Journal of Clinical Sciences

: 2019  |  Volume : 16  |  Issue : 1  |  Page : 1--6

A comparison of propofol - fentanyl with midazolam – pentazocine combination for sedation and analgesia during colonoscopy in Ibadan Nigeria

Tinuola Abiodun Adigun1, Adegboyega Akere2, Omobolaji O Ayandipo3, Oludolapo O Afuwape3,  
1 Department of Anaesthesia, University College Hospital, Ibadan, Nigeria
2 Department of Medicine, University College Hospital, Ibadan, Nigeria
3 Department of Surgery, University College Hospital, Ibadan, Nigeria

Correspondence Address:
Dr. Tinuola Abiodun Adigun
Department of Anaesthesia, College of Medicine, University of Ibadan and University College Hospital, Ibadan


Background: Benzodiazepines, narcotics, and propofol in different combinations are administered to provide sedation and analgesia during colonoscopy. The study aimed to compare the efficacy and safety of midazolam-pentazocine with the propofol-fentanyl combination for sedation and analgesia during colonoscopy. Patients and Methods: This prospective randomized, double-blind study was conducted in 62 adults aged 18–82 years scheduled for colonoscopy. Patients were assigned into two groups, Group A (n = 31) received midazolam 2.5–5.0 mg with pentazocine 15–30 mg, whereas Group B (n = 31) received propofol 0.5 mg/kg with fentanyl 0.5ug/kg before the procedure. Efficacy was measured by the depth of sedation using Ramsay sedation score (RSS), pain score, and recovery from sedation, whereas safety was evaluated with heart rate, blood pressure (BP), and oxygen saturation. Results: There was no statistically significant difference between the two groups with respect to demographic and clinical data. The patients in Group B were more sedated with a mean RSS of 4.1 ± 0.79 compared with 2.07 ± 0.74 in Group A (P = 0.001). The mean pain score during the procedure was lower in Group B 3.19 ± 1.9 compared with 4.8 ± 1.9 in Group A (P = 0.001). The recovery time was faster in Group B compared with Group A, 24 versus 46 min, respectively (P = 0.001). The systolic BP at 5 and 10 min was lower in Group B (P = 0.024 and P = 0.001), respectively, as well as the diastolic BP at 5 and 10 min (P = 0.042 and P = 0.04), respectively. Hypotension was observed in six patients in Group B compared to two patients in Group A. There was no difference in the heart rates in both groups. Two patients in both groups had desaturation <90%, and oxygen was administered to maintain the oxygenation. No patient developed apnea that would have warranted endotracheal intubation. Conclusion: Propofol-fentanyl combination provided better sedation, less painful procedure, and shorter recovery time with minimal cardiorespiratory complication.

How to cite this article:
Adigun TA, Akere A, Ayandipo OO, Afuwape OO. A comparison of propofol - fentanyl with midazolam – pentazocine combination for sedation and analgesia during colonoscopy in Ibadan Nigeria.J Clin Sci 2019;16:1-6

How to cite this URL:
Adigun TA, Akere A, Ayandipo OO, Afuwape OO. A comparison of propofol - fentanyl with midazolam – pentazocine combination for sedation and analgesia during colonoscopy in Ibadan Nigeria. J Clin Sci [serial online] 2019 [cited 2019 Mar 23 ];16:1-6
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Colonoscopy is one of the most commonly performed outpatient procedures worldwide either as a screening, diagnostic, or therapeutic procedure for colorectal diseases.[1] The goal of sedation and analgesia in colonoscopy is to control pain, anxiety, and provide an appropriate degree of memory loss.[2] According to the study by Fanti and Testoni, the most common complication in gastrointestinal endoscopy is related to deep sedation resulting in cardio-respiratory adverse events such as hypoxemia, hypoventilation, apnea, arrhythmias, and hypotension.[3]

The choice of sedatives generally consists of benzodiazepines (midazolam or diazepam) used either alone or in combination with an opiate.[4] Most endoscopists in Nigeria favor midazolam because of its fast onset of action, short duration of action, and high amnesic properties, as shown in a survey conducted by Nwokediuko and Obienu. Their survey showed that Benzodiazepine alone was used by 85.7% of endoscopists in Nigeria during upper gastrointestinal endoscopy, whereas the rest had little experience with opioid with no experience with propofol at all.[5] Recently, propofol (2, 6-diisopropyl phenol) an ultra-short-acting hypnotic agent was added to the drug armamentarium of sedatives for endoscopy.[6] Propofol possesses sedative and amnestic effects, it has fast onset of action and no hangover effect suitable for day case procedure like colonoscopy. It is used alone or in combination with an opiate.[7] Opioids commonly used in combination with benzodiazepine or propofol are fentanyl, alfentanil, remifentanil, pentazocine, or meperidine[8] Alatise et al. compared propofol with traditional sedative methods for colonoscopy in southwest Nigeria and found that propofol sedation was safe and propofol with opioid helped in reducing the dose of propofol with better recovery when compared with the traditional sedatives suggesting the use of propofol over benzodiazepine as sedative in colonoscopy.[9]

The best combination for sedation and analgesia during gastrointestinal endoscopy is still debatable. The combination of midazolam and pentazocine is the traditional sedative method at our center. Experience and adequate information on propofol and fentanyl combination for day-case colonoscopy at our center is lacking.

This study aimed to compare the efficacy and safety of propofol-fentanyl with the midazolam-pentazocine combination in patients undergoing colonoscopy at a tertiary center.

 Patients and Methods

This prospective randomized, double-blind study was conducted on patients scheduled for colonoscopy at the endoscopy suite. Ethical approval for the study was obtained from the State Ministry of Health.

Adult patients with the American Society of Anesthesiologist (ASA) physical Status I–III who were 18 years and above scheduled for colonoscopy were recruited for this study. Patients aged <18 years, uncooperative or those who refused to give informed consent, allergic to the study drug, obese, pregnant, and ASA Physical Status IV were excluded from the study.

Bowel preparation for the procedure consisted of liquid diet, six sachets of Epsom salts mixed with 3 L of water and taken orally a day before the procedure in two divided doses, and three sachets mixed with 1 L of water taken early morning of the procedure. All the patients had an overnight fast of about 10–12 h, except the Epsom salt solution taken on the morning of the procedure.

Digital rectal examination was carried out on all the patients before the insertion of the colonoscope and written informed consent was obtained from each patient before the procedure. Colonoscopy was thereafter performed per protocol using Olympus Exera III video colonoscope (CF HQ 190 L, Olympus, UK) with the patient in the left lateral position.

Anesthetic protocol

All patients underwent a thorough preanesthetic evaluation before the colonoscopy.

Each patient was taught on how to use the verbal rating scale (VRS) in simple terms to describe the intensity of their pain during the procedure. VRS was described thus: no pain, (0) mild pain (1–3), moderate pain (4–6), and severe pain (7–10).

Intravenous line was established using a large bore cannula size 18G. The patients were randomized into two groups by simple table of randomization, Group A (n = 31) received midazolam 2.5 mg with pentazocine 15 mg, whereas Group B received (n = 31) propofol 0.5 mg/kg with Fentanyl 0.5ug/kg before the procedure. The patients and the endoscopist were blinded to the randomization procedure, but the anesthetist was not because of the knowledge of the physical appearance of the study drugs.

The patients received no other premedication except intravenous propofol 0.5 ug/kg – fentanyl 0.5 ug/kg combination or midazolam 2.5 mg and pentazocine 15 mg combination. If the patients complained of pain, additional dose of 0.25 ug/kg fentanyl or propofol 10 mg incremental boluses, 2.5 mg midazolam or 15 mg pentazocine were given. However, when patients demonstrated signs of dysarthria or ptosis additional drugs were omitted.

The sedation level was assessed using the Ramsay sedation score (RSS) before the insertion of the scope. Oxygen was not routinely given to all the patients, and the cardio-respiratory monitoring such as blood pressure (BP), heart rate, and arterial oxygen saturation (SpO2) were done every 5 min throughout the procedure and into the recovery room. The data collected was age, sex, weight, height, ASA Status, sedation score, pain score, heart rate, BP, and SpO2.

Colonoscopy time was defined as the period between the induction of sedation to completion of the procedure. Recovery time was defined as the time between the induction of sedation to the time when the RSS is ≤2. The total amount of drug used and complications was also recorded.

Hypotension was defined as >30% change in baseline systolic and diastolic BP, bradycardia as heart rate <50 beats/min and oxygen desaturation as Spo2 <90%.

Treatment of complications included intravenous normal saline and ephedrine 3 mg for hypotension, atropine 0.5 mg for bradycardia, oxygen at 3l/min by facemask if saturation was <90%, Naloxone an opioid antagonist at 200–400 mcg titrated to desired effect in treating respiratory depression (respiratory cycles of <8/min), nausea and vomiting by intravenous metoclopramide 10 mg and deep sedation with Ramsay score of 5 or 6 by intubation and ventilation.

RSS included RSS1: Patient is anxious and agitated or restless or both, RSS 2: Patient is cooperative, oriented and calm, RSS 3: Patient responds to command only RSS 4: Patient exhibits brisk response to glabella tap or loud auditory stimulus, RSS 5: Patient exhibits sluggish response to glabella tap or loud auditory stimulus, RSS 6. No response. Pain was assessed at the end of the procedure.

Patients were discharged from the hospital with stable vital signs, free from pain, alert, able to drink orally without nausea and vomiting, and accompanied by a relation.

Efficacy was measured with pain score, depth of sedation, and recovery time while safety was evaluated with heart rate, BP and SpO2.

Statistical analysis

Results were analyzed using Statistical Package for Social Sciences (SPSS) for Windows version 20.0, Chicago, IL, USA. Statistical associations were determined using the Chi-square test for pain intensity, sedation score, recovery time, and t-test for continuous variables such as age, weight, height, and hemodynamic changes. Data were presented using tables. A value of P < 0.05 was considered statistically significant.


A total of 62 patients were recruited into the study, 31 patients in each group. There were no differences in the two groups for age, gender, weight, duration of the procedure, and the ASA status of the patients [Table 1].{Table 1}

Patients in Group A received mean the dose of midazolam 2.5mg+/-0.00 and 17.65 ± 5.8 mg of pentazocine, whereas Group B received mean dose 47.1 ± 9.57 mg of propofol and 52.6 ± 12.51 ug of fentanyl. An additional dose of propofol given was 28.46 ± 4.6 mg, additional dose of fentanyl was 30 ± 11.8 ug while additional dose of 15 mg of pentazocine was given to complete the procedure.

The patients in Group B were more significantly sedated with a mean RSS of 4.1 ± 0.79 compared to 2.07 ± 0.74 in Group A (P = 0.001).

The mean pain score during the procedure was significantly lower in Group B (3.19 ± 1.9) compared with 4.8 ± 1.9 in Group A (P = 0.001).

The recovery time from sedation was faster in Group B (24 min) compared with Group A 46 min. The duration of the procedure was 45 min in both groups, and at the end of the procedure all the patients had recovered from the effect of sedation [Table 1].

There was no significant difference in the baseline hemodynamic parameters of the two groups [Table 2].{Table 2}

There was a significant difference in the systolic BP between the two groups at 5 and 10 min P = 0.024 and P = 0.005, respectively, as well as in the diastolic BP at 5 and 10 min (P = 0.042 and 0.04, respectively) [Table 3] and [Table 4].{Table 3}{Table 4}

No patient had a heart rate <50 beats/min in both groups, and there was no significant difference in the heart rates between the two groups.

[Table 5] shows the side effects in both groups. Transient hypotension was observed in six patients in Group B compared to two patients in Group A with no record of severe hypotension in both groups. Two patients in both groups had oxygen desaturation < 90%, and oxygen was given to maintain the oxygenation. No patient developed apnea that needed endotracheal intubation. Nausea was observed in only one patient in Group A which resolved without medication. No patient received metoclopramide or naloxone.{Table 5}


Colonoscopy is usually performed under sedation and analgesia at our center. The procedure may be painful and unpleasant for some patients; such discomfort arises during insertion of the colonoscope, mesenteric traction maneuvers, colonic distension by air insufflations, and occasional looping of the colonoscope within the colon. Chelazzi et al.[10] found that 8.9% of their unsedated patients had their procedure discontinued due to excessive discomfort or pain. Consequently, sedation and analgesia have become an integral component of gastrointestinal endoscopy.[11]

Propofol and midazolam have sedative properties, but when used alone it may be inadequate and thus necessitate the addition of analgesics to alleviate pain during colonoscopy.[7] Both fentanyl and pentazocine have been used successfully with either propofol or midazolam as boluses or continuous infusions with good effect during gastrointestinal endoscopy.[12] Fentanyl is a pure miu opioid agonist while pentazocine is a miu agonist and antagonist. Fentanyl is more potent than pentazocine although both of them have been found to reduce abdominal pain and discomfort during gastrointestinal endoscopy, but the latter may cause prolonged sedation.[11],[12]

In this study, the mean age of the patients in the propofol-fentanyl group (61.62 ± 12.9 years) was similar to 60.76 ± 11.32 years in the midazolam–pentazocine group. This was an older population compared with those previously studied at the same center by Irabor and Akere et al. whose mean ages were 54 years and 57.9 ± 14.2 years, respectively.[13],[14]

The mean dose of propofol used in this study was 47.0 ± 9.57 mg with fentanyl 52.6 ± 12.51 ug as an analgesic given as bolus. This low dose of propofol is similar to the dose used in a study by Alatise et al.[8] in Ile Ife. This implies that a combination of propofol with opioid might reduce the dose requirement of propofol with a resultant reduction in the risk of deep sedation.[9] On the contrary, when propofol was used as the sole anesthetic agent in a study by Fanti et al., a very high dose of up to 14.9 mg/kg/h was required.[15] Age was one of the determinants of drug dosage in this study; older patients required a lower dose compared to younger patients and dose reduction is associated with increased drug clearance.[16]

This study also showed that patients who had propofol-fentanyl combination were more sedated than patients that had midazolam–pentazocine combination. Propofol has a rapid redistribution pattern after bolus doses hence top-up doses were frequently administered in the propofol-fentanyl group than the midazolam-pentazocine group. In a study Koshy et al.[8] comparing propofol and fentanyl with midazolam and meperidine in a nonrandomized group of 274 patients undergoing upper endoscopy and colonoscopy, the propofol and fentanyl group was 2.04 times more comfortable and 1.84 times more sedated than the midazolam group.[8] Sipe et al. in a randomized study of 80 patients undergoing colonoscopy comparing propofol alone with midazolam-meperidine found that propofol group had faster mean onset time of action, greater depth of sedation with modest improvement in satisfaction score and faster recovery rate than midazolam group.[7] This is similar to our observations in this current study.

The current study also found that the pain score was lower in the propofol-fentanyl group compared to the midazolam-pentazocine group. Lazaraki et al.[17] in a study comparing mean dose of 36 microgram fentanyl with midazolam 4.6 mg for colonoscopy found that the pain score was lower in the fentanyl group (2.59) compared to the midazolam group (4.43). It was therefore concluded that fentanyl administration in low incremental dose was sufficient to achieve pain control during colonoscopy.[17] However, a study by Ekkelenkamp et al.[18] comparing propofol alone with midazolam and meperidine, the pain score in propofol group was 0.03 ± 0.76 compared to 0.00 in the midazolam-meperidine group (P = 0.002), which implied that pain perception was more in the propofol alone group. They, therefore, concluded that successful colonoscopy without significant discomfort in the majority of the patients required more analgesia rather than deep sedation.[18]

Another observation in this study is that the midazolam-pentazocine combination had a longer recovery time and lingering sedative effect compared to the propofol-fentanyl combination. In a study of patients undergoing endoscopic retrograde cholangiopancreatography receiving midazolam and pentazocine combination or propofol alone. Wehrmann et al. observed full recovery after 19 ± 8 min in the propofol group compared with 29 ± 8 min in the midazolam-pentazocine group.[19] In a meta-analysis, propofol was reported to allow a shorter recovery time of 15 min versus 50–55 min in the midazolam based regimen.[2] In a study by Vargo et al.[20] where 75 patients were randomized into propofol or midazolam-meperidine group, recovery was shorter in propofol group (18.5 min) compared to 70.5 min in the midazolam-meperidine group. The dose of midazolam in their study was 9.2 mg which was much higher than in the present study, and this could explain the prolonged recovery of their patients compared to our study.

Heart rate, BP, and SpO2 were monitored regularly during the procedure. According to previous studies, the most common complications in gastrointestinal endoscopy are cardiorespiratory adverse effects such as hypoxemia, hypoventilation, apnea, arrhythmia, and hypotension.[3],[21]

The lower incidence of respiratory and hemodynamic instability observed in the present study might be due to careful titration of the drugs with low doses of propofol, midazolam, and opioids used.

The incidence of hypotension was more frequent in the propofol-fentanyl group compared with the midazolam-pentazocine group while no difference was found in the heart rates in the two groups. Vargo et al.[20] did not find any difference between propofol group and midazolam-meperidine group with respect to the incidence of hypotension, bradycardia, and oxygen desaturation, whereas Wehrmann et al.[19] observed that 11/98 patients had a drop in SpO2 level in the propofol group compared to 8/98 in the midazolam group.[19] In a study by Sipe et al.,[7] five cardiopulmonary complications were reported in 80 patients one patient with oxygen desaturation was in the propofol group, whereas the other four were in the midazolam meperidine group (one each with bradycardia and tachycardia, and two with hypotension). However, in a meta-analysis by Qadeer et al.,[21] the incidence of cardiopulmonary complication was found to be lower in the propofol group compared with traditional sedation like midazolam.

Although propofol sedation was administered by an anesthetist in this current study, studies have shown that propofol can also be given by nurses or endoscopists. However, the nurses and endoscopists must be trained in airway management and carefully select their patients.[7],[22] Safety with propofol administered by nonanesthetist has been reported in several studies,[7],[22],[23] but an anesthetist who has experience in airway management must always be available to cover the endoscopy suite irrespective of the physical status of the patients selected by the endoscopists or the nurses.


Propofol-fentanyl combination provided better sedation, less painful procedure, and shorter recovery time with minimal cardiorespiratory complications. This combination can be administered by both anesthetists and nonanesthetists but requires adequate monitoring.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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