Effects of ketamine and ketamine with midazolam on emergence agitation in children following sevoflurane anesthesia
Keywords:
emergence agitation; ketamine; sevoflurane;Abstract
Background:
Emergence agitation is a distressful phenomenon
associated with inhalational agents such as
Sevoflurane in short surgical procedures. Various
drugs have been used in the past but some come at
the cost of increased complications. We aim to study
the effects of ketamine alone and ketamine with
midazolam on emergence agitation and their effects
on recovery and discharge times.
Methods:
We conducted a prospective randomized controlled
trial among 94 patients aged two to ten years
presenting for ophthalmic surgeries in which 45
patients were allocated to each group: group K
(Ketamine) and group KM (Ketamine with
Midazolam). Group K received Ketamine 0.3 mg/kg
IV and Group KM received Ketamine 0.3 mg/kg IV
and Midazolam 0.03 mg/kg IV. Intraoperatively heart
rate and post-operatively emergence agitation,
recovery times, discharge times were studied.
Results:
Demographic variables were comparable between
the two groups. Median Pediatric Anesthesia
Emergence Delirium score of 6 with IQR (4-6)
in group K was comparable to the median score of 5
with IQR (4-6) in group KM. The mean recovery time
of 22±4.82 min in group K was significantly lower
compared to the mean time of 25.75±3.32 min in
group KM. Mean time to discharge of 67±11 min
from the hospital in group K was significantly shorter
compared to that in group KM (108±18 mins).
Conclusion:
We concluded from our study that ketamine alone is
as effective as ketamine with midazolam in reducing
the emergence agitation following Sevoflurane
anesthesia for ophthalmic surgery.
References
1. Aono J, Ueda W, Mamiya K, Takimoto E,
Manabe M. Greater incidence of delirium during
recovery from sevoflurane anesthesia in
preschool boys. Anesthesiology. 1997
Dec;87(6):1298–300.
https://doi.org/10.1097/00000542-199712000-
00006
PMid:9416712
2. Welborn LG, Hannallah RS, Norden JM,
Ruttimann UE, Callan CM. Comparison of
emergence and recovery characteristics of
sevoflurane, desflurane, and halothane in
pediatric ambulatory patients. Anesth Analg.
1996 Nov;83(5):917–20.
https://doi.org/10.1213/00000539-199611000-
00005
PMid:8895263
3. Lerman J, Davis PJ, Welborn LG, Orr RJ, Rabb
M, Carpenter R, et al. Induction, recovery, and
safety characteristics of sevoflurane in children
undergoing ambulatory surgery. A comparison
with halothane. Anesthesiology. 1996
Jun;84(6):1332–40.
https://doi.org/10.1097/00000542-199606000-
00009
PMid:8669674
4. Viitanen H, Annila P, Viitanen M, Yli-Hankala a.
Midazolam premedication delays recovery from
propofol-induced sevoflurane anesthesia in
children 1-3 yr. Can J Anaesth. 1999;46(8):766–
71.
https://doi.org/10.1007/BF03013912
PMid:10451136
5. Cohen IT, Finkel JC, Hannallah RS, Hummer KA,
Patel KM. The effect of fentanyl on the
emergence characteristics after desflurane or
sevoflurane anesthesia in children. Anesth Analg.
2002;94.
https://doi.org/10.1097/00000539-200205000-
00023
6. Wells LT, Rasch DK. Emergence "delirium" after
sevoflurane anesthesia: a paranoid delusion?
Anesth Analg. 1999 Jun;88(6):1308–10.
https://doi.org/10.1213/00000539-199906000-
00020
PMid:10357335
7. Grundmann U, Uth M, Eichner A, Wilhelm W,
Larsen R. Total intravenous anaesthesia with
propofol and remifentanil in paediatric patients:
a comparison with a desflurane-nitrous oxide
JSAN 2017; 4(2):57-65
Journal of Society of Anesthesiologists of Nepal
64
inhalation anaesthesia. Acta Anaesthesiol Scand.
1998 Aug;42(7):845–50.
https://doi.org/10.1111/j.1399-
6576.1998.tb05332.x
PMid:9698963
8. Davis PJ, Cohen IT, McGowan FX, Latta K.
Recovery characteristics of desflurane versus
halothane for maintenance of anesthesia in
pediatric ambulatory patients. Vol. 80,
Anesthesiology. 1994.
https://doi.org/10.1097/00000542-199402000-
00009
PMid:8311312
9. Johannesson GP, Florén M, Lindahl SG.
Sevoflurane for ENT-surgery in children. A
comparison with halothane. Acta Anaesthesiol
Scand. 1995 May;39(4):546–50.
https://doi.org/10.1111/j.1399-
6576.1995.tb04116.x
PMid:7676795
10. Viitanen H, Annila P, Viitanen M, Yli-Hankala
A. Midazolam premedication delays recovery
from propofol-induced sevoflurane anesthesia in
children 1-3 yr. Vol. 46, Canadian journal of
anaesthesia = Journal canadien d'anesthesie.
1999.
11. Kim MS, Moon BE, Kim H, Lee JR, Hemmings
HC. Comparison of propofol and fentanyl
administered at the end of anaesthesia for
prevention of emergence agitation after
sevoflurane anaesthesia in children. Br J Anaesth.
2013;110(2):274–80.
https://doi.org/10.1093/bja/aes382
PMid:23103775
12. Galinkin JL, Fazi LM, Cuy RM, Chiavacci RM,
Kurth CD, Shah UK, et al. Use of intranasal
fentanyl in children undergoing myringotomy and
tube placement during halothane and
sevoflurane anesthesia. Anesthesiology. 2000
Dec;93(6):1378–83.
https://doi.org/10.1097/00000542-200012000-
00006
PMid:11149429
13. Cravero J, Surgenor S, Whalen K. Emergence
agitation in paediatric patients after sevoflurane
anaesthesia and no surgery: a comparison with
halothane. Paediatr Anaesth. 2000
Jan;10(4):419–24.
https://doi.org/10.1046/j.1460-
9592.2000.00560.x
PMid:10886700
14. Beskow A, Westrin P. Sevoflurane causes
more postoperative agitation in children than
does halothane. Acta Anaesthesiol Scand. 1999
May;43(5):536–41.
https://doi.org/10.1034/j.1399-
6576.1999.430508.x
PMid:10342001
15. Khattab AM, El-Seify ZA. Sevofluraneemergence
agitation: Effect of supplementary
low-dose oral ketamine premedication in
preschool children undergoing dental surgery.
Saudi J Anaesth. 2009;3:61–6.
https://doi.org/10.4103/1658-354X.57878
PMid:20532105 PMCid:PMC2876942
16. Zhang C, Li J, Zhao D, Wang Y. Prophylactic
midazolam and clonidine for emergence from
agitation in children after emergence from
sevoflurane anesthesia: a meta-analysis. Clin
Ther. 2013 Oct;35(10):1622–31.
https://doi.org/10.1016/j.clinthera.2013.08.016
PMid:24075150
17. Ko YP, Huang CJ, Hung YC, Su NY, Tsai PS,
Chen CC, et al. Premedication with low-dose oral
midazolam reduces the incidence and severity of
emergence agitation in pediatric patients
following sevoflurane anesthesia. Acta
Anaesthesiol Sin. 2001 Dec;39(4):169–77.
PMid:11840583
18. Chen JY, Jia JE, Liu TJ, Qin MJ, Li WX.
Comparison of the effects of dexmedetomidine,
ketamine, and placebo on emergence agitation
after strabismus surgery in children. Can J Anesth.
2013;60:385–92.
https://doi.org/10.1007/s12630-013-9886-x
PMid:23344921
19. Dahmani S, Stany I, Brasher C, Lejeune C,
Bruneau B, Wood C, et al. Pharmacological
prevention of sevoflurane and desflurane-related
emergence agitation in children: a meta-analysis
of published studies. Br J Anaesth. 2010
Feb;104(2):216–23.
https://doi.org/10.1093/bja/aep376
PMid:20047899
20. Bauer KP, Dom PM, Ramirez AM, O'Flaherty
JE. Preoperative intravenous midazolam: benefits
beyond anxiolysis. J Clin Anesth. 2004
May;16(3):177–83.
https://doi.org/10.1016/j.jclinane.2003.07.003
PMid:15217656
21. Gooden R, Tennant I, James B, Augier R,
Crawford-Sykes A, Ehikhametalor K, et al. The
incidence of emergence delirium and risk factors
following sevoflurane use in pediatric patients for
day case surgery, Kingston, Jamaica. Brazilian J
Anesthesiol. Jan;64(6):413–8.
22. Eckenhoff JE, Kneale DH, Dripps RD. The
incidence and etiology of postanesthetic
JSAN 2017; 4(2):57-65
Journal of Society of Anesthesiologists of Nepal
65
excitement. A clinical survey. Anesthesiology.
Jan;22:667–73.
23. Viitanen H, Annila P, Viitanen M, Tarkkila P.
Premedication with midazolam delays recovery
after ambulatory sevoflurane anesthesia in
children. Vol. 89, Anesthesia and analgesia. 1999.
24. Alomar MJ. Factors affecting the
development of adverse drug reactions (Review
article). Saudi Pharm J SPJ Off Publ Saudi Pharm
Soc. 2014 Apr;22(2):83–94.
https://doi.org/10.1016/j.jsps.2013.02.003
25. Lee YS, Kim WY, Choi JH, Son JH, Kim JH, Park
YC. The effect of ketamine on the incidence of
emergence agitation in children undergoing
tonsillectomy and adenoidectomy under
sevoflurane general anesthesia. Korean J
Anesthesiol. 2010 May;58(5):440–5.
https://doi.org/10.4097/kjae.2010.58.5.440
PMid:20532051 PMCid:PMC2881518
26. Aldrete JA, Kroulik D. A postanesthetic
recovery score. Anesth Analg. Jan;49(6):924–34.
27. Sikich N, Lerman J. Development and
psychometric evaluation of the pediatric
anesthesia emergence delirium scale.
Anesthesiology. 2004 May;100(5):1138–45.
https://doi.org/10.1097/00000542-200405000-
00015
PMid:15114210
28. Bajwa SA, Costi D, Cyna AM. A comparison of
emergence delirium scales following general
anesthesia in children. Paediatr Anaesth. 2010
Aug;20(8):704–11.
https://doi.org/10.1111/j.1460-
9592.2010.03328.x
PMid:20497353
29. Chung F. Discharge criteria--a new trend. Can
J Anaesth. 1995 Nov;42(11):1056–8.
https://doi.org/10.1007/BF03011083
PMid:8590498
30. Kim KM, Lee KH, Kim YH, Ko MJ, Jung J-W,
Kang E. Comparison of effects of intravenous
midazolam and ketamine on emergence agitation
in children: Randomized controlled trial. J Int
Med Res. 2016 Apr 1;44(2):258–66.
https://doi.org/10.1177/0300060515621639
PMid:26880794 PMCid:PMC5580063
31. Erk G, Örnek D, Dönmez NF, Taşpinar V. The
use of ketamine or ketamine-midazolam for
adenotonsillectomy. Int J Pediatr
Otorhinolaryngol. 2007;71(6):937–41.
https://doi.org/10.1016/j.ijporl.2007.03.004
PMid:17418428
32. Khattab AM, El-Seify ZA, Shaaban A, Radojevic
D, Jankovic I. Sevoflurane-emergence agitation:
effect of supplementary low-dose oral ketamine
premedication in preschool children undergoing
dental surgery. Eur J Anaesthesiol. 2010
Apr;27(4):353–8.
https://doi.org/10.1097/EJA.0b013e328335b2ec
PMid:20035226
33. Abu-Shahwan I, Chowdary K. Ketamine is
effective in decreasing the incidence of
emergence agitation in children undergoing
dental repair under sevoflurane general
anesthesia. Paediatr Anaesth. 2007
Sep;17(9):846–50.
https://doi.org/10.1111/j.1460-9592.2007.02298.x
PMid:17683402
34. Ozcan A, Kaya AG, Ozcan N, Karaaslan GM, Er
E, Baltaci B, et al. [Effects of ketamine and
midazolam on emergence agitation after
sevoflurane anaesthesia in children receiving
caudal block: a randomized trial]. Rev Bras
Anestesiol. Jan;64(6):377–81.
Manabe M. Greater incidence of delirium during
recovery from sevoflurane anesthesia in
preschool boys. Anesthesiology. 1997
Dec;87(6):1298–300.
https://doi.org/10.1097/00000542-199712000-
00006
PMid:9416712
2. Welborn LG, Hannallah RS, Norden JM,
Ruttimann UE, Callan CM. Comparison of
emergence and recovery characteristics of
sevoflurane, desflurane, and halothane in
pediatric ambulatory patients. Anesth Analg.
1996 Nov;83(5):917–20.
https://doi.org/10.1213/00000539-199611000-
00005
PMid:8895263
3. Lerman J, Davis PJ, Welborn LG, Orr RJ, Rabb
M, Carpenter R, et al. Induction, recovery, and
safety characteristics of sevoflurane in children
undergoing ambulatory surgery. A comparison
with halothane. Anesthesiology. 1996
Jun;84(6):1332–40.
https://doi.org/10.1097/00000542-199606000-
00009
PMid:8669674
4. Viitanen H, Annila P, Viitanen M, Yli-Hankala a.
Midazolam premedication delays recovery from
propofol-induced sevoflurane anesthesia in
children 1-3 yr. Can J Anaesth. 1999;46(8):766–
71.
https://doi.org/10.1007/BF03013912
PMid:10451136
5. Cohen IT, Finkel JC, Hannallah RS, Hummer KA,
Patel KM. The effect of fentanyl on the
emergence characteristics after desflurane or
sevoflurane anesthesia in children. Anesth Analg.
2002;94.
https://doi.org/10.1097/00000539-200205000-
00023
6. Wells LT, Rasch DK. Emergence "delirium" after
sevoflurane anesthesia: a paranoid delusion?
Anesth Analg. 1999 Jun;88(6):1308–10.
https://doi.org/10.1213/00000539-199906000-
00020
PMid:10357335
7. Grundmann U, Uth M, Eichner A, Wilhelm W,
Larsen R. Total intravenous anaesthesia with
propofol and remifentanil in paediatric patients:
a comparison with a desflurane-nitrous oxide
JSAN 2017; 4(2):57-65
Journal of Society of Anesthesiologists of Nepal
64
inhalation anaesthesia. Acta Anaesthesiol Scand.
1998 Aug;42(7):845–50.
https://doi.org/10.1111/j.1399-
6576.1998.tb05332.x
PMid:9698963
8. Davis PJ, Cohen IT, McGowan FX, Latta K.
Recovery characteristics of desflurane versus
halothane for maintenance of anesthesia in
pediatric ambulatory patients. Vol. 80,
Anesthesiology. 1994.
https://doi.org/10.1097/00000542-199402000-
00009
PMid:8311312
9. Johannesson GP, Florén M, Lindahl SG.
Sevoflurane for ENT-surgery in children. A
comparison with halothane. Acta Anaesthesiol
Scand. 1995 May;39(4):546–50.
https://doi.org/10.1111/j.1399-
6576.1995.tb04116.x
PMid:7676795
10. Viitanen H, Annila P, Viitanen M, Yli-Hankala
A. Midazolam premedication delays recovery
from propofol-induced sevoflurane anesthesia in
children 1-3 yr. Vol. 46, Canadian journal of
anaesthesia = Journal canadien d'anesthesie.
1999.
11. Kim MS, Moon BE, Kim H, Lee JR, Hemmings
HC. Comparison of propofol and fentanyl
administered at the end of anaesthesia for
prevention of emergence agitation after
sevoflurane anaesthesia in children. Br J Anaesth.
2013;110(2):274–80.
https://doi.org/10.1093/bja/aes382
PMid:23103775
12. Galinkin JL, Fazi LM, Cuy RM, Chiavacci RM,
Kurth CD, Shah UK, et al. Use of intranasal
fentanyl in children undergoing myringotomy and
tube placement during halothane and
sevoflurane anesthesia. Anesthesiology. 2000
Dec;93(6):1378–83.
https://doi.org/10.1097/00000542-200012000-
00006
PMid:11149429
13. Cravero J, Surgenor S, Whalen K. Emergence
agitation in paediatric patients after sevoflurane
anaesthesia and no surgery: a comparison with
halothane. Paediatr Anaesth. 2000
Jan;10(4):419–24.
https://doi.org/10.1046/j.1460-
9592.2000.00560.x
PMid:10886700
14. Beskow A, Westrin P. Sevoflurane causes
more postoperative agitation in children than
does halothane. Acta Anaesthesiol Scand. 1999
May;43(5):536–41.
https://doi.org/10.1034/j.1399-
6576.1999.430508.x
PMid:10342001
15. Khattab AM, El-Seify ZA. Sevofluraneemergence
agitation: Effect of supplementary
low-dose oral ketamine premedication in
preschool children undergoing dental surgery.
Saudi J Anaesth. 2009;3:61–6.
https://doi.org/10.4103/1658-354X.57878
PMid:20532105 PMCid:PMC2876942
16. Zhang C, Li J, Zhao D, Wang Y. Prophylactic
midazolam and clonidine for emergence from
agitation in children after emergence from
sevoflurane anesthesia: a meta-analysis. Clin
Ther. 2013 Oct;35(10):1622–31.
https://doi.org/10.1016/j.clinthera.2013.08.016
PMid:24075150
17. Ko YP, Huang CJ, Hung YC, Su NY, Tsai PS,
Chen CC, et al. Premedication with low-dose oral
midazolam reduces the incidence and severity of
emergence agitation in pediatric patients
following sevoflurane anesthesia. Acta
Anaesthesiol Sin. 2001 Dec;39(4):169–77.
PMid:11840583
18. Chen JY, Jia JE, Liu TJ, Qin MJ, Li WX.
Comparison of the effects of dexmedetomidine,
ketamine, and placebo on emergence agitation
after strabismus surgery in children. Can J Anesth.
2013;60:385–92.
https://doi.org/10.1007/s12630-013-9886-x
PMid:23344921
19. Dahmani S, Stany I, Brasher C, Lejeune C,
Bruneau B, Wood C, et al. Pharmacological
prevention of sevoflurane and desflurane-related
emergence agitation in children: a meta-analysis
of published studies. Br J Anaesth. 2010
Feb;104(2):216–23.
https://doi.org/10.1093/bja/aep376
PMid:20047899
20. Bauer KP, Dom PM, Ramirez AM, O'Flaherty
JE. Preoperative intravenous midazolam: benefits
beyond anxiolysis. J Clin Anesth. 2004
May;16(3):177–83.
https://doi.org/10.1016/j.jclinane.2003.07.003
PMid:15217656
21. Gooden R, Tennant I, James B, Augier R,
Crawford-Sykes A, Ehikhametalor K, et al. The
incidence of emergence delirium and risk factors
following sevoflurane use in pediatric patients for
day case surgery, Kingston, Jamaica. Brazilian J
Anesthesiol. Jan;64(6):413–8.
22. Eckenhoff JE, Kneale DH, Dripps RD. The
incidence and etiology of postanesthetic
JSAN 2017; 4(2):57-65
Journal of Society of Anesthesiologists of Nepal
65
excitement. A clinical survey. Anesthesiology.
Jan;22:667–73.
23. Viitanen H, Annila P, Viitanen M, Tarkkila P.
Premedication with midazolam delays recovery
after ambulatory sevoflurane anesthesia in
children. Vol. 89, Anesthesia and analgesia. 1999.
24. Alomar MJ. Factors affecting the
development of adverse drug reactions (Review
article). Saudi Pharm J SPJ Off Publ Saudi Pharm
Soc. 2014 Apr;22(2):83–94.
https://doi.org/10.1016/j.jsps.2013.02.003
25. Lee YS, Kim WY, Choi JH, Son JH, Kim JH, Park
YC. The effect of ketamine on the incidence of
emergence agitation in children undergoing
tonsillectomy and adenoidectomy under
sevoflurane general anesthesia. Korean J
Anesthesiol. 2010 May;58(5):440–5.
https://doi.org/10.4097/kjae.2010.58.5.440
PMid:20532051 PMCid:PMC2881518
26. Aldrete JA, Kroulik D. A postanesthetic
recovery score. Anesth Analg. Jan;49(6):924–34.
27. Sikich N, Lerman J. Development and
psychometric evaluation of the pediatric
anesthesia emergence delirium scale.
Anesthesiology. 2004 May;100(5):1138–45.
https://doi.org/10.1097/00000542-200405000-
00015
PMid:15114210
28. Bajwa SA, Costi D, Cyna AM. A comparison of
emergence delirium scales following general
anesthesia in children. Paediatr Anaesth. 2010
Aug;20(8):704–11.
https://doi.org/10.1111/j.1460-
9592.2010.03328.x
PMid:20497353
29. Chung F. Discharge criteria--a new trend. Can
J Anaesth. 1995 Nov;42(11):1056–8.
https://doi.org/10.1007/BF03011083
PMid:8590498
30. Kim KM, Lee KH, Kim YH, Ko MJ, Jung J-W,
Kang E. Comparison of effects of intravenous
midazolam and ketamine on emergence agitation
in children: Randomized controlled trial. J Int
Med Res. 2016 Apr 1;44(2):258–66.
https://doi.org/10.1177/0300060515621639
PMid:26880794 PMCid:PMC5580063
31. Erk G, Örnek D, Dönmez NF, Taşpinar V. The
use of ketamine or ketamine-midazolam for
adenotonsillectomy. Int J Pediatr
Otorhinolaryngol. 2007;71(6):937–41.
https://doi.org/10.1016/j.ijporl.2007.03.004
PMid:17418428
32. Khattab AM, El-Seify ZA, Shaaban A, Radojevic
D, Jankovic I. Sevoflurane-emergence agitation:
effect of supplementary low-dose oral ketamine
premedication in preschool children undergoing
dental surgery. Eur J Anaesthesiol. 2010
Apr;27(4):353–8.
https://doi.org/10.1097/EJA.0b013e328335b2ec
PMid:20035226
33. Abu-Shahwan I, Chowdary K. Ketamine is
effective in decreasing the incidence of
emergence agitation in children undergoing
dental repair under sevoflurane general
anesthesia. Paediatr Anaesth. 2007
Sep;17(9):846–50.
https://doi.org/10.1111/j.1460-9592.2007.02298.x
PMid:17683402
34. Ozcan A, Kaya AG, Ozcan N, Karaaslan GM, Er
E, Baltaci B, et al. [Effects of ketamine and
midazolam on emergence agitation after
sevoflurane anaesthesia in children receiving
caudal block: a randomized trial]. Rev Bras
Anestesiol. Jan;64(6):377–81.
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Published
2018-08-06
How to Cite
Sharma, A., & Rana, R. B. (2018). Effects of ketamine and ketamine with midazolam on emergence agitation in children following sevoflurane anesthesia. Journal of Society of Anesthesiologists of Nepal, 4(2), 57-65. Retrieved from http://www.jsan.org.np/jsan/index.php/jsan/article/view/198
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