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Analgesia: Research Reports

Continuous Epicapsular Ropivacaine 0.3% Infusion After Minimally Invasive Hip Arthroplasty

A Prospective, Randomized, Double-Blinded, Placebo-Controlled Study Comparing Continuous Wound Infusion with Morphine Patient-Controlled Analgesia

Aguirre, Jose MD, MSc*; Baulig, Barbara MD*; Dora, Claudio MD; Ekatodramis, Georgios MD*; Votta-Velis, Gina MD, PhD*; Ruland, Philipp MD*; Borgeat, Alain MD*

Author Information
doi: 10.1213/ANE.0b013e318239dc64

The use of wound infiltration with local anesthetics as part of multimodal analgesia after surgery is based on the recognition of the important role played by parietal nociceptive afferent nervesin eliciting pain and in the pathophysiologic repercussions induced by surgery.13

The primary end-point of this study was to evaluate whether continuous wound infusion (CWI) of epicapsular ropivacaine 0.3% with a 15-cm multihole catheter would have an impact on morphine consumption after minimally invasive hip arthroplasty (MIS).

METHODS

After local ethics committee approval of this double-blind study and written informed consent were obtained, 76 adult patients scheduled for MIS were prospectively included and randomized to either the ropivacaine 0.3% (R-) group (n = 38) or in the placebo (P-) group (NaCl 0.9%) (n = 38). An electrocardiogram was recorded the day before surgery.

Spinal anesthesia with 15 mg hyperbaric bupivacaine 0.5% was performed and acetaminophen 1 g was given to all patients after spinal anesthesia and repeated every 6 hours until T96.4 All operations were performed by 2 surgeons using the same standardized technique.5 During surgery, the elastomeric pumps (MultirateInfusor LV, 300 mL volume, Baxter AG, Switzerland) and the syringes for the bolus were filled by a pharmacist with either ropivacaine 0.3% or placebo (NaCl 0.9%) under aseptic conditions. Two 300-mL pumps were connected with a Y-connector to assure a total flow rate of 8 mL/h (each pump had a flow rate of 4 mL/h) for 48 hours without any need for further manipulation of the pumps. After implantation of the prosthesis, the sterile fenestrated 19G multihole 15-cm catheter (PAINfusor Catheter 15, Baxter AG, Switzerland) was placed by the surgeon epicapsularlyon the closed capsule, and 20 mL of ropivacaine 0.3% or placebo was injected into the wound. The wound suction catheter was placed distally from the multihole wound catheter and clamped until complete wound closure. The distal part of the catheter was adhered to the capsule and the proximal was placed subcutaneously. Application of the initial bolus was defined as T0 (start of the study). In the postanesthesia care unit, pain was assessed using the visual analog scale (VAS) (0–100). All patients received a patient-controlled analgesia device for IV morphine administration with the following settings: no basal infusion, 2 mg bolus, and 8 minutes lockout time. Patients were discharged to the ward according to the criteria of the modified Aldrete score6 and VAS score was <30. The wound catheter and patient-controlled analgesia were removed at T48.

All data were collected by a research fellow unaware of the study group assignment. The primary end-point was total IV morphine consumption after the first 48 hours (T0–T48).

Other variables assessed were postoperative pain at rest and with motion (defined as holding the lifted operated leg at a distance of 10 cm between the patient's heel and the bed for 5 seconds); electrocardiogram at baseline and T48; skin inflammation or infection at the catheter insertion site assessed daily until T96; patient satisfaction concerning postoperative pain therapy at T72 using VAS ranging from (0 = not satisfied) to 100 (very satisfied); and ambulation. Total and unbound ropivacaine plasma concentrations7 were measured at T0, T6, T24, T48 (=time of catheter removal).

Patients were called 3 months after surgery and queried regarding the least, average, and worst pain scores using VAS, oral analgesics/opioid consumption, and wound discomfort to touch and pressure using VAS ranging from 0 to 100. In addition, patients were asked about the presence of any new onset of sensory and motor deficits during their normal daily activities.

After this type of surgery, patients consume an average 25 ± 10 mg of morphine during the first postoperative day. To detect a clinically significant reduction in morphine consumption of 30% (7.5 mg) between the groups with an α risk of 0.05 and a power of 80%, we needed a sample size of 36 patients in each group. To compensate for possible dropouts and assuming a common 6% dropout rate, we included 76 patients. The Lilliefors test was used to verify normal distribution of continuous variables. Continuous variables are expressed as mean ± SD or median with interquartile range as appropriate, and categorical variables are reported as percentages. Normally distributed continuous variables (patient characteristics and surgical time) were compared using 2-group Student t test, whereas Mann–Whitney test with Bonferroni correction was used for comparison of VAS (VAS was assessed at T0, T6, T12, T24, T36, and T48) and morphine requirements. All analyses were 2-tailed, and P < 0.05 was considered statistically significant. Confidence interval was calculated with Hodges–Lehmann method using Confidence Interval Analysis (CIA) Software/Statistics with Confidence seconded (BMJ Books 2000). All other analyses were made using computer SigmaStat Version 16 (SPSS Science, Chicago, IL).

RESULTS

Seventy-six patients were included in this study. Four patients had to be excluded after allocation (Fig. 1). Thirty-six patients per group successfully completed the study. Patients' and surgical characteristics did not differ between the 2 groups (Table 1).

Figure 1
Figure 1:
Flow diagram of the different trial phases.
Table 1
Table 1:
Patient and Surgical Data

Mean morphine consumption was significantly lower in the R-group than in the P-group during the first 48 postoperative hours: 45.4 ± 9.5 vs 69.7 ± 9.6 (P < 0.0001). There was a mean reduction of 14.4 mg for the first 24 postoperative hours (95% confidence interval [CI] 12.6 to 16.1) and 20.8 mg for the next 24 hours (95% CI 19.1 to 22.4) (Fig. 2).

Figure 2
Figure 2:
Morphine consumption (in milligrams) at T0-T24 and T0-T48 (Tx for X = hours after T0). Continuous wound infusion with ropivacaine represented with open bars, placebo with solid bars. Measurements were made 24 and 48 hours postoperatively. The solid horizontal lines indicate the median. The box represents the 25th–75th percentiles. The extended bars represent the 10th–90th percentiles. *Significant differences between the 2 groups (P < 0.0001).

Pain scores at rest and in motion were significantly lower at T4, T6, T12, and T24 (Table 2, Fig. 3, A and B) in the R-group.

Table 2
Table 2:
Morphine Consumption and Pain Scores
Figure 3
Figure 3:
A, Pain after total hip arthroplasty at rest at different time points after initial local anesthetic bolus application (T0) until T48 (Tx for X = hours after T0). Continuous wound infusion with ropivacaine represented with open bars, placebo with solid bars. VAS = visual analog scale from 0 = no pain to 100 = worst pain imaginable. The solid horizontal lines indicate the median. The box represents the 25th–75th percentiles. The extended bars represent the 10th–90th percentiles. *Significant differences between the 2 groups (P < 0.0001). B, Pain after total hip arthroplasty with motion at different time points after initial local anesthetic bolus application (T0) until T48 (Tx for X = hours after T0). Continuous wound infusion with ropivacaine represented with open bars, placebo with solid bars. VAS = visual analog scale from 0 = no pain to 100 = worst pain imaginable. The solid horizontal lines indicate the median. The box represents the 25th–75th percentiles. The extended bars represent the 10th–90th percentiles. *Significant differences between the 2 groups (P < 0.0001).

Total ropivacaine plasma concentrations were 0.09 ± 0.08, 1.68 ± 1.39, 5.98 ± 4.25, and 7.77 ± 5.65 μgmol/L at T0, T6, T12, and T24, respectively. The unbound fractions of ropivacaine were 0.0 ± 0.0, 0.06 ± 0.04, 0.14 ± 0.12, and 0.11 ± 0.11 μgmol/L at T0, T6, T12, and T24, respectively. The threshold for toxicity of free ropivacaine is >1.8 μgmol/L.

All fenestrated wound catheters were removed at T48 without any problems. No local inflammation or infection was reported in either group. All fenestrated wound catheters after removal were flushed with saline over a dark surface area to assess patency. No obstruction that could have influenced the flow through the catheter holes was noted in any catheter.

Patient satisfaction was significantly higher at 22.7 in the R-group (95% CI 15.9 to 29.6) (P < 0.0001).

At the telephone follow-up evaluation 3 months after surgery, there was no difference in analgesic consumption, motor/sensory function, or pain during normal daily activities. A significant reduction in wound discomfort to touch (31.2; 95% CI 27.7 to 34.7) (P < 0.0001) and pressure pain (24; 95% CI 20.1 to 27.9) (P < 0.0001) was reported in the R-group (Table 1).

DISCUSSION

This study shows that after MIS, continuous epicapsular infusion of ropivacaine 0.3% for 48 hours has a beneficial effect on pain relief, reduces morphine consumption, and postoperative nausea and vomiting. Moreover, a positive effect on superficial and deep wound pain was still present 3 months later.

Ropivacaine was chosen for its wider safety margin in comparison with other long-lasting local anesthetics.8 The 0.3% concentration was chosen because a previous pilot study (unpublished results) has shown that ropivacaine 0.2% was insufficient to control pain in this setting.

CWI is not new in orthopedic surgery,3,9,10 but to our knowledge, no study has investigated the effects of epicapsular catheter placement after MIS. One randomized controlled study evaluated the effects of CWI of ropivacaine 0.2% after standard hip arthroplasty.11 Although results of this study are mostly in accordance with ours,12 the exact placement of the catheter was not given. Some epidemiological studies focusing on wound infusion and hip arthroplasty have been published,1316 but the majority of them specifically include the local infiltration technique, making direct comparison with our study difficult. Three randomized controlled trials have analyzed the effects of the local infiltration technique introduced by Parvataneni et al.17 and further developed by Kerr and Kohan.14 These investigations showed promising results.1820 However, it has to be emphasized that the methodology of these studies is not similar to ours.

The reduction of wound pain after 3 months in the R-group could be explained by the loop of the catheter, creating both an epicapsular infusion and an infusion near the lateral femoral cutaneous nerve. Although the superiority of local anesthetic spread through a 15-cm multihole catheter towards a triple-orifice epidural catheter has been challenged by Andersen et al.,21 their comparative study used manual bolus injection of a catheter placed subfascially. Moreover, wound pain is reduced after single or continuous wound instillation with ropivacaine.3 In animal22 and in human23 models a positive effect of local anesthetics on prevention of neuropathic pain, secondary hyperalgesia, and inflammation24 has been demonstrated. Skin injury is not only associated with the development of tissue hyperalgesia but also with the local release of inflammatory and nociceptive mediators.2527 Studies in animal models of incisional pain28 and clinical trials29 have demonstrated that single analgesic treatment (peripheral or neuraxial) before the incision does not reduce postoperative pain behaviors beyond the expected duration of the analgesic effect. Interestingly, drugs like systemic ketamine or spinal clonidine, which have been shown to modulate central sensitization and to affect the incidence of persistent postsurgical pain,30 might reduce chronic pain after total hip replacement.31 It is likely that pregabalin32 will also show similar results. A combination of these drugs with CWI would also be interesting and should be further evaluated.

The measurement of the remaining volume in the pump was within the 10% difference range described by the manufacturers. These results contrast with other findings reporting a different in vivo reliability in comparison with the in vitro results.33 No delay in wound healing or wound infection was observed. This is in agreement with observations of previous investigations.34,35

In conclusion, the use of CWI with ropivacaine 0.3% was associated with better postoperative pain control, a reduction of opioid consumption, and a long-lasting positive effect on superficial and deep wound pain after continuous wound infiltration with ropivacaine 0.3%.

DISCLOSURES

Name: Jose Aguirre, MD, MSc.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Jose Aguirre has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Name: Barbara Baulig, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Barbara Baulig has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Claudio Dora, MD.

Contribution: This author helped design the study and conduct the study.

Attestation: Claudio Dora has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Georgios Ekatodramis, MD.

Contribution: This author helped design the study and conduct the study.

Attestation: Georgios Ekatodramis has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Gina Votta-Velis, MD, PhD.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Gina Votta-Velis has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Philipp Ruland, MD.

Contribution: This author helped analyze the data and write the manuscript.

Attestation: Philipp Ruland has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Alain Borgeat, MD.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Alain Borgeat has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

This manuscript was handled by: Terese T. Horlocker, MD.

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