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Use of chloral hydrate as a sedative for auditory brainstem response testing in a pediatric population
International Journal of Pediatric Otorhinolaryngology 75 (2011) 760–763
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Use of chloral hydrate as a sedative for auditory brainstem response testing in a pediatric population Eirini Avlonitou a,1, Dimitrios G. Balatsouras b,*, Eleftherios Margaritis a,2, Polyvios Giannakopoulos a,3, Dimitrios Douniadakis a,4, Michael Tsakanikos a,5 a b
ENT Department of Pediatric Hospital ‘‘Aglaia Kyriakou’’, Thivon & Levadias Street, GR-11527, Athens,Greece ENT Department of Tzanion General Hospital, 11 Zani & Afentouli Street, GR-18536, Piraeus,Greece
A R T I C L E I N F O
A B S T R A C T
Article history: Received 19 January 2011 Received in revised form 6 February 2011 Accepted 9 February 2011
Objective: Chloral hydrate (CH) is an oral sedative widely used to sedate infants and young children during auditory brainstem response (ABR) testing. The aim of this study was to record effectiveness, complications and safety of CH as a sedative for ABR. Methods: From January of 2003 until December of 2007, 1903 children were tested for ABR, 568 of them being under the age of 6 months. CH (8%) was used for sedation at a dose of 40 mg/kg with a repeat dose, if necessary, for an adequate sedation, in 20–30 min. We recorded the effectiveness of CH as a sedative for ABR examination, as well as all complications related to the use of CH such as vomiting, rash, hyperactivity, respiratory distress and apnea. The statistical method used was the absolute and percentage frequency distribution of the occurrences. Results: Sedation with CH was necessary to perform testing in 1591 (83.6%) of the examined children. However, in the population of the examined infants, only 341 (60%) were sedated with CH, because the remaining 227 (40%) fell asleep by themselves. Complications included hyperactivity in 152 children (8%), minor respiratory distress in 10 children (0.4%), vomiting in 217 children (11.4%), apnea in 4 children (0.2%) and rash in 10 children (0.4%). The complications of hyperactivity, vomiting and rash resolved without any medical treatment. The apnea cases were managed effectively by supplying ventilation to the children via a mask in the presence of an anesthesiologist. Conclusions: The use of CH at a dose of 40 mg/kg up to 80 mg/kg is safe and effective when administered in a setting with adequate equipment and the presence of well trained personnel. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Chloral hydrate Auditory brainstem responses Apnea
1. Introduction Auditory brainstem responses (ABR) is an objective method of testing the auditory pathway and is especially useful in the detection of hearing loss in infants and young children that are not eligible for testing with puretone audiometry. Testing, however, must be performed with the child completely relaxed. In the case
* Corresponding author at: 23 Achaion Street – Ag. Paraskevi, GR-15343 Athens, Greece. Tel.: +30 210 600 4683; fax: +30 210 4592 671. E-mail addresses: [email protected] (E. Avlonitou), [email protected], [email protected] (D.G. Balatsouras), [email protected] (E. Margaritis), [email protected] (P. Giannakopoulos), [email protected] (D. Douniadakis), [email protected] (M. Tsakanikos). 1 5 Marathonos Street, Glifada, GR-16674 Athens, Greece. Tel.: +30 210 9619567. 2 Tel.: +30 210 77775611. 3 Tel.: +30 210 77775612. 4 Tel.: +30 210 77775613. 5 Tel.: +30 210 77775619. 0165-5876/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2011.02.010
of infants, this may be obtained, after feeding with milk. In most other cases, mild sedation is required to reduce anxiety. Chloral hydrate (CH) is a widely used oral sedative hypnotic drug which has been used for several decades in pediatrics for diagnostic procedures, such as ABR, computerized tomography or magnetic resonance imaging. CH is one of the oldest synthetic agents, considering that this substance was synthesized in 1832 [1]. It is administered orally or rectally and is rapidly absorbed from the gastrointestinal tract. CH is metabolized to trichloroethanol which is the active metabolite and is responsible for the hypnotic action [2]. The halflife of CH is short (a few minutes) whereas for trichloroethanol it is 8–12 h. It should be noticed that in infants, the half-life is 3–4 times greater than in older children [2,3]. The mechanism of the sedative action of CH is still unknown. It is believed that its sedative effect on the central nervous system is mediated by gamma aminobutyric acid-A receptors (GABA), since the use of flumazenil (a GABA antagonist) in treating cases with CH overdose, has been proven successful [4].
E. Avlonitou et al. / International Journal of Pediatric Otorhinolaryngology 75 (2011) 760–763
CH interacts with alcohol [5], anticoagulants [3], amitriptyline [1], flumazenil [4,6], furosemide [7], fluoxetine [8], as well as with other CNS suppressants [3] or stimulants [9]. The recommended dose for sedative action is 20–100 mg/kg, although for infants dose adjustment is required. Various side effects of CH have been reported [1,10] including vomiting, nausea, rash, hyperactivity, respiratory distress, apnea and arrhythmias, whereas some studies, based only on animal research, have reported that CH may have a carcinogenic effect [11,12]. In case of overdose, the first symptoms are ataxia and lethargy, further progressing to deep coma, which generally occurs within 1–2 h [3]. Deaths have been reported to occur after the ingestion of at least 5 g of CH [3]. The use of CH is not recommended in cases with a history of gastric ulcer, hepatic distress, breathing distress and porphyria [1]. In the audiology laboratory of our hospital, CH is being used for more than 2 decades, for the sedation of infants and young children examined by the ABR test. Although, CH is a widely used drug as a pediatric sedative, issues concerning its safety and efficacy continue to arise. Various relevant reports include only a limited number of subjects [e.g. 10,13]. The aim of this study was both to determine the effectiveness of CH in sedating, as well as to investigate the safety of its use in a large number of young children. 2. Methods The subjects of this study were 1903 children, who were examined with ABR at our audiology laboratory from January 2003 to December 2007. Five hundred and sixty-eight of these children were under 6 months of age whereas the remaining 1335 were older, with maximum age 14 years. According to our laboratory protocol, instructions were given to all parents to bring their children to the laboratory awake but drowsy and without having eaten for the last 3 h before the examination. In addition, the parents are asked to bring whatever food or drink consider appropriate, in order to mix it with CH. This commonly includes milk for infants and juice, milk, cream or yogurt for older children. Special emphasis is given to their medical history. Children with severe pulmonary disease and recent upper respiratory tract infection had their appointments rescheduled until they met the criteria for sedation. CH is given at a concentration of 8%. It is given at an initial dose of 40 mg/kg, with a repeat equal dose, if required, to obtain adequate sedation after 20–30 min. The maximum dose is 80 mg/ kg (with the total dose not exceeding 1 g), which is consistent with the American Academy of Pediatrics (AAP) sedation guidelines [14]. For infants under 6 months of age, the maximum dose was 40 mg/kg, and this was only given in cases where the infant had not fallen asleep spontaneously within 10–20 min. CH was mixed with a banana-flavored liquid, in order to improve its bitter taste. In the rare cases where the infant did not cooperate or repeatedly vomited, the sedative was inserted into its stomach via a nasogastric tube. After CH ingestion, the children remained in a quiet and dark room with their parents until they were fully asleep. Subsequently, the children were transferred to the examination room and the ABR test was begun. During the whole course of the examination, the children were under the care of a qualified sedation nurse who observed them for any complications occurring due to CH intake, such as apnea, breathing distress, cyanosis, vomiting, hyperactivity, or cardiac rate changes. Children with minor respiratory distress were connected to a pulse oximeter for observation of their blood saturation. Children presenting with cyanosis or apneas were immediately monitored with the guidelines suggested by AAP. The average time for the
761
Table 1 Data of sedation with chloral hydrate. Children 6 months (N = 568)
Children > 6 months (N = 1335)
1st dose of CH 2nd dose CH if required
40 mg/kg No
Time before 1st dose Time between 1st and 2nd dose Success rate of first dose Total time of preparation and examination
15 5 min –
40 mg/kg 40 mg/kg (total dose not exceeding 1 g) No delay 24 7 min
100% 34 14 min
72% (961/1335 children) 49 22 min
preparation and measurement of ABR was about 40–50 min. Following the end of the ABR examination the children remained in the audiology laboratory under the supervision of the sedation nurse until they recovered from sedation. Subsequently, instructions were given to the parents and then the children were sent home. The statistical method used for the results of the study was the absolute and percentage distribution of occurrences. 3. Results Of the 1903 children examined by ABR, 1586 (83.3%) were sedated by CH, whereas 312 (16.4%) were quite relaxed to avoid sedation during testing and 5 (0.3%) couldn’t be sedated with CH. Considering the group of the 568 infants under the age of 6 months, CH sedation was needed in a smaller percentage (60%) of subjects (341 infants), whereas the remaining 227 (40%) fell asleep spontaneously. In the second group of the 1335 children over the age of 6 months, 1245 (93.2%) required sedation with CH, only 85 (6.4%) slept spontaneously and another 5 (0.4%) required sedation intravenously. Our data of CH administration are shown in Table 1. It should be mentioned, that a naso-gastric tube for the administration of CH was used in 50 children (2.6%) over the age of 3.5 years who could not take the CH orally or those who were hyperactive or vomited. The final results, considering the sedating effect of CH, indicated a success rate of 99.7%. Complications were observed in 393 (20.6)% out of the 1903 children (Table 2). 4. Discussion The development and clinical application of otoacoustic emissions marked the beginning of a new era in the field of screening for congenital hearing loss, because it allowed for an objective evaluation of hearing almost as soon as the babies were born [15,16]. A step further was the application of automated auditory brainstem responses, which is more time consuming, but it is generally reported to obtain a lower referral rate [17]. Combination of these two methods permits objective evaluation of both cochlear and retrocochlear hearing, and even newborns at risk for auditory neuropathy may be identified. Routine use of these methods in newborns, does not demand use of sedatives, but neverthless sedation is necessary in performing diagnostic ABR. Table 2 Side effects of CH sedation used for ABR testing. Side effect
Number of children
Percentage
Hyperactivity Vomiting Rash Minor breathing distress Apnea
152 217 10 10 4
8% 11.4% 0.5% 0.5% 0.2%
762
E. Avlonitou et al. / International Journal of Pediatric Otorhinolaryngology 75 (2011) 760–763
Application of diagnostic ABR has not been decreased in the modern era, because this method is the gold standard in audiological diagnosis in infants and children. Additionally, universal application of hearing screening programs, results in a large number of dubious cases, which should be further examined, to conclude if these are truly positive or false positive cases. Accordingly, use of diagnostic ABR under sedation is nowadays even more common than in the past, and the issue of the appropriate sedative, and specifically their efficacy and safety, are always interesting. CH is the most widely used sedative agent in children, and we performed this study to evaluate its efficacy and safety in a great number of subjects, because literature is lacking in large scale studies. In the present study, we obtained to sedate the majority (83.6%) of children under examination with ABR, by using only CH. It appears, thus, that CH is an effective medication for this task. These results correspond well with those obtained in various other studies, although we have examined a significantly greater number of children. Hijazi et al. [13] found that 79% of children were sedated effectively with CH, at an average dose of 56.9 9.3 mg, whereas after a second dose of 18.5 6.4 mg, the success rate rose to 95%. In a study of children undergoing CT and MRI imaging, Vade et al. [18] found that CH sedation was successful in 100% for all the children having CT, and 100% for children 1–4 years old and 97% for children less than 1 year old for the children having MRI. In smaller scale studies, Allegaert et al. [19] obtained meaningful ABR results in all of the examined infants, and furthermore, Reich and Wiatrak [20] sedated 17 out of 18 patients with CH and in only one child, an additional drug was required for sedation. From our results, it appears that CH is a safe drug. Although complications were observed in 20.7% of the examined children, most of them subsided without demanding medical treatment. The most common complications included hyperactivity, vomiting and rash, accounting for a rate of 19.9% of the children, and only the remaining 0.7% of the patients presented with minor breathing distress (0.5%) and apnea (0.2%). Children with one of the former minor complications were placed under observation for about 2 h and then returned home without any further undesirable side effects being observed. In the 10 cases (0.5%) where a minor level of breathing distress was observed, the children were awakened, placed on their side and supplementary oxygen was given. The most serious side effect related to CH use was apnea, which occurred in only 4 patients (0.2%). Of these, in 3 of the children the apnea lasted for less than 15 s, and blood saturation remained above 88%. These three apneas were resolved spontaneously. After the resolution of the apnoic episodes, blood saturation and vital signs were monitored, while supplementary oxygen was given to the children under the supervision of an anesthesiologist. However, the fourth case was more serious, with the blood saturation dropping below 85% and the child was immediately transferred to the recovery section of the surgical headquarters. Oxygen ventilation was supplied via a mask, while the vital signs were monitored and observed by the anesthesiologists until the total recovery of the child. It may be, thus, concluded that although apnea is a rare complication of CH use, medical personnel trained in cardiopulmonary resuscitation and the use of standard monitoring equipment is recommended for the safe administration of sedation. From the data recorded above, it can be seen that sedation with an 8% concentration of CH at a dose of 40 mg/kg, and if needed, increasing up to 80 mg/kg (maximum dose) is an effective method with a relatively low rate of unwanted side effects. The issue of CH dose for adequate sedation has been extensively discussed. Reich and Wiatrak [20] in a survey of 75 Children’s American Hospitals using appropriate questionnaires, found that in 32% of the surveyed practitioners, 32% used 50 mg/kg and 29% administered
up to 75 mg/kg. However, the dosages of the rest varied widely and in one case a maximum dose of 2000 mg was administered. Repetitive doses of CH may be used occasionally to maintain prolonged sedation in infants and children during mechanical ventilation and this practice may arise concern, due to accumulation of active metabolites [14]. However, when CH is routinely used to obtain sedation for the performance of ABR, more than one dose repetition is rarely needed. On the other hand, overdose is a major concern, because it includes liver disease, gastric irritation, cardiac irritability and central nervous system depression [7]. Even deaths due to CH overdose after more than 10 g have been taken were reported [21,22], but most of these consequences have been primarily documented in adults [23], with rare exceptions [24]. A serious concern regarding the use of CH as a standard sedative in children is its potential carcinogenicity, based on the assumption that CH is a reactive metabolite of trichloroethylene, which is an industrial solvent carcinogenic in some laboratory animal species [14,25,26]. Studies with mice have shown that CH occasionally induced liver disease, adenomas or tumors, attributed to its metabolite trichloracetic acid. Very high doses of CH have been reported to cause aneuploidy, a term denoting alteration of the number of chromosomes in the cellular level. However, CH does not cross-link DNA or proteins in vitro, suggesting that it is minimally or non genotoxic. Multiple epidemiologic studies in humans have failed to document an increase in cancer incidence associated with trichloroethylene exposure [27,28]. In conclusion, CH is an effective sedative for children, which is safe at doses of 40–80 mg/kg, provided that it is used in a hospital setting, with appropriately trained staff and cardiopulmonary resuscitation facilities, following the AAP guidelines.
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Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Use of chloral hydrate as a sedative for auditory brainstem response testing in a pediatric population Eirini Avlonitou a,1, Dimitrios G. Balatsouras b,*, Eleftherios Margaritis a,2, Polyvios Giannakopoulos a,3, Dimitrios Douniadakis a,4, Michael Tsakanikos a,5 a b
ENT Department of Pediatric Hospital ‘‘Aglaia Kyriakou’’, Thivon & Levadias Street, GR-11527, Athens,Greece ENT Department of Tzanion General Hospital, 11 Zani & Afentouli Street, GR-18536, Piraeus,Greece
A R T I C L E I N F O
A B S T R A C T
Article history: Received 19 January 2011 Received in revised form 6 February 2011 Accepted 9 February 2011
Objective: Chloral hydrate (CH) is an oral sedative widely used to sedate infants and young children during auditory brainstem response (ABR) testing. The aim of this study was to record effectiveness, complications and safety of CH as a sedative for ABR. Methods: From January of 2003 until December of 2007, 1903 children were tested for ABR, 568 of them being under the age of 6 months. CH (8%) was used for sedation at a dose of 40 mg/kg with a repeat dose, if necessary, for an adequate sedation, in 20–30 min. We recorded the effectiveness of CH as a sedative for ABR examination, as well as all complications related to the use of CH such as vomiting, rash, hyperactivity, respiratory distress and apnea. The statistical method used was the absolute and percentage frequency distribution of the occurrences. Results: Sedation with CH was necessary to perform testing in 1591 (83.6%) of the examined children. However, in the population of the examined infants, only 341 (60%) were sedated with CH, because the remaining 227 (40%) fell asleep by themselves. Complications included hyperactivity in 152 children (8%), minor respiratory distress in 10 children (0.4%), vomiting in 217 children (11.4%), apnea in 4 children (0.2%) and rash in 10 children (0.4%). The complications of hyperactivity, vomiting and rash resolved without any medical treatment. The apnea cases were managed effectively by supplying ventilation to the children via a mask in the presence of an anesthesiologist. Conclusions: The use of CH at a dose of 40 mg/kg up to 80 mg/kg is safe and effective when administered in a setting with adequate equipment and the presence of well trained personnel. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Chloral hydrate Auditory brainstem responses Apnea
1. Introduction Auditory brainstem responses (ABR) is an objective method of testing the auditory pathway and is especially useful in the detection of hearing loss in infants and young children that are not eligible for testing with puretone audiometry. Testing, however, must be performed with the child completely relaxed. In the case
* Corresponding author at: 23 Achaion Street – Ag. Paraskevi, GR-15343 Athens, Greece. Tel.: +30 210 600 4683; fax: +30 210 4592 671. E-mail addresses: [email protected] (E. Avlonitou), [email protected], [email protected] (D.G. Balatsouras), [email protected] (E. Margaritis), [email protected] (P. Giannakopoulos), [email protected] (D. Douniadakis), [email protected] (M. Tsakanikos). 1 5 Marathonos Street, Glifada, GR-16674 Athens, Greece. Tel.: +30 210 9619567. 2 Tel.: +30 210 77775611. 3 Tel.: +30 210 77775612. 4 Tel.: +30 210 77775613. 5 Tel.: +30 210 77775619. 0165-5876/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2011.02.010
of infants, this may be obtained, after feeding with milk. In most other cases, mild sedation is required to reduce anxiety. Chloral hydrate (CH) is a widely used oral sedative hypnotic drug which has been used for several decades in pediatrics for diagnostic procedures, such as ABR, computerized tomography or magnetic resonance imaging. CH is one of the oldest synthetic agents, considering that this substance was synthesized in 1832 [1]. It is administered orally or rectally and is rapidly absorbed from the gastrointestinal tract. CH is metabolized to trichloroethanol which is the active metabolite and is responsible for the hypnotic action [2]. The halflife of CH is short (a few minutes) whereas for trichloroethanol it is 8–12 h. It should be noticed that in infants, the half-life is 3–4 times greater than in older children [2,3]. The mechanism of the sedative action of CH is still unknown. It is believed that its sedative effect on the central nervous system is mediated by gamma aminobutyric acid-A receptors (GABA), since the use of flumazenil (a GABA antagonist) in treating cases with CH overdose, has been proven successful [4].
E. Avlonitou et al. / International Journal of Pediatric Otorhinolaryngology 75 (2011) 760–763
CH interacts with alcohol [5], anticoagulants [3], amitriptyline [1], flumazenil [4,6], furosemide [7], fluoxetine [8], as well as with other CNS suppressants [3] or stimulants [9]. The recommended dose for sedative action is 20–100 mg/kg, although for infants dose adjustment is required. Various side effects of CH have been reported [1,10] including vomiting, nausea, rash, hyperactivity, respiratory distress, apnea and arrhythmias, whereas some studies, based only on animal research, have reported that CH may have a carcinogenic effect [11,12]. In case of overdose, the first symptoms are ataxia and lethargy, further progressing to deep coma, which generally occurs within 1–2 h [3]. Deaths have been reported to occur after the ingestion of at least 5 g of CH [3]. The use of CH is not recommended in cases with a history of gastric ulcer, hepatic distress, breathing distress and porphyria [1]. In the audiology laboratory of our hospital, CH is being used for more than 2 decades, for the sedation of infants and young children examined by the ABR test. Although, CH is a widely used drug as a pediatric sedative, issues concerning its safety and efficacy continue to arise. Various relevant reports include only a limited number of subjects [e.g. 10,13]. The aim of this study was both to determine the effectiveness of CH in sedating, as well as to investigate the safety of its use in a large number of young children. 2. Methods The subjects of this study were 1903 children, who were examined with ABR at our audiology laboratory from January 2003 to December 2007. Five hundred and sixty-eight of these children were under 6 months of age whereas the remaining 1335 were older, with maximum age 14 years. According to our laboratory protocol, instructions were given to all parents to bring their children to the laboratory awake but drowsy and without having eaten for the last 3 h before the examination. In addition, the parents are asked to bring whatever food or drink consider appropriate, in order to mix it with CH. This commonly includes milk for infants and juice, milk, cream or yogurt for older children. Special emphasis is given to their medical history. Children with severe pulmonary disease and recent upper respiratory tract infection had their appointments rescheduled until they met the criteria for sedation. CH is given at a concentration of 8%. It is given at an initial dose of 40 mg/kg, with a repeat equal dose, if required, to obtain adequate sedation after 20–30 min. The maximum dose is 80 mg/ kg (with the total dose not exceeding 1 g), which is consistent with the American Academy of Pediatrics (AAP) sedation guidelines [14]. For infants under 6 months of age, the maximum dose was 40 mg/kg, and this was only given in cases where the infant had not fallen asleep spontaneously within 10–20 min. CH was mixed with a banana-flavored liquid, in order to improve its bitter taste. In the rare cases where the infant did not cooperate or repeatedly vomited, the sedative was inserted into its stomach via a nasogastric tube. After CH ingestion, the children remained in a quiet and dark room with their parents until they were fully asleep. Subsequently, the children were transferred to the examination room and the ABR test was begun. During the whole course of the examination, the children were under the care of a qualified sedation nurse who observed them for any complications occurring due to CH intake, such as apnea, breathing distress, cyanosis, vomiting, hyperactivity, or cardiac rate changes. Children with minor respiratory distress were connected to a pulse oximeter for observation of their blood saturation. Children presenting with cyanosis or apneas were immediately monitored with the guidelines suggested by AAP. The average time for the
761
Table 1 Data of sedation with chloral hydrate. Children 6 months (N = 568)
Children > 6 months (N = 1335)
1st dose of CH 2nd dose CH if required
40 mg/kg No
Time before 1st dose Time between 1st and 2nd dose Success rate of first dose Total time of preparation and examination
15 5 min –
40 mg/kg 40 mg/kg (total dose not exceeding 1 g) No delay 24 7 min
100% 34 14 min
72% (961/1335 children) 49 22 min
preparation and measurement of ABR was about 40–50 min. Following the end of the ABR examination the children remained in the audiology laboratory under the supervision of the sedation nurse until they recovered from sedation. Subsequently, instructions were given to the parents and then the children were sent home. The statistical method used for the results of the study was the absolute and percentage distribution of occurrences. 3. Results Of the 1903 children examined by ABR, 1586 (83.3%) were sedated by CH, whereas 312 (16.4%) were quite relaxed to avoid sedation during testing and 5 (0.3%) couldn’t be sedated with CH. Considering the group of the 568 infants under the age of 6 months, CH sedation was needed in a smaller percentage (60%) of subjects (341 infants), whereas the remaining 227 (40%) fell asleep spontaneously. In the second group of the 1335 children over the age of 6 months, 1245 (93.2%) required sedation with CH, only 85 (6.4%) slept spontaneously and another 5 (0.4%) required sedation intravenously. Our data of CH administration are shown in Table 1. It should be mentioned, that a naso-gastric tube for the administration of CH was used in 50 children (2.6%) over the age of 3.5 years who could not take the CH orally or those who were hyperactive or vomited. The final results, considering the sedating effect of CH, indicated a success rate of 99.7%. Complications were observed in 393 (20.6)% out of the 1903 children (Table 2). 4. Discussion The development and clinical application of otoacoustic emissions marked the beginning of a new era in the field of screening for congenital hearing loss, because it allowed for an objective evaluation of hearing almost as soon as the babies were born [15,16]. A step further was the application of automated auditory brainstem responses, which is more time consuming, but it is generally reported to obtain a lower referral rate [17]. Combination of these two methods permits objective evaluation of both cochlear and retrocochlear hearing, and even newborns at risk for auditory neuropathy may be identified. Routine use of these methods in newborns, does not demand use of sedatives, but neverthless sedation is necessary in performing diagnostic ABR. Table 2 Side effects of CH sedation used for ABR testing. Side effect
Number of children
Percentage
Hyperactivity Vomiting Rash Minor breathing distress Apnea
152 217 10 10 4
8% 11.4% 0.5% 0.5% 0.2%
762
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Application of diagnostic ABR has not been decreased in the modern era, because this method is the gold standard in audiological diagnosis in infants and children. Additionally, universal application of hearing screening programs, results in a large number of dubious cases, which should be further examined, to conclude if these are truly positive or false positive cases. Accordingly, use of diagnostic ABR under sedation is nowadays even more common than in the past, and the issue of the appropriate sedative, and specifically their efficacy and safety, are always interesting. CH is the most widely used sedative agent in children, and we performed this study to evaluate its efficacy and safety in a great number of subjects, because literature is lacking in large scale studies. In the present study, we obtained to sedate the majority (83.6%) of children under examination with ABR, by using only CH. It appears, thus, that CH is an effective medication for this task. These results correspond well with those obtained in various other studies, although we have examined a significantly greater number of children. Hijazi et al. [13] found that 79% of children were sedated effectively with CH, at an average dose of 56.9 9.3 mg, whereas after a second dose of 18.5 6.4 mg, the success rate rose to 95%. In a study of children undergoing CT and MRI imaging, Vade et al. [18] found that CH sedation was successful in 100% for all the children having CT, and 100% for children 1–4 years old and 97% for children less than 1 year old for the children having MRI. In smaller scale studies, Allegaert et al. [19] obtained meaningful ABR results in all of the examined infants, and furthermore, Reich and Wiatrak [20] sedated 17 out of 18 patients with CH and in only one child, an additional drug was required for sedation. From our results, it appears that CH is a safe drug. Although complications were observed in 20.7% of the examined children, most of them subsided without demanding medical treatment. The most common complications included hyperactivity, vomiting and rash, accounting for a rate of 19.9% of the children, and only the remaining 0.7% of the patients presented with minor breathing distress (0.5%) and apnea (0.2%). Children with one of the former minor complications were placed under observation for about 2 h and then returned home without any further undesirable side effects being observed. In the 10 cases (0.5%) where a minor level of breathing distress was observed, the children were awakened, placed on their side and supplementary oxygen was given. The most serious side effect related to CH use was apnea, which occurred in only 4 patients (0.2%). Of these, in 3 of the children the apnea lasted for less than 15 s, and blood saturation remained above 88%. These three apneas were resolved spontaneously. After the resolution of the apnoic episodes, blood saturation and vital signs were monitored, while supplementary oxygen was given to the children under the supervision of an anesthesiologist. However, the fourth case was more serious, with the blood saturation dropping below 85% and the child was immediately transferred to the recovery section of the surgical headquarters. Oxygen ventilation was supplied via a mask, while the vital signs were monitored and observed by the anesthesiologists until the total recovery of the child. It may be, thus, concluded that although apnea is a rare complication of CH use, medical personnel trained in cardiopulmonary resuscitation and the use of standard monitoring equipment is recommended for the safe administration of sedation. From the data recorded above, it can be seen that sedation with an 8% concentration of CH at a dose of 40 mg/kg, and if needed, increasing up to 80 mg/kg (maximum dose) is an effective method with a relatively low rate of unwanted side effects. The issue of CH dose for adequate sedation has been extensively discussed. Reich and Wiatrak [20] in a survey of 75 Children’s American Hospitals using appropriate questionnaires, found that in 32% of the surveyed practitioners, 32% used 50 mg/kg and 29% administered
up to 75 mg/kg. However, the dosages of the rest varied widely and in one case a maximum dose of 2000 mg was administered. Repetitive doses of CH may be used occasionally to maintain prolonged sedation in infants and children during mechanical ventilation and this practice may arise concern, due to accumulation of active metabolites [14]. However, when CH is routinely used to obtain sedation for the performance of ABR, more than one dose repetition is rarely needed. On the other hand, overdose is a major concern, because it includes liver disease, gastric irritation, cardiac irritability and central nervous system depression [7]. Even deaths due to CH overdose after more than 10 g have been taken were reported [21,22], but most of these consequences have been primarily documented in adults [23], with rare exceptions [24]. A serious concern regarding the use of CH as a standard sedative in children is its potential carcinogenicity, based on the assumption that CH is a reactive metabolite of trichloroethylene, which is an industrial solvent carcinogenic in some laboratory animal species [14,25,26]. Studies with mice have shown that CH occasionally induced liver disease, adenomas or tumors, attributed to its metabolite trichloracetic acid. Very high doses of CH have been reported to cause aneuploidy, a term denoting alteration of the number of chromosomes in the cellular level. However, CH does not cross-link DNA or proteins in vitro, suggesting that it is minimally or non genotoxic. Multiple epidemiologic studies in humans have failed to document an increase in cancer incidence associated with trichloroethylene exposure [27,28]. In conclusion, CH is an effective sedative for children, which is safe at doses of 40–80 mg/kg, provided that it is used in a hospital setting, with appropriately trained staff and cardiopulmonary resuscitation facilities, following the AAP guidelines.
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