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Local and Intra-articular Infiltration of Bupivacaine Before Surgery: Effect on Postoperative Pain After Anterior

Cruciate Ligament Reconstruction

Jt t rgen H6her , M.D. , Dan i e l Kers ten , M.D. , Ber t i l Boui l lon , M.D. , E d w a r d N e u g e b a u e r , Ph.D. ,

a n d T h o m a s T i l i n g , M . D .

Summary: In a double-blind, randomized trial, 40 patients undergoing open anterior cruciate ligament (ACL) reconstruction using a bone-patellar tendon-bone autograft were randomly allocated to two groups: group A (n = 20) received an intra-articular instillation of 20 mL bupivacaine (0.25%) and a local infiltration of 20 mL bupivacaine (0.5%) 15 minutes before surgery. Group B (n = 20) received an injection of saline solution in the same manner. Patient-controlled on-demand analgesia (PCA) with intravenous piritramid was used for postoperative pain control. A significant decrease in pain scores on a visual analog scale (VAS scale, 0 to 10) was found in the bupivacaine group (group A) at bedrest on the day of surgery only (pain score, 5.5 v 7.3 (scale, 0 to 10), P < .05). At all other times, no significant differences were found. The overall supplemental opioid requirements were not different between the study groups (63.9 v 62.6 mg piritramid/72 hours). A long-lasting, clinically relevant, pain-reducing effect with infiltration of bupivacaine before surgery could not be shown with this study. Key Words: Local anesthetic--Postoperative pain control--Opioid--Patient-controlled analgesia-- Knee surgery--Anterior cruciate ligament.

A nterior cruciate ligament (ACL) reconstruction using a bone-pate l lar tendon-bone autograft

leads to significant postoperative pain, usually in the first 2 days after the operation, m Several methods con- tribute to a reduction in postoperative pain in knee surgery and have been used in the past (Table 1). 3-5 Despite many nonpharmacological methods being helpful in pain reduction, intravenously administered opioids are frequently used for analgesia after surgery. 2,6,7

From the Division of Trauma Surgery, and the Biochemical and Experimental Division (E.N.), lind Department of Surgery, Univer- sity of Cologne, Ostmerheimer Strasse 200, 51109 Cologne, Ger- many.

Address correspondence and reprint requests to Jiirgen HOher, M.D., Division of Trauma Surgery, Second Department of Surgery, University of Cologne, Ostmerheimer St200, D-51109, Cologne, Germany.

© 1997 by the Arthroscopy Association of North America 0749-8063/97/1302-149053.00/0

Local anesthetics have been shown to be effective for analgesia of the knee for knee arthroscopies with minor surgery. 812 Many investigators suggest the instillation of local anesthetics into the knee joint at the end of arthroscopic surgery under general anesthesia for postoperative pain reduction. 13-19

Others recommend the application of local anesthetics at the beginning of surgery under general anesthesia to reduce postoperative pain. 2°-24 It is hypothesized that the neural blockade by analgetics or local anesthesia prevents the transmission of nociceptor impulses to the central nervous system during and immediately after surgery. Thus, a sustained hyperexictable state in the central nervous system responsible for the mainte- nance of postoperative pain is suppressed. 24-26 Some experimental studies support the effectiveness of this concept, 27'28 whereas others do not. z9 Clinical studies also have controversial results; some show a significant postoperative pain decrease with this procedure 3°'31 and some do not. 32-38 In tonsillectomies, herniotomies, and

210 Arthroscopy." The Journal of Arthroscopic and Related Surgery, Vol 13, No 2 (April), 1997: pp 210-217

L O C A L INTRA-ARTICULAR I N F I L T R A T I O N OF B UPIVA CAINE 211

TABLE 1. Methods Used to Reduce Postoperative Pain in ACL Surgery

Preoperative Patient counselling and encouragement (explanation of the

procedure, talking about anxiety, mental counselling) Intraoperative

Pharmacological Local anesthetic infiltration of the wound and knee joint

before surgery (pre-emptive analgesia) Local anesthetic infiltration of the knee joint at the end of

surgery Limitation of surgical trauma

Length of operation/tourniquet time Kind of reconstructive procedure (autograft-allograft) Operative technique (arthroscopic, miniarthrotomy, additional

lateral incision) Application of wound drainages (size and localization)

Postoperative Pharmacological

Regional Femoral nerve block Lumbar plexus block Peridural catheter

Systemic NSAI-drugs (oral or IV) IV opioids (PCA or nurse-controlled) IM opioids

Nonpharmocological Local ice application Positioning of the leg, knee immobilizer, wound wrapping Mode of physical activity Patient counselling, placebo effects

NOTE. See references 3-5.

orthopaedic foot operations a significant reduction of postoperative pain was shown after infiltration of bupivacaine at the beginning of surgery) °'21'24 The concept of local infiltration of drugs at the beginning of surgery is still controversial and the subject of contradicting opinions.

An infiltration of local anesthetics at the beginning of ACL reconstruction has not yet been described in the literature. It was the objective of this study to investigate the effect of local and intra-articular infiltration of bupivacaine at the begin of surgery on the postoperative pain in patients undergoing ACL reconstruction.

PATIENTS AND METHODS

Study Design and Patient Selection The study was designed as a prospective, controlled,

double-blind, randomized trial. The study protocol was approved by our local ethical committee (University of Cologne, Germany), and written informed consent was obtained from each patient before surgery. Patients over the age of 18 years who were admitted to our hospital for ACL reconstruction were included into

the study. Exclusion criteria were spinal anesthesia, a history of chronic drug abuse (analgesics, alcohol, illegal drugs), metabolic diseases like diabetes mellitus, liver disease, known allergy against the applied drugs, insufficient knowledge of the German language, disap- proval of randomization, and additional open knee surgery. Eleven patients could not be enrolled because of exclusion criteria (spinal anesthesia in 6 cases, a history of illegal drug consumption in 1 case, and addi- tionnal interventions during surgery (medial collateral ligament repair and patellar tendon graft harvesting from the contralateral knee) in 4 cases. Patients suitable for inclusion were informed of the aim and characteris- tics of the study the day before the operation. On the same day, the postoperative pain treatment with a patient-controlled analgesia system (PCA system) was explained to the patient. Forty patients were enrolled into the study and were randomly allocated into two groups.

Performance of the Study On the morning of the operation, one randomization

card (dosed envelope) was picked by the operating room nurse. For one group of patients (group A, n = 20), an intra-articular injection (syringe l) with 20 mL bupivacaine 0.25% (Carbostesin; Astra Chemicals, Wedel, Germany) was prepared. A second, subcutaneous injection (syringe 2) was prepared with 20 mL bupivacaine 0.5%. Another group of patients (group B, n = 20) received an intra-articular and subcutaneous injection with 20 mL saline solution). The intra-articular injection into the lateral superior pouch of the knee was performed by the surgeon after the desinfection of the knee. The knee was then moved through the range of motion three times. With the second injection, the peripatellar tendon tissue, the periosteum of tibia's tubercle, the distal aspect of the patella, and the anteromedial aspect of the proximal tibia were infiltrated.

For all patients, a standardized anesthetic technique was used. Premedication consisted of midazolam (7.5 rag) orally 1 hour before surgery. General anesthesia was induced with atropine 0.5 mg and thiopentane (4 mg/kg). After administration of succinylcholine and pancuronium, endotracheal intubation was performed. Anesthesia was maintained with isofluorane or fluo- thane and mechanical ventilation. Arthroscopy was performed through an anterolateral and anteromedial portal of the joint. To harvest the patellar tendon graft, an anterolateral incision of approximately 8 to 10 cm was made. The knee joint was opened by incision of the infrapatellar fat pad through the graft defect of the patellar tendon. The tibial bone tunnel was drilled with

212 J. HOHER ET AL.

a 9-mm cannulated reamer over a previously placed k-wire. At the femoral insertion of the ACL, a 40-mm bone tunnel was drilled in an inside-out-direction with a 8-ram cannulated reamer over a previously placed k-wire. Before drilling the femoral tunnel, isometry of the bone tunnels was tested with a house-custom technique. Afterwards, the graft was pulled into the knee joint and the bone blocks were secured with inter- ference screws (7 × 20 mm, De Puy Corp, Limbach, Germany). Two suction drains (14F and 12F, respectively) were inserted into the knee joint and into the subcutanous layer of the anteromedial tibia. After wound closure, an immobilization brace (Stortz Corp, Cologne, Germany) was applied to the knee and in bed the leg was placed at slight elevation.

Immediately after the end of anesthesia, the patients received the opioids pethidine (Dolantin; Hoechst AG, Frankfurt, Germany) or piritramid (Dipidolor; Janssen GmbH, Neuss, Germany) intravenously for acute pain treatment by our anethesiologists. After discharge from the recovery room to the general ward, intravenous on- demand analgesia was started (PACOM on-demand analgesia computer system; Fresenius AG, Bad Hom- burg, Germany). For on-demand analgesia piritramid (Dipidolor) was used. The pharmacodynamic proper- ties of piritramid are similar to morphine. The demand dose was 2 mg with a pump refractory time of 5 minutes between valid demands, the maximum dose was set to 60 mg in 16 hours and 90 mg in 24 hours, respectively, s9 The consumption of piritramid was re- corded by the PACOM software system and analyzed by a personal computer. Intravenous on-demand analgesia was usually discontinued when no request for pain medication had been made for more than 8 hours. After removal of the wound drains on the second postoperative day, the pain treatment was usually changed to oral analgesic medication with ibuprofen 500 mg orally 3 tablets per day (Imbun; Merckle Corp, Ulm, Germany).

Study Data and Endpoints Study data included patient age, gender, weight,

height, and the determination of acute or chronic injury. Additionally, the time between bupivacaine infiltration and inflation of the torniquet, the time interval between infiltration and start of surgery, the length of the operation, and the overall torniquet time and the amount of analgesics applied in the recovery room before PCA-analgesia were documented.

The primary study endpoints were the intensity of pain assessed by the visual analog scale (VAS) with regard to the level of physical activity (bedrest, ambu-

TABLE 2. Demographic and Clinical Data of the Study Population

Group A Group B (n = 20) (n = 20)

M e ~ ±SD Mean ±SD

Age (yr) 25.2 4.0 25.1 5.3 Height (cm) 179.2 7.8 175.3 7.5 Body weight (kg) 76.2 9.4 72.1 10.4 Time interval: injection to begin

of tourniquet (min) 8.8 8.0 10.5 5.5 Time interval: injection to begin

of surgery (min) 14.1 5.1 14.9 4.2 Duration of surgery (min) 117.4 15.8 123.2 26.7 Duration of tourniquet (rain) 110.9 16.7 111.4 28.4 Gender (M/F) 17:3 14:6 Type of injury (acute/chronic) 8:12 7:13

NOTE. Group A, bupivacaine group; group B, saline group (con- uol). No statistical differences were determined between the study groups. SD, standard deviation.

lation, physical therapy) and the requirements of analgesics.

Pain intensity was assessed with a modified VAS that consisted of 11 continuously lined up boxes an- chored by two extreme pain values ("no pain" and the other "worst pain imaginable"). The patients were asked to mark the actual intensity of pain with the related kind of physical activity every 2 hours on a prepared sheet. Thus, a continuous intensity of pain profile could be drawn for the postoperative period. For comparative analysis, the maximum perceived pain during the day at bedrest, during ambulation, and during physiotherapy was documented by the patient on a VAS in the evening of days 0, 1, 2, 3, and 7 after surgery on a separate sheet.

The consumption of analgesics was documented ex- actly by the PCA software regarding time and amount of medication. By means of computer protocol analysis, interval consumption rates were calculated during the first 6 hours after the operation, and until the morning and the evening (8 AM and 8 PM) of each day after surgery, until the PCA application was discontinued. Additionally, the overall consumption of analgesics was calculated for each patient with regard to body weight. To compare different pain medication, equivalent doses for tramadole and pethidine were calculated. Additionally, the patient was asked to report side effects and the localization of pain at the evening of every day with intravenous analgesic application.

Statistics For an estimated reduction of pain intensity of 1.5

according to VAS (range, 0 to 10; standard deviation,

LOCAL INTRA-ARTICULAR INFILTRATION OF BUPIVACAINE 213

< >

10

9

8 *

7 , m

6 - - -

4

3

2

1

0 l 0

days after surgery

2

bupivacaine

m saline

3 // 7

FIG 1. Intensity of Pain at bedrest: max imum score (VAS) during the day. *Mean of bupivacaine group significantly different than mean of saline group (P < .05).

O3 < >

10

9

8

7

6

5

4

3

2,

0 I

days after surgery

I 2 3

bupivacaine

m saline

ill // 7

F IG 3. Intensity of Pain during physical therapy: maximum score during the day. Score numbers missing at the day of the operation because no regular physical therapy was performed.

1.5) the sample size was calculated to be 17 patients per group for an alpha-error of 0.05 and a beta error of 0.20. In the final study protocol, the desired number of patients per group was set at 20.

Data were analyzed by a statistical package on a personal computer (Stat View; Abacus Concepts Inc, Berkely, CA). Groups were compared using rank tests (Mann-Whitney U-Test) for pain intensity data and continuous variables. Values of P < .05 were considered significant.

RESULTS

Demographic and Clinical Data Table 2 shows the personal and clinical data of the

patients. There were no significant differences found

10 ' ' " ;sine

9

8

7

6 O3 < 5 >

4

3

2

1

0 1 2 3 7

days after surgery

FIG 2. Intensity of Pain when getting out of bed: maximum score (VAS) during the day. Score values missing at the day of the opera- fion because patients usually did not get up.

between study groups (P > .05, Mann-Whitney U- Test).

Intensity of Pain (VAS Score) On the day of surgery, the mean maximum intensity

of pain score at rest was 5.5 in the bupivacaine group and 7.3 in the control group. This difference was statis- tically significant (P < .05, Mann-Whitney U-Test) (Fig 1). All other pain scores were not significantly different on the following days during bedrest or move- ment (Fig. 2-3).

As patients do not usually move on the day of surgery and do not receive regular physical therapy until

intensity of pain (VAS)

10

getting out of bed

8

P,T.

2 bedrest t v v ~ ! VV L.-J ~

0 1 2

days after surgery

3 4 5 6 7

FIG 4. Supplemental consumption of intravenous opioids. Applied pethidine calculated as equivalent dose piritramid. " 2 h " , " 6 h " = 2 hours and 6 hours, respectively, after the end of the operation; "10 pro" = 8 to 11 hours after the end of the operation.

214 J. HOHER ET AL.

100,0

90,0

80,0

,~ 70,0

60,0

50,0

40,0

30,0

20,0

100

0,0

b u p i v a c a i n e 'T J

• , 6

2 h 6 h 10 p,rn, 7 am 7 p m 7 am overa[I day of operation day 1 p.o. day 2 po.

FIG 5. Intensity of Pain: example of individual profile. VAS (0 to 10); PT, physical therapy.

the second day after surgery data on the intensity of pain are not availabe at these time points.

A representative example of a pain profile for an individual patient is shown in Fig. 4. The graph shows apparent changes in intensity of pain with regard to the level of physical activity.

Consumption of Analgesics At all time intervals after surgery, no difference re-

garding the consumption of analgesics was shown between the study groups. The supplemental and periodic analgesic consumption of piritramid was not significantly different between the two groups (P > .05, Mann-Whitney U-Test). The supplemental consumption was 63.9 mg for the bupivacaine group and 62.6 mg for the control group. Comparing supplemental analgesic consumption in relation to body weight (mg/ kg), no significant difference could be shown between study groups at any time. The most apparent difference between study groups was a 40% lower analgesic re- quirement of the patients in the bupivacaine group within the first 6 hours after surgery compared with the control group (5.4 and 8.2 mg piritramid, respectively; P = .051, Mann-Whimey U-Test) (Fig 5).

DISCUSSION

It was the purpose of this study to investigate the effect of the injection of bupivacaine at the begin of surgery on postoperative pain after ACL reconstruction. The intensity of pain at rest was significantly lower at the day of surgery in the bupivacaine infiltrated patients. The mean difference was 2.8 on a 10- point scale. According to Ure et al., 38 a difference of 1.5 points is regarded to be clinically relevant. At later times, no pain-reducing effect of bupicvacaine can be

found. Moving, walking on crutches, and initial range of motion exercises under physical therapy cause maximum pain values higher than 5 in almost all patients. A desired reduction of pain at this stage cannot be achieved by bupivacaine and causes high piritramid consumption up to the second day after surgery.

We found no difference between the study groups regarding the consumption of analgesics. Even if pain scores were different on the day of the operation in our study, this did not obviously influence the consumption of intravenous opioids overall.

In our study, bias could be minimized to a great extent. A randomization of patients in a double-blind setting and the use of PCA are essential criteria designed to minimize bias in a clinical pain study. The investigator's bias in pain assessment is reduced by using a visual analog scale on a sheet that is marked by the patient alone. 4°'4~ The use of PCA avoids a delay between the patient's desire for analgesics and the application of the drug to the patient. 6'7 It was an apparent finding of our study that VAS score numbers vary significantly in regard to the kind of physical activity. Because patients are motivated to move as much as tolerated after surgery, it is our recommendation to obtain pain scores in regard to the present kind of activity. Physical therapy was the most painful activity in the postoperative period and analgesia during or after physical therapy deserves more attention.

PCA has been widely used in recent years for postoperative pain reduction. 6'v ACL reconstruction is a painful operation and frequently makes intravenous opioids necessary. Matheny et al. 2 found a demand for 50 to 80 mg morphine per day by PCA in patients undergoing ACL reconstruction. This is a similar finding to our study, with a supplemental consumption of 63.9 mg and 62.6 mg of piritramid, respectively.

Local anesthetic drugs are well accepted in arthroscopic surgery of the knee. Diagnostic arthroscopies and arthroscopies with minor surgery can be performed with local anesthetics, alone. Some authors favor the use of lidocaine, 8'is whereas others use bupivacaine t°'ll o r b o t h . 9 An additional measure for pain control is the infiltration of the portals. T M

The pharmacokinetics of bupivacaine after instillation into the knee joint has been investigated by many a u t h o r s . 42-4a According to these studies, 30 mL bupivacaine 0.5% (150 rag) are considered to be safe and do not lead to toxic blood level concentrations.

Many authors used bupivacaine at the end of surgery to achieve postoperative pain reduction after knee arthroscopy. Before removing the arthroscope, a cer- tain amount of bupivacaine was instillated into the

LOCAL INTRA-ARTICULAR INFILTRATION OF BUPIVACAINE 215

TABLE 3. An Overview of Studies With Bupivacaine After Knee Arthroscopy

Stuay Study Dosage Design Result

Milligan 16 1988 20 mL 0.5% pr ran db No effect Chirwa ~3 1989 20 mL 0.25% pr ran db Less pain, less analg Kaeding ~5 1990 40 mL 0.25% pr ran db Less pain, less analg Henderson 14 1990 30 mL 0.25 pr ran db No effect Sorensen TM 1991 10 mL 0.5% pr ran db No effect

+E Tolksdorf ~9 1991 10 mL 0.5% pr ran Less pain (-8h)

blind Osborne ~v 1993 20 mL 0.5% pr ran db Less pain (diff study

+ E gr) Geutjens 49 1994 10 mL 0.5% pr ran db Less pain (op day) Ares 5° 1994 10 mL 0.5% pr ran db No effect Boden s6 1994 20 mL 0.5% pr ran Less pain

+ E blind

Abbreviations: E, epinephrine; pr, prospective; ran, randomized; db, double-blind; analg, consumption of analgesics.

knee joint. However, the results of this technique are controversial. Table 3 gives an overview of studies using bupivacaine for postoperative pain reduction.

Chirwa et al.13 found a significant pain reduction and a reduction in analgesic medication in a prospective, randomized trial using 20 mL bupivacaine 0.25 %. Pos- itive results have also been reported by Kaeding et al.15 using 40 mL bupivacaine 0.25%, and by Osborne and Keene 17 using 20 mL bupivacaine with epinephrine for vasoconstriction in randomized, double-blind trials. Tolksdorf et al. 19 described a pain-reducing effect of up to 8 hours after surgery by using 10 mL bupivacaine 0.5% in a randomized blinded study. Geutgens and Hambidge 49 found a significant effect with the same amount of bupivacaine in a blind study the evening of surgery, but not the next day.

Milligan et al) 6 and Henderson et al. 14 found no analgesic effect when using 20 mL of bupivacaine 0.5%, and 30 mL of bupivacaine 0.25%, respectively, in prospective randomized studies. The same negative result was described by SCrensen et al.18 using 10 mL bupivacaine 0.5% plus epinephrine and by Ates et al. 5°

It is a problem of all studies described that they were done on arthroscopies with only minor surgical interventions (e.g., partial meniscectomy). It is our experience that most of these patients do not perceive relevant postoperative pain and do not need intravenous opioid analgesia. In ACL reconstruction, however, the intensity of pain perception after surgery is much higher and usually intravenous opioid analgesia is necessary. To date no final evaluation on the effect of bupivacaine used at the end of the operation is possible. 51

One explanation for a limited effect of the preopera- tively instillated bupivacaine is the fact that, because of irrigation of the knee joint during arthroscopy a washout effect of bupivacaine is present. The loss of local anesthetic during arthroscopy with saline irrigation approximately 10 minutes after instillation is be- lieved to be about 50%. 52 Whether or not a better pain reduction could have been achieved by additional instillation of bupivacaine at the end of surgery has to be questioned when analyzing the results from the literature.

Morphine has been introduced as an alternative to local anesthetic drugs for local pain reduction in the knee joint. 53 In clinical trials a significant reduction of postoperative pain was shown after the instillation morphine into the knee joint after knee arthroscopies 53 and after ACL surgery, s4 Comparative studies showed a better postoperative pain reduction with the application of 5 mg morphine compared with 62.5 mg bupivacaine. 54'55 Boden et al. 56 found the best analgesic effect in a combination of bupivacaine and morphine. In con- trast to this, no effect was found by Ruwe et al. 57

These results support the hypothesis that bupivacaine infiltration into the knee joint leads to a reduction of postoperative pain. However, the duration of the pain reducing effect and the clinical relevance of this effect have to be a matter of debate. In our study, a positive effect of bupivacaine instillation could be shown only on the day of the operation. The overall amount of opioid analgesics and high pain scores in the first postoperative night and on day 1 and 2 after surgery could not be reduced by the bupivacaine instillation. Thus, in our study setting with an ACL reconstruction performed with several overnight stays, the instillation of bupivacaine before surgery is probably of no clinically relevant use. However, when ACL reconstruction is performed as an outpatient procedure, the significant difference in VAS scores on the day of surgery might be of greater importance. The patient being discharged on the same day of the operation must expect higher noxious stimuli due to his transportation effort. Under these circumstances, a better pain relief at that time may be subjectively more valuable.

In the future, additional techniques should be fa- vored to reduce pain intensity and intravenous opioid consumption after ACL surgery. Regional, techniques like the use of a peridural catheter or a three-in-one catheter seem to be more promising for postoperative pain treatment at the moment ) It should be the subject of further studies to evaluate alternative local applica- ble drugs like morphine and to find methods for longer application of local drugs to the knee after surgery. 5a

216 J. HOHER ET AL.

Further, changes in operative techniques such as the performance of arthroscopic-assisted procedures and the avoidance of wound drainages might also contrib- ute to better postoperative patient comfort.

Conclusion The local and intraarticular instillation of bupiva-

caine at the beginning of surgery in ACL reconstruction cannot be routinely recommended because a long- lasting, clinically relevant reduction of postoperative pain could not be shown in the present study.

A c k n o w l e d g m e n t : No financial support was accepted for conduct ing this study. The authors thank K. Nasskau for her technical help in preparing the manuscript.

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