Journal of Research in Pharmacy Practice

Midazolam premedication for Ketamine-induced emergence phenomenon: A prospective observational study

Authors

. Deepa Kameswari Perumal 1
. Mangaiarkkarasi Adhimoolam 1
. Nitya Selvaraj 1
. Suneeth Pullikotil Lazarus 2
. Meher Ali Raja Mohammed 1

1 Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India

2 Department of Anesthesia, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India

Abstract
Objective: Ketamine administration is known to induce hemodynamic pressor response 
and psychomimetic effects which could be attenuated by appropriate premedication. The 
present study was designed to evaluate the effect of midazolam on hemodynamic stability 
and postoperative emergence phenomenon following ketamine anesthesia.
Methods: This was a prospective observational study including 30 adult patients with 
American Society of Anesthesiologists physical grades I and II scheduled for elective 
short surgeries under ketamine anesthesia. Patients were premedicated with midazolam 
(0.02 mg/kg intravenously) before the ketamine induction (1 mg/kg intravenously). 
Demographic data and hemodynamic variables were observed during the perioperative 
period. Pain score by visual analog scale score and psychomimetic effects were recorded 
postoperatively.
Findings: The mean ± standard deviation of heart rate, systolic blood pressure, diastolic 
blood pressure, and respiratory rate were decreased postoperatively (85.3 ± 11.4, 120.7 ± 8.2, 
79.2 ± 5.5, 13.5 ± 1.8, respectively) compared to intraoperative period (88.53 ± 14.1, 
123.83 ± 13.8, 83 ± 9.1, 14.13 ± 2.0, respectively). There was statistically significant decrease 
in systolic (P = 0.03) and diastolic (P = 0.002) blood pressure, but not with heart rate and 
respiratory rate. Eighty percent of patients had no pain at ½ hour and 1 hour, while this 
increased to 90% at 2 hours postoperatively. Mild emergence delirium was noted in 13.3% and 
16.7% at ½ hour and 1 hour, respectively, which decreased to 13.3% at 2 hours. Dreams were 
noticed in 20%, 27% and 10% of patients at ½ hour, 1 and 2 hours after surgery, respectively.
Conclusion: Midazolam premedication in ketamine anesthesia effectively attenuated 
the hemodynamic pressor response and postoperative emergence phenomenon. Hence, 
the combination of midazolam with ketamine can be safely used for short surgical painful 
procedures in adults.

Keywords

Emergence phenomenon
Ketamine anesthesia
Midazolam
premedication
1. Sawhney S, Agarwal RP. Combination of low dose ketamine 
and pentazocine – A clinical experience. Indian J Anaesth 
2003;47:439‑42.
2. WhitePF, HamJ, WayWL, TrevorAJ. Pharmacology of ketamine 
isomers in surgical patients. Anesthesiology 1980;52:231‑9.
3. Somashekara SC, Govindadas D, Devashankaraiah G, 
Mahato R, Deepalaxmi S, Srinivas V, et al. Midazolam 
premedication in attenuating ketamine psychic sequelae. 
J Basic Clin Pharm 2010;1:209‑13.
4. Kain ZN, Mayes LC, Bell C, Weisman S, Hofstadter MB, 
Rimar S. Premedication in the United States: A status report. 
Anesth Analg 1997;84:427‑32.
5. Deng XM, Xiao WJ, Luo MP, Tang GZ, Xu KL. The use 
of midazolam and small‑dose ketamine for sedation and 
analgesia during local anesthesia. Anesth Analg 2001;93:1174‑7.
6. Gupta K, Gupta A, Gupta PK, Rastogi B, Agarwal S, 
Lakhanpal M. Dexmedetomidine premedication in relevance 
to ketamine anesthesia: Aprospective study. Anesth Essays Res 
2011;5:87‑91.
7. Tobias JD. Dexmedetomidine and ketamine: An effective 
alternative for procedural sedation? Pediatr Crit Care Med 
2012;13:423‑7.
8. Warden V, Hurley AC, Volicer L. Development and 
psychometric evaluation of the Pain Assessment in Advanced 
Dementia (PAINAD) scale. J Am Med Dir Assoc 2003;4:9‑15.
9. Chudnofsky CR, Weber JE, Stoyanoff PJ, Colone PD, 
WilkersonMD, Hallinen DL, et al. Acombination of midazolam 
and ketamine for procedural sedation and analgesia in adult 
emergency department patients. Acad Emerg Med 2000;7:228‑35.
10. Kurdi MS, Theerth KA, Deva RS. Ketamine: Current 
applications in anesthesia, pain, and critical care. Anesth 
Essays Res 2014;8:283‑90.
11. Mion G, Villevieille T. Ketamine pharmacology: An update 
(pharmacodynamics and molecular aspects, recent findings). 
CNS Neurosci Ther 2013;19:370‑80.
12. Orser BA, Pennefather PS, MacDonald JF. Multiple 
mechanisms of ketamine blockade of N‑methyl‑D‑aspartate 
receptors. Anesthesiology 1997;86:903‑17.
13. Levänen J, Mäkelä ML, Scheinin H. Dexmedetomidine 
premedication attenuates ketamine‑induced cardiostimulatory 
effects and postanesthetic delirium. Anesthesiology 
1995;82:1117‑25.
14. Sener S, Eken C, Schultz CH, Serinken M, OzsaracM. Ketamine 
with and without midazolam for emergency department 
sedation in adults: A randomized controlled trial. Ann Emerg 
Med 2011;57:109‑14.e2.
15. Kolhe EP, Dhumal PR, Kurhekar VA. Comparative study of 
midazolam and diazepam to supplement ketamine as total 
intravenous anaesthesia in short orthopedic procedures. Int 
J Pharm Biomed Res 2013;4:15‑20.
16. Mihic JS, Harris RA. Hypnotics and sedatives. In: Brunton LL, 
Chabner BA, Knollman BC, editors. Goodman and Gilman’s 
Pharmacological Basis of Therapeutics. 12th ed. New York: 
McGraw‑Hill; 2011. p. 457‑80.
17. Gupta R, Sharma K, Dhiman UK. Effect of a combination of 
oral midazolam and low‑dose ketamine on anxiety, pain, 
swelling, and comfort during and after surgical extractions 
of mandibular third molars. Indian J Dent Res 2012;23:295‑6.
18. Gündüz M, Sakalli S, Günes Y, Kesiktas E, Ozcengiz D, Isik G. 
Comparison of effects of ketamine, ketamine‑dexmedetomidine 
and ketamine‑midazolam on dressing changes of burn 
patients. J Anaesthesiol Clin Pharmacol 2011;27:220‑4.
19. Lohit K, Srinivas V, Kulkarni C, Shaheen. A clinical 
evaluation of the effects of administration of midazolam on 
ketamine‑induced emergence phenomenon. J Clin Diagn Res 
2011;5:320‑3.
20. Ramoska EA, Linkenheimer R, Glasgow C. Midazolam use 
in the emergency department. J Emerg Med 1991;9:247‑51.
Journal of Research in Pharmacy Practice
Volume 4, Issue 2
Spring 2015
Pages 89-93

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