in cardiovascular disease, J. Clin. Endocrinol. Metab. 87 (2002) 447.