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Epidural patient-controlled analgesia (PCA): an alternative to continuous epidural infusions
91
Pain, 37 (1989) 97-101
Elsevier
PAI 01397
Clinical Note
Epidural patient-controlled analgesia ( PCA) : an alternative to continuous epidural infusions Steven Marlowe and
*, Ray Engstrom
* and Paul F. White
**
* Department ofAnesthesia, Stanford University School of Medicine, Stanford, CA 94305 (U.S.A.), * * Department of Anesthesiology, Washington University School of Medicine, St. L.&s, MO 63110 (U.S.A.) (Received 10 May 1988, revision received and accepted 18 November 1988)
In a clinical study involving 16 surgical patients receiving epidural hydromorphone for postoperative analgesia, we SummarY compared the use of a continuous infusion technique to an intermittent bolus technique (involving the use of a PCA device). Although comparable analgesia was achieved in the 2 treatment groups during the 48 h study period, the hydromorphone usage (mean value f S.D.) was significantly higher in the continuous infusion group (10.2 + 3.6 mg vs. 4.6 f 2.2 mg in the intermittent bolus group). In spite of this difference in the analgesic dosage requirement, the side effect profile was similar for the 2 groups. Further studies are needed to confirm this observation and to determine the implications with respect to postoperative recovery.
Key words: Opioid analgesic, hydromorphone, Dilaudid”; Pain, acute, postoperative; Techniques, epidural opiate infusion, epidural PCA
Introduction Use of epidural opioids has become an increasingly popular technique for the management of acute postoperative pain. Recent studies would indicate that it is possible to achieve superior analgesia with lower doses of opioid medication when these drugs are administered in the extradural space (versus intramuscular or intravenous routes of administration) [l-4]. However, with the long-acting opioid compounds (e.g., morphine), narcotic-induced side effects (e.g., itching, nausea,
Correspondence to: Dr. P.F. White, Department of Anesthesiology, Washington University School of Medicine, Box 8054, 660 South Euclid Avenue, St. Louis, MO 63110, U.S.A. 03043959/89/$03.50
vomiting, urinary retention) are more common following epidural administration [5]. On the other hand, use of the more rapid and shorter-acting opioids (e.g., fentanyl) requires frequent redosing through the epidural catheter [6]. In an attempt to provide improved postoperative analgesia with fewer side effects, investigators have evaluated the use of continuous epidural infusions of opioid analgesics [7-lo]. More recently, investigators have reported on the use of patient-controlled analgesia via the epidural route of administration [4,8,10]. We compared the epidural dosage requirements and side-effect profiles when hydromorphone, a more potent and rapidacting derivative of morphine [ll], was administered either by continuous infusion or intermittent bolus injections ‘on demand’ using a patient-controlled analgesia (PCA) delivery system.
0 1989 Elsevier Science Publishers B.V. (Biomedical Division)
Methods Sixteen consenting patients undergoing a variety of elective surgical procedures received epidural hydromorphone (preservative-free Dilaudid) for control of acute postoperative pain (Table I). The epidural catheter was placed in the lumbar region (at L,,, or L,,, levels). After an epidural hydromorphone loading dose of 0.5-3.0 mg (depending on the patient’s age and body weight), these patients were randomly assigned to receive either: (1) an epidural hydromorphone infusion at an initial rate of 0.15-0.3 mg/h using a Valley Lab volumetric pump, or (2) intermittent bolus injections from an Abbott Life Care PCA syringe pump programmed to deliver hydromorphone, 0.15-0.3 mg, bolus doses on demand at minimum lockout intervals of 15-30 min (to minimize the possibility of the patient administering a bolus dose before the previous bolus dose had time to exert its analgesic effect). Increases or decreases in the infusion rate or bolus dose were made at the
discretion of the analgesia research nurse depending on the individual patient’s analgesic response. The analgesia research nurse evaluated the patients’ pain scores at intervals of O-4 h, 18-24 h and 24-48 h after the operation using a 10 cm linear analog scale (with 0 = no pain to 10 = severe pain). Comparisons of the analgesia scores, hydromorphone dosage requirements, and side-effect profiles were made between the 2 study groups. Data are expressed as mean values & S.D. Statistical analysis consisted of l-way analysis of variance and Chi-square test, with a P value < 0.05 considered to be statistically significant.
Results
The infusion and PCA bolus groups were comparable with respect to age (55 + 17 versus 54 + 16 years), weight (70 + 16 versus 82 + 17 kg), gender (4 males and 4 females) and initial (loading) hy-
TABLE I DEMOGRAPHIC DATA AND INITIAL LOADING DOSE OF THE OPIOID ANALGESIC EITHER AN EPIDURAL INFUSION OR THE EPIDURAL PCA TECHNIQUE
FOR PATIENTS
RECEIVING
Patient
Age
Weight
Sex
IlO.
(years)
(kg)
@f/F)
Operative procedure
Hydromorphone dose (mg)
Infusiongroup 1
41
2 3 4 5 6 7 8
19 69 71 68 60 69 40
55 70 66 68 60 87 50 loo
F M F M M M F F
laminectomy lower abdominal major orthopedic upper abdominal thoraco-abdominal thoraco-abdominal lower abdominal lower abdominal
1.0 1.0 1.5 1.5 1.75 2.0 1.0 1.5
Mean + S.D.
55 * 17
PCA group 1 2 3 4 5 6 7 8
21 65 62 48 63 70 63 40
Mean * S.D.
54z!z 16
70+
16
M M F M F F M F
60 100 90 80 loo 50 95 80 82f
1.4 + 0.4
17
lower abdominal major orthopedic major orthopedic lower abdominal upper abdominal major orthopedic thoracic upper abdominal
0.5 2.0 2.0 1.0 3.0 1.0 1.5 1.5 1.6 f 0.7
99
dromorphone dosage (1.4 -f 0.4 versus 1.6 + 0.7 mg) (Table I). The mean ( f S.D.) weight-corrected hydromorphone loading doses were 0.020 f 0.005 and 0.018 f 0.006 mg/kg for the infusion and bolus groups, respectively. Although the analgesia (pain) scores were comparable for the 2 treatment groups during the 48 h study period, the total opioid dosage requirement was significantly less when the intermittent bolus injection technique was utilized (Table II). Additionally, 5 patients in the infusion group required supplemental bolus doses for adequate pain control. The side-effect profiles were similar for the 2 treatment groups (Table III). Although no patient experienced significant respiratory depression, nalbuphine was administered to 2 patients in each of the study groups to control opioid-induced side-effects (e.g., pruritus, sedation). All 16 pa-
TABLE III POSTOPERATIVE SIDE-EFFECT PROFILE FOR DURAL HYDROMORPHONE INFUSION VERSUS THERAPY *
Nausea/vomiting Pruritis Sedation/somnoIence Urinary retention * * Respiratory depression
Infusion
PCA
l/8 2/8 2/8 O/7 O/8
l/8 3/8 l/8 O/5 O/8
EPIPCA
* Proportion of patients in each study group manifesting symptoms during the first 48 h after surgery. ** Patients without Foley catheters.
tients were highly satisfied with their postoperative analgesic therapy.
Discussion TABLE II POSTOPERATIVE PAIN SCORES AND HYDROMORPHONE DOSE ~QUIREMENT (mg/48 h) Patient no.
Pain scores * Time interval after operation Hydromorphone O-4 h
18-24 h
24-48 h (mg/48
Infwion gmup 1 0 2 0 3 0 4 0 5 3 6 2.5 7 3 8 3
1 2.5 0 3 2.5 1 2 0.5
0 5 0 2.5 0 1.5 1 0
7.8 11.6 4.8 14.1 16.6 7.7 10.4 8.7
MeanfS.D.
1.6+1.0
1.3rt1.6
10.2&3.6
PCA group 1 0.5 2 0 3 0 4 2 5 0 6 0 7 0 8 3
0.5 5 0 2 0 0 0 3
0.5
3.0
1
6.9
0 2 0 0 0 3
8.0 4.0 2.5 1.5 4.5 6.4
MeanfSD.
1.3kl.7
0.8il.I
4.6k2.2
1.4*1.4
0.9*1.1
h,
**
* Pain scores on a scale from 0 ( = none) to 10 ( = severe). ** PCA group significantly different from infusion group, P c 0.05.
Patient”controlled analgesia (PCA) has become an increasingly popular technique for mana~ng acute postoperative pain [12,13] and chronic cancer pain [14,15]. Yet, most carefully controlled studies have reported comparable pain scores with PCA and other conventional treatment modalities [l-3,16,17]. Nevertheless, patient acceptance of PCA is extremely high [2,3] because it provides patients with an opportunity to participate in their own care and to overcome the inherent pharmacokinetic and pharmacodynamic differences which exist among patients [13]. In addition, with PCA therapy there may be a decreased need for nursing inte~entions to provide supplements analgesia when compared to intramuscular opioid injections, intercostal nerve blocks or epidural narcotic therapy [16]. Analogous to PCA, epidural administration of opioid analgesics has become more widely utilized as an alternative to intramuscular therapy in the management of both acute and chronic pain [l-4,11,18-20]. Although epidural opiates can provide superior analgesia with lower dosages of analgesic medication compared to conventional intramuscular and intravenous therapy [l-4], the high incidence of side-effects (e.g., pruritis, urinary dysfunction) and the need for additional professional support (e.g., monitoring, redosing) have
100
limited the use of this otherwise excellent therapeutic modality. The possibility of combining the advantages of epidural opioid therapy with the flexibility of PCA therapy has led investigators to evaluate the technique of epidural PCA. In 1985, Chrubasik and Wiemers [8] first described the use of a continuous-plus ‘on demand’ epidural morphine infusion for postoperative pain relief. According to these investigators, this method of pain control provided ‘constant analgesia and the possibility of individualized treatment’ after major abdominal operations. More recently SjoStrom et al. [4] have compared epidural PCA to their earlier experience with i.v. PCA after abdominal surgery. The epidural PCA morphine requirement was 80% less than the previously reported i.v. PCA consumption. Given the slow onset of action of epidural morphine, Chrubasik et al. [lo] subsequently evaluated the analgesic effectiveness of the more lipid-soluble opioid compounds, fentanyl and alfentanil. Although continuous-plus on demand epidural infusions of alfentanil produced analgesia similar to that of morphine (and fentanyl), the requirement for supplemental sedative-anxiolytic medication was alledgedly decreased as a result of alfentanil’s more rapid onset of analgesia. These data suggest that more lipophilic analgesics might be more effective when using an epidural PCA technique. We have recently reported that hydromorphone, a more potent and lipid-soluble derivative of morphine, was highly effective when used for patient-controlled analgesia [Zl]. In a pilot study, we found that hydromorphone had a rapid onset of effect (< 5 min) when administered into the epidural space. Since our previous studies involving intravenously administered narcotics revealed decreases in total analgesic dosage when these drugs were administered by a variable rate infusion during surgery (compared to the more traditional intermittent bolus technique) [22,23], we were interested in comparing these 2 administration techniques via the epidural route of administration. In contrast to intravenous administration, we found a significantly lower opioid dosage requirement when intermittent bolus doses (vs. continuous infusions) were administered in the lumbar epidural space.
There are many possible explanations for the differences in the opioid dosage requirement between the bolus and infusion groups in this preliminary study. First, the infusion group may have included more extensive and painful operations (e.g., thoraco-abdominal and upper abdominal procedures). Secondly, the use of a continuous (rather than variable rate) hydromorphone infusion may have contributed to suboptimal titration of the analgesic medication. In clinical practice, one of the major problems in using epidural infusions relates to the difficulty in determining the optimal infusion rate given the marked pharmacokinetic-dynamic variability which exists among patients [24]. In order to minimize the administered dose, it is important to vary the infusion rate to determine the lowest effective dose. Thirdly, pharmacokinetic differences with respect to the drug’s systemic absorption and transfer across the dura mater could also contribute to the differing dosage requirements for the 2 epidural delivery systems. Fourthly, the use of a continuous opioid infusion may have contributed to the more rapid development of tolerance [25]. Finally, the small group sizes (n = 8) limit the statistical power of our data analysis. In conclusion, epidural PCA may offer advantages over continuous epidural infusions for the treatment of postoperative pain. Further studies involving larger numbers of patients are necessary to determine the optimal technique for administering epidural opioid analgesics.
Acknowledgement The authors would like to thank Kathy Vivenzo, R.N., for her invaluable assistance in obtaining the analgesia scores during this preliminary study.
References 1 Rawal, N., Sjastrand, U., Christoffersson, E., DahlstrGm, B., Arvill, A. and Rydman, H., Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly obese: influence on postoperative ambulation and pulmonary function, Anesth. Analg., 63 (1984) 583-592.
101 2 Eisenach, J.C., Grice_ SC. and Dewan, D.M., Patient-controlled analgesia feBowing cesarean section: a comparison with epidural and ~ntr~us~ar narcotics, Anesthesiology, 68 (1988) 444-448. 3 Harrison, D.M., Sinatra, R., Morgese, L. and Chung, J.H.. Epidural narcotic and patient-cantrolled analgesia for post-cesarean section pain relief, Anesthesiology, 68 (1988) 454-451. 4 Sjtistriim, S., Hartvig, D. and Tamsen, A., Patient-controlled analgesia with extradural morphine or pethidine, Br. J. Anaesth., 60 (1988) 358-366. 5 Bramage, P.R., Camporesi, E.M., Durant, P.A. and Nielsen, C.H., Nonrespiratory side effects of epidural morphine, Anesth. Analg.. 61 (1982) 490-495. 6 Wolf, M.J. and Davies, G.K., Analgesic action of extradurai fentar@, Br. 5. Anaesth., 52 (1980) 357-358. 7 El-Bar, N.M.I., Faber- P.L. and .Iens~k~ J., Continuous epidural infusion of morphine for treatment of pain after thoracic surgery: a new technique, Anesth. Am&., 63 (1984) 757-764. 8 Chrubasik, J. and Wiemers. K., Continuuus-plus-on-demand epidural infusion of morphine for postoperative pain relief by means of a small, externally worn infusion device, Anesthesiology, 62 (1985) 263-267. 9 S&&in, B., Asantila, R. and Orko, R., The effect of bupivacaine and morphine on pain and bowel function after coionic surgery, Acta Anaesthesiol, Stand., 31 (1987) 16X1-164. 10 Chrubasik, J., Wust, H., SchulteMonting, J., Tbon, K. and Zindler, M., Relative analgesic potency of epidural fentanyl, alfentanil, and morphine in treatment of postoperative pain, Anesthesiology. 68 (1988) 929-933. II Bromage, P.R., Camporesi, E. and Chestnut, D., Epidural narcotics for postoperative analgesia, Anesth. Anafg., 59 (I980) 473-480. I2 Graves, D.A., Foster, T.S., Batenhorst, R.L. et al., Patientcontrolled analgesia, Ann. Intern. Med., 99 (1983) 360-366. 13 White, P.F., Use of patient-controlled analgesia for management of acute pain, JAMA, 259 (1988) 243-247. 14 Citron, ML.. Johnston-Early, A., Bayer, M., Krasnow, S.H., Hoed, M. and Cohen, M.H., Patient-controlled anal-
15
16
17
IX
19
20
21
gesia for severe cancer pain, Arch. Intern. Med., 146 (1986) 734-736. Kerr* LG., Sane, M., De Angel&, C., Iscoe, N., MacKenzie, R. and Schueller, T., Continuous narcotic infusion with patient-controlled analgesia for chronic cancer pain in outpatients, Ann. Intern. Med., 108 (1988) 554-557. Rosenberg, PX., Heino, A. and Scheinin, B., Comparison of intramuscular analgesia, intercostal block, cpidural morphine, and on-demand i.v. fentanyl in the control of pain after upper abdominal surgery, Acta Amtesthesiol. Stand., 28 (1984) 603-607. Dahl, J.B., Daugaard, J.J., Larsen, H.V., Mourdsen, P., Nielsen, T.H. and Kristoffersen, E., Patient-controlled analgesia: a controlled triai, Acta Anaesthesiol. Stand., 31 (1987) 744-747. Rawal, N., SjGstrand, U. and Dahfstrijm, B., Postoperative pain relief by epidural morphine, Anesth. Analg., 60 (1981) 726-731. Stenseth, R., Sellevold, 0. and Breivik, H., Epidural morphine for postoperative pain: experience with 7085 patients, Acta Anaesthesiol. Stand., 29 (1985) 148-156. Coomhs, D. W., Saunders. R.L., Gaylor, M. and Pageau, M.G., Epidural narcotic infusion reservoir: implantation technique and efficacy, Anesthesiology, 56 (1982) 469-473. Urquhart, ML., Klapp, K. and White, P.F., Patient-controlled analgesia: a comparison of intravenous versus subcutaneous hydromorphone. Anesthesiology, 69 (1988) 428-432.
22 White, P-F., Use of con~nuous infusion versus intermittent b&us administration of fentany~ or ketamine during outpatient anesthesia, Anesthesiology, 59 (1983) 294-300. 23 White, P.F., Coe, V., Shafer, A. and Sung, M.-L.. Comparison of alfentanil with fentanyl as adjuvants during outpatient surgery, Anesthesiology, 64 (1986) 99-106. 24 Gourlay, G.K., Kowalski, R.S., Plummer, J.L., Cousins, M.J. and Armstrong, P.J., Fentanyl blood concentrationanalgesic response relationship in the treatment of postop erative pain, Anesth. Analg., 67 (1988) 329-337. 25 Marshall, H., Porteous, C., McMillan, I. et al., Rehef of pain by infusion of morphine after operation does tolerance develop?, Br. Med. J., 291 (1985) 19-21.
Pain, 37 (1989) 97-101
Elsevier
PAI 01397
Clinical Note
Epidural patient-controlled analgesia ( PCA) : an alternative to continuous epidural infusions Steven Marlowe and
*, Ray Engstrom
* and Paul F. White
**
* Department ofAnesthesia, Stanford University School of Medicine, Stanford, CA 94305 (U.S.A.), * * Department of Anesthesiology, Washington University School of Medicine, St. L.&s, MO 63110 (U.S.A.) (Received 10 May 1988, revision received and accepted 18 November 1988)
In a clinical study involving 16 surgical patients receiving epidural hydromorphone for postoperative analgesia, we SummarY compared the use of a continuous infusion technique to an intermittent bolus technique (involving the use of a PCA device). Although comparable analgesia was achieved in the 2 treatment groups during the 48 h study period, the hydromorphone usage (mean value f S.D.) was significantly higher in the continuous infusion group (10.2 + 3.6 mg vs. 4.6 f 2.2 mg in the intermittent bolus group). In spite of this difference in the analgesic dosage requirement, the side effect profile was similar for the 2 groups. Further studies are needed to confirm this observation and to determine the implications with respect to postoperative recovery.
Key words: Opioid analgesic, hydromorphone, Dilaudid”; Pain, acute, postoperative; Techniques, epidural opiate infusion, epidural PCA
Introduction Use of epidural opioids has become an increasingly popular technique for the management of acute postoperative pain. Recent studies would indicate that it is possible to achieve superior analgesia with lower doses of opioid medication when these drugs are administered in the extradural space (versus intramuscular or intravenous routes of administration) [l-4]. However, with the long-acting opioid compounds (e.g., morphine), narcotic-induced side effects (e.g., itching, nausea,
Correspondence to: Dr. P.F. White, Department of Anesthesiology, Washington University School of Medicine, Box 8054, 660 South Euclid Avenue, St. Louis, MO 63110, U.S.A. 03043959/89/$03.50
vomiting, urinary retention) are more common following epidural administration [5]. On the other hand, use of the more rapid and shorter-acting opioids (e.g., fentanyl) requires frequent redosing through the epidural catheter [6]. In an attempt to provide improved postoperative analgesia with fewer side effects, investigators have evaluated the use of continuous epidural infusions of opioid analgesics [7-lo]. More recently, investigators have reported on the use of patient-controlled analgesia via the epidural route of administration [4,8,10]. We compared the epidural dosage requirements and side-effect profiles when hydromorphone, a more potent and rapidacting derivative of morphine [ll], was administered either by continuous infusion or intermittent bolus injections ‘on demand’ using a patient-controlled analgesia (PCA) delivery system.
0 1989 Elsevier Science Publishers B.V. (Biomedical Division)
Methods Sixteen consenting patients undergoing a variety of elective surgical procedures received epidural hydromorphone (preservative-free Dilaudid) for control of acute postoperative pain (Table I). The epidural catheter was placed in the lumbar region (at L,,, or L,,, levels). After an epidural hydromorphone loading dose of 0.5-3.0 mg (depending on the patient’s age and body weight), these patients were randomly assigned to receive either: (1) an epidural hydromorphone infusion at an initial rate of 0.15-0.3 mg/h using a Valley Lab volumetric pump, or (2) intermittent bolus injections from an Abbott Life Care PCA syringe pump programmed to deliver hydromorphone, 0.15-0.3 mg, bolus doses on demand at minimum lockout intervals of 15-30 min (to minimize the possibility of the patient administering a bolus dose before the previous bolus dose had time to exert its analgesic effect). Increases or decreases in the infusion rate or bolus dose were made at the
discretion of the analgesia research nurse depending on the individual patient’s analgesic response. The analgesia research nurse evaluated the patients’ pain scores at intervals of O-4 h, 18-24 h and 24-48 h after the operation using a 10 cm linear analog scale (with 0 = no pain to 10 = severe pain). Comparisons of the analgesia scores, hydromorphone dosage requirements, and side-effect profiles were made between the 2 study groups. Data are expressed as mean values & S.D. Statistical analysis consisted of l-way analysis of variance and Chi-square test, with a P value < 0.05 considered to be statistically significant.
Results
The infusion and PCA bolus groups were comparable with respect to age (55 + 17 versus 54 + 16 years), weight (70 + 16 versus 82 + 17 kg), gender (4 males and 4 females) and initial (loading) hy-
TABLE I DEMOGRAPHIC DATA AND INITIAL LOADING DOSE OF THE OPIOID ANALGESIC EITHER AN EPIDURAL INFUSION OR THE EPIDURAL PCA TECHNIQUE
FOR PATIENTS
RECEIVING
Patient
Age
Weight
Sex
IlO.
(years)
(kg)
@f/F)
Operative procedure
Hydromorphone dose (mg)
Infusiongroup 1
41
2 3 4 5 6 7 8
19 69 71 68 60 69 40
55 70 66 68 60 87 50 loo
F M F M M M F F
laminectomy lower abdominal major orthopedic upper abdominal thoraco-abdominal thoraco-abdominal lower abdominal lower abdominal
1.0 1.0 1.5 1.5 1.75 2.0 1.0 1.5
Mean + S.D.
55 * 17
PCA group 1 2 3 4 5 6 7 8
21 65 62 48 63 70 63 40
Mean * S.D.
54z!z 16
70+
16
M M F M F F M F
60 100 90 80 loo 50 95 80 82f
1.4 + 0.4
17
lower abdominal major orthopedic major orthopedic lower abdominal upper abdominal major orthopedic thoracic upper abdominal
0.5 2.0 2.0 1.0 3.0 1.0 1.5 1.5 1.6 f 0.7
99
dromorphone dosage (1.4 -f 0.4 versus 1.6 + 0.7 mg) (Table I). The mean ( f S.D.) weight-corrected hydromorphone loading doses were 0.020 f 0.005 and 0.018 f 0.006 mg/kg for the infusion and bolus groups, respectively. Although the analgesia (pain) scores were comparable for the 2 treatment groups during the 48 h study period, the total opioid dosage requirement was significantly less when the intermittent bolus injection technique was utilized (Table II). Additionally, 5 patients in the infusion group required supplemental bolus doses for adequate pain control. The side-effect profiles were similar for the 2 treatment groups (Table III). Although no patient experienced significant respiratory depression, nalbuphine was administered to 2 patients in each of the study groups to control opioid-induced side-effects (e.g., pruritus, sedation). All 16 pa-
TABLE III POSTOPERATIVE SIDE-EFFECT PROFILE FOR DURAL HYDROMORPHONE INFUSION VERSUS THERAPY *
Nausea/vomiting Pruritis Sedation/somnoIence Urinary retention * * Respiratory depression
Infusion
PCA
l/8 2/8 2/8 O/7 O/8
l/8 3/8 l/8 O/5 O/8
EPIPCA
* Proportion of patients in each study group manifesting symptoms during the first 48 h after surgery. ** Patients without Foley catheters.
tients were highly satisfied with their postoperative analgesic therapy.
Discussion TABLE II POSTOPERATIVE PAIN SCORES AND HYDROMORPHONE DOSE ~QUIREMENT (mg/48 h) Patient no.
Pain scores * Time interval after operation Hydromorphone O-4 h
18-24 h
24-48 h (mg/48
Infwion gmup 1 0 2 0 3 0 4 0 5 3 6 2.5 7 3 8 3
1 2.5 0 3 2.5 1 2 0.5
0 5 0 2.5 0 1.5 1 0
7.8 11.6 4.8 14.1 16.6 7.7 10.4 8.7
MeanfS.D.
1.6+1.0
1.3rt1.6
10.2&3.6
PCA group 1 0.5 2 0 3 0 4 2 5 0 6 0 7 0 8 3
0.5 5 0 2 0 0 0 3
0.5
3.0
1
6.9
0 2 0 0 0 3
8.0 4.0 2.5 1.5 4.5 6.4
MeanfSD.
1.3kl.7
0.8il.I
4.6k2.2
1.4*1.4
0.9*1.1
h,
**
* Pain scores on a scale from 0 ( = none) to 10 ( = severe). ** PCA group significantly different from infusion group, P c 0.05.
Patient”controlled analgesia (PCA) has become an increasingly popular technique for mana~ng acute postoperative pain [12,13] and chronic cancer pain [14,15]. Yet, most carefully controlled studies have reported comparable pain scores with PCA and other conventional treatment modalities [l-3,16,17]. Nevertheless, patient acceptance of PCA is extremely high [2,3] because it provides patients with an opportunity to participate in their own care and to overcome the inherent pharmacokinetic and pharmacodynamic differences which exist among patients [13]. In addition, with PCA therapy there may be a decreased need for nursing inte~entions to provide supplements analgesia when compared to intramuscular opioid injections, intercostal nerve blocks or epidural narcotic therapy [16]. Analogous to PCA, epidural administration of opioid analgesics has become more widely utilized as an alternative to intramuscular therapy in the management of both acute and chronic pain [l-4,11,18-20]. Although epidural opiates can provide superior analgesia with lower dosages of analgesic medication compared to conventional intramuscular and intravenous therapy [l-4], the high incidence of side-effects (e.g., pruritis, urinary dysfunction) and the need for additional professional support (e.g., monitoring, redosing) have
100
limited the use of this otherwise excellent therapeutic modality. The possibility of combining the advantages of epidural opioid therapy with the flexibility of PCA therapy has led investigators to evaluate the technique of epidural PCA. In 1985, Chrubasik and Wiemers [8] first described the use of a continuous-plus ‘on demand’ epidural morphine infusion for postoperative pain relief. According to these investigators, this method of pain control provided ‘constant analgesia and the possibility of individualized treatment’ after major abdominal operations. More recently SjoStrom et al. [4] have compared epidural PCA to their earlier experience with i.v. PCA after abdominal surgery. The epidural PCA morphine requirement was 80% less than the previously reported i.v. PCA consumption. Given the slow onset of action of epidural morphine, Chrubasik et al. [lo] subsequently evaluated the analgesic effectiveness of the more lipid-soluble opioid compounds, fentanyl and alfentanil. Although continuous-plus on demand epidural infusions of alfentanil produced analgesia similar to that of morphine (and fentanyl), the requirement for supplemental sedative-anxiolytic medication was alledgedly decreased as a result of alfentanil’s more rapid onset of analgesia. These data suggest that more lipophilic analgesics might be more effective when using an epidural PCA technique. We have recently reported that hydromorphone, a more potent and lipid-soluble derivative of morphine, was highly effective when used for patient-controlled analgesia [Zl]. In a pilot study, we found that hydromorphone had a rapid onset of effect (< 5 min) when administered into the epidural space. Since our previous studies involving intravenously administered narcotics revealed decreases in total analgesic dosage when these drugs were administered by a variable rate infusion during surgery (compared to the more traditional intermittent bolus technique) [22,23], we were interested in comparing these 2 administration techniques via the epidural route of administration. In contrast to intravenous administration, we found a significantly lower opioid dosage requirement when intermittent bolus doses (vs. continuous infusions) were administered in the lumbar epidural space.
There are many possible explanations for the differences in the opioid dosage requirement between the bolus and infusion groups in this preliminary study. First, the infusion group may have included more extensive and painful operations (e.g., thoraco-abdominal and upper abdominal procedures). Secondly, the use of a continuous (rather than variable rate) hydromorphone infusion may have contributed to suboptimal titration of the analgesic medication. In clinical practice, one of the major problems in using epidural infusions relates to the difficulty in determining the optimal infusion rate given the marked pharmacokinetic-dynamic variability which exists among patients [24]. In order to minimize the administered dose, it is important to vary the infusion rate to determine the lowest effective dose. Thirdly, pharmacokinetic differences with respect to the drug’s systemic absorption and transfer across the dura mater could also contribute to the differing dosage requirements for the 2 epidural delivery systems. Fourthly, the use of a continuous opioid infusion may have contributed to the more rapid development of tolerance [25]. Finally, the small group sizes (n = 8) limit the statistical power of our data analysis. In conclusion, epidural PCA may offer advantages over continuous epidural infusions for the treatment of postoperative pain. Further studies involving larger numbers of patients are necessary to determine the optimal technique for administering epidural opioid analgesics.
Acknowledgement The authors would like to thank Kathy Vivenzo, R.N., for her invaluable assistance in obtaining the analgesia scores during this preliminary study.
References 1 Rawal, N., Sjastrand, U., Christoffersson, E., DahlstrGm, B., Arvill, A. and Rydman, H., Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly obese: influence on postoperative ambulation and pulmonary function, Anesth. Analg., 63 (1984) 583-592.
101 2 Eisenach, J.C., Grice_ SC. and Dewan, D.M., Patient-controlled analgesia feBowing cesarean section: a comparison with epidural and ~ntr~us~ar narcotics, Anesthesiology, 68 (1988) 444-448. 3 Harrison, D.M., Sinatra, R., Morgese, L. and Chung, J.H.. Epidural narcotic and patient-cantrolled analgesia for post-cesarean section pain relief, Anesthesiology, 68 (1988) 454-451. 4 Sjtistriim, S., Hartvig, D. and Tamsen, A., Patient-controlled analgesia with extradural morphine or pethidine, Br. J. Anaesth., 60 (1988) 358-366. 5 Bramage, P.R., Camporesi, E.M., Durant, P.A. and Nielsen, C.H., Nonrespiratory side effects of epidural morphine, Anesth. Analg.. 61 (1982) 490-495. 6 Wolf, M.J. and Davies, G.K., Analgesic action of extradurai fentar@, Br. 5. Anaesth., 52 (1980) 357-358. 7 El-Bar, N.M.I., Faber- P.L. and .Iens~k~ J., Continuous epidural infusion of morphine for treatment of pain after thoracic surgery: a new technique, Anesth. Am&., 63 (1984) 757-764. 8 Chrubasik, J. and Wiemers. K., Continuuus-plus-on-demand epidural infusion of morphine for postoperative pain relief by means of a small, externally worn infusion device, Anesthesiology, 62 (1985) 263-267. 9 S&&in, B., Asantila, R. and Orko, R., The effect of bupivacaine and morphine on pain and bowel function after coionic surgery, Acta Anaesthesiol, Stand., 31 (1987) 16X1-164. 10 Chrubasik, J., Wust, H., SchulteMonting, J., Tbon, K. and Zindler, M., Relative analgesic potency of epidural fentanyl, alfentanil, and morphine in treatment of postoperative pain, Anesthesiology. 68 (1988) 929-933. II Bromage, P.R., Camporesi, E. and Chestnut, D., Epidural narcotics for postoperative analgesia, Anesth. Anafg., 59 (I980) 473-480. I2 Graves, D.A., Foster, T.S., Batenhorst, R.L. et al., Patientcontrolled analgesia, Ann. Intern. Med., 99 (1983) 360-366. 13 White, P.F., Use of patient-controlled analgesia for management of acute pain, JAMA, 259 (1988) 243-247. 14 Citron, ML.. Johnston-Early, A., Bayer, M., Krasnow, S.H., Hoed, M. and Cohen, M.H., Patient-controlled anal-
15
16
17
IX
19
20
21
gesia for severe cancer pain, Arch. Intern. Med., 146 (1986) 734-736. Kerr* LG., Sane, M., De Angel&, C., Iscoe, N., MacKenzie, R. and Schueller, T., Continuous narcotic infusion with patient-controlled analgesia for chronic cancer pain in outpatients, Ann. Intern. Med., 108 (1988) 554-557. Rosenberg, PX., Heino, A. and Scheinin, B., Comparison of intramuscular analgesia, intercostal block, cpidural morphine, and on-demand i.v. fentanyl in the control of pain after upper abdominal surgery, Acta Amtesthesiol. Stand., 28 (1984) 603-607. Dahl, J.B., Daugaard, J.J., Larsen, H.V., Mourdsen, P., Nielsen, T.H. and Kristoffersen, E., Patient-controlled analgesia: a controlled triai, Acta Anaesthesiol. Stand., 31 (1987) 744-747. Rawal, N., SjGstrand, U. and Dahfstrijm, B., Postoperative pain relief by epidural morphine, Anesth. Analg., 60 (1981) 726-731. Stenseth, R., Sellevold, 0. and Breivik, H., Epidural morphine for postoperative pain: experience with 7085 patients, Acta Anaesthesiol. Stand., 29 (1985) 148-156. Coomhs, D. W., Saunders. R.L., Gaylor, M. and Pageau, M.G., Epidural narcotic infusion reservoir: implantation technique and efficacy, Anesthesiology, 56 (1982) 469-473. Urquhart, ML., Klapp, K. and White, P.F., Patient-controlled analgesia: a comparison of intravenous versus subcutaneous hydromorphone. Anesthesiology, 69 (1988) 428-432.
22 White, P-F., Use of con~nuous infusion versus intermittent b&us administration of fentany~ or ketamine during outpatient anesthesia, Anesthesiology, 59 (1983) 294-300. 23 White, P.F., Coe, V., Shafer, A. and Sung, M.-L.. Comparison of alfentanil with fentanyl as adjuvants during outpatient surgery, Anesthesiology, 64 (1986) 99-106. 24 Gourlay, G.K., Kowalski, R.S., Plummer, J.L., Cousins, M.J. and Armstrong, P.J., Fentanyl blood concentrationanalgesic response relationship in the treatment of postop erative pain, Anesth. Analg., 67 (1988) 329-337. 25 Marshall, H., Porteous, C., McMillan, I. et al., Rehef of pain by infusion of morphine after operation does tolerance develop?, Br. Med. J., 291 (1985) 19-21.