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Ketamine in post-tonsillectomy pain
International Journal of Pediatric Otorhinolaryngology (2007) 71, 735—739
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Ketamine in post-tonsillectomy pain ¨ mer Lu ¨ksu a, Cengiz Alpay b, Azize Bes¸tas¸ a,* O ¨tfi Erhan a, Hu ¨lya Go a b
Fırat University Medical Faculty, Department of Anesthesiology and Reanimation, 23119 Elazıg, Turkey Fırat University Medical Faculty, Department of Otorhinolaryngology, Elazıg˘, Turkey
Received 2 December 2006; received in revised form 5 January 2007; accepted 6 January 2007
KEYWORDS Tonsillectomy; Ketamine; Analgesia
Summary Objective: There has yet been no ideal method for postoperative analgesia in children. Ketamine demonstrates a potent analgesic effect by central blockage of perception of pain with sub-anesthetic doses. Preoperative intramuscular administration of ketamine for sedation decreases the pain during swallowing after tonsillectomy, while it provides long-term analgesia when applied around the incision. The aim of this study is to compare the effectiveness of ketamine administered to the tonsillar region following tonsillectomy for postoperative pain management. Methods: After obtaining consent from the local ethics committee and the parents, 60 patients from the ASA groups I and II, between 3 and 7 years of age, planned for adenotonsillectomy as outpatients, were included in the study. Subjects were randomly assigned to two equal groups and 2 ml 0.9% saline for group S, and 0.5 mg kg 1 ketamine and saline 2 ml in volume for group K were administered into the tonsillar region. All subjects were monitored in a standard manner and SpO2, systolic arterial pressure (SAP), and cardiac pulse rates were recorded in 5 min intervals. The CHEOPS and Wilson sedation scale were used to evaluate pain levels and sedative condition, respectively. Nausea and vomiting scores of the subjects were also noted. The time of the first analgesic administration and the total amount of analgesics in an 8-hour period were recorded. Student-T and Chi-Square tests were used for the statistical evaluation of the data and a p value of <0.05 was accepted as significant. Results: There were no significant differences between groups according to age, sex, weight, intermittent SAP and cardiac pulse rates. However, the CHEOPS value, the first analgesic need and the total amount of analgesic need were in favor of ketamine ( p < 0.05). Conclusions: In previous studies, no significant differences were demonstrated in preemptive analgesia with ketamine, magnesium, morphine, and clonidine. The dose of ketamin and the volume used in this study caused no sedation or nausea and provided a high level of analgesia. Ketamine infiltration into the tonsillar region after tonsillectomy was found to be easy and effective. # 2007 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Tel.: +90 532 340 2332; fax: +90 424 238 8096. E-mail addresses: [email protected], [email protected] (A. Bes¸tas¸). 0165-5876/$ — see front matter # 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2007.01.008
¨ .L. Erhan et al. O
736
1. Introduction Pain results in the activation of physiologic stress response, which causes significant changes in the cardiovascular system, metabolism, the immune system, and organs [1,2]. Postoperative pain in the paediatric group is an important problem that overstrains the child, family, and hospital staff. Oral analgesics used in the postoperative period are mostly insufficient, and despite parenteral opioids being effective, they may cause sedation, respiratory depression, constipation, nausea and vomiting [3,4]. Local anesthetic agents are usually preferred for postoperative analgesia in children. Use of topical forms before injections has been on a gradual increase [5]. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has a potent analgesic effect in sub- anesthetic doses. Intraoperative IV ketamine at a dose of 0.15 mg kg 1 has been shown to be effective in postoperative pain management [6]. Ketamine administered preoperatively at 0.1 mg kg 1 IM for sedation, decreases the pain in swallowing following tonsillectomy [7]. Ketamine analgesia differs from local anesthetics by preventing central perception of pain like in other NMDA antagonists [8]. Bupivacaine infiltration with ketamine prolongs local analgesia duration [9], and may continue for one week after infiltration [10]. Besides, the peripheral analgesic effect of ketamine [11,12], its antihyperalgesic effect is shown by local administration in a preclinical study [13]. The aim of our study was to observe the efficacy of ketamine infiltrated into the tonsillar region immediately after tonsillectomy in children for whom adeno-tonsillectomy is planned.
2. Methods With written consents obtained from the ethics committee and parents, 60 patients of the ASA physical status I or II, 3—7 years of age and scheduled for outpatient adenotonsillectomy were enrolled in the study. Children with systemic disease, metabolic and endocrine disorders, growth,
developmental, and motor-mental retardation, in addition to those who received analgesics, were excluded from the study. Subjects were randomly assigned into two equal groups: saline and ketamine. Subjects were fasted for 6 h prior to surgery, and were given premedication with IM atropine at 0.01 mg kg 1. Peripheral oxygen saturation (SpO2), end tidal carbon dioxide (ETCO2), systolic blood pressure (SBP), electrocardiography (ECG) and cardiac pulse rate were monitored in the operation room. Anesthesia induction was performed by sevoflurane, increased within every 2 or 3 breaths in 0.5% concentrations in 50— 50% O2—N2O. IV cannulation was done by a 24G cannula through a vein in the dorsum of the hand. Preoperative fluid administration was given with 1/3 isodeks (Eczacıbası/Baxter, Istanbul, Tu ¨rkiye) solution (3—5 ml kg 1 h 1). Following sufficient muscle relaxation by 0.1 mg kg 1 vecuronium, subjects were intubated with spiral cuffed endotracheal tubes. They were then mechanically ventilated with the adjustment of 6—8 ml kg 1 tidal volume and 30— 40 mmHg ETCO2 pressure. Anesthesia maintenance was provided with 2.5% sevoflurane in 50% O2 and 50% N2O. Following surgical procedure, the administration of anesthetic agents was ceased and all subjects received 100% O2. In the saline group (group S) 2 ml of saline and in the ketamine group (group K) 0.5 mg kg 1 of ketamine (50 mg ml 1) added to saline to achieve at total of 2 ml of solution was infiltrated into the tonsillar fossa of separate group respectively. Residual neuromuscular block was antagonized with atropine sulphate (0.02 mg kg 1 IV) and neostigmin (0.05 mg kg 1 IV). The prevailing trend for outpatient surgery at our hospital is to discharge children to home within 8 h. Therefore, we observed subjects for 8 h after surgery. Subjects were observed by an investigator who was blinded to the treatment assignment, at the postoperative 1st (continuously), 2nd, 4th, 6th and 8th hour. Pain levels were evaluated by The Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) established by McGrath et al. (Table 1) [14]. In this postoperative pain evaluation, behavior scoring (crying score, facial impression, verbal complaints, position and movement of the body,
Table 1 Modified CHEOPS scoring Score
0
1
2
Cry Facial Verbal Torso Legs
No cry Smiling Positive statement Neutral Neutral
Crying, moaning Neutral Negative statement Variable, taot, upright Kicking
Scream Grimace Suffering from pain, another complament Streched Stretched, continuous move
Ketamine in post-tonsillectomy pain
737
Table 2 Wilson sedation scale Score
Degree of sedation
1 2 3 4 5
Fully awake, orientated Lethargic Opens eyes with verbal stimulus Opens eyes with moderate pain Does not respond moderate pain
response when the wound was touched, and whether the child pointed to the wound) was assessed by an experienced observer [14]. The sedative condition was evaluated with the Wilson sedation scale (Table 2) [15]. Nausea and vomiting scores were determined as (0: absent, 1: nausea and 2: vomiting). Cardiac pulse rate, SBP, respiratory rate, and sedation scores at 5, 15, 30, and 60 min, pain scores at the postoperative 5th, 15th, 30th, and 60th minute and 2nd, 4th, 6th, and 8th hour were recorded. Subjects were observed for hallucinations and negative behaviors in the postoperative period. Subjects with postoperative CHEOPS values of 5 and over were given 1 mg kg 1 tramadol hydrochloride IV, and subjects with pain in the ward received ibuprofen suspension (100 mg) by the oral route. The first analgesic requirement time and total analgesic amount in the first postoperative 8 h were recorded. Metoclopramide at 0.1 mg kg 1 IV was administered to subjects with nausea. Data were expressed as mean standard deviation (S.D.). Student-T and x2-test were used for the statistical analysis of the data.
SpO2 level was over 92% in all subjects (Table 3). Just after subjects were taken into the recovery room, a CHEOPS score between 0 and 4 was considered as no pain. This score was 3 in the control group and 26 in the ketamine group. Twenty-seven out of 30 in the control group and only 4 out of 30 in the ketamine group needed analgesics. This was significant ( p < 0.05). When the two groups were compared for the initial analgesic requirement, it was 2.4 0.14 h for the control group and 4.7 0.29 h for the ketamine group. This period was significantly shorter ( p < 0.05). Although all subjects in the control group required analgesics in the first eight hours, 24 subjects in the ketamine group required analgesics. Seventeen patients in the control group and one patient in the ketamine group required two doses of analgesics (Table 4). Total analgesic consumption in eight hours was significantly higher in group S than group K ( p < 0.05). The CHEOPS scores in the two groups at 8 h after surgery were similar, and no subjects had a CHEOPS score of over 4. In the postoperative 8th-hour observation period, subjects in both groups were awake and orientated, and the incidence of nausea and vomiting was statistically insignificant. No hallucinations or probable complication resembling a negative behavior were observed. From both two groups no patients were discharged from the hospital beyond 8 h and readmitted to the hospital.
4. Discussion 3. Results Demographic characteristics, the mean duration of surgery and the mean duration of anesthesia, intraoperative hemodynamic findings were similar and
Pain is evaluated according to child’s age and cooperation using personal expression, observed behaviors and physiological measurements. Certain scales in evaluating pain and related symptoms in adults and children were used. Choice of the method
Table 3 Age, height, weight, operation and anesthesia durations of the groups (mean S.D.) Group
Age (year)
Height (cm)
Weight (kg)
Operation duration (min)
Anesthesia duration (min)
Group S (n = 30) Group K (n = 30)
4.98 1.40 5.30 1.38
101.8 12.62 108.9 12.83
20.13 4.03 19.13 3.85
32.16 12.65 28.73 11.32
40.16 13.98 38.16 12.42
Table 4 CHEOPS scoring, first analgesic time, amount of total analgesic and number of nausea of the groups (mean S.D.) Group
CHEOPS (0—4)
CHEOPS (5)
First analgesic time (h)
Amount of total analgesic (criterion)
Nausea (%)
Group S (n = 30) Group K (n = 30)
3/30 26/30 *
27/30 4/30 *
2.4 0.14 4.7 0.29 *
30/30 (47 criterions) 24/30* (25 criterions)
16/30 (%59) 11/30 (%40.7)
*
p < 0.05 compared with group S.
¨ .L. Erhan et al. O
738 should be made according to general status, age, and the level of pain perception of the child [16]. In order to relieve post-tonsillectomy pain in children, various groups of medications have been used through different routes. Local anesthetic infiltration or spraying have been widely used to relieve/block post-tonsillectomy pain. Different concentrations and volumes of lidocaine hydrochloride, bupivacaine, and ropivacaine have been applied for this purpose [17,18—21]. For post-tonsillectomy analgesia in children (3— 12 years), IV ketamine and magnesium, and preemptive morphine, ketamine, and clonidine did not reveal a significant difference [4]. In another study with a similar purpose, the effects of tramadol and diclofenac also demonstrated no difference [22]. ¨ zko O ¨se et al. [23] observed that low dose tramadol administration during anesthesia induction decreased the postoperative early analgesic requirement. In an analgesia study on children, Antila et al. [24] investigated the post-tonsillectomy effects of saline, ketoprofen, and tramadol following induction. In the ketoprofen group, pain was significantly lower in the first eight hours and the need for bolus fentanyl was significantly low. Similar nausea levels between groups were contributed to a duration of operation shorter than 30 min, as well other reasons. Stewart et al. [25] showed that dexamethasone administered with or without piroxicam was effective in pain relief following tonsillectomy. Pain relief with dexamethasone continued up to eighth postoperative day. In these studies, postoperative pain relief is significant in analgesic groups compared with controls. Romsing et al. [26] investigated the analgesic efficacy of acetaminophen given by oral or rectal route following tonsillectomy. Acetaminophen at therapeutic doses was not so effective and additional analgesic supplementation was needed in discharged patients. Courtney and Cabraal [27] used tramadol and diclofenac for this purpose; however, they could not find any difference. In this study, the route and timing of ketamine administration was different from these studies, and the postoperative analgesic efficacy was found to be higher than that in the control group. While pain in the first 8 h was significantly relieved, the total analgesic amount required in the cases, was significantly decreased. ¨ zalevli et al. [28] compared tramadol and morO phine administration during tonsillectomy by patient-controlled analgesia. Pain, total analgesic dose in the first 24 h, nausea and vomiting were evaluated. Although pain was significantly relieved in both groups, this decrease in the first four hours in the morphine group was higher. Frequency in nausea
was observed to be higher in the morphine group. Analgesic efficacy of bupivacaine with ketamine infiltration through an inguinal hernia incision and the length of local anesthesia are doubled through peripheral mechanisms [9]. The local anesthetic effect of ketamine is over 90 min and it lasts for one week after infiltration [10]. Although ketamine shows its analgesic effect by blockage of sodium and potassium channels in peripheral nerves, other mechanisms may also be effective [11,12]. In preclinical studies, peripheral local ketamine is shown to have an antihyperalgesic effect [13]. Ostergaard et al. [29] investigated the analgesic effectiveness of diclofenac and acetaminophen following tonsillectomy and evaluated pain at intervals for three days postoperatively. Although no significant difference was found between pain levels, the diclofenac group showed a significant decrease in the incidence of nausea and vomiting. In the acetaminophen group, an increase in nausea was observed on the second and third days. Since volume and dose of ketamine administered in our study entered systemic circulation at a slower rate as opposed to IV administration, it caused no sedation and less nausea. In conclusion, ketamine infiltration into the tonsillar region immediately after tonsillectomy for pain blockage, was found to be effective and without side effects.
References [1] Committee on psychosocial Aspects of child and family health, Task force pain in infants, children and adolescents, Pediatrics 108 (2001) 793—797. [2] B. Golianu, E.J. Krane, K.S. Galloway, et al., Pediatric acute pain management, Pediatr. Clin. North Am. 47 (2000) 559— 587. [3] G.A. Walco, R.C. Cassidy, N.L. Schechter, Pain, hurt, and harm: the ethics of pain control in infants and children, N. Engl. J. Med. 331 (1994) 541—544. [4] A.J. Altman, N.L. Schechter, S.J. Weisman, in: A.R. Ablin (Ed.), The Management of Pain. In Supportive Care of Children with Cancer: current therapy and guidelines from the children’s oncology group, second ed., The Johns Hopkins University Press, Baltimore, USA, 1997, pp. 155—174. [5] H. Holthusen, P. Backhaus, F. Boeminghaus, M. Breulmann, P. Lipfert, Preemptive analgesia: no relevant advantage of preoperative compared with postoperative intravenous administration of morphine, ketamine, and clonidine in patients undergoing transperitoneal tumor nephrectomy, Regional Anesth. Pain Med. 27 (2002) 249—253. [6] J.E. O’Flaherty, C.X. Lin, Does ketamine or magnesium affect posttonsillectomy pain in children? Paediatr. Anaesth. 13 (2003) 413—417. [7] M. Elhakim, Z. Khalafallah, H.A. El-Fattah, S. Farouk, A. Khattab, Ketamine reduces swallowing-evoked pain after paediatric tonsillectomy, Acta Anaesthesiol. Scand. 47 (2003) 604—609.
Ketamine in post-tonsillectomy pain [8] L.M. Breau, G.A. Finley, P.J. McGrath, C.S. Camfield, Validation of the non-communicating children’s pain checklist-postoperative version, Anesthesiology 96 (2002) 528—535. [9] M. Tverskoy, M. Oren, M. Vaskovich, I. Dashkovsky, I. Kisin, Ketamine enhances local anesthetic and analgesic effects of bupivacaine by peripheral mechanism: a study in postoperative patients, Neurosci. Lett. 215 (1996) 5—8. [10] T. Warncke, E. Jorum, A. Stubbaug, Local treatment with the N-methyl-D-aspartate receptor antagonist ketamine, inhibit development of secondary hyperalgesia in man by a peripheral action, Neurosci. Lett. 227 (1997) 1—4. [11] J.L. Pedersen, T.S. Galle, H. Kehlet, Peripheral analgesic effects of ketamine in acute inflammatory pain, Anesthesiology 89 (1998) 58—66. [12] M. Oatway, A. Reid, J. Sawynok, Peripheral antihyperalgesic and analgesic actions of ketamine and amitriptyline in a model of mild thermal injury in the rat, Anesth. Analg. 97 (2003) 168—173. [13] J. Sawynok, A.R. Reid, Modulation of formalin-induced behaviors and edema by local and systemic administration of dextromethorphan, memantine and ketamine, Eur. J. Pharmacol. 450 (2002) 153—162. [14] P.J. McGrath, G. Johnson, J.T. Goodman, et al., CHEOPS: a behavioral scale for rating postoperative pain in children, in: H.L. Fields, R. Dubner, F. Cervero (Eds.), Advances in Pain Research and Therapy, vol. 9, Raven Press, New York, 1985, pp. 395—402. [15] M. Kakinohana, K. Sugahara, Level of consciousness affects the excitability of spinal motor neurones during propofol sedation in humans, Br. J. Anaesth. 96 (2006) 742—746. [16] P.B. Gaukroger, Pediatric analgesia. Which drug? Which dose?, Drugs 41 (1991) 52—59. [17] C.B. Berde, N.F. Sethna, Analgesics for thetreatment of pain in children, N. Engl. J. Med. 347 (2002) 1094—1103. [18] S. Molliex, P. Haond, D. Baylot, et al., Effect of pre- vs postoperative tonsillar infiltration with local anesthetics on
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postoperative pain after tonsillectomy, Acta Anaesthesiol. Scand. 40 (1996) 1210—1215. M.Z. Naja, M. El-Rajab, W. Kabalan, M.F. Zaide, M.A. AlTannir, Pre-incisional infiltration for pediatric tonsillectomy: a randomized double-blind clinical trial, Int. J. Pediatr. Otorhinolaryngol. 69 (2005) 1333—1341. J.A. Jebeles, J.S. Reilly, J.F. Gutierrez, E.L. Bradley Jr., I. Kisin, The effect of pre-incisional infiltration of tonsils with bupivacaine on the pain following tonsillectomy under general anesthesia, Pain 47 (1991) 305—308. N.R. Vasan, S. Stevenson, M. Ward, Arch. Otolaryngol. Head Neck Surg. 128 (2002) 145—149. R.C.B. Manworren, L.S. Hynan, Clinical validation of FLACC: preverbal patient pain scale, Pediatric. Nursing 29 (2003) 140—146. ¨ zko ˘lu, S. Sezenler, Relief of Z. O ¨se, M. Akc¸abay, Y.K. Kemalog posttonsillectomy pain with low-dose tramadol given at induction of anesthesia in children, Int. J. Pediatr. Otorhinolaryngol. 53 (2000) 207—214. H. Antila, T. Manner, Ketoprofen and tramadol for analgesia during early recovery after tonsillectomy in children, Pediatr. Anesth. 16 (2006) 548—553. R. Stewart, R. Bill, Dexamethasone reduces pain after tonsillectomy in adults, Clin. Otolaryngol. 27 (2002) 321—326. J. Romsing, S. Hertel, Examination of acetaminophen for outpatient management of postoperative pain in children, Paediatr. Anaesth. 8 (1998) 205. M.J. Courtney, D. Cabraal, Tramadol vs. diclofenac for tonsillectomy analgesia, Arch. Otolaryngol. Head Neack Surg. 127 (2001) 385—388. ¨ zalevli, H. U ¨ nlu M. O ¨genc¸, Comparison of morphine and tramadol by patient-controlled analgesia for postoperative analgesia after tonsillectomy in children, Pediatr. Anesth. 15 (2005) 979—984. D. Ostergaard, G. Ravn, Diclofenac or acetaminophen for analgesia in paediatric tonsillectomy outpatients, Acta Anesthesiol. Scand. 44 (2000) 291—295.
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Ketamine in post-tonsillectomy pain ¨ mer Lu ¨ksu a, Cengiz Alpay b, Azize Bes¸tas¸ a,* O ¨tfi Erhan a, Hu ¨lya Go a b
Fırat University Medical Faculty, Department of Anesthesiology and Reanimation, 23119 Elazıg, Turkey Fırat University Medical Faculty, Department of Otorhinolaryngology, Elazıg˘, Turkey
Received 2 December 2006; received in revised form 5 January 2007; accepted 6 January 2007
KEYWORDS Tonsillectomy; Ketamine; Analgesia
Summary Objective: There has yet been no ideal method for postoperative analgesia in children. Ketamine demonstrates a potent analgesic effect by central blockage of perception of pain with sub-anesthetic doses. Preoperative intramuscular administration of ketamine for sedation decreases the pain during swallowing after tonsillectomy, while it provides long-term analgesia when applied around the incision. The aim of this study is to compare the effectiveness of ketamine administered to the tonsillar region following tonsillectomy for postoperative pain management. Methods: After obtaining consent from the local ethics committee and the parents, 60 patients from the ASA groups I and II, between 3 and 7 years of age, planned for adenotonsillectomy as outpatients, were included in the study. Subjects were randomly assigned to two equal groups and 2 ml 0.9% saline for group S, and 0.5 mg kg 1 ketamine and saline 2 ml in volume for group K were administered into the tonsillar region. All subjects were monitored in a standard manner and SpO2, systolic arterial pressure (SAP), and cardiac pulse rates were recorded in 5 min intervals. The CHEOPS and Wilson sedation scale were used to evaluate pain levels and sedative condition, respectively. Nausea and vomiting scores of the subjects were also noted. The time of the first analgesic administration and the total amount of analgesics in an 8-hour period were recorded. Student-T and Chi-Square tests were used for the statistical evaluation of the data and a p value of <0.05 was accepted as significant. Results: There were no significant differences between groups according to age, sex, weight, intermittent SAP and cardiac pulse rates. However, the CHEOPS value, the first analgesic need and the total amount of analgesic need were in favor of ketamine ( p < 0.05). Conclusions: In previous studies, no significant differences were demonstrated in preemptive analgesia with ketamine, magnesium, morphine, and clonidine. The dose of ketamin and the volume used in this study caused no sedation or nausea and provided a high level of analgesia. Ketamine infiltration into the tonsillar region after tonsillectomy was found to be easy and effective. # 2007 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Tel.: +90 532 340 2332; fax: +90 424 238 8096. E-mail addresses: [email protected], [email protected] (A. Bes¸tas¸). 0165-5876/$ — see front matter # 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2007.01.008
¨ .L. Erhan et al. O
736
1. Introduction Pain results in the activation of physiologic stress response, which causes significant changes in the cardiovascular system, metabolism, the immune system, and organs [1,2]. Postoperative pain in the paediatric group is an important problem that overstrains the child, family, and hospital staff. Oral analgesics used in the postoperative period are mostly insufficient, and despite parenteral opioids being effective, they may cause sedation, respiratory depression, constipation, nausea and vomiting [3,4]. Local anesthetic agents are usually preferred for postoperative analgesia in children. Use of topical forms before injections has been on a gradual increase [5]. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has a potent analgesic effect in sub- anesthetic doses. Intraoperative IV ketamine at a dose of 0.15 mg kg 1 has been shown to be effective in postoperative pain management [6]. Ketamine administered preoperatively at 0.1 mg kg 1 IM for sedation, decreases the pain in swallowing following tonsillectomy [7]. Ketamine analgesia differs from local anesthetics by preventing central perception of pain like in other NMDA antagonists [8]. Bupivacaine infiltration with ketamine prolongs local analgesia duration [9], and may continue for one week after infiltration [10]. Besides, the peripheral analgesic effect of ketamine [11,12], its antihyperalgesic effect is shown by local administration in a preclinical study [13]. The aim of our study was to observe the efficacy of ketamine infiltrated into the tonsillar region immediately after tonsillectomy in children for whom adeno-tonsillectomy is planned.
2. Methods With written consents obtained from the ethics committee and parents, 60 patients of the ASA physical status I or II, 3—7 years of age and scheduled for outpatient adenotonsillectomy were enrolled in the study. Children with systemic disease, metabolic and endocrine disorders, growth,
developmental, and motor-mental retardation, in addition to those who received analgesics, were excluded from the study. Subjects were randomly assigned into two equal groups: saline and ketamine. Subjects were fasted for 6 h prior to surgery, and were given premedication with IM atropine at 0.01 mg kg 1. Peripheral oxygen saturation (SpO2), end tidal carbon dioxide (ETCO2), systolic blood pressure (SBP), electrocardiography (ECG) and cardiac pulse rate were monitored in the operation room. Anesthesia induction was performed by sevoflurane, increased within every 2 or 3 breaths in 0.5% concentrations in 50— 50% O2—N2O. IV cannulation was done by a 24G cannula through a vein in the dorsum of the hand. Preoperative fluid administration was given with 1/3 isodeks (Eczacıbası/Baxter, Istanbul, Tu ¨rkiye) solution (3—5 ml kg 1 h 1). Following sufficient muscle relaxation by 0.1 mg kg 1 vecuronium, subjects were intubated with spiral cuffed endotracheal tubes. They were then mechanically ventilated with the adjustment of 6—8 ml kg 1 tidal volume and 30— 40 mmHg ETCO2 pressure. Anesthesia maintenance was provided with 2.5% sevoflurane in 50% O2 and 50% N2O. Following surgical procedure, the administration of anesthetic agents was ceased and all subjects received 100% O2. In the saline group (group S) 2 ml of saline and in the ketamine group (group K) 0.5 mg kg 1 of ketamine (50 mg ml 1) added to saline to achieve at total of 2 ml of solution was infiltrated into the tonsillar fossa of separate group respectively. Residual neuromuscular block was antagonized with atropine sulphate (0.02 mg kg 1 IV) and neostigmin (0.05 mg kg 1 IV). The prevailing trend for outpatient surgery at our hospital is to discharge children to home within 8 h. Therefore, we observed subjects for 8 h after surgery. Subjects were observed by an investigator who was blinded to the treatment assignment, at the postoperative 1st (continuously), 2nd, 4th, 6th and 8th hour. Pain levels were evaluated by The Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) established by McGrath et al. (Table 1) [14]. In this postoperative pain evaluation, behavior scoring (crying score, facial impression, verbal complaints, position and movement of the body,
Table 1 Modified CHEOPS scoring Score
0
1
2
Cry Facial Verbal Torso Legs
No cry Smiling Positive statement Neutral Neutral
Crying, moaning Neutral Negative statement Variable, taot, upright Kicking
Scream Grimace Suffering from pain, another complament Streched Stretched, continuous move
Ketamine in post-tonsillectomy pain
737
Table 2 Wilson sedation scale Score
Degree of sedation
1 2 3 4 5
Fully awake, orientated Lethargic Opens eyes with verbal stimulus Opens eyes with moderate pain Does not respond moderate pain
response when the wound was touched, and whether the child pointed to the wound) was assessed by an experienced observer [14]. The sedative condition was evaluated with the Wilson sedation scale (Table 2) [15]. Nausea and vomiting scores were determined as (0: absent, 1: nausea and 2: vomiting). Cardiac pulse rate, SBP, respiratory rate, and sedation scores at 5, 15, 30, and 60 min, pain scores at the postoperative 5th, 15th, 30th, and 60th minute and 2nd, 4th, 6th, and 8th hour were recorded. Subjects were observed for hallucinations and negative behaviors in the postoperative period. Subjects with postoperative CHEOPS values of 5 and over were given 1 mg kg 1 tramadol hydrochloride IV, and subjects with pain in the ward received ibuprofen suspension (100 mg) by the oral route. The first analgesic requirement time and total analgesic amount in the first postoperative 8 h were recorded. Metoclopramide at 0.1 mg kg 1 IV was administered to subjects with nausea. Data were expressed as mean standard deviation (S.D.). Student-T and x2-test were used for the statistical analysis of the data.
SpO2 level was over 92% in all subjects (Table 3). Just after subjects were taken into the recovery room, a CHEOPS score between 0 and 4 was considered as no pain. This score was 3 in the control group and 26 in the ketamine group. Twenty-seven out of 30 in the control group and only 4 out of 30 in the ketamine group needed analgesics. This was significant ( p < 0.05). When the two groups were compared for the initial analgesic requirement, it was 2.4 0.14 h for the control group and 4.7 0.29 h for the ketamine group. This period was significantly shorter ( p < 0.05). Although all subjects in the control group required analgesics in the first eight hours, 24 subjects in the ketamine group required analgesics. Seventeen patients in the control group and one patient in the ketamine group required two doses of analgesics (Table 4). Total analgesic consumption in eight hours was significantly higher in group S than group K ( p < 0.05). The CHEOPS scores in the two groups at 8 h after surgery were similar, and no subjects had a CHEOPS score of over 4. In the postoperative 8th-hour observation period, subjects in both groups were awake and orientated, and the incidence of nausea and vomiting was statistically insignificant. No hallucinations or probable complication resembling a negative behavior were observed. From both two groups no patients were discharged from the hospital beyond 8 h and readmitted to the hospital.
4. Discussion 3. Results Demographic characteristics, the mean duration of surgery and the mean duration of anesthesia, intraoperative hemodynamic findings were similar and
Pain is evaluated according to child’s age and cooperation using personal expression, observed behaviors and physiological measurements. Certain scales in evaluating pain and related symptoms in adults and children were used. Choice of the method
Table 3 Age, height, weight, operation and anesthesia durations of the groups (mean S.D.) Group
Age (year)
Height (cm)
Weight (kg)
Operation duration (min)
Anesthesia duration (min)
Group S (n = 30) Group K (n = 30)
4.98 1.40 5.30 1.38
101.8 12.62 108.9 12.83
20.13 4.03 19.13 3.85
32.16 12.65 28.73 11.32
40.16 13.98 38.16 12.42
Table 4 CHEOPS scoring, first analgesic time, amount of total analgesic and number of nausea of the groups (mean S.D.) Group
CHEOPS (0—4)
CHEOPS (5)
First analgesic time (h)
Amount of total analgesic (criterion)
Nausea (%)
Group S (n = 30) Group K (n = 30)
3/30 26/30 *
27/30 4/30 *
2.4 0.14 4.7 0.29 *
30/30 (47 criterions) 24/30* (25 criterions)
16/30 (%59) 11/30 (%40.7)
*
p < 0.05 compared with group S.
¨ .L. Erhan et al. O
738 should be made according to general status, age, and the level of pain perception of the child [16]. In order to relieve post-tonsillectomy pain in children, various groups of medications have been used through different routes. Local anesthetic infiltration or spraying have been widely used to relieve/block post-tonsillectomy pain. Different concentrations and volumes of lidocaine hydrochloride, bupivacaine, and ropivacaine have been applied for this purpose [17,18—21]. For post-tonsillectomy analgesia in children (3— 12 years), IV ketamine and magnesium, and preemptive morphine, ketamine, and clonidine did not reveal a significant difference [4]. In another study with a similar purpose, the effects of tramadol and diclofenac also demonstrated no difference [22]. ¨ zko O ¨se et al. [23] observed that low dose tramadol administration during anesthesia induction decreased the postoperative early analgesic requirement. In an analgesia study on children, Antila et al. [24] investigated the post-tonsillectomy effects of saline, ketoprofen, and tramadol following induction. In the ketoprofen group, pain was significantly lower in the first eight hours and the need for bolus fentanyl was significantly low. Similar nausea levels between groups were contributed to a duration of operation shorter than 30 min, as well other reasons. Stewart et al. [25] showed that dexamethasone administered with or without piroxicam was effective in pain relief following tonsillectomy. Pain relief with dexamethasone continued up to eighth postoperative day. In these studies, postoperative pain relief is significant in analgesic groups compared with controls. Romsing et al. [26] investigated the analgesic efficacy of acetaminophen given by oral or rectal route following tonsillectomy. Acetaminophen at therapeutic doses was not so effective and additional analgesic supplementation was needed in discharged patients. Courtney and Cabraal [27] used tramadol and diclofenac for this purpose; however, they could not find any difference. In this study, the route and timing of ketamine administration was different from these studies, and the postoperative analgesic efficacy was found to be higher than that in the control group. While pain in the first 8 h was significantly relieved, the total analgesic amount required in the cases, was significantly decreased. ¨ zalevli et al. [28] compared tramadol and morO phine administration during tonsillectomy by patient-controlled analgesia. Pain, total analgesic dose in the first 24 h, nausea and vomiting were evaluated. Although pain was significantly relieved in both groups, this decrease in the first four hours in the morphine group was higher. Frequency in nausea
was observed to be higher in the morphine group. Analgesic efficacy of bupivacaine with ketamine infiltration through an inguinal hernia incision and the length of local anesthesia are doubled through peripheral mechanisms [9]. The local anesthetic effect of ketamine is over 90 min and it lasts for one week after infiltration [10]. Although ketamine shows its analgesic effect by blockage of sodium and potassium channels in peripheral nerves, other mechanisms may also be effective [11,12]. In preclinical studies, peripheral local ketamine is shown to have an antihyperalgesic effect [13]. Ostergaard et al. [29] investigated the analgesic effectiveness of diclofenac and acetaminophen following tonsillectomy and evaluated pain at intervals for three days postoperatively. Although no significant difference was found between pain levels, the diclofenac group showed a significant decrease in the incidence of nausea and vomiting. In the acetaminophen group, an increase in nausea was observed on the second and third days. Since volume and dose of ketamine administered in our study entered systemic circulation at a slower rate as opposed to IV administration, it caused no sedation and less nausea. In conclusion, ketamine infiltration into the tonsillar region immediately after tonsillectomy for pain blockage, was found to be effective and without side effects.
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