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Comparison of propofol with propofol–ketamine combination in pediatric patients undergoing auditory brainstem response testing
International Journal of Pediatric Otorhinolaryngology (2005) 69, 1541—1545
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Comparison of propofol with propofol—ketamine combination in pediatric patients undergoing auditory brainstem response testing Aynur Akin *, Aliye Esmaoglu, Zeynep Tosun, Nebahat Gulcu, Harun Aydogan, Adem Boyaci Department of Anesthesiology, Erciyes University School of Medicine, Kayseri, Alpaslan Mah, Kandilli Sok, Bezciler Sitesi 3, Blok No. 6/11, 38030 Kayseri, Turkey Received 1 March 2005; accepted 20 April 2005
KEYWORDS Auditory brainstem response test; Sedation; Child; Propofol; Ketamine
Summary Objective: The aim of our study was to compare propofol with propofol—ketamine combination for sedation and also to compare related complications in children undergoing auditory brainstem response (ABR) testing. Methods: Sixty ASA I—II patients aged between 1 and 13 years of age were sedated for ABR testing. Propofol 1.5 mg/kg was used in group P (n = 30), and ketamine 0.5 mg/ kg + propofol 1.5 mg/kg, i.v., in group PK (n = 30). Sedation levels of patients were maintained between scores 3 and 4 according to Ramsey sedation scores; when necessary, half of the starting drug dosage was administered for the maintainence of sedation. Side effects which occurred during or within the first 24 h of the procedure were assessed. Results: Additional dosage was needed for 21 cases in group P and eight cases in group PK ( p = 0.002). While oxygen desaturation and apnea were not observed in any of the patients in group PK, there were four patients (11.4%) with oxygen desaturation, and six (17.1%) with apnea in group P ( p < 0.05). Conclusions: In pediatric cases where ABR testing was applied, addition of low dose ketamine to propofol avoided the risk of respiratory depression due to propofol and lowered the need for additional dose of propofol. Therefore, the co-administration of propofol and ketamine appears to be a safe and useful technique for ABR testing. # 2005 Elsevier Ireland Ltd. All rights reserved.
1. Introduction * Corresponding author. Tel.: +90 352 4374901x24039; fax: +90 352 4377333. E-mail address: [email protected] (A. Akin).
Number of therapeutic and diagnostic interventions performed outside the operating room has considerably increased during recent years. Issues such as
0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.04.011
1542
sedation, and immobilization have become particularly important in children for a successful intervention and auditory brainstem response (ABR) test is among these interventions. Children and those who are mentally impaired frequently require sedation to attain accurate results when testing ABR. Since children are discharged and allowed to go their homes soon after the intervention, early recovery from anesthesia as well as keeping the possible side effects to a minimum level are usually aimed at. Propofol is an intravenous sedative—hypnotic agent which helps smooth recovery from aneshesia without dysphoria; antiemetic feature as well as rapid recovery from anesthesia are other advantages. On the other hand, propofol may have some side effects such as respiratory or cardiovascular depression and painful injection. Occasionally, adequate level of analgesia cannot be obtained, therefore, a combination with the opioids is necessary to get the desired level of analgesia [1,2]. However, when opioids are combined with propofol, risk of respiratory depression considerably increases [3,4]. Ketamine is usually preferred for pediatric sedation during procedures performed outside operating room [5—7] because of its analgesic and amnesic effects; preservation of the respiratory reflexes is also an important advantage. On the other hand, side effects such as hallucination and nausea can occur with its use. Ketamine is, therefore, combined with short acting benzodiazepines, to block such side effects. However, this leads to longer recovery time from anesthesia [8]. Recent investigations carried out in adult patients demonstrated that addition of low levels of ketamine to propofol can provide adequate sedation and shorter recovery time without causing respiratory depression [9,10]. Although this combination has been investigated in other diagnostic interventions in children [11,12] it has not been studied previously during ABR testing. The aim of our study was to compare propofol with propofol—ketamine combination for sedation in children undergoing ABR testing, and also to compare related complications.
2. Methods Sixty ASA I—II cases were included in the study after the approval of the local ethics comittee. Consent was obtained from the parents or legal guardians of the patients. The ages of the patients ranged between 1 and 13 years. ABR testing was planned in all patients and the patients were kept starved 4— 6 h before the intervention. A 22 G intravenous (i.v.)
A. Akin et al.
Table 1
Ramsay sedation score [13]
1. Nervous, agitated and/or restless 2. Cooperative, orientated, quite patient 3. Only obeying the orders 4. Sleeping, responding to hitting the glabella and high voice suddenly 5. Sleeping, responding to hitting the glabella and high voice slowly 6. No response to any of these stimulations
catheter was inserted after the application of EMLA 5% (AstraZeneca) on the dorsal side of hand 45— 60 min before the procedure. Propofol 1.5 mg/kg was used in group P (n = 30), and propofol 1.5 mg/ kg + ketamine 0.5 mg/kg, i.v., in group PK (n = 30). Sedation levels of cases were evaluated by Ramsay Sedation Scores [13] (Table 1) and kept constant around 3—4 by administration of half the starting dose of the medications when necessary. Continuous pulse oxymeter moniterization was performed. Blood pressure, respiratory rates, peripheral oxygen saturation (SpO2) were recorded at the beginning, immediately after the administration and at 3, 5, 10 min, after the administration of the drugs. Oxygen desaturation was regarded as a 10% fall in the SpO2 when compared to the starting level; apnea was regarded as cessation of respiration for a period of 15 s or more. ABR test was applied by DISA Neuromatic 2000 C device after sedation. An active electrode was attached to the vertex, reference electrode to ipsilateral apex and ground electrode to forehead. IDH-39 type earphones were applied, the contralateral ear was masked and 100 ms-long click stimuli were given. Twenty clicks per second were given for every second to make a total of 2000 clicks. Hemodynamic changes more than 20% of the starting levels, and complications observed during or after the procedure were recorded. Twenty-four hours after the cases were discharged from the hospital, a telephone call was made and information obtained with regard to any possible complications that could have occurred. Unpaired Student’s t-test was used for comparison of hemodynamic measurements, duration of interventions; chi-square and Fisher’s exact tests were used to compare distribution of sexes and differences between side effects occurred in the groups. A p-value less than 0.05 was considered as statistically significant.
3. Results It was possible to complete the study in all of our cases. There was not a statistically significant dif-
Comparison of propofol with propofol—ketamine combination in pediatric patients
Table 2 Demographic data and procedure time
Gender (M/F) Age (years) Height (cm) Weight (kg) Procedure time (min)
Group P (n = 30)
Group PK (n = 30)
18/17 5.6 3.0 104 10.5 17.7 5.7 9.2 3.2
20/15 4.3 2.8 98.5 12.9 15.1 5.3 9.7 2.6
Data are presented as mean S.D. P, propofol; PK, propofol + ketamine combination.
Table 3
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Comparison of side effects between groups
During sedation Oxygen desaturation Apnea Injection pain Increased oral secretions Bradycardia After sedation (first 24 h) Nausea Vomiting Dizziness
Group P (n = 30)
Group PK (n = 30)
4 6* 18* 1 2
0 0 2 1 0
0 0 3
1 1 0
P, propofol; PK, propofol + ketamine combination. * p < 0.05 when compared with group PK.
Side effects which occurred during or after the intervention are shown on Table 3.
4. Discussion Fig. 1 Systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) in groups; *p < 0.05; P, propofol; PK, propofol + ketamine combination.
ference between groups in terms of demographic data and procedure times (Table 2). Additional dosage was needed for 21 cases in group P and eight cases in group PK ( p = 0.002). While oxygen desaturation and apnea were not observed in any of the patients in group PK, there were four cases (11.4%) with oxygen desaturation, and six (17.1%) with apnea in group P ( p < 0.05). In group P, systolic arterial pressure, heart rate, and respiratory rates immediately after the administration of the drugs and at 3 and 5 min were significantly lower than the corresponding values in group PK ( p < 0.05; Figs. 1 and 2).
Fig. 2 Heart rate (HR) and respiratory rate (RR) in groups; *p < 0.05; P, propofol; PK, propofol + ketamine combination.
Our study showed that addition of ketamine to propofol preserved respiration better than propofol in pediatric cases where ABR testing was applied; this combination also lowered the need for additional dose. Therapeutic and diagnostic pediatric interventions performed outside the operating room have considerably increased during recent years. ABR testing is one of these interventions. Jerger et al. published their clinical results in pediatric cases in whom ABR testing was applied and reported that 136 children out of 167 required sedation [14]. On the other hand, investigations in children in whom ABR had been applied with the purpose of sedation are limited. Two of these limited investigations had been performed by Reich and Wiatrak [15], and Baranak et al. [16] and oral chloral hydrate had been used in these studies. Although diagnostic pediatric interventions generally do not carry high risk, requirement of sedation and immobilization may add risk to the procedure. Lowrie et al. [17] reported a complication rate of 12% in 458 pediatric cases; they stated that in 2.4% of these cases, the procedure could not be completed and that the most frequently observed complications were hypotension and hypoxemia. Malviya et al. [18] reported a complication rate of 20.1% due to inadequate sedation and oxygen desaturation. The same investigators, in another study reported that increased age and usage of benzodiazepines as the sole agent increased the incidence of inadequate sedation in a series of 922 pediatric cases [19].
1544
Tomatir et al. [11] have used propofol plus ketamine in pediatric cases to undergo magnetic resonance imaging, and Kogan et al. [12] have used the same combination in pediatric cases during cardiac catheterization. In both of these studies, it was reported that propofol—ketamine combination was safe and hemodynamically stable. However, this combination has not been studied previously in pediatric cases to undergo ABR testing. Ketamine is usually the preferred agent since it does not interfere with respiration. The effect of ketamine on the respiratory system is considerably different from other sedative drugs. Ketamine protects laryngeal and pharyngeal reflexes and induces bronchodilation; its depressive effect on the central respiratory drive is minimal and it preserves response to CO2 [20]. Mortero et al. [21] reported that in patients who received propofol plus fentanyl, a significant increase in end-expiratory PaCO2 was observed and that when ketamine was added to this combination, no such increase in end-expiratory PaCO2 was observed; the authors suggested that ketamine-induced sympathoadrenal activation could regulate ventilation. Mildh et al. [22] reported that fentanyl-induced decrease in the alveolar ventilation and decrease in minute volume could be inhibited by ketamine. Godambe et al. [8] reported that in pediatric patients who received propofol—fentanyl combination, desaturation was reported in 31% of the cases. Skokan et al. [23] stated that oxygen desaturation was observed in 30% of the pediatric cases in which emergency intervention was required and that opioids and propofol were used for this purpose. In our study, although we found the rate of desaturation as 11.4% and apnea as 17.1% in the propofol group, no such complication occurred in the propofol—ketamine group. It is possible to explain this by the positive effect of ketamine on the respiratory system whereas propofol caused respiratory depression. Ketamine has some side effects such as psychomimethic disorders and nausea; ketamine is usually combined with midazolam to prevent psycomimethic effects. In our study, we did not observe any psychomimethic effects in any of the cases since we used low dose ketamine and co-administered this with propofol. On the other hand, nausea and vomiting occurred in only one case. Incidence of ketamine-induced emesis was reported as between 0% and 43% and that of vomiting as 8.5% [6]. Bauman et al. [24] reported that they did not observe any nausea or vomiting in pediatric cases where propofol plus fentanyl was used for sedation and analgesia. It is also reported that lower doses of propofol had antiemetic effects via antagonizing dopamin D2
A. Akin et al.
receptors and that this proved useful to treat refractory nausea and vomiting in patients receiving chemotherapy [25]. In our study, incidence of vomiting and nausea was lower in both groups; we attribituted this to the antiemetic characteristics of propofol. We conclude in pediatric cases where ABR testing was applied, addition of low dose ketamine to propofol inhibited the risk of respiratory depression due to propofol; it also lowered the need for additional propofol dosage. Therefore, co-administration of propofol and ketamine appears to be a safe and useful method during ABR testing in children.
References [1] C. Smith, A.I. McEwan, R. Jhaveri, M. Wilkinson, D. Goodman, L.R. Smith, et al. The interaction of fentanyl on the Cp 50 of propofol for loss of consciousness and skin incision, Anesthesiology 81 (1994) 820—828. [2] J. Vuky, T. Lim, F.H. Engbers, A.G. Burm, A.A. Vietter, J.G. Bovill, et al. The pharmacodynamic interaction of propofol and alfentanil during lower abdominal surgery in women, Anesthesiology 83 (1995) 8—22. [3] M.M. Sa Rego, M.F. Watcha, P.F. White, The changing role of monitored anesthesia care in the ambulatory setting, Anesth. Analg. 85 (1997) 1020—1036. [4] M.N. Avramov, I. Smith, P.F. White, Interactions between midazolam and remifentanil during monitored anesthesia care, Anesthesiology 85 (1996) 1283—1289. [5] S.M. Green, R. Nakamura, N.E. Johnson, Ketamine sedation for pediatric procedures. Part 1. A prospective series, Ann. Emerg. Med. 19 (1990) 1024—1032. [6] S.M. Green, N.E. Johnson, Ketamine sedation for pediatric procedures. Part 2. Review and implications, Ann. Emerg. Med. 19 (1990) 1033—1046. [7] S.M. Green, S.G. Rothrock, T. Harris, G.A. Hopkins, W. Garrett, T. Sherwin, Intravenous ketamine for pediatric sedation in emergency department: safety profile with 156 cases, Acad. Emerg. Med. 5 (1998) 971—976. [8] S.A. Godambe, V. Elliot, D. Matheny, J. Pershad, Comparison of propofol/fentanyl versus ketamine/midazolam for brief orthopedic procedural sedation in a pediatric emergency department, Pediatrics 112 (2003) 116—123. [9] K. Frey, R. Sukhani, J. Pawlowski, A.L. Pappas, M. MikatStevens, S. Slogoff, Propofol versus propofol—ketamine sedation for retrobulber nerve block: comparison of sedation quality, intraocular pressure changes, and recovery profiles, Anesth. Analg. 89 (1999) 317—321. [10] S. Badrinath, M.N. Avramov, M. Shadrick, T.R. Witt, A.D. Ivankovich, The use of ketamine—propofol combination during monitored anesthesia care, Anesth. Analg. 90 (2000) 858—862. [11] E. Tomatir, H. Atalay, E. Gurses, H. Erbay, P. Bozkurt, Effect of low dose ketamine before induction on propofol anesthesia for pediatric magnetic resonance imaging, Paediatr. Anaesth. 14 (2004) 845—850. [12] A. Kogan, R. Efrat, J. Katz, B.A. Vidne, Propofol—ketamine mixture for anesthesia in pediatric patients undergoing cardiac catheterization, J. Cardiothorac. Vasc. Anesth. 17 (2003) 691—693. [13] M.A. Ramsay, T.M. Savege, B.R. Simpson, R. Goodwin, Controlled sedation with alphaxalone—alphadolone, Br. Med. J. 2 (1974) 656—659.
Comparison of propofol with propofol—ketamine combination in pediatric patients
[14] J. Jerger, D. Hayes, C. Jordan, Clinical experience with auditory brainstem response audiometry in pediatric assessment, Ear Hear. 1 (1980) 19—25. [15] D.S. Reich, B.J. Wiatrak, Methods of sedation for auditory brainstem response testing, Int. J. Pediatr. Otorhinolaryngol. 38 (1996) 131—141. [16] C.C. Baranak, R.R. Marsh, W.P. Potsic, Sedation in brainstem response audiometry, Int. J. Pediatr. Otorhinolaryngol. 8 (1984) 55—59. [17] L. Lowrie, A.H. Weiss, C. Lacombe, The pediatric sedation unit: a mechanism for pediatric sedation, Pediatrics 102 (1998) 1—9. [18] S. Malviya, T. Voepel-Lewis, A.R. Taiat, Adverse events and risk factors associated with the sedation of children by nonanesthesiologists, Anesth. Analg. 85 (1997) 1207— 1213. [19] S. Malviya, T. Voepel-Lewis, O.P. Eldevik, D.T. Rockwell, J.H. Wong, A.R. Tait, Sedation and general anaesthesia in children undergoing MRI and CT: adverse events and outcomes, Br. J. Anaesth. 84 (2000) 743—748.
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[20] H.P. Frizelle, J. Duranteau, K. Samii, A comparison of propofol with a propofol—ketamine combination for sedation during spinal anesthesia, Anesth. Analg. 84 (1997) 1318— 1322. [21] R.F. Mortero, L.D. Clark, M.M. Tolan, R.J. Metz, K. Tsueda, R.A. Sheppard, The effects of small-dose ketamine on propofol sedation: respiration, postoperative mood, perception, cognition, and pain, Anesth. Analg. 92 (2001) 1465— 1469. [22] L. Mildh, M. Taittonen, K. Leino, O. Kirvela, The effect of low-dose ketamine on fentanyl-induced respiratory depression, Anaesthesia 53 (1998) 965—970. [23] E.G. Skokan, C. Pribble, K.E. Bassett, D.S. Nelson, Use of propofol sedation in a pediatric emergency department: a prospective study, Clin. Pediatr. 40 (2001) 663—671. [24] L.A. Bauman, I. Kish, R.C. Baumann, G.D. Politis, Pediatric sedation with analgesia, Am. J. Emerg. Med. 17 (1999) 1—3. [25] I. Smith, P.F. White, M. Nathanson, R. Gouldson, Propofol: an update on its clinical use, Anesthesiology 81 (1994) 1005— 1043.
www.elsevier.com/locate/ijporl
Comparison of propofol with propofol—ketamine combination in pediatric patients undergoing auditory brainstem response testing Aynur Akin *, Aliye Esmaoglu, Zeynep Tosun, Nebahat Gulcu, Harun Aydogan, Adem Boyaci Department of Anesthesiology, Erciyes University School of Medicine, Kayseri, Alpaslan Mah, Kandilli Sok, Bezciler Sitesi 3, Blok No. 6/11, 38030 Kayseri, Turkey Received 1 March 2005; accepted 20 April 2005
KEYWORDS Auditory brainstem response test; Sedation; Child; Propofol; Ketamine
Summary Objective: The aim of our study was to compare propofol with propofol—ketamine combination for sedation and also to compare related complications in children undergoing auditory brainstem response (ABR) testing. Methods: Sixty ASA I—II patients aged between 1 and 13 years of age were sedated for ABR testing. Propofol 1.5 mg/kg was used in group P (n = 30), and ketamine 0.5 mg/ kg + propofol 1.5 mg/kg, i.v., in group PK (n = 30). Sedation levels of patients were maintained between scores 3 and 4 according to Ramsey sedation scores; when necessary, half of the starting drug dosage was administered for the maintainence of sedation. Side effects which occurred during or within the first 24 h of the procedure were assessed. Results: Additional dosage was needed for 21 cases in group P and eight cases in group PK ( p = 0.002). While oxygen desaturation and apnea were not observed in any of the patients in group PK, there were four patients (11.4%) with oxygen desaturation, and six (17.1%) with apnea in group P ( p < 0.05). Conclusions: In pediatric cases where ABR testing was applied, addition of low dose ketamine to propofol avoided the risk of respiratory depression due to propofol and lowered the need for additional dose of propofol. Therefore, the co-administration of propofol and ketamine appears to be a safe and useful technique for ABR testing. # 2005 Elsevier Ireland Ltd. All rights reserved.
1. Introduction * Corresponding author. Tel.: +90 352 4374901x24039; fax: +90 352 4377333. E-mail address: [email protected] (A. Akin).
Number of therapeutic and diagnostic interventions performed outside the operating room has considerably increased during recent years. Issues such as
0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.04.011
1542
sedation, and immobilization have become particularly important in children for a successful intervention and auditory brainstem response (ABR) test is among these interventions. Children and those who are mentally impaired frequently require sedation to attain accurate results when testing ABR. Since children are discharged and allowed to go their homes soon after the intervention, early recovery from anesthesia as well as keeping the possible side effects to a minimum level are usually aimed at. Propofol is an intravenous sedative—hypnotic agent which helps smooth recovery from aneshesia without dysphoria; antiemetic feature as well as rapid recovery from anesthesia are other advantages. On the other hand, propofol may have some side effects such as respiratory or cardiovascular depression and painful injection. Occasionally, adequate level of analgesia cannot be obtained, therefore, a combination with the opioids is necessary to get the desired level of analgesia [1,2]. However, when opioids are combined with propofol, risk of respiratory depression considerably increases [3,4]. Ketamine is usually preferred for pediatric sedation during procedures performed outside operating room [5—7] because of its analgesic and amnesic effects; preservation of the respiratory reflexes is also an important advantage. On the other hand, side effects such as hallucination and nausea can occur with its use. Ketamine is, therefore, combined with short acting benzodiazepines, to block such side effects. However, this leads to longer recovery time from anesthesia [8]. Recent investigations carried out in adult patients demonstrated that addition of low levels of ketamine to propofol can provide adequate sedation and shorter recovery time without causing respiratory depression [9,10]. Although this combination has been investigated in other diagnostic interventions in children [11,12] it has not been studied previously during ABR testing. The aim of our study was to compare propofol with propofol—ketamine combination for sedation in children undergoing ABR testing, and also to compare related complications.
2. Methods Sixty ASA I—II cases were included in the study after the approval of the local ethics comittee. Consent was obtained from the parents or legal guardians of the patients. The ages of the patients ranged between 1 and 13 years. ABR testing was planned in all patients and the patients were kept starved 4— 6 h before the intervention. A 22 G intravenous (i.v.)
A. Akin et al.
Table 1
Ramsay sedation score [13]
1. Nervous, agitated and/or restless 2. Cooperative, orientated, quite patient 3. Only obeying the orders 4. Sleeping, responding to hitting the glabella and high voice suddenly 5. Sleeping, responding to hitting the glabella and high voice slowly 6. No response to any of these stimulations
catheter was inserted after the application of EMLA 5% (AstraZeneca) on the dorsal side of hand 45— 60 min before the procedure. Propofol 1.5 mg/kg was used in group P (n = 30), and propofol 1.5 mg/ kg + ketamine 0.5 mg/kg, i.v., in group PK (n = 30). Sedation levels of cases were evaluated by Ramsay Sedation Scores [13] (Table 1) and kept constant around 3—4 by administration of half the starting dose of the medications when necessary. Continuous pulse oxymeter moniterization was performed. Blood pressure, respiratory rates, peripheral oxygen saturation (SpO2) were recorded at the beginning, immediately after the administration and at 3, 5, 10 min, after the administration of the drugs. Oxygen desaturation was regarded as a 10% fall in the SpO2 when compared to the starting level; apnea was regarded as cessation of respiration for a period of 15 s or more. ABR test was applied by DISA Neuromatic 2000 C device after sedation. An active electrode was attached to the vertex, reference electrode to ipsilateral apex and ground electrode to forehead. IDH-39 type earphones were applied, the contralateral ear was masked and 100 ms-long click stimuli were given. Twenty clicks per second were given for every second to make a total of 2000 clicks. Hemodynamic changes more than 20% of the starting levels, and complications observed during or after the procedure were recorded. Twenty-four hours after the cases were discharged from the hospital, a telephone call was made and information obtained with regard to any possible complications that could have occurred. Unpaired Student’s t-test was used for comparison of hemodynamic measurements, duration of interventions; chi-square and Fisher’s exact tests were used to compare distribution of sexes and differences between side effects occurred in the groups. A p-value less than 0.05 was considered as statistically significant.
3. Results It was possible to complete the study in all of our cases. There was not a statistically significant dif-
Comparison of propofol with propofol—ketamine combination in pediatric patients
Table 2 Demographic data and procedure time
Gender (M/F) Age (years) Height (cm) Weight (kg) Procedure time (min)
Group P (n = 30)
Group PK (n = 30)
18/17 5.6 3.0 104 10.5 17.7 5.7 9.2 3.2
20/15 4.3 2.8 98.5 12.9 15.1 5.3 9.7 2.6
Data are presented as mean S.D. P, propofol; PK, propofol + ketamine combination.
Table 3
1543
Comparison of side effects between groups
During sedation Oxygen desaturation Apnea Injection pain Increased oral secretions Bradycardia After sedation (first 24 h) Nausea Vomiting Dizziness
Group P (n = 30)
Group PK (n = 30)
4 6* 18* 1 2
0 0 2 1 0
0 0 3
1 1 0
P, propofol; PK, propofol + ketamine combination. * p < 0.05 when compared with group PK.
Side effects which occurred during or after the intervention are shown on Table 3.
4. Discussion Fig. 1 Systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) in groups; *p < 0.05; P, propofol; PK, propofol + ketamine combination.
ference between groups in terms of demographic data and procedure times (Table 2). Additional dosage was needed for 21 cases in group P and eight cases in group PK ( p = 0.002). While oxygen desaturation and apnea were not observed in any of the patients in group PK, there were four cases (11.4%) with oxygen desaturation, and six (17.1%) with apnea in group P ( p < 0.05). In group P, systolic arterial pressure, heart rate, and respiratory rates immediately after the administration of the drugs and at 3 and 5 min were significantly lower than the corresponding values in group PK ( p < 0.05; Figs. 1 and 2).
Fig. 2 Heart rate (HR) and respiratory rate (RR) in groups; *p < 0.05; P, propofol; PK, propofol + ketamine combination.
Our study showed that addition of ketamine to propofol preserved respiration better than propofol in pediatric cases where ABR testing was applied; this combination also lowered the need for additional dose. Therapeutic and diagnostic pediatric interventions performed outside the operating room have considerably increased during recent years. ABR testing is one of these interventions. Jerger et al. published their clinical results in pediatric cases in whom ABR testing was applied and reported that 136 children out of 167 required sedation [14]. On the other hand, investigations in children in whom ABR had been applied with the purpose of sedation are limited. Two of these limited investigations had been performed by Reich and Wiatrak [15], and Baranak et al. [16] and oral chloral hydrate had been used in these studies. Although diagnostic pediatric interventions generally do not carry high risk, requirement of sedation and immobilization may add risk to the procedure. Lowrie et al. [17] reported a complication rate of 12% in 458 pediatric cases; they stated that in 2.4% of these cases, the procedure could not be completed and that the most frequently observed complications were hypotension and hypoxemia. Malviya et al. [18] reported a complication rate of 20.1% due to inadequate sedation and oxygen desaturation. The same investigators, in another study reported that increased age and usage of benzodiazepines as the sole agent increased the incidence of inadequate sedation in a series of 922 pediatric cases [19].
1544
Tomatir et al. [11] have used propofol plus ketamine in pediatric cases to undergo magnetic resonance imaging, and Kogan et al. [12] have used the same combination in pediatric cases during cardiac catheterization. In both of these studies, it was reported that propofol—ketamine combination was safe and hemodynamically stable. However, this combination has not been studied previously in pediatric cases to undergo ABR testing. Ketamine is usually the preferred agent since it does not interfere with respiration. The effect of ketamine on the respiratory system is considerably different from other sedative drugs. Ketamine protects laryngeal and pharyngeal reflexes and induces bronchodilation; its depressive effect on the central respiratory drive is minimal and it preserves response to CO2 [20]. Mortero et al. [21] reported that in patients who received propofol plus fentanyl, a significant increase in end-expiratory PaCO2 was observed and that when ketamine was added to this combination, no such increase in end-expiratory PaCO2 was observed; the authors suggested that ketamine-induced sympathoadrenal activation could regulate ventilation. Mildh et al. [22] reported that fentanyl-induced decrease in the alveolar ventilation and decrease in minute volume could be inhibited by ketamine. Godambe et al. [8] reported that in pediatric patients who received propofol—fentanyl combination, desaturation was reported in 31% of the cases. Skokan et al. [23] stated that oxygen desaturation was observed in 30% of the pediatric cases in which emergency intervention was required and that opioids and propofol were used for this purpose. In our study, although we found the rate of desaturation as 11.4% and apnea as 17.1% in the propofol group, no such complication occurred in the propofol—ketamine group. It is possible to explain this by the positive effect of ketamine on the respiratory system whereas propofol caused respiratory depression. Ketamine has some side effects such as psychomimethic disorders and nausea; ketamine is usually combined with midazolam to prevent psycomimethic effects. In our study, we did not observe any psychomimethic effects in any of the cases since we used low dose ketamine and co-administered this with propofol. On the other hand, nausea and vomiting occurred in only one case. Incidence of ketamine-induced emesis was reported as between 0% and 43% and that of vomiting as 8.5% [6]. Bauman et al. [24] reported that they did not observe any nausea or vomiting in pediatric cases where propofol plus fentanyl was used for sedation and analgesia. It is also reported that lower doses of propofol had antiemetic effects via antagonizing dopamin D2
A. Akin et al.
receptors and that this proved useful to treat refractory nausea and vomiting in patients receiving chemotherapy [25]. In our study, incidence of vomiting and nausea was lower in both groups; we attribituted this to the antiemetic characteristics of propofol. We conclude in pediatric cases where ABR testing was applied, addition of low dose ketamine to propofol inhibited the risk of respiratory depression due to propofol; it also lowered the need for additional propofol dosage. Therefore, co-administration of propofol and ketamine appears to be a safe and useful method during ABR testing in children.
References [1] C. Smith, A.I. McEwan, R. Jhaveri, M. Wilkinson, D. Goodman, L.R. Smith, et al. The interaction of fentanyl on the Cp 50 of propofol for loss of consciousness and skin incision, Anesthesiology 81 (1994) 820—828. [2] J. Vuky, T. Lim, F.H. Engbers, A.G. Burm, A.A. Vietter, J.G. Bovill, et al. The pharmacodynamic interaction of propofol and alfentanil during lower abdominal surgery in women, Anesthesiology 83 (1995) 8—22. [3] M.M. Sa Rego, M.F. Watcha, P.F. White, The changing role of monitored anesthesia care in the ambulatory setting, Anesth. Analg. 85 (1997) 1020—1036. [4] M.N. Avramov, I. Smith, P.F. White, Interactions between midazolam and remifentanil during monitored anesthesia care, Anesthesiology 85 (1996) 1283—1289. [5] S.M. Green, R. Nakamura, N.E. Johnson, Ketamine sedation for pediatric procedures. Part 1. A prospective series, Ann. Emerg. Med. 19 (1990) 1024—1032. [6] S.M. Green, N.E. Johnson, Ketamine sedation for pediatric procedures. Part 2. Review and implications, Ann. Emerg. Med. 19 (1990) 1033—1046. [7] S.M. Green, S.G. Rothrock, T. Harris, G.A. Hopkins, W. Garrett, T. Sherwin, Intravenous ketamine for pediatric sedation in emergency department: safety profile with 156 cases, Acad. Emerg. Med. 5 (1998) 971—976. [8] S.A. Godambe, V. Elliot, D. Matheny, J. Pershad, Comparison of propofol/fentanyl versus ketamine/midazolam for brief orthopedic procedural sedation in a pediatric emergency department, Pediatrics 112 (2003) 116—123. [9] K. Frey, R. Sukhani, J. Pawlowski, A.L. Pappas, M. MikatStevens, S. Slogoff, Propofol versus propofol—ketamine sedation for retrobulber nerve block: comparison of sedation quality, intraocular pressure changes, and recovery profiles, Anesth. Analg. 89 (1999) 317—321. [10] S. Badrinath, M.N. Avramov, M. Shadrick, T.R. Witt, A.D. Ivankovich, The use of ketamine—propofol combination during monitored anesthesia care, Anesth. Analg. 90 (2000) 858—862. [11] E. Tomatir, H. Atalay, E. Gurses, H. Erbay, P. Bozkurt, Effect of low dose ketamine before induction on propofol anesthesia for pediatric magnetic resonance imaging, Paediatr. Anaesth. 14 (2004) 845—850. [12] A. Kogan, R. Efrat, J. Katz, B.A. Vidne, Propofol—ketamine mixture for anesthesia in pediatric patients undergoing cardiac catheterization, J. Cardiothorac. Vasc. Anesth. 17 (2003) 691—693. [13] M.A. Ramsay, T.M. Savege, B.R. Simpson, R. Goodwin, Controlled sedation with alphaxalone—alphadolone, Br. Med. J. 2 (1974) 656—659.
Comparison of propofol with propofol—ketamine combination in pediatric patients
[14] J. Jerger, D. Hayes, C. Jordan, Clinical experience with auditory brainstem response audiometry in pediatric assessment, Ear Hear. 1 (1980) 19—25. [15] D.S. Reich, B.J. Wiatrak, Methods of sedation for auditory brainstem response testing, Int. J. Pediatr. Otorhinolaryngol. 38 (1996) 131—141. [16] C.C. Baranak, R.R. Marsh, W.P. Potsic, Sedation in brainstem response audiometry, Int. J. Pediatr. Otorhinolaryngol. 8 (1984) 55—59. [17] L. Lowrie, A.H. Weiss, C. Lacombe, The pediatric sedation unit: a mechanism for pediatric sedation, Pediatrics 102 (1998) 1—9. [18] S. Malviya, T. Voepel-Lewis, A.R. Taiat, Adverse events and risk factors associated with the sedation of children by nonanesthesiologists, Anesth. Analg. 85 (1997) 1207— 1213. [19] S. Malviya, T. Voepel-Lewis, O.P. Eldevik, D.T. Rockwell, J.H. Wong, A.R. Tait, Sedation and general anaesthesia in children undergoing MRI and CT: adverse events and outcomes, Br. J. Anaesth. 84 (2000) 743—748.
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[20] H.P. Frizelle, J. Duranteau, K. Samii, A comparison of propofol with a propofol—ketamine combination for sedation during spinal anesthesia, Anesth. Analg. 84 (1997) 1318— 1322. [21] R.F. Mortero, L.D. Clark, M.M. Tolan, R.J. Metz, K. Tsueda, R.A. Sheppard, The effects of small-dose ketamine on propofol sedation: respiration, postoperative mood, perception, cognition, and pain, Anesth. Analg. 92 (2001) 1465— 1469. [22] L. Mildh, M. Taittonen, K. Leino, O. Kirvela, The effect of low-dose ketamine on fentanyl-induced respiratory depression, Anaesthesia 53 (1998) 965—970. [23] E.G. Skokan, C. Pribble, K.E. Bassett, D.S. Nelson, Use of propofol sedation in a pediatric emergency department: a prospective study, Clin. Pediatr. 40 (2001) 663—671. [24] L.A. Bauman, I. Kish, R.C. Baumann, G.D. Politis, Pediatric sedation with analgesia, Am. J. Emerg. Med. 17 (1999) 1—3. [25] I. Smith, P.F. White, M. Nathanson, R. Gouldson, Propofol: an update on its clinical use, Anesthesiology 81 (1994) 1005— 1043.