Patient-Controlled Drug Administration during Local Anesthesia: A Comparison of Midazolam, Propofol, and Alfentanil Ahmed F. Ghouri, MD,* Ellis Taylor, MD,? Paul F. White, MD, PBD, FFARACS$ Department of Anesthesiology and Pain Southwestern Medical Center, Dallas, TX.
*Research
Associate
tStaff Anesthesiologist, St. Louis, MO. $Professor,
Jewish
and McDermott
Hospital,
Chair
Address reprint requests to Dr. White at the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9068, USA. This study was supported in part by a grant (8894) from the Ambulatory Anesthesia Research Foundation, Los Altos, CA. (Dr. White is a member of the Board of Directors.) Received for publication April 23, 1992; revised manuscript accepted for publication July 1, 1992.
Management,
University
of Texas
Study Objective: To eualuate the perioperative effects of alfentanil, midazolam, and propofol when administered using a patient-controlled analgesia (PCA) device during local anesthesia. Design: Randomized, single-blind comparative study. Setting: Outpatient surgery center at a university teaching hospital. Patients: Ninety outpatients undergoing minor elective surgical procedures with local anesthetic infiltration were assigned to one of three treatment groups. Interventions: After premeditation with midazolam 1 mg intravenously (IV) and fentanyl 5Opg IV, patients were allowed to self-administer 2 ml bolus doses of either alfentanil250 pglml, midarolam 0.4 mglml, orpropofoll0 mglml at minimal intervals of 3 minutes to supplement a basal infusion rate of 5 mllhr. Measurements and Main Results: The total intraoperatiue dosages of alfentanil, midazolam, and propofol were 2.7 t 1 .I mg, 4.7 2 2.7 mg, and 114 + 42 mg, respectively, for procedures lasting 48 ~?r28 minutes to 51 k 19 minutes (means t SD). Propofol produced more pain on injection (39% vs. 4% and 6% in the alfentanil and midazolam groups, respectively). Episodes of arterial oxygen saturation less than 90% were more frequent with alfentanil(Z8%) than with midazolam (3 %) or propofol (13%). Using the visual analog scale, patients reported comparable levels of discomfort, anxiety, and sedation during the operation in all three treatment groups. Postoperative picture recall was signa~icant~ decreased with midazolam versus alfentanil and propofol. Finally, postoperative nausea was reported more frequently in the alfentanil group (29%) than in the midazolam (10%) or propofol (18%) groups, contributing to a significant prolongation of the discharge time in the alfentanil-treated patients. Conclusions: When self-administered as adjuvants during local anesthesia using a PCA delivery system, alfentanil, midazolam, and propofol were equally acceptable to patients. However, propofol and midazolam were associated with fewer perioperatiur complications than was alfentanil.
0 1992 Butterworth-Heinemann J. Clin. Anesth. 4:476-479,
476
J. Clin.
Anesth.,
1992.
Keywords: controlled;
vol. 4, November/December
1992
Alfentanil; propofol.
anesthesia,
local; midazolam;
analgesia,
patient-
Patient-controlled drug administration during local anesthesia: Ghouri et al.
Introduction Preliminary studies suggest that patient-controlled sedation and analgesia are safe and effective techniques when used during ambulatory procedures involving local anesthesia.‘,* A previous study suggested that patient-controlled administration of a fixed-dose combination of midazolam and fentanyl during epidural anesthesia was subjectively superior to anesthesiologist administration of the same medications.3 Recently, investigators reported that patient satisfaction with patient-controlled administration of propofol was higher than physiciancontrolled sedation using standard titrated doses of midazolam and fentany14 The relative safety and effectiveness of different sedative and analgesic drugs has not been evaluated using a patient-controlled delivery system during surgery. We designed a study to compare three different techniques for providing sedation and/or analgesia during outpatient surgery. In this single-blind prospective study, we compared patient-controlled administration of alfentanil, midazolam, and propofol during local anesthesia with regard to clinical efficacy, recovery characteristics, and patient satisfaction.
Materials and Methods Ninety consenting ASA physical status I and II adult outpatients undergoing surgical procedures with local anesthetic infiltration were studied according to a singleblind protocol approved by the Human Studies Committee at the Washington University School of Medicine. Patients scheduled to undergo breast biopsies, endoscopic sinus surgeries, or lymph node biopsies with local anesthetic infiltration under monitored anesthesia care (MAC) were randomly assigned to one of three intraoperative patient-controlled drug administration treatment groups. After written informed consent was obtained, all patients were asked to complete a preoperative questionnaire to assess their need to be in control, as well as their desired level of sedation (sleepiness) during the operation. The patients were asked to evaluate their desire to be in control of their intraoperative medication on a scale of 1 to 5 (with 1 = no control to 5 = complete control). Similarly, patients were asked to indicate their desired level of sedation during the operation on a scale of 1 to 4 (with 1 = totally awake to 4 = completely asleep). Visual analog scale (VAS) scores were used to assess the patients’ degree of anxiety and sedation (or sleepiness) prior to receiving any medication (with 0 mm = none to 100 mm = maximum effect).5 The results of the preoperative questionnaire and baseline VAS scores were not used to determine a patient’s acceptability for participation in the study. Patients were monitored with an electrocardiogram, a noninvasive automatic blood pressure cuff (Dinamap, Tampa, FL), a digital pulse oximeter (Nellcor, Hayward, CA), and a precordial stethoscope. Patients received supplemental oxygen at 4 L/min via a nasal cannula. Mean arterial pressure, heart rate, and oxygen saturation (SpO,)
were recorded at 5-minute intervals throughout the operative procedure. SpO, values less than 90% for longer than 10 seconds were considered to represent transient oxygen desaturation. After we obtained initial (baseline) vital signs, all patients were premeditated with midazolam 1 mg intravenously (IV) and fentanyl 50 kg IV, then randomly assigned to one of three drug treatment groups: Group 1 received alfentanil 250 pg/ml; Group 2 received midazolam 0.4 mg/ml; Group 3 received propofol 10 mg/ ml. At the time of local anesthetic infiltration, all patients were given a loading dose of 3 ml over 1 to 2 minutes, followed by a basal infusion of 5 ml/hr, which could be supplemented with 2 ml bolus doses on demand using a Bard patient-controlled analgesia (PCA) device (PCA I’“, Bard Medsystems, North Reading, MA) with a mandatory lockout interval of 3 minutes. This PCA device was available to the patient throughout the operation. All patients received instruction in the use of the device immediately prior to receiving the preanesthetic medication. To assess perioperative amnesia, patients were shown three pictures: one before the operation, one immediately after the operation, and one upon arrival in the recovery room. A standardized questionnaire was completed at the time of discharge from the outpatient facility to assess patient recall of perioperative events and overall satisfaction with the patient-controlled drug administration technique. Discharge time was recorded by a blinded nurse-observer when the patient was oriented to time and place, had stable vital signs on sitting up and mobilizing, could void urine, and was able to ambulate without assistance. Statistical Analysis Continuous variables were analyzed using a one-way analysis of variance (ANOVA). Descriptive variables were analyzed using chi-square analysis or Fisher’s exact test when appropriate. Wilcoxon’s rank-sum test was used to compare median values between the three treatment groups. A p-value less than 0.05 was considered statistically significant. Data are reported as means 2 SD or medians (ranges).
Results The three drug treatment groups were similar with respect to the number of patients and their age, weight, height, sex, and ASA physical status (Table 1). The three groups also were comparable with regard to the patients’ subjective desire to be in control, their preferred level of sedation during the procedure, and their anxiety and sedation scores in the holding area prior to the operation (Table 2). The duration of surgery, average drug administration rate, and total drug dosage for the three treatment groups are shown in Table 3. Patients in the propofol group required IV lidocaine to treat pain on initial injection of the study drug more frequently than did those in the alfentanil group. Alfentanil-treated patients had an increased frequency of J. Clin. Anesth., vol. 4, November/December
1992
477
Original
Contribution\
Table 1. Demographic Characteristics of the Three Drug Treatment Groups
Number Age (yr) Weight (kg) Height (cm) Sex (M/F) ASA physical status (I/II)
Alfentanil
Midazolam
Propofol
27 53 + 15 74 -r- 22 173 Z!Z9 17110
32 48 r 16 73 r 16 175 c 8 20112
31 49 * 16 76 t 18 171 + 11 19/12
15112
2418
21/10
Note: Data are means 2 SD.
Table 2. Pretreatment Patient Assessment Scores for the Three Treatment Groups
Number Sedation score (mm)* Anxiety score (mm)* Patient’s desire to be in control? Patient’s desired level of drowsiness$
Alfentanil
Midazolam
Propofol
27
32
31
18 + 22 31 2 30
14 + 16 34 * 29
16 + 19 32 t 29
4(1 to5)
4(1 to5)
4 (1 to 5)
2 (1 to 3)
2 (1 to 3)
2 (1 to 3)
*Data are means 2 SD. Visual analog scale scores are based on scales from 0 = wide awake to 100 = asleep for sedation; 0 = calm to 100 = extremely
nervous
for anxiety.
tData are median values (ranges). Scores are based on a scale from 1 = no control to 5 = complete control. *Data are median values (ranges). Scores are based on a scale from 1 = totally awake to 4 = completely asleep.
Table 4. Intraoperative Data and Results of the Postoperative Questionnaire for the Three Treatment Groups
Number Complained pain on injection
Alfentanil Number 27 Duration of surgery (min) 49 ? 28 Average infusion rate (mg/min) 0.06 * 0.02 Total drug dosage (mg) 2.7 + 1.1
Midazolam
Propofol
32
31
48 ? 28
51 * 19
0.10 + 0.03
2.4 t 0.8
4.7 + 2.7
114 + 42
Note: Data are means ? SD. transient oxygen desaturation (Table 4). However, no differences were noted with regard to pain or discomfort during the injection of the local anesthetic solution or during the surgical procedure as indicated by the patients’ responses to the discharge questionnaire (Table 4). Finally, patients in each group reported comparable levels of anxiety and sedation during the operation (Table 4). Postoperatively, there was a higher frequency of nau478
J. Clin. Anesth., vol. 4, November/December 1992
Midazolam
Propofol
27
32
31
4
6
39*
28*
3
13
21
18
26
20
23
19
19 ? 21
21 * 20
17 2 21
63 -+ 25
68 * 29
73 2 24
15 (0 to 81)
18 (0 to 101)
16 (0 to 117)
4 (0 to 23)
4 (0 to 12)
of of
study drug (‘%) Transient oxygen desaturation (%) Recalled pain during local anesthetic injection (%) Recalled discomfort during the operation (70) Anxiety score during the operation
(mm)t Sedation level during the operation (mm)? PCA bolus demands (n)$ Delivered doses
4 (0 to 12)
(n)S *p < 0.05;
significantly
different
from
the other
groups.
tData are means t SD. Visual analog scale scores are based on 0 = wide awake to 100 = asleep for sedation; 0 = calm to 100 = extremely nervous for anxiety. $Data are median
Table 3. Duration of Surgery, Drug Administration Rate, and Total Drug Dosage for the Three Treatment Groups
Alfentanil
values
PCA = patient-controlled
(ranges). analgesia.
sea among patients who received alfentanil (29% versus 10% and 18% in the midazolam and propofol groups, respectively). There were no differences with regard to the patients’ ability to recall pictures shown prior to administration of the preanesthetic medication. However, patients in the midazolam group demonstrated a decreased ability to recall pictures shown to them immediately after the operation and following arrival in the postanesthesia care unit when compared with the alfentanil and propofol groups (Table 5.). Discharge times were similar in the groups receiving propofol (95 t 49 minutes) and midazolam (90 + 32 minutes), but were significantly longer in the group receiving alfentanil(l26 + 56 minutes, p < 0.05.) Although the mean number of demands for the study medication in each group was significantly greater than the actual number of delivered doses, all patients stated that they were satisfied with their sedation and analgesia during the procedure. Irrespective of which drug was self-administered, more than 95% of patients stated that
Patient-controlled drug administration during local anesthesia: Ghouri et al. Table 5. Perioperative
Recall
in the Three
Treatment
Groups*
Recalled Recalled Recalled *Picture eration;
picture picture picture
Alfentanil
Midazolam
Propofol
100 75 82
96 44t
97 71
567
82
1 (%) 2 (%) 3 (%)
1 = preoperative; picture 3 = upon
tp < 0.05;significantly
be willing they would again in the future.
picture 2 = immediately after the oparrival in the postanesthesia care unit.
different
from
the other
groups.
to use the same PCA
technique
Discussion The three sedative-analgesic techniques were safe and effective when used as a part of a MAC technique. These data are consistent with other preliminary studies involving patient-controlled sedation and/or analgesia during surgery. 1-4 No clinically significant side effects were noted during self-administration of alfentanil, midazolam, or propofol. Although the possibility of overmedication exists with patient-controlled drug administration, the mandatory lockout interval and drug dosage limitations decreased the likelihood of this occurring during the operation. The primary advantage of PCA over physician-controlled drug administration is that it allows the patient to become an active participant in the medication process. Since administration of sedation and analgesic drugs is highly subjective, PCA might provide improved patient comfort by involving the patient in the decision-making process. Regardless of the sedative-analgesic technique, nearly all patients participating in this study stated that they liked self-administration of intraoperative medication and would use the same technique for a similar operation in the future. Osborne et al.4 found that patient-controlled sedation using propofol was superior to anesthetist-administered midazolam and fentanyl with regard to overall patient satisfaction and subjective feelings. In the current study, however, we were unable to demonstrate significant differences in the patients’ subjective assessments of or satisfaction with self-administered propofol, midazolam, or alfentanil during similar surgical procedures. The differences between these two studies may relate to the fact that different dosage regimens were used. It is interesting to note that the number of patient demands were significantly greater than the number of actual delivered doses in each of the three drug groups because of the mandatory lockout (or delay) interval between successive bolus doses. Parker et aL6 reported similar findings when PCA was used with a basal opioid infusion for postoperative pain relief. Despite this dis-
crepancy between the number of patient demands and the number of delivered doses, patients reported a high degree of satisfaction with the patient-controlled techniques. Given the fact that patients were drowsy and/or amnestic during the operation itself, it is possible that they were not actually aware of when medication was being administered, nor could they accurately perceive the duration of the lockout interval. Thus, many patients were probably unaware of the fact that on average, only one-fourth of their demands were being met. In addition, it is possible that patient satisfaction with selfadministration techniques is primarily a function of the positive psychological effect produced when patients are allowed to control their own drug administration rather than a function of the particular drug or dosage regimen used. In conclusion, self-administration of alfentanil, propofol, and midazolam using a PCA device was without clinically significant adverse effects when used to supplement local anesthesia. The three drugs were equally acceptable to patients. However, propofol was associated with a higher frequency of pain on injection, while patients receiving alfentanil experienced a higher frequency of intraoperative oxygen desaturation and postoperative nausea. The higher frequency of emetic symptoms may have contributed to prolonging the recovery room stay in the alfentanil treatment group.7 Since alfentanil is a different type of drug (i.e., an analgesic with sedative properties versus a sedative-hypnotic), caution should be used in concluding that it is less satisfactory than midazolam or propofol. Further controlled studies are needed to determine whether self-administration of sedative and analgesic drugs alone or in combination offer any advantages over conventional physician-controlled drug administration techniques.
References 1. Rudkin GE, Osborne GA, Curtis NJ: lntra-operative patientcontrolled sedation. Anaesthesia 1991;46:90-2. 2. Zelcer J, White PF, Chester S, Paul1 JD, Molnar R: lntraoperative patient-controlled analgesia: An alternative to physician administration during outpatient monitored anesthesia care. Anesth Analg 1992;75:41-4. 3. Park WY, Watkins PA: Patient-controlled sedation during epidural anesthesia. Anesth Analg 1991;72:304-7. 4. Osborne GA, Rudkin GE, Curtis NJ, Vickers D, Craker AJ: Intraoperative patient-controlled sedation. Comparison of patient-controlled propofol with anaesthetist-administered midazolam and fentanyl. Anaesthesia 1991;46:553-6. 5. Bond A, Lader M: The use of analogue scales in rating subjective feelings. Br J Med Psycho1 1974;47:21 l-8. 6. Parker RK, Holtmann B, White PF: Patient controlled analgesia: does a concurrent opioid infusion improve pain management after surgery? JAMA 1991;266:1947-52. 7. Doze VA, Shafer A, White PF: Nausea and vomiting after outpatient anesthesia-effectiveness of droperidol alone and in combination with metoclopramide [Abstract]. Anesth Analg 1987;66:S41.
J. Clin.
Anesth.,
vol. 4, November/December
1992
479
*Research
Associate
tStaff Anesthesiologist, St. Louis, MO. $Professor,
Jewish
and McDermott
Hospital,
Chair
Address reprint requests to Dr. White at the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9068, USA. This study was supported in part by a grant (8894) from the Ambulatory Anesthesia Research Foundation, Los Altos, CA. (Dr. White is a member of the Board of Directors.) Received for publication April 23, 1992; revised manuscript accepted for publication July 1, 1992.
Management,
University
of Texas
Study Objective: To eualuate the perioperative effects of alfentanil, midazolam, and propofol when administered using a patient-controlled analgesia (PCA) device during local anesthesia. Design: Randomized, single-blind comparative study. Setting: Outpatient surgery center at a university teaching hospital. Patients: Ninety outpatients undergoing minor elective surgical procedures with local anesthetic infiltration were assigned to one of three treatment groups. Interventions: After premeditation with midazolam 1 mg intravenously (IV) and fentanyl 5Opg IV, patients were allowed to self-administer 2 ml bolus doses of either alfentanil250 pglml, midarolam 0.4 mglml, orpropofoll0 mglml at minimal intervals of 3 minutes to supplement a basal infusion rate of 5 mllhr. Measurements and Main Results: The total intraoperatiue dosages of alfentanil, midazolam, and propofol were 2.7 t 1 .I mg, 4.7 2 2.7 mg, and 114 + 42 mg, respectively, for procedures lasting 48 ~?r28 minutes to 51 k 19 minutes (means t SD). Propofol produced more pain on injection (39% vs. 4% and 6% in the alfentanil and midazolam groups, respectively). Episodes of arterial oxygen saturation less than 90% were more frequent with alfentanil(Z8%) than with midazolam (3 %) or propofol (13%). Using the visual analog scale, patients reported comparable levels of discomfort, anxiety, and sedation during the operation in all three treatment groups. Postoperative picture recall was signa~icant~ decreased with midazolam versus alfentanil and propofol. Finally, postoperative nausea was reported more frequently in the alfentanil group (29%) than in the midazolam (10%) or propofol (18%) groups, contributing to a significant prolongation of the discharge time in the alfentanil-treated patients. Conclusions: When self-administered as adjuvants during local anesthesia using a PCA delivery system, alfentanil, midazolam, and propofol were equally acceptable to patients. However, propofol and midazolam were associated with fewer perioperatiur complications than was alfentanil.
0 1992 Butterworth-Heinemann J. Clin. Anesth. 4:476-479,
476
J. Clin.
Anesth.,
1992.
Keywords: controlled;
vol. 4, November/December
1992
Alfentanil; propofol.
anesthesia,
local; midazolam;
analgesia,
patient-
Patient-controlled drug administration during local anesthesia: Ghouri et al.
Introduction Preliminary studies suggest that patient-controlled sedation and analgesia are safe and effective techniques when used during ambulatory procedures involving local anesthesia.‘,* A previous study suggested that patient-controlled administration of a fixed-dose combination of midazolam and fentanyl during epidural anesthesia was subjectively superior to anesthesiologist administration of the same medications.3 Recently, investigators reported that patient satisfaction with patient-controlled administration of propofol was higher than physiciancontrolled sedation using standard titrated doses of midazolam and fentany14 The relative safety and effectiveness of different sedative and analgesic drugs has not been evaluated using a patient-controlled delivery system during surgery. We designed a study to compare three different techniques for providing sedation and/or analgesia during outpatient surgery. In this single-blind prospective study, we compared patient-controlled administration of alfentanil, midazolam, and propofol during local anesthesia with regard to clinical efficacy, recovery characteristics, and patient satisfaction.
Materials and Methods Ninety consenting ASA physical status I and II adult outpatients undergoing surgical procedures with local anesthetic infiltration were studied according to a singleblind protocol approved by the Human Studies Committee at the Washington University School of Medicine. Patients scheduled to undergo breast biopsies, endoscopic sinus surgeries, or lymph node biopsies with local anesthetic infiltration under monitored anesthesia care (MAC) were randomly assigned to one of three intraoperative patient-controlled drug administration treatment groups. After written informed consent was obtained, all patients were asked to complete a preoperative questionnaire to assess their need to be in control, as well as their desired level of sedation (sleepiness) during the operation. The patients were asked to evaluate their desire to be in control of their intraoperative medication on a scale of 1 to 5 (with 1 = no control to 5 = complete control). Similarly, patients were asked to indicate their desired level of sedation during the operation on a scale of 1 to 4 (with 1 = totally awake to 4 = completely asleep). Visual analog scale (VAS) scores were used to assess the patients’ degree of anxiety and sedation (or sleepiness) prior to receiving any medication (with 0 mm = none to 100 mm = maximum effect).5 The results of the preoperative questionnaire and baseline VAS scores were not used to determine a patient’s acceptability for participation in the study. Patients were monitored with an electrocardiogram, a noninvasive automatic blood pressure cuff (Dinamap, Tampa, FL), a digital pulse oximeter (Nellcor, Hayward, CA), and a precordial stethoscope. Patients received supplemental oxygen at 4 L/min via a nasal cannula. Mean arterial pressure, heart rate, and oxygen saturation (SpO,)
were recorded at 5-minute intervals throughout the operative procedure. SpO, values less than 90% for longer than 10 seconds were considered to represent transient oxygen desaturation. After we obtained initial (baseline) vital signs, all patients were premeditated with midazolam 1 mg intravenously (IV) and fentanyl 50 kg IV, then randomly assigned to one of three drug treatment groups: Group 1 received alfentanil 250 pg/ml; Group 2 received midazolam 0.4 mg/ml; Group 3 received propofol 10 mg/ ml. At the time of local anesthetic infiltration, all patients were given a loading dose of 3 ml over 1 to 2 minutes, followed by a basal infusion of 5 ml/hr, which could be supplemented with 2 ml bolus doses on demand using a Bard patient-controlled analgesia (PCA) device (PCA I’“, Bard Medsystems, North Reading, MA) with a mandatory lockout interval of 3 minutes. This PCA device was available to the patient throughout the operation. All patients received instruction in the use of the device immediately prior to receiving the preanesthetic medication. To assess perioperative amnesia, patients were shown three pictures: one before the operation, one immediately after the operation, and one upon arrival in the recovery room. A standardized questionnaire was completed at the time of discharge from the outpatient facility to assess patient recall of perioperative events and overall satisfaction with the patient-controlled drug administration technique. Discharge time was recorded by a blinded nurse-observer when the patient was oriented to time and place, had stable vital signs on sitting up and mobilizing, could void urine, and was able to ambulate without assistance. Statistical Analysis Continuous variables were analyzed using a one-way analysis of variance (ANOVA). Descriptive variables were analyzed using chi-square analysis or Fisher’s exact test when appropriate. Wilcoxon’s rank-sum test was used to compare median values between the three treatment groups. A p-value less than 0.05 was considered statistically significant. Data are reported as means 2 SD or medians (ranges).
Results The three drug treatment groups were similar with respect to the number of patients and their age, weight, height, sex, and ASA physical status (Table 1). The three groups also were comparable with regard to the patients’ subjective desire to be in control, their preferred level of sedation during the procedure, and their anxiety and sedation scores in the holding area prior to the operation (Table 2). The duration of surgery, average drug administration rate, and total drug dosage for the three treatment groups are shown in Table 3. Patients in the propofol group required IV lidocaine to treat pain on initial injection of the study drug more frequently than did those in the alfentanil group. Alfentanil-treated patients had an increased frequency of J. Clin. Anesth., vol. 4, November/December
1992
477
Original
Contribution\
Table 1. Demographic Characteristics of the Three Drug Treatment Groups
Number Age (yr) Weight (kg) Height (cm) Sex (M/F) ASA physical status (I/II)
Alfentanil
Midazolam
Propofol
27 53 + 15 74 -r- 22 173 Z!Z9 17110
32 48 r 16 73 r 16 175 c 8 20112
31 49 * 16 76 t 18 171 + 11 19/12
15112
2418
21/10
Note: Data are means 2 SD.
Table 2. Pretreatment Patient Assessment Scores for the Three Treatment Groups
Number Sedation score (mm)* Anxiety score (mm)* Patient’s desire to be in control? Patient’s desired level of drowsiness$
Alfentanil
Midazolam
Propofol
27
32
31
18 + 22 31 2 30
14 + 16 34 * 29
16 + 19 32 t 29
4(1 to5)
4(1 to5)
4 (1 to 5)
2 (1 to 3)
2 (1 to 3)
2 (1 to 3)
*Data are means 2 SD. Visual analog scale scores are based on scales from 0 = wide awake to 100 = asleep for sedation; 0 = calm to 100 = extremely
nervous
for anxiety.
tData are median values (ranges). Scores are based on a scale from 1 = no control to 5 = complete control. *Data are median values (ranges). Scores are based on a scale from 1 = totally awake to 4 = completely asleep.
Table 4. Intraoperative Data and Results of the Postoperative Questionnaire for the Three Treatment Groups
Number Complained pain on injection
Alfentanil Number 27 Duration of surgery (min) 49 ? 28 Average infusion rate (mg/min) 0.06 * 0.02 Total drug dosage (mg) 2.7 + 1.1
Midazolam
Propofol
32
31
48 ? 28
51 * 19
0.10 + 0.03
2.4 t 0.8
4.7 + 2.7
114 + 42
Note: Data are means ? SD. transient oxygen desaturation (Table 4). However, no differences were noted with regard to pain or discomfort during the injection of the local anesthetic solution or during the surgical procedure as indicated by the patients’ responses to the discharge questionnaire (Table 4). Finally, patients in each group reported comparable levels of anxiety and sedation during the operation (Table 4). Postoperatively, there was a higher frequency of nau478
J. Clin. Anesth., vol. 4, November/December 1992
Midazolam
Propofol
27
32
31
4
6
39*
28*
3
13
21
18
26
20
23
19
19 ? 21
21 * 20
17 2 21
63 -+ 25
68 * 29
73 2 24
15 (0 to 81)
18 (0 to 101)
16 (0 to 117)
4 (0 to 23)
4 (0 to 12)
of of
study drug (‘%) Transient oxygen desaturation (%) Recalled pain during local anesthetic injection (%) Recalled discomfort during the operation (70) Anxiety score during the operation
(mm)t Sedation level during the operation (mm)? PCA bolus demands (n)$ Delivered doses
4 (0 to 12)
(n)S *p < 0.05;
significantly
different
from
the other
groups.
tData are means t SD. Visual analog scale scores are based on 0 = wide awake to 100 = asleep for sedation; 0 = calm to 100 = extremely nervous for anxiety. $Data are median
Table 3. Duration of Surgery, Drug Administration Rate, and Total Drug Dosage for the Three Treatment Groups
Alfentanil
values
PCA = patient-controlled
(ranges). analgesia.
sea among patients who received alfentanil (29% versus 10% and 18% in the midazolam and propofol groups, respectively). There were no differences with regard to the patients’ ability to recall pictures shown prior to administration of the preanesthetic medication. However, patients in the midazolam group demonstrated a decreased ability to recall pictures shown to them immediately after the operation and following arrival in the postanesthesia care unit when compared with the alfentanil and propofol groups (Table 5.). Discharge times were similar in the groups receiving propofol (95 t 49 minutes) and midazolam (90 + 32 minutes), but were significantly longer in the group receiving alfentanil(l26 + 56 minutes, p < 0.05.) Although the mean number of demands for the study medication in each group was significantly greater than the actual number of delivered doses, all patients stated that they were satisfied with their sedation and analgesia during the procedure. Irrespective of which drug was self-administered, more than 95% of patients stated that
Patient-controlled drug administration during local anesthesia: Ghouri et al. Table 5. Perioperative
Recall
in the Three
Treatment
Groups*
Recalled Recalled Recalled *Picture eration;
picture picture picture
Alfentanil
Midazolam
Propofol
100 75 82
96 44t
97 71
567
82
1 (%) 2 (%) 3 (%)
1 = preoperative; picture 3 = upon
tp < 0.05;significantly
be willing they would again in the future.
picture 2 = immediately after the oparrival in the postanesthesia care unit.
different
from
the other
groups.
to use the same PCA
technique
Discussion The three sedative-analgesic techniques were safe and effective when used as a part of a MAC technique. These data are consistent with other preliminary studies involving patient-controlled sedation and/or analgesia during surgery. 1-4 No clinically significant side effects were noted during self-administration of alfentanil, midazolam, or propofol. Although the possibility of overmedication exists with patient-controlled drug administration, the mandatory lockout interval and drug dosage limitations decreased the likelihood of this occurring during the operation. The primary advantage of PCA over physician-controlled drug administration is that it allows the patient to become an active participant in the medication process. Since administration of sedation and analgesic drugs is highly subjective, PCA might provide improved patient comfort by involving the patient in the decision-making process. Regardless of the sedative-analgesic technique, nearly all patients participating in this study stated that they liked self-administration of intraoperative medication and would use the same technique for a similar operation in the future. Osborne et al.4 found that patient-controlled sedation using propofol was superior to anesthetist-administered midazolam and fentanyl with regard to overall patient satisfaction and subjective feelings. In the current study, however, we were unable to demonstrate significant differences in the patients’ subjective assessments of or satisfaction with self-administered propofol, midazolam, or alfentanil during similar surgical procedures. The differences between these two studies may relate to the fact that different dosage regimens were used. It is interesting to note that the number of patient demands were significantly greater than the number of actual delivered doses in each of the three drug groups because of the mandatory lockout (or delay) interval between successive bolus doses. Parker et aL6 reported similar findings when PCA was used with a basal opioid infusion for postoperative pain relief. Despite this dis-
crepancy between the number of patient demands and the number of delivered doses, patients reported a high degree of satisfaction with the patient-controlled techniques. Given the fact that patients were drowsy and/or amnestic during the operation itself, it is possible that they were not actually aware of when medication was being administered, nor could they accurately perceive the duration of the lockout interval. Thus, many patients were probably unaware of the fact that on average, only one-fourth of their demands were being met. In addition, it is possible that patient satisfaction with selfadministration techniques is primarily a function of the positive psychological effect produced when patients are allowed to control their own drug administration rather than a function of the particular drug or dosage regimen used. In conclusion, self-administration of alfentanil, propofol, and midazolam using a PCA device was without clinically significant adverse effects when used to supplement local anesthesia. The three drugs were equally acceptable to patients. However, propofol was associated with a higher frequency of pain on injection, while patients receiving alfentanil experienced a higher frequency of intraoperative oxygen desaturation and postoperative nausea. The higher frequency of emetic symptoms may have contributed to prolonging the recovery room stay in the alfentanil treatment group.7 Since alfentanil is a different type of drug (i.e., an analgesic with sedative properties versus a sedative-hypnotic), caution should be used in concluding that it is less satisfactory than midazolam or propofol. Further controlled studies are needed to determine whether self-administration of sedative and analgesic drugs alone or in combination offer any advantages over conventional physician-controlled drug administration techniques.
References 1. Rudkin GE, Osborne GA, Curtis NJ: lntra-operative patientcontrolled sedation. Anaesthesia 1991;46:90-2. 2. Zelcer J, White PF, Chester S, Paul1 JD, Molnar R: lntraoperative patient-controlled analgesia: An alternative to physician administration during outpatient monitored anesthesia care. Anesth Analg 1992;75:41-4. 3. Park WY, Watkins PA: Patient-controlled sedation during epidural anesthesia. Anesth Analg 1991;72:304-7. 4. Osborne GA, Rudkin GE, Curtis NJ, Vickers D, Craker AJ: Intraoperative patient-controlled sedation. Comparison of patient-controlled propofol with anaesthetist-administered midazolam and fentanyl. Anaesthesia 1991;46:553-6. 5. Bond A, Lader M: The use of analogue scales in rating subjective feelings. Br J Med Psycho1 1974;47:21 l-8. 6. Parker RK, Holtmann B, White PF: Patient controlled analgesia: does a concurrent opioid infusion improve pain management after surgery? JAMA 1991;266:1947-52. 7. Doze VA, Shafer A, White PF: Nausea and vomiting after outpatient anesthesia-effectiveness of droperidol alone and in combination with metoclopramide [Abstract]. Anesth Analg 1987;66:S41.
J. Clin.
Anesth.,
vol. 4, November/December
1992
479
