Article Text


The use of propofol for procedural sedation and analgesia in the emergency department: a comparison with midazolam
  1. Nik H N A Rahman1,
  2. Ahmad Hashim2
  1. 1Department of Emergency Medicine, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kota Bharu, Malaysia
  2. 2Department of Emergency and Trauma, Queen Elizabeth Hospital, Sabah, Malaysia
  1. Correspondence to Associate Professor Dr Nik H N A Rahman, Department of Emergency Medicine, School of Medical Sciences, USM, Kubang Kerian 16150, Malaysia; nhliza{at}


Introduction This study aimed to determine the effectiveness of propofol as an alternative agent for procedural sedation and analgesia (PSA) in the emergency department (ED) and to make a comparison between two different sedative (propofol vs midazolam) drugs used in combination with fentanyl.

Objectives To compare outcomes between a combination of fentanyl and propofol with fentanyl and midazolam in patients during and after PSA.

Methodology A randomised single blinded control trial carried out in the ED of a university hospital. 40 patients were randomly allocated equally into two groups: group A, 20 subjects received intravenous fentanyl 3 μg/kg as a bolus dose and a titration maximum bolus dose of propofol 1 mg/kg followed by a maximum titration top-up of 0.5 mg/kg if needed; group B, 20 subjects received intravenous fentanyl 3 μg/kg as a bolus dose and a titration maximum bolus dose of midazolam 0.1 mg/kg and a maximum titration top-up of 0.1 mg/kg if needed. The target sedation level was a Ramsay score of 3 or 4. Outcomes included the presence of any adverse events related to PSA and time to discharge. The Mann–Whitney U test was used to compare the two groups.

Results None of the patients developed any significant adverse events during and after procedures. The mean length of stay in the propofol and midazolam groups was 29.25 (11.03) and 71.75 (60.64) min, respectively (p<0.001).

Conclusion Both propofol and midazolam given at the recommended doses were equally safe and effective for PSA in the ED. The propofol group was discharged much earlier than to the midazolam group.

Statistics from

Procedural sedation and analgesia (PSA) is defined as a technique of administering sedatives or dissociative agents with or without analgesics to induce a state that allows patients to tolerate unpleasant procedures while maintaining cardiorespiratory function.1 It was previously referred to as ‘conscious sedation’. This technique is often used in the emergency department (ED) for performing painful or uncomfortable procedures. It has been used for fracture manipulation reduction, draining abscesses, reducing dislocations, performing endoscopy, interventional imaging procedures, cardioversion and dental procedures.2

The main goal of PSA is to provide patients with some relief from both pain and anxiety. In addition to that this technique has been clinically shown to be effective in reducing the stress response and improves patients' compliance when undergoing a painful procedure.3 In general, PSA should be accompanied by analgesia simply because analgesia is able to reduce the stress response. This results in a low requirement to use sedatives. As more nurses and care providers are trained in administering sedatives, PSA can be safely carried out, which will eventually minimise inpatient hospital charges.4 Shorter recovery times and rapid return to the presedation state will require much less expensive nursing care and a shorter duration of hospitalisation. This makes it a very suitable technique for use in developed and developing countries with scarce manpower and resources. Other settings that were found to be of benefit to patients undergoing PSA include procedures performed in dentistry (dental and oral surgery), medical (bronchoscopy, endoscopy, cardiac studies, pacemaker placement) and gynaecology (in-vitro fertilisation).5 6

One of the factors contributing to success and effective PSA is making the right choice of pharmacological agents. For this reason, midazolam has been widely used as an effective sedating agent with clinically confirmed minimal adverse effects. Propofol has recently become increasingly popular among emergency physicians for PSA in the ED.7 8 The effect is almost immediate when it is given by the intravenous route. This study was carried out in an attempt to determine the effectiveness of propofol for PSA in the ED and to make a comparison between the two different sedative drugs (propofol vs midazolam) used in combination with fentanyl. This study was approved by the ethics and research committee of the hospital where the study was carried out. The study was also conducted by the use of a short-term grant provided by the medical school, registered under JKP/PPSP/USM/06.


To compare the outcomes between a combination of fentanyl and propofol with fentanyl and midazolam in subjects during and after PSA.

The outcome measurements are:

  1. Vital signs

    • –Systolic and diastolic blood pressure

    • –Respiratory rate

    • –Heart rate

    • –Mean arterial pressure

    • –Oxygen saturation

  2. End-tidal carbon dioxide.

  3. Time interval between the start of the procedure and discharge from the ED.


This was a randomised single blinded control trial that was carried out in the ED of a university hospital. All of the 40 patients were selected by convenience sampling and they were randomly divided equally into two groups with 20 patients in each group using computer-generated random permuted blocks of four patients. According to the sample calculation based on the 80% power of the study and a previous published paper, we needed 50 samples (25 for each group). However, due to time and grant limitations (1 year study), we had to recruit a sample of up to 40 into the study. All patients were unaware of the drugs they would receive. Each group received either drug A or drug B. The drugs were supplied by the pharmacy department and wrapped individually and placed in an envelope. Each envelope was sealed and labelled accordingly as drug A or drug B. The operators, who consisted of emergency physicians and senior residents in emergency medicine, did not know the exact drugs to be given until the envelope was opened before the administration of the medication to the patients in which the dose of drug had to be precisely calculated according to the subject's body weight.

Inclusion criteria

The suitability of the subjects will be evaluated based on the following criteria: (1) all trauma (except head injury) and non-trauma adult patients; (2) all patients aged 12 years and above who gave verbal and written consent to participate in the study. Parental consent was obtained if the patient's age was between 12 and 18 years; (3) all patients who were indicated for procedural sedation; (4) all patients with a physical status of ASA I and II based upon the American Society of Anaesthesiologists risk classification.

The following procedures were carried out uniformly during the recruitment of samples for this study:

  1. Full history taking and thorough physical examination.

  2. Patients were randomly allocated to one of the two groups by using computer-generated permuted blocks of four patients:

    •  –Group A subjects received intravenous fentanyl 3 μ/kg as a bolus dose and a titration maximum bolus dose of propofol 1 mg/kg followed by a maximum titration top-up of 0.5 mg/kg if needed.

    •  –Group B subjects received intravenous fentanyl 3 μg/kg as a bolus dose and a titration maximum bolus dose of midazolam 0.1 mg/kg and a maximum titration top-up of 0.1 mg/kg if needed.

    • The reason for the titration technique is to target to achieve a Ramsay sedation score of 3 or 4 (table 1).

  3. Detailed explanation regarding the study and the drugs used for PSA were provided to all subjects before getting both verbal and written consent. The explanations given included the effects and the side-effects of the drugs under study. Patients also received explanation about the process that would take place during the PSA.

  4. Both verbal and written consent were obtained as required by the university research ethical committee.

  5. Standard monitoring of systolic and diastolic blood pressure, heart rate, respiratory rate and oxygen saturation were carried out on each patient recruited into the study. One bed was allocated in the resuscitation room equipped with resuscitation instruments throughout the study.

  6. Oxygen was given to the patient via the modified nasal prong (microstream capnograph tubing) directly and at the same time to enable detection of end-tidal carbon dioxide. In addition, each of the patients received intravenous normal saline continuously via either a 16 or 18 gauge cannula that was inserted into the upper limb veins. This is accordance with department standard precautions and protocols for any PSA carried out in the department.

  7. All patients initially received intravenous fentanyl and vital signs were recorded. The studied drugs A or B were administered intravenously using the titrating technique, 2–5 min later.

  8. Similar vital signs were monitored continuously and recorded every 5–10 min until the procedure ended. Any adverse reactions during the procedures were closely observed, documented and managed according to standard guidelines. Any evidence of compromised vital signs could be traced from the electronic recording paper printout from the wall-mounted cardiac monitors. Furthermore, the presence of any significant adverse events would set off the alarm on the machine as the upper and lower limit of the recording were set by the investigator before the study.

  9. The time interval from the start of the procedure until discharge from the department in each subject was charted upon completion of the procedure.

  10. Vital signs were continuously recorded for 5–10 min after the procedure ended.

  11. Upon regaining ful consciousness subjects would be reviewed by the attending medical officer before a decision was made either to discharge them from the ED or transfer to specific wards for other interventions.

Table 1

Modified Ramsay scoring system

For statistical analysis of this study, the non-parametric method was used due to the small sample size. The Mann–Whitney U test was used to compare the two groups of drugs.


Comparison of demographic and other initial parameters for both groups is as shown in table 2. This study was dominated by male subjects who comprised almost 80% of the sample and were not shown to have any clinical significance statistically. None of the patients in either group developed any significant adverse events during or after the procedures. No statistically significant dropped in blood pressure, heart rate, respiratory rate, end-tidal carbon dioxide and pulse oximetry was observed during or after the procedures. Even though a few parameters such as mean arterial pressure, systolic and diastolic blood pressure dropped intraprocedure, these values normalised postprocedure and the changes were statistically insignificant within and between the groups (tables 3 and 4). The main outcome of time interval to discharge in a fully conscious state is as shown in table 5. The propofol group took a much shorter time to discharge, with a mean value of 29 min (95% CI 27.6 to 31.6) when compared with the midazolam group who took twice as long to discharge (mean 71.75; 95% CI 68.7 to 73.4; p<0.001).

Table 2

Demographic data and vital sign parameters for both treatment groups

Table 3

Comparing propofol and midazolam by SBP, DBP and MAP

Table 4

Comparisons of respiratory parameters for both treatment groups

Table 5

Comparison of time interval to discharge between propofol and midazolam


During critical situations, procedures may be indicated and such patients are subjected to some forms of chemical induction to facilitate the procedure planned either to save their lives or salvage the remaining functioning organs or limbs. A collective decision needs to be made to choose the most appropriate form of chemical induction for the purpose of analgesia or sedation. The superiority of one of these drugs and the lack of dangerous adverse reactions would determine the appropriate choice of such drugs to be recommended in the ED setting. We will discuss a few significant findings from the study that might change our clinical practice.

The specific tendency of male gender and young age was adequately explained by the presence of many trauma cases related to motorcycle injuries, which predominantly affected the male and younger age groups. As this study did not include any paediatric age group less than 12 years of age, no conclusion could be drawn as to the safety of procedural sedation as well as the safety profile and effectiveness of the drugs used in procedural sedation within this age group. This study did not show remarkable differences between the two drugs used, namely propofol and midazolam, in procedural sedation. Both drugs were found to be safe to use and did not cause any serious adverse side-effects such as hypoventilation, hypotension, apnoea, hypoxia or allergic reaction. None of the patients involved in this study developed any complications throughout the process of PSA. These findings were consistent with and supported the study conducted by Gabopoulou et al9 on procedural sedation using intravenous propofol for 48 patients undergoing elective orthopaedic surgery under regional blockade. They firmly concluded that propofol is a safe and effective drug to be used in PSA with no respiratory or cardiovascular depression or other undesirable adverse effects. Cheol et al,10 who conducted a randomised double blind comparative study using propofol alone and combined propofol and midazolam in colonoscopy, found that both propofol alone and combined propofol and midazolam are safe and effective. A combination of propofol and midazolam on the other hand is judged more effective than using propofol alone in producing sedation without significant adverse effects.11 12

However, some results were found in this trial that remained significant and may illustrate the relevant direction in their future use in the ED setting.

Time interval from start of procedure to discharge

This study has shown beyond any doubt that propofol is much superior to midazolam in terms of the duration taken for patients to regain full consciousness after procedural sedation has been delivered. The shorter time taken to reverse a patient undergoing PSA may offer excellent indications to use propofol in the ED. The shorter time taken to recover fully without adverse side-effects may reduce the need for long hospital stays in the emergency ward or the need to transfer patients to other wards for further observation. This finding is supported by a study carried out looking at the quality of psychomotor recovery of patients who underwent procedural sedation for routine endoscopic procedures after receiving propofol alone compared with midazolam combined with pethidine.13 Based on a randomised controlled study involving 96 patients, Riphaus et al14 found that the mean recovery time as well as the quality of recovery was significantly better in patients who received propofol sedation than midazolam with the time taken to recover reported as 14 min versus 25 min (p<0.01). These findings further supported the proposed recommendation to expand the usage of propofol in the ED setting as well as in the outpatient setting. Other studies have also shown similar outcomes.15 16

Changes in the blood pressure recorded during procedural sedation

There was a significant and relevant observation recorded in terms of variation of the blood pressure before, during and after a procedure had been carried out. It was found in this study that propofol had caused a reduction in both the systolic and diastolic blood pressures during the procedures when compared with midazolam. However, the reduction in blood pressure was not severe enough to cause harm to the studied subjects and was still within the normal range set by the investigators. This was well anticipated by the researchers, knowing the pharmacological properties of propofol, which is well known to cause hypotension and respiratory depression. This is one of the reasons why the study was conducted in a controlled environment and performed by experienced staff. Another explanation for this finding is probably the steps taken according to the department protocol for PSA, such as intravenous normal saline administration via a large bore cannula to all patients undergoing procedures.

End-tidal carbon dioxide

This study utilised a sidestream microstream capnograph device that measures the respiratory gas concentration remotely by aspirating a small sample of gas from the breathing circuit through tubing to a sensor located inside the monitor. Any adverse changes or complications that arise can be easily detected by capnography. Early detection ensures immediate interventions can be undertaken on the patients.17 18

In this study, the end-tidal carbon dioxide in the propofol group did not show much variation between the pre and intraprocedural readings. There were no marked differences in end-tidal carbon dioxide readings between these two drugs. Jennifer et al19 pointed out that capnography is capable of providing important data regarding airway permeability, cardiac and circulatory function and ventilator performance apart from its ability to evaluate alveolar ventilation. The use of capnography could replace the need to analyse arterial blood gas in a non-invasive manner.20 It is important to emphasise that all subjects in both groups A and B were provided with continuous oxygen via microstream tubing throughout the PSA. In a review performed by Vargo,21 the author stressed the significance of unrecognised respiratory difficulty and hypoxaemia as a major factor contributing to morbidity and mortality among patients undergoing procedural sedation in the ambulatory setting.22 To overcome these potential risks, the author strongly recommended the use of capnography, which has the ability to monitor and detect any evidence of respiratory compromise early with the combined use of pulse oxymetry.

Limitations of the study

There were several limitations in this study.

  1. The study was carried out for a duration of 1 year as part of the requirement for the completion of the master programme in emergency medicine using the available short-term grant. Unfortunately, we were only able to recruit 40 subjects within the stipulated time. However, the research would be continued upon the approval of the second phase of the short-term grant.

  2. During the process of administration of drugs under study, the operators were aware of drugs that were given to patients when the envelope was opened. The operator could easily recognise the types of drug given by the different sizes of ampoules, the colour of the ampoules, the drug's inscription on the ampoule and the quantity of the drug in the ampoule.

  3. As the main objective of the study was to observe the outcomes of the drugs propofol and midazolam on vitals signs, end-tidal carbon dioxide and the time interval to discharge, other cofounders such as the clinical procedures and amount of doses of the drug top-ups were not included in the data analysis.


This study did not detect any occurrence of hypoxaemia, hypoventilation and apnoea in any of the subjects who participated in this trial despite evidence to indicate that both propofol and midazolam do cause the above complications. This is due to the fact that the study used appropriate doses to commence PSA in the ED setting. As both of these drugs are safe and effective, the main researcher would like to recommend the following doses to be administered when performing procedural sedation in the ED setting. For propofol, the recommended dose is 1 mg/kg body weight as a bolus dose followed by 0.5 mg/kg if required in a titrating dose. For midazolam the recommended dose is 0.1 mg/kg body weight as a bolus dose followed by 0.1 mg/kg in a titrating dose when necessary. Despite these drugs being regarded as safe and effective, caution is still needed to ensure that any possible complications are minimised.

A capnograph is a very useful instrument to monitor the arterial partial pressure of carbon dioxide indirectly during PSA. It is a very sensitive tool to pick up these changes at the very early stages of hypoventilation and its accuracy in detection is strongly supported by numerous studies worldwide. It is recommended that capnography should be used when PSA is performed in the ED setting. Early intervention could be instituted once an abnormal partial pressure of carbon dioxide is detected.

Finally, all patients planned for PSA in the ED must be thoroughly assessed, which involves a detailed medical history in order to prevent the development of unexpected complications and delayed recovery after a procedure has been completed.


Both propofol and midazolam given at the recommended doses are equally safe and effective in PSA that is performed in the ED setting. Propofol has been found to shorten the recovery process after PSA and is the drug of choice over midazolam.


The authors would like to thank the nurses from the Emergency Department, Hospital Universiti Sains Malaysia, who assisted the trial.


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  • Funding This study was conducted by the use of a short-term grant provided by the medical school of Universiti Sains Malaysia, registered under JKP/PPSP/USM/06.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Research and Ethics Committee, School of Medical Sciences, Universiti Sains Malaysia.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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