European Review for Medical and Pharmacological Sciences 2015; 19: 3522-3527

Comparison of propofol-remifentanil and

propofol-ketamine combination for dilatation
and currettage: a randomized double blind
prospective trial
M. ARIKAN1, B. ASLAN2, O. ARIKAN3, A. BUT4, E. HORASANLI4
1
Department of Anesthesiology, Faculty of Medicine, Karabuk University, Karabuk, Turkey.
2
Department of Anesthesiology, Zekai Tahir Burak Education and Research Hospital, Ankara, Turkey.
3
Department of Surgery, Karabuk State Hospital, Karabuk, Turkey.
4
Department of Anesthesiology, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey.

These authors contributed equally to this work.

Abstract. – OBJECTIVE: The purpose of Key Words:

this study was to compare the propofol- Dilatation and curettage, Propofol, Ketamine, Remifen-
remifentanil combination and propofol-keta- tanil.
mine combination for Dilatation and Curettage
(DC) procedure.
PATIENTS AND METHODS: This prospective,
double blind, and randomized study comprised Introduction
81 female patients undergoing diagnostic DC.
Patients were randomly allocated to one of two Dilatation and Curettage (DC), a brief and
groups; propofol-remifentanil (Group PR, n= 44) painful procedure, is performed for the diagnosis
or propofol-ketamine (Group PK, n= 37). The and treatment of endometrial and intrauterine
level of sedation was assessed with the Ram-
say Sedation Score (RSS). The patients’ RSS disorders. The procedure is one of the most fre-
scores were maintained at 4-5 with an addition- quently performed gynecological surgical proce-
al 0.5 mg/kg bolus dose of propofol. Heart rate dures. It causes considerable pain during cervical
(HR), mean blood pressure (MBP), peripheral dilatation and tissue extraction1.
oxyg en saturation (SpO 2 ), and RSS were Therefore, drugs that are used for this proce-
recorded. The Modify Aldrete Score (MAS) was dure, should ensure a rapid onset of action, an
used for postoperative recovery evaluation, and
the time to reach MAS score of 10 was record-
adequate level of sedation, analgesia, and muscle
ed. Total dose of propofol, procedure time, side relaxation for a short period of time, as well
effects, and satisfaction scores of patient and should also provide rapid recovery. The most im-
surgeon were also recorded. portant objectives, in such operations, are main-
RESULTS: The mean HR and MBP values of taining the hemodynamic-respiratory stability
Group PR were lower than those of Group PK, and minimizing the side effects of drugs2.
at all recording times. Sedation levels were sig- Propofol is a short-acting intravenous hypnotic,
nificantly higher in Group PK. The total dose of
propofol consumed was significantly higher in and provides rapid onset and complete recovery
Group PR. The recovery time of Group PK was from anesthesia3. It is commonly used during brief
significantly longer than that of Group PF surgical intervention. However, it has not an anal-
(p<0.05). Nausea-vomiting and bradycardia gesic effect. The use of high-doses propofol may
were more frequent in the Group PR. There was cause severe complications, such as hypotension,
no difference in patient and surgeon satisfac- respiratory depression and bradicardia4.
tion between the two groups.
CONCLUSIONS: Ketamine-propofol combina-
Combining propofol with opioids or ketamine
tion provides better hemodynamic stability and is recommended for improving the quality of se-
better quality of sedation than propofol- dation and analgesia, and minimizing the poten-
remifentanil combination. Ketamine still seems tial adverse effects of drug-related events, and
as an advantageous and safe drug for such pro- maintaining a stable cardiovascular and respira-
cedure. tory status3,4.

3522 Corresponding Author: Müge Arikan, MD; e-mail: mugearikan@hotmail.com.tr

 Ketamine or remifentanil for sedation

Ketamine, a neuroleptic anesthetic agent, pro- ence of a psychiatric disorder with chronic med-
vides excellent amnesia and analgesia without af- ical treatment, presence of liver or kidney dys-
fecting spontaneous respiration4. On the other functions, cardiac and endocrine diseases and
hand, it may cause significant adverse effects in- non-cooperative patients. The participants, whose
cluding sympathomimetic effects and vomiting operations exceeded 15 minute, were excluded.
when administered in sedating doses. The combi- After informed consent form was obtained, pa-
nation of propofol and ketamine has several ben- tients were randomly divided into two groups by
efits because of hemodynamic stability and lack closed envelope method as Group PR: propofol
of respiratory depression. It may be an appropri- plus remifentanil group (n = 44), and Group PK:
ate option for painful procedures5. propofol plus ketamine group (n = 37).
Remifentanil, a potent short-acting opioid, All patients fasted for at least 6 hours before
provides both analgesia and sedation6-8. It also the procedure. In the operation room, a peripher-
ensures a rapid recovery profile due to its brief al intravenous (iv) line was provided by 18G can-
half-life. The drug may be a good option for brief nula on patients, and 6-8 mL/kg/h crystalloid so-
and painful procedures like DC. However, lition was started. Electrocardiogram, noninva-
remifentanil may cause nausea-vomiting, hy- sive blood pressure, and pulse oxymeter were
potension, and respiratory depression9. monitored and recorded. Patients were premed-
Various combinations, such as remifentanil- icated with midazolam (0.03 mg/kg, iv) before
propofol, fentanyl-propofol, alfentanil-propofol starting the procedure, and received supplemen-
or ketamine-propofol, were shown to provide a tary oxygen (6 L/min) with a facemask during
safe and effective hypnosis and analgesia for DC the procedure.
procedures1,2,6,7. Group PR: patients who received 1 µg/kg
However, there are only a limited number of remifentanil over a period of 30 sec.
studies concerning the use of ketamine, and the Group PK: patients who received 0.5 mg/kg
use of bolus-dose remifentanil for DC ketamine. Then, induction was maintained with 1
procedures1,2,6. mg/kg propofol in both groups.
We designed this randomized, double-blind Depth of sedation was assessed with the Ram-
study to evaluate the administration of remifen- say Sedation Score (RSS)10. The patients’ RSS
tanil versus ketamine when combined with scores were maintained at 4-5 with an additional
propofol during DC procedures. We compared 0.5 mg/kg bolus dose of propofol when required.
hemodynamic effects, propofol consumption, se- The anesthesiologist, who administered the
dation scores, recovery time, side effects, and the drugs, was not included in the study. Another anes-
satisfaction of the patients as well as the surgeon. thesiologist (who was blinded to the drug alloca-
To our knowledge, the present study is the first tion) evaluated the depth of sedation, and adminis-
that compares the use of remifentanil bolus doses tered additional doses of propofol. Patients and sur-
with ketamine for the DC procedure. geons were also blind to the group application.
Heart rate (HR), mean blood pressure (MBP),
peripheral oxygen saturation (SpO2), and RSS
Patients and Methods values of all patients were recorded at baseline
(before the induction), 1st, 3rd, 5th, 10th and 15th
This double-blind, prospective randomized tri- minute.
al was performed after approval of the Ethic During the procedures, complications and side
Committee. This study was conducted at the De- effects such as hypotension, bradycardia, nausea
partment of Anesthesiology and Obstetrics and and vomiting, respiratory depression were
Gynecology, Zekai Tahir Burak Training and recorded, and treated as required.
Reaserch Hospital, Ankara, Turkey, from No- Recovery time was assesed with Modified Al-
vember 2009 to August 2010. drete Score (MAS) (Table I)11. The time from the
Eighty-one, American Society of Anesthesiol- completion of the procedure to reach MAS of 10
ogist Physical Status Classification I or II (ASA) was recorded. Patients were transported to the re-
patients, age between 18 and 40, subjected to DC covery room.
procedure were included into the investigation. Surgeon and patient satisfaction were rated on a
Exclusion criteria were ASA ≥ III, BMI ≥ 35, scale of 1 to 4 (1=perfect, 2=good, 3=moderate,
history of allergic reaction to study drugs, chron- 4=bad). The surgeons’ satisfaction were assessed
ic use of sedatives or opioid analgesics, and pres- after completion of the operation. Patients were

3523
 M. Arıkan, B. Aslan, O. Arıkan, A. But, E. Horasanlı

Table I. Modified Aldrete Score11.

Activity Score

Able to move 4 extremities voluntarily or on command 2

Able to move 2 extremities voluntarily or on command 1
Able to move 0 extremities voluntarily or on command 0
Respiration
Able to breathe deeply and cought freely 2
Dyspnea or limited breathing
Apneic 0
Consciousness
Fully awake 2
Arousable on calling 1
Not responding 0
Circulation
Blood pressure ±20% of preanesthetic level 2
Blood pressure ±20% to 50% of preanesthetic level 1
Blood pressure ±50% of preanesthetic level 0
O2 Saturation
Maintains > 92% on room air 2
Needs O2 inhalation to maintain O2 saturation > 90% 1
Saturation < 90% even with supplemental oxygen 0

visited 2 hours later on the floor to assess their sat- Results

isfaction. The patients’ and the surgeons’ satisfac-
tion scores were recorded. The additional doses of Eighty-one patients successfully completed
propofol and procedure times were also recorded. this study. The demographic characteristics in-
cluding age, weight, ASA status, and procedure
times of two groups are shown in Table II. There
Statistical Analysis was no statistical difference between groups in
Statistical analysis was performed using SPSS terms of these parameters.
for Windows, version 11.5 (SPSS, Chicago, IL, The baseline recordings of HR, MBP, and
USA), p values < 0.05 were considered signifi- SpO 2 did not differ significantly between the
cant. Data are presented as mean ± standard devi- groups. In Group PK, HR and MBP values were
ation (SD). Chi-square (χ2) test was used for cate- similar for all recording times. However, in
gorical data. Parametric continuous variables Group PR, MBP and HR were significantly low-
were analyzed using the Student’s t-test. Based on er at all recording times compared to baseline.
a previous study, a priori power analysis was per- These parameters of Group PR were also signifi-
formed using two-sided analysis with an (alpha) cantly lower than those of Group PK for all
error of 0.05 and a power of 0.8 to detect a differ- recording times. The RSS scores of Group PK
ence of 60% for recovery times. Thirty patients were higher than those of Group PR for all
were calculated to be needed for each group. recording times (p<0.05, Table III).

Table II. Demographic characteristics and procedure times of the patients.

Group PR (n=44) Group PK (n=37) p

Age (year) 28.3 ± 5.9 27.8 ± 5.9 0.708

Weight (kg) 67.1 ± 12.8 65.8 ± 10.6 0.922
ASA I/II (n) 36/8 31/6 0.816
Procedure time (min) 8.15 ± 2.8 9.25 ± 3.4 0.061

Data are expressed as mean ± SD, or number of patients. There were no statistically significant differences between the groups.
ASA: The American Society of Anesthesiologists.

3524
 Ketamine or remifentanil for sedation

Table III. Hemodynamic parameters and RSS values of the groups.

Baseline 1st 3rd 5th 10th 15th

MBP
Group PR 92.1 ± 14.0 72.9 ± 11.5+* 76.7 ± 16.1+* 74.8 ± 11.2+* 72.5 ± 10.6+* 74.1 ± 12.3+*
Group PK 91.5 ± 6.5 89.2 ± 9.9 86.3 ± 11.5 85.5 ± 8.6 87.2 ± 12.2 88.4 ± 14.6
HR
Group PR 83.0 ± 9.8 65.7 ± 9.1+* 67.4 ± 10.9+* 69.7 ± 11.1+* 70.2 ± 9.6+* 71.9 ± 10.8+*
Group PK 80.8 ± 7.8 78.2 ± 11.6 82.5 ± 7.0 82.6 ± 9.5 79.9 ± 10.2 80.1 ± 11.4
RSS
Group PR 4.02 ± 0.4* 3.95 ± 0.5* 3.86 ± 0.4*++ 3.68 ± 0.6* 2.96 ± 0.2*
Group PK 4.62 ± 0.6 5.02 ± 0.5 4.84 ± 0.5 4.26 ± 0.6 3.85 ± 0.4

Data are means ± SD. +p<0.05, significant changes compared to baseline values in the same group. *p<0.05, significant inter-
group differences.
Bpm: beats per minute. MBP: mean blood pressure (mmHg). HR: heart rat (bpm). RSS: Ramsey Sedation Score.

The total propofol consumption of Group PR sures more stable hemodynamics. In ketamine
was significantly higher than that of Group PK (p group, the mean consumption of propofol, ad-
<0.05). The mean recovery time of Group PK verse effects such as, nausea/vomiting, and
was significantly longer than that of Group PR bradycardia were lower.
(p<0.05) (Table IV). Ketamine produces dose-related unconscious-
The prevalence of hypotension (≥ 20% de- ness and analgesia with minimal effect on the
crease from the baseline value), and apnea (SpO2 central respiratory drive while stable hemody-
<92%) were comparable in the two groups. How- namics are maintained12.
ever, the occurrence of nausea/vomiting, and The combination of propofol and ketamine
bradycardia (heart rate <60 beats per minute) provides an adequate sedation and analgesia for
were higher in Group PR. For two groups, sur- brief painful procedures, and it has been used in
geons’ and patients’ satisfaction scores were simi- various departments13-15.
lar (Table IV). There are only a limited number of investiga-
tion concerning the use of propofol-ketamine for
sedation in gynecological procedures1,2.
Discussion Sahin et al2 compared alfentanil (10 µg/kg)
and ketamine (0.5 mg/kg) in combination with
The present report shows that remifentanil propofol (0.7 mg/kg) for DC procedures, and
group had a significantly shorter recovery time found the mean consumption of propofol was
than the ketamine group. However, ketamine pro- higher, and the orientation time was longer in ke-
vides more deeper sedation levels, and also en- tamine group than in the alfentanil group. In the

Table IV. Side effects, total propofol consumption, recovery times, surgeon and patient satisfaction scores.

Group PR (n=44) Group PK (n=37)

Bradycardia 8 (18.2%)* 0
Hypotension 2 (4.5%) 0
Nausea/vomiting 1/6 (15.9%)* 1/0 (2.7%)
Apnea 2 (4.5%) 0
Surgeon satisfaction score 3.15 ± 0.8 3.95 ± 1.0
Patient satisfaction score 3.32 ± 0.8 3.65 ± 0.9
Total propofol consumption (mg) Propofol Dose (mg) 135.65 ± 40.2* 91.42 ± 23.7*
Recovery time (minutes) 10.2 ± 3.5* 17.3 ± 3.2*

Data are expressed as proportions and numbers (yes/no) or means ± SD. *Statistically significant, p<0.05.

3525
 M. Arıkan, B. Aslan, O. Arıkan, A. But, E. Horasanlı

current study, we found that the time to reach quality of sedation compared with propofol-
MAS score of 10 was earlier in the remifentanil remifentanil combination. It also reduces need for
group, which was consistent with Sahin et al’s additional propofol doses. Despite its excellent
findings2. However; the mean consumption of properties, it has a long recovery time.
propofol was lower in the ketamine group than The potential limitations of our study are lack
that in the remifentanil group. of postoperative follow-up of patients in terms of
Akin et al13 compared a combination of propo- side effects and the pain, and not using bispectral
fol and fentanyl with propofol and ketamine, in index monitoring.
40 adult patients undergoing endometrial biopsy.
They observed that there was no difference in the
recovery times, but the discharge was delayed in Conclusions
the ketamine group. They also reported that the
frequency of patient satisfaction was 95% in the Ketamine-propofol combination is superior to
fentanyl group, and 60% in the ketamine group. propofol-remifentanil combination for such pro-
Yüce et al1 reported that propofol-ketamine cedures in terms of hemodynamic stability and
combination is associated with shorter orienta- lesser incidence of side effects such as, bradycar-
tion times than propofol alone, with similar he- dia and nausea-vomiting. Ketamine still seems as
modynamic stability without any important side a perfect drug for such procedures. Further stud-
effects in DC anesthesia. ies concerning the comparison of different doses
Remifentanil is a new and short-acting drug of it with opioids should be planned.
with a half life of 9-11 minutes, and provides a
fast recovery profile. The use of bolus-dose
remifentanil may be an appropriate option for –––––––––––––––––-––––
analgesia during short painful procedures like Conflict of Interest
DC6. The Authors declare that they have no conflict of interests.
In gynecologic settings, Castillo et al7 com-
pared different bolus doses of remifentanil in di-

In Oğurlu et al’s study6, propofol (2 mg/kg)

latation and sharp curettage.
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