Appendix 1.
Table 6. Excluded studies
Study
Ratio
(K:P)
Regimen
Details
Akin[1]
Child bolus
Nonrandomized
trial
n 30, 1 – 13 y
ABR
1:3
Andolfatto[2]
2010
Adult bolus
PCS
n 219, 1 – 20 y
PSA in ED
1:1
Andolfatto[3]
2011
Adult bolus
PCS
n 728,
21 – 99 y
PSA in ED
1:1
Aouad[4]
Child bolus
DB-RCT
n 33, 3 – 9 y
LP or BMA
1:1
Adult IVI
- 50 min
DB-RCT
n 100,
50 – 55 y,
breast biopsy
Three ratios of
KP via IVI
1:3.3
1:5
1:10
Badrinath[5]
David,
Shipp[6]
Method
LD = K 0.5, P
1.5 mg/kg
+ aliquots ½ LD
PRN titrated to
sedation level
K/P 0.5 mg⁄kg
PRN aliquots
Q30-60 sec
titrated to
sedation level
K/P 0.125 – 0.25
mg⁄kg PRN
aliquots Q30-60
sec
titrated to
sedation level
LD K/P 0.5
mg/kg
+ aliquots of P
0.5 mg/kg PRN
Q1 – 2 min
LD = 0.3 mg/kg
of P component
IVI 6 mg/kg/h of
P component,
titrated Q1 – 3
min by +/- 1.5
mg/kg/h
Exclusion reasons
No report of recovery times
48% received pre-procedural or
adjuvant sedation or analgesia,
mostly IV morphine
Frequency, size and duration of
dosing not reported
48% received pre-procedural or
adjuvant sedation or analgesia,
mostly IV morphine
All patients given fentanyl as part of
PSA
Fentanyl also given during PSA
All had 2 mg IV midazolam premedication and sufentanil 2.5 μg IV
‘rescue’ boluses in up to 40% of
patients per group
LD =
1:2
LD K 0.5, P 1.0
mg/kg
+ aliquots of P
0.5 mg/kg PRN
All patients given fentanyl five min
before KP
No defined age groups or per kilo
dosing of subsequent P recorded
Recovery times not reported
All patients received suxamethonium
and were post-ictal on recovery
Child &
Adult bolus
DB-RCT
n 97, 2 – 83 y
Erdogan
Kayhan[7]
Adult bolus
DB-RCT
n 24, 18 – 65 y
ECT
1:1
LD = K/P 0.5
mg/kg
+ extra PRN 0.4
mg/kg in 74% of
cases
Frey[8]
Adult bolus
n 33, > 65 y
Retro-bulbar
nerve blocks
1:3.3
LD = K 0.085, P
0.28 mg/kg
Frizelle[9]
Adult IVI
- 42 min
n 20, 38 – 72 y
RA for uro. or
ortho. surgery
1:4
LD = K 0.1, P
0.4 mg/kg,
IVI = K 0.42, P
1.68 mg/kg/h
Messenger[10]
Adult bolus
DB-RCT
n 32, 14 – 65 y
PSA in ED
1:5*
Mortero[11]
Adult IVI
- 37 min
RCT
n 19, 22 – 54 y
Day surgery
procedures
1:10
LD = K 0.3, P
0.4 mg/kg
+ aliquots P 0.1
mg/kg Q30 sec
PRN
(Ave. total P 1.5
mg/kg)
Per-kilo LD not
reported
IVI = K 0.22, P
1.98 mg/kg/h
Elderly patients. midazolam or
fentanyl given 'at discretion' but not
recorded
All patients received hydroxyzine
100 mg premedication
No times given
Low dose KP was adjunct for spinal
anesthesia
Pre-med opiates in 38% followed by
30 min washout period
Only outcome time given is
‘recovery time’, defined as
‘discharge readiness’ rather than
consciousness – PKPD model not
designed to predict this
All patients given midazolam and
fentanyl pre-medication
Recovery time not recorded precisely
1:4
LD = K 0.1, P
0.4 mg/kg
IVI = K 0.3, P
1.2 mg/kg/h
All given premedication alprazolam
0.25 mg in the morning, spinal
anesthesia was given, then KP started
– hence very low dose. IVI time too
long
1:1
Per-kilo dosing
not reported
No reporting of recovery times
Nengroo[12]
Adult IVI
- 59 min
n 30, 17 – 75 y
RA for uro.
surgery
IVI – 59 min
Phillips[13]
Adult bolus
PCS
n 14, > 21 y
PSA in ED
Shah[14]
Child bolus
n 67, 2 – 17 y
PSA in ED
1:1
Sharieff[15]
Child bolus
n 20, 3 – 15 y
PSA in ED
1:2
Singh[16]
Child IVI
- 68 min
RCT
n 20, 3 – 8 y
RA for lower
abdo surgery
1:4
Tomatir[17]
Tosun[18]
Child IVI
– 27 min
n 23, 8 m – 6 y
Sedation for
MRI
Child Bolus
DB-RCT
n 46, 1 – 16 y
Gastroscopy
1:3
(LD)
1:1.2
LD = K 0.5, P
0.5 mg/kg
+ aliquots of P
0.5 mg/kg PRN
LD K 0.5, P 1.0
mg/kg
LD = K 0.4, P
1.6 mg/kg
IVI = K 0.8, P
3.2 mg/kg/h,
titrated to
sedation level
LD = K 0.5, P
1.5 mg/kg
IVI = P 4.5
mg/kg/h
LD = K 1.0, P
1.2 mg/kg
+ aliquots of P
0.5 – 1 mg/kg
PRN
LD = K/P 1.7
mg/kg
IVI = K/P 0.72 –
1.68 mg/kg/h
46% given opiate pre-PSA
Subsequent top-up doses were either
K or P or both – details not reported
'All children were awake within 10
min of IVI discontinuation' - no
definition or further details given
Low-dose propofol sedation preceded
by LD of ketamine. Combined model
predicts 50% of all age groups awake
before pump stopped but not
designed to investigate single agent
effects
Propofol top-up amount and timing
not reported
Unclear reporting of recovery times
PCS
n 18, 4 – 17 y
Mean length of IVI 2.5 hours –
Weatherall[19]
1:1
ortho. surgery
beyond scope of ED PSA
+ RA
PCS
1 - 3 mL aliquots 38% given opiate premed, mostly
Willman,
n 114,
Adult bolus
1:1
(0.14 - 0.42
morphine without washout period.
Andolfatto[20]
20 – 58 y
mg/kg) PRN
Recovery time not reported
PSA in ED
DB-RCT
Per-kilo dosing
All patients received suxamethonium
Yalcin[21]
Adult bolus
n 30, 20 – 35 y 1:1
not reported
and were post-ictal on recovery
ECT
ABR= auditory brainstem response testing, AD= anesthesia duration (time from first dose until recovery), BMA =
bone marrow aspiration, DB = double blind, ECT = electro-convulsive therapy, ED = emergency department, IVI
= infusion, K = ketamine, LD = loading dose, LP = lumbar puncture, P = propofol, PCS = prospective case series,
PRN = pro re nata (as required), PSA = procedural sedation/ analgesia, RA = regional anesthesia (epidural or
spinal), RCT = randomized control trial, RT = recovery time (time fromlast dose until consciousness).
Child &
Adult IVI
– 154 min
References
1. Akin A, Esmaoglu A, Tosun Z, et al. Comparison of propofol with propofolketamine combination in pediatric patients undergoing auditory brainstem response
testing. Int J Pediatr Otorhinolaryngol 2005;69:1541-5.
2. Andolfatto G, Willman E. A prospective case series of pediatric procedural
sedation and analgesia in the emergency department using single-syringe ketaminepropofol combination (ketofol). Acad Emerg Med 2010;17:194-201.
3. Andolfatto G, Willman E. A prospective case series of single-syringe ketaminepropofol (Ketofol) for emergency department procedural sedation and analgesia in
adults. Acad Emerg Med 2011;18:237-45.
4. Aouad MT, Moussa AR, Dagher CM, et al. Addition of ketamine to propofol for
initiation of procedural anesthesia in children reduces propofol consumption and
preserves hemodynamic stability. Acta Anaesthesiol Scand 2008;52:561-5.
5. Badrinath S, Avramov MN, Shadrick M, et al. The use of a ketamine-propofol
combination during monitored anesthesia care. Anesth Analg 2000;90:858-62.
6. David H, Shipp J. A randomized controlled trial of ketamine/propofol versus
propofol alone for emergency department procedural sedation. Ann Emerg Med
2011;57:435-41.
7. Erdogan Kayhan G, Yucel A, Colak YZ, et al. Ketofol (mixture of ketamine and
propofol) administration in electroconvulsive therapy. Anaesth Intensive Care
2012;40:305-10.
8. Frey K, Sukhani R, Pawlowski J, et al. Propofol versus propofol-ketamine sedation
for retrobulbar nerve block: comparison of sedation quality, intraocular pressure
changes, and recovery profiles. Anesth Analg 1999;89:317-21.
9. Frizelle HP, Duranteau J, Samii K. A comparison of propofol with a propofolketamine combination for sedation during spinal anesthesia. Anesth Analg
1997;84:1318-22.
10. Messenger DW, Murray HE, Dungey PE, et al. Subdissociative-dose ketamine
versus fentanyl for analgesia during propofol procedural sedation: a randomized
clinical trial. Acad Emerg Med 2008;15:877-86.
11. Mortero RF, Clark LD, Tolan MM, et al. The effects of small-dose ketamine on
propofol sedation: respiration, postoperative mood, perception, cognition, and pain.
Anesth Analg 2001;92:1465-9.
12. Nengroo S, Lone AQ, Naqash I. Circulatory responses to propofol-ketamine
combination compared to propofol alone for sedation during spinal anesthesia.
Internet Journal of Medical Update-EJOURNAL 2011;6.
13. Phillips W, Anderson A, Rosengreen M, et al. Propofol versus propofol/ketamine
for brief painful procedures in the emergency department: clinical and bispectral
index scale comparison. J Pain Palliat Care Pharmacother 2010;24:349-55.
14. Shah A, Mosdossy G, McLeod S, et al. A blinded, randomized controlled trial to
evaluate ketamine/propofol versus ketamine alone for procedural sedation in children.
Ann Emerg Med 2011;57:425-33 e2.
15. Sharieff GQ, Trocinski DR, Kanegaye JT, et al. Ketamine-propofol combination
sedation for fracture reduction in the pediatric emergency department. Pediatr Emerg
Care 2007;23:881-4.
16. Singh R, Batra YK, Bharti N, et al. Comparison of propofol versus propofolketamine combination for sedation during spinal anesthesia in children: randomized
clinical trial of efficacy and safety. Paediatr Anaesth 2010;20:439-44.
17. Tomatir E, Atalay H, Gurses E, et al. Effects of low dose ketamine before
induction on propofol anesthesia for pediatric magnetic resonance imaging. Paediatr
Anaesth 2004;14:845-50.
18. Tosun Z, Aksu R, Guler G, et al. Propofol-ketamine vs propofol-fentanyl for
sedation during pediatric upper gastrointestinal endoscopy. Paediatr Anaesth
2007;17:983-8.
19. Weatherall A, Venclovas R. Experience with a propofol-ketamine mixture for
sedation during pediatric orthopedic surgery. Paediatr Anaesth 2010;20:1009-16.
20. Willman EV, Andolfatto G. A prospective evaluation of "ketofol"
(ketamine/propofol combination) for procedural sedation and analgesia in the
emergency department. Ann Emerg Med 2007;49:23-30.
21. Yalcin S, Aydogan H, Selek S, et al. Ketofol in electroconvulsive therapy
anesthesia: two stones for one bird. J Anesth 2012;26:562-7.