Nursing use between 2 methods of procedural sedation: midazolam versus propofol

Joel S. Holger MD^a,*, Paul A. Satterlee MD^b, Stephanie Haugen RN^c

^aEmergency Medicine Department, Regions Hospital, St Paul, MN 55101, USA

^bEmergency Medicine Department, North Memorial Hospital, Robbinsdale, MN 55422, USA

^cEmergency Medicine Department, Bronson Hospital, Kalamazoo, MI 49007, USA

Received 6 April 2002; accepted 15 January 2002

Abstract We compared propofol (P) and midazolam (M) use in sedation using nurses’ (RN’s) monitoring times, costs, and Visual analog scale satisfaction scores. We randomized 40 patients to either P or M groups. The P group received 0.5 mg/kg IV followed by titration to a Ramsay Sedation Scale of 3 or 4. The M group received 1 mg IV every 2 minutes to a Ramsay Sedation Scale of 3 or 4. Time for sedation, procedure, and recovery were compared. VAS scores were measured for the patient, RN, and physician. Thirty-two patients completed the study. Median RN monitoring time was 52 minutes for the M group and 36 minutes for the P group. VAS score differences were significant only in the physician group. We concluded that compared with midazolam, propofol required less RN monitoring and had lower costs. Physician satisfaction was higher with propofol sedation than with midazolam and required less time. D 2005

Introduction

Many recent emergency medicine publications have ad- dressED procedural sedation techniques. Although there are many agents and techniques that are safe and effective, there have been concerns expressed about the relevance of some of this research and the safety of certain medications [1-3]. These concerns have led to calls to move in different research directions including the use of ultrashort-acting agents and the evaluation of resource use [4 – 6]. The availability and use of nursing (RN) resources are often a limiting factor in a busy ED that affects patient flow and departmental efficiency. RN

Presented as an oral presentation at the Society for Academic Emergency Medicine annual meeting in Atlanta, Ga; May 2001.

T Corresponding author. Tel.: +1 651 254 4788; fax: +1 651 254 5216.

E-mail address: [email protected] (J.S. Holger).

presence is required for patient monitoring during procedural sedation, and their availability may affect physician decision making in the choice of sedation medications.

In this study, we chose to evaluate the differences between midazolam, which has been stated to be the most commonly used drug for procedure sedation in children and adults [4], and propofol, an ultrashort-acting drug. The goals of the study were to (1) assess time of RN use for continuous patient monitoring; (2) calculate a cost compar- ison using RN time and drug cost; and (3) assess satisfaction levels of sedation by the patient, RNs, and physicians for these 2 sedation drugs.

Materials and methods

We conducted a prospective randomized trial comparing midazolam and propofol for the sedation of adult patients

0735-6757/$ – see front matter D 2005 doi:10.1016/j.ajem.2005.01.001

Light

1 = Anxious and agitated or restless or both

2 = Cooperative, orientated, and tranquil

3 = Responds to commands only Deep

4 = Brisk response to a light glabellar or loud auditory stimulus

5 = Sluggish response to a light glabellar tap or loud auditory stimulus

6 = No response to a light glabellar tap or loud auditory stimulus

Table 1 Modified RSS score

undergoing painful procedures. We compared the duration of sedation; nursing time use, patient; physician, and Nurse satisfactions levels; and cost (RN time and drug cost) for midazolam and propofol. The institutional review board approved the trial, and written informed patient consent was obtained from all patients enrolled.

The trial was conducted in an urban teaching hospital ED with 65000 visits annually. We enrolled a convenience sample of patients undergoing painful procedures that required sedation between November 1999 and May 2000. Inclusion criteria included (1) age 18 to 65 and competent to give informed consent, (2) expected procedure length of 15 minutes or less, and (3) American Society of Anesthesi- ologists class I or II. Exclusion criteria included (1) evidence of alcohol or drug intoxication; (2) pregnancy;

(3) allergy to midazolam, fentanyl, or propofol; and (4) evidence of significant hypovolemia or severe cardiac or pulmonary disease.

Patients were randomized to either the propofol or the midazolam group. Neither the RN nor the physician was blinded to study medications. The patient was blinded to the randomized drug. The Ramsay Sedation Scale (RSS) was used to score the level of sedation for all patients [7] (Table 1). The goal was to achieve a level 3 or 4 before the beginning of the procedure. The RSS was assessed at the beginning of the sedation, the start of the procedure, the end of the procedure, and at the discontinuation of RN monitoring. Times of these events were recorded.

Patients were also enrolled if they received prior narcotic medication as necessary for evaluation of their condition before the procedure to simulate more accurately the course of events in a typical ED. An example would be a patient with a Joint dislocation that required narcotic medication before obtaining an x-ray evaluation. When the procedure was ready to be performed in these patients, pain relief had to be judged adequate by the attending physician. If no prior narcotic was administered, fentanyl, at 2 lg/kg IV, was given before sedation.

In each medication group, a 2-minute period elapsed after administration of the fentanyl dose. Patients in the propofol group then received an initial bolus of propofol of

0.5 mg/kg IV push. Additional boluses of 0.25 mg/kg IV push were given every 30 to 45 seconds until a minimum

RSS score of 3 was obtained. The procedure was then begun. Additional boluses of 0.25 mg/kg IV were used per physician judgment if during the procedure, the patient became less sedated and the RSS became less than 3. After administration of narcotics, patients in the midazolam group received an initial bolus of midazolam of 1 mg IV. Additional doses of 1 mg were given every 2 minutes until a minimum RSS score of 3 was obtained. The procedure was then begun. Additional boluses were given if the RSS became less than 3 during the procedure per physician judgment. The physician had the option to begin the procedure if there was difficulty in obtaining an RSS of 3. If this occurred, no further data were recorded, and the patient was not included in the final data set.

All patients received oxygen by a nonrebreather mask for 5 minutes before each procedure until recovery. continuous monitoring of oxygen saturation and cardiac rhythm was performed. Blood pressure was recorded every 5 minutes. Continuous RN monitoring of the patient was required from the beginning of the sedation until recovery. Recovery was defined as the patient having (1) normal vital signs; (2) orientation to person, place, and time without slurred speech;

(3) the ability to sit on the side of the bed unassisted; and (4) if the patient was able to walk before the procedure, the ability to walk 5 steps and return unassisted were also required.

At the conclusion of each patient study, visual analog scale scoring was used to determine satisfaction levels. Each scale was a 100-mm horizontal line with vertical lines at each end. Outside these were the words bextremely unsatisfiedQ at the 0-mm end and bextremely satisfiedQ at the 100-mm end. A brief question was placed below the scale asking the patient to rate their satisfaction of the procedural sedation. The physician and the RN marked 3 separate VAS scores, each with identical anchors with questions relating to either the titration, the level of sedation, or the recovery from the sedation. Each patient was given a questionnaire to return after a minimum 24-hour period. Recall (none, some, most, or all) of the procedure and complications (nausea, vomiting, anxiety, and sleepiness) were measured.

The primary outcome measure was RN monitoring time. Secondary measures included adverse events (hypoxia, hypotension, and bradycardia), maximum RSS scores, VAS scores, and 24-hour recall and complications. Using Cohen’s formula, a power table was derived estimating a common SD of 17.2 (nQuery, version 1, Statistical Solutions, Saugus, MA). SDs of mean Recovery times for midazolam and propofol were obtained from Carlson and Grattidge [8]. This computation estimated the mean difference of 20 minutes in time to recovery between the

Table 2 Total RN monitoring time (minutes)
	Q1	Median	Q3	P value
Midazolam	40	52	63	.007
Propofol	24	36	41

Table 5 Maximum RSS scores

RSS 3 4

Midazolam 53% 47%

Propofol 47% 20%

5 or 6

0%

33%

P value

.023

Midazolam	2	6	8	.33
Propofol	1	5	8
Time of recovery
Midazolam	26	35	40	.107
Propofol	15	24	35

2 groups and was equal to the effect size. We assumed that a 20-minute difference in monitoring time would be mean- ingful for RN functioning in the flow of events in a busy ED. Each group required 16 patients with an a (2-tailed) of

Table 3 RN monitoring time analysis (minutes)

Q1 Median Q3 P value

Time to sedation

Midazolam Propofol

Time of procedure

6

3

12

4

16

7

.013

.05 and a minimum power of 90%. The Cost-effective analysis defined cost as drug cost (midazolam, US$10.91 per vial; propofol, US$7.98 per vial) plus nursing cost (average of US$32.00 per hour, salary plus benefits). Multiple vials were accounted for if necessary.

RN monitoring times were compared between the

2 groups using nonparametric Wilcoxon rank sum tests. Demographics and other characteristics were compared using v² and Fisher exact test for categorical variables and t tests for continuous variables. Multiple Linear regression models were performed for nursing and procedure times and costs. Maximum RSS scores, complications, and 24-hour recalls were compared using Fisher exact test. SAS 8.0 software (SAS, Cary, NC) was used for statistical analyses.

Results

Forty patients were enrolled. Thirty-two patients com- pleted the study and were included in the analysis. Eight patients failed to reach an RSS of 3 and were excluded (procedure begun and no further data obtained). Seven of these 8 were assigned to the midazolam group, 1 to the propofol group. There were no significant differences

Table 4 VAS satisfaction scores (medians)

Titration Sedation

Recovery

RN Midazolam	75	85	89
Propofol	85	90	91
P value	.10	.23	.32
Physician Midazolam	66	73	75
Propofol	95	92	93
P value	.02	.11	.10
Patient (overall) Midazolam	89
Propofol	94
P value	.13

between these 8 (other than the drug group) and the 32 included patients with respect to age, sex, or procedure.

Of the patients that completed the study, 17 were randomized to the midazolam group and 15 to the propofol group. There were no differences between these groups with respect to age, sex, weight, or procedure. Orthopedic reductions and abscess incision and drainage were the most common procedures in both groups. Fifteen patients in the midazolam group and 12 in the propofol group received fentanyl for pain management ( P = .65). The mean dose of midazolam was 5.4 mg, and the mean dose of propofol was

0.96 mg/kg.

Patients in the midazolam group had significantly longer total RN monitoring times ( P b .01). The median total monitoring time (titration, procedure time, and recovery time) was 52 minutes (range, 29-129) in the midazolam group and 36 minutes (range 19-146) in the propofol group (Table 2). Analysis of the total RN monitoring component times revealed that patients in the midazolam group had significantly longer titration times to sedation but not in procedure length or time to recovery (Table 3).

Patients in the midazolam group had significantly higher costs ( P b .001) with a difference of US$11.99 per patient. RNs and patients did not significantly differ in VAS satisfaction scores between the 2 groups. Physicians were more satisfied in the propofol group in sedation titration ( P = .02) but not in the other 2 measures (Table 4).

Maximum sedation levels were significantly different between the 2 groups ( P = .02). Five of the patients in the propofol group obtained a maximum sedation score of 5 or 6 (Table 5). One patient in each group experienced vomiting during the procedure. No other adverse events were noted. Twenty-four-hour recall of the procedure was not different between the groups, nor were any minor adverse events reported during that time.

Discussion

Previous studies have assessed the time efficiency of various sedation protocols in the ED. Chudnofsky et al [9] looked at the effect of reversing the sedation because of midazolam using flumazenil and found a 14-minute reduction in patients’ return to baseline alertness. This did not affect time to patient discharge, however, which may have been caused by their own study requirements of a minimum of 60 minutes of postreversal monitoring. Todd

[6] editorialized that this difference in time may not be useful to the practicing emergency physician. Havel et al

[10] compared propofol to midazolam in pediatric orthope-

dic reductions and found a greater than 60 -minute differ- ence in mean recovery time in favor of propofol. They used a double-blind technique and combined boluses of propofol with a continuous infusion to obtain an RSS score of 4 or 5. A 24 – minute time difference in total ED time was noted in favor of propofol. Our study demonstrates that the total time commitment for continuous RN patient monitoring during procedural sedation is decreased in patients who are given propofol as the sedation drug as compared with midazolam. Our data also demonstrate that satisfaction levels for the RN and the patient are similar for these drugs, whereas physicians are more satisfied with propofol during the titration phase of sedation because it requires less time.

We chose to use RN utilization as our primary outcome measure rather than patient Time to discharge. In the ED, the commitment of the RN for monitoring the sedated patient can be very time consuming. This is reflected not only in the recovery of the patient but also, as our data show, in the titration phase of sedation. The shorter the amount of time committed to patient sedation will release the RN to care for other patients. Measuring time to discharge as an outcome measure does not take into account other events happening simultaneously in the ED that impacts sedation and does not account for potential delays encountered in patients that require admission.

By a relatively simple cost calculation using only drug cost and RN salary, we were able to show that the use of propofol in these patients costs less than using midazolam. The actual relevance of the amount of this difference when compared with the Total costs of the ED encounter may be debatable. We did, however, want to ascertain that the cost of one drug was not disproportionately higher that the other.

We limited our study to only those that achieved a minimum RSS score of 3 before the beginning of the procedure. By doing this, we found that 7 patients dropped out in the midazolam group as compared with one in the propofol group. The majority of physicians stated frustration in waiting for an RSS of 3 to occur as the reason to drop the patient from the study. It appears that midazolam is more highly variable in its ability to induce a consistent level of sedation than propofol. If these patients had been included in our analysis, the time measurements and titration satisfaction scores likely would have been even more favorable for the propofol group. Physicians clearly favored propofol over midazolam in time to sedation with a 29-point difference in the VAS scores. This did not show a bceiling affect,Q that is, the inability of satisfaction VAS scores to measure a difference because of skewing of scores at the favorable end of the scale [11]. Physicians must be present at the bedside at the beginning of the sedation to direct the titration phase. The decrease in time commitment of 8 minutes during this phase may represent a meaningful gain in Physician Efficiency. Satisfaction levels in time to recovery were not significantly different for physicians or RNs. Physicians are not routinely present during the

recovery phase, and we believe that these VAS measure- ments of satisfaction are less reliable. This study was not powered to identify differences in Adverse event rates. Such a study would require many more enrolled patients. We also did not consider deeper levels of sedation (RSS of 5 or 6) to be adverse events. Our data are similar to those of Havel et al concerning propofol in that one third of these patients became boversedated,Q although Havel also found this proportion in his midazolam group. These levels of sedation (RSS of 5 or 6) did not prolong patient recovery when compared with the midazolam group. Hypoxia was not noted in any of our patients, possibly because of the brief nature of the procedures and the supplementation of oxygen.

Limitations

Our study was completed using a convenience sample of patients with a relatively small sample size. The staff physician was responsible for both the titration of the sedation and the procedure, whereas the RN was responsible for the assessment of sedation depth, patient monitoring, and administering of medications. These responsibilities required that the staff was not blinded to the drug group, and this may have affected the VAS scoring. This design was intended to simulate what takes place in actual patient care. Many of the physicians and RNs in our ED have prior experience with propofol, and previous perceptions and Comfort levels with this medication were not measured, and this may bias the VAS results.

In our design, propofol was dosed in milligram per kilogram, but the midazolam dose was not weight-based. This, again, was meant to simulate how the majority of physicians actually order these medications in adults. Changing midazolam ordering to the milligram-per-kilogram basis may have changed the results.

The relationship of the bmixQ of fentanyl to propofol and fentanyl to midazolam may have affected the recovery times. The fentanyl dose at 2 lg/kg may have required lesser amounts of propofol or fentanyl to achieve the target RSS goal and prolonged recovery times for both groups. If smaller doses of fentanyl were used, the requirements of propofol and midazolam would theoretically be increased to achieve the target RSS. This may favor propofol even more in the time to recovery comparison because the clinical effects of propofol resolve much more rapidly than midazolam.

Conclusion

When midazolam was compared with propofol in ED procedural sedation, the use of propofol required less RN monitoring and resulted in lower costs in our study. Less time commitment by physicians for sedation was required when propofol was used. These results may have beneficial effects on the efficiency of resource use in the ED. Physician satisfaction was higher with propofol in time to

sedation compared with midazolam, whereas there were no differences in RN or patient satisfaction.

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