The THAs were performed through a direct lateral approach. Operative anesthesia was either general or spinal. The anesthetic regime was standardized. No long-acting analgesics were used and spinal anesthesia was performed using spinal bupivacaine hydrochloride, ranging from 10 to 15 mg. Twenty-three patients in the injected group and 24 in the noninjected group had a general anesthetic. Nine patients in the injected group and eight in the noninjected group had a spinal anesthetic. With these small numbers, there was no difference (chi square test, p = 0.78) between general versus spinal anesthetic, which was selected at the anesthesiologist's discretion.
The injection contained 400 mg ropivacaine (ropivacaine HCl; Astra Zeneca Canada Inc, Ontario, Canada), 30 mg ketorolac (Toradol®; Sabex Inc, Boucherville, Canada), 0.6 mL epinephrine (1:1000; Abbott Laboratories, Abbott Park, IL), and 5 mg preservative-free morphine (Sabex Inc). These were mixed with sterile normal saline and made up to a combined volume of 100 mL in the operating room . During the operation, 20 mL of the mixture was injected into the posterior capsule after femoral component insertion and another 20 mL in the anterior capsule before hip reduction and capsular closure. The remaining 60 mL was placed in the fat and subcuticular tissues. Five patients in each group had blood samples taken at 30 minutes, 1 hour, and 4 hours postoperation to measure venous blood (protein-bound) ropivacaine levels.
All patients received PCA for 24 hours postsurgery (morphine: bolus 1.5 mg, lockout 6 minutes and maximum 15 mg/hour). All patients had a lower limb ultrasound to exclude a deep vein thrombosis at Day 5 postsurgery.
Postoperative PCA consumption was measured for the first 24 hours and the patient's overall analgesic consumption until discharge was measured and converted to morphine equivalents to allow for comparison of the groups. Other analgesics used by the patients during the postoperative period included Percocet™ (acetaminophen 325-650 mg, oxycodone 5-10 mg; Endo Pharmaceuticals Inc, West Chester, PA), Tylenol® (acetaminophen 325 mg, caffeine 15 mg, codeine 8 mg; McNeil Consumer Healthcare, Fort Washington, PA), and Tylenol® 3 (acetaminophen 300 mg, codeine 30 mg; McNeil Consumer Healthcare). The following conversion ratios were used for calculating morphine equivalents: morphine:oxycodone 1:2 and morphine:codeine 1:20 . The total dose of a drug was calculated for the period of interest and then converted to morphine equivalents for analysis. We measured ropivacaine levels in five patients 4 hours postoperation. The criteria for hospital discharge were the ability to safely walk up and down a flight of stairs and a safe environment for discharge.
Patients were assessed using VAS scores for pain, at rest and during activity, and for patient satisfaction, in the preoperative assessment clinic (2-3 weeks before surgery), on the day of surgery, in the postanesthetic care unit (PACU), at some time during the inpatient stay, and finally at 6 weeks' followup. The VAS for pain and satisfaction ran from 0 mm (indicating no pain or completely dissatisfied) to 100 mm (indicating extreme pain or completely satisfied) in 10-mm increments. The activity performed relating to the VAS assessment of pain on activity was leg movements while supine within the limits of any regional anesthesia while in the PACU. At other times, the activity was the rehabilitation activity relevant to that stage of the patient's recovery. Specific note was made of any signs of cardiac (chest pain, shortness of breath, or electrocardiogram changes) or central nervous system toxicity (visual and hearing disturbances, dysarthria, tingling, perioral numbness, dizziness, paresthesia, light-headedness, muscular twitching, or muscular rigidity), or wound complications. We observed wounds daily and noted any wound drainage, erythema, swelling, blisters, desquamation, dehiscence, protuberant suture material, or signs of infection. As part of our routine clinical care during the period of this study, Harris hip scores and WOMAC scores were collected prospectively for all patients (Table 2). These data were available out to 2 years by the time of this study. All patients had a lower limb ultrasound to assess for the presence of deep vein thrombosis before discharge.
We determined differences in postoperative PCA requirements, postoperative VAS scores for pain and satisfaction, the operating time, and the length of hospital stay between the injected and noninjected cohorts using a two-tailed unpaired t test. In all five of these analyses, the data passed the Kolmogorov-Smirnov test for normality (p < 0.05). We determined the difference in the incidence of complications between the injected and noninjected cohorts using Fisher's exact test (nonparametric). SPSS® (Version 11.5; SPSS Inc, Chicago, IL) was used for the analyses.
Patients undergoing THA who had received the multimodal drug infiltration used less (p = 0.0023) PCA at 6 hours postoperation (11.1 mg morphine [SD, 9.7 mg] versus 19.6 mg morphine [SD, 11.6 mg]). The overall PCA requirement was less (p = 0.0093) during the first 24 hours after surgery for the injected patients (28.5 mg morphine [SD, 18.9 mg] versus 43.3 mg morphine [SD, 24.7 mg]) (Fig. 2).
The VAS score for pain on activity was lower (p = 0.0019) in the injected group in the PACU (0.35 [SD, 0.31] versus 0.59 [SD, 0.28]) (Fig. 3). There was no difference between the VAS scores for pain at rest.
The average operating times (skin incision until dressing application) were similar (p = 0.86) for the two groups: 85.5 minutes (SD, 19.7 minutes) for the injected group and 84.7 minutes (SD, 14.9 minutes) for the noninjected group.
There was no difference (p = 0.24) in average hospital stay (125.8 hours [SD, 30.6] for injected group versus 139.0 hours [SD, 54.7] for the noninjected group).
The rate of wound complications was similar (p = 0.35) in the two groups. Three patients had a minor wound problem in the injected group and one in the noninjected group. These included three patients with blisters related to their dressings and one prominent suture requiring trimming. One patient in the injected group had a deep vein thrombosis postoperatively.
The maximum dose of unbound ropivacaine observed among the five patients was 60 ng/mL, which is 2.5 times below the toxic levels reported by Knudsen et al.  (150 ng/mL). No cardiac or central nervous system toxicity was observed.
We acknowledge several limitations. The first relates to its size. The study was underpowered to establish whether the observed reduction in postoperative PCA requirements would translate into a lower incidence of the side effects associated with postoperative opioid use. Second, we explored only the use of this analgesic modality with one surgical approach to the hip and the findings might not apply to other joints (eg, the knee). Third, we focused on the early postoperative period; although we would not expect a difference in the groups beyond 6 weeks, additional study would evaluate whether this is the case. This would be of added value in terms of determining whether the reduced PCA requirements translate into a lower incidence of chronic pain developing in these patients. A postal questionnaire followup of patients in Denmark who had THA indicated the incidence of substantial pain after THA may be as much as 12.1% and the state of this pain was related to the recalled early postoperative pain experience .
We observed a decrease in the PCA requirements of patients receiving an intraoperative injection, which targets numerous sites of action. Inflamed tissues have abundant opioid receptors [20, 32]. These receptors are expressed shortly after trauma and are an effective site for sensory blockade by opioids . NSAIDs exert their analgesic effect by numerous pathways in the periphery including inhibition of prostaglandin synthesis, inhibition of cyclooxygenase 2 activity, and in some NSAIDs, inhibition of the lipoxygenase pathway and interference with G-protein-mediated signal transduction . The reduction in PCA use was substantial in the PACU with no difference between the groups at 7 to 24 hours. This early substantial reduction was reflected in a substantially lower total during the 24-hour period. Peters et al.  observed reduced postoperative narcotic requirements with one intraoperative periarticular injection. Andersen et al.  observed reduced postoperative narcotic requirements with an intraoperative periarticular injection and top-up via catheter after 8 hours. Kerr and Kohan  reported a series of 325 patients undergoing THAs, TKAs, and hip resurfacings who received a perioperative injection and additional infiltration via a catheter at 15 to 20 hours postoperation. They reported satisfactory pain control in all patients with no morphine required in two-thirds of their patients.
The VAS scores for pain for our patients showed reduced pain on activity in the PACU only. There was no difference in the VAS scores for pain at rest. Peters et al.  observed reduced pain on activity on Postoperative Day 2 but at no other time. They also reported reduced pain at rest on Postoperative Days 1 and 2; interestingly, there was increased pain at rest in the injected group on the day of surgery. Kerr and Kohan  did not compare their data with a noninjected cohort. Hebl et al.  reported on two groups of 20 patients who had minimally invasive THA and TKA with an anesthetic protocol using a peripheral nerve blockade. Good pain relief was achieved but with side effects and a 3% rate of failed blocks.
We observed similar VAS satisfaction scores in the two groups. This result was surprising given there was a decrease in pain on activity scores in the PACU. An increase in pain reportedly correlates with a decrease in patient satisfaction . Parvataneni et al.  reported an increase in patient satisfaction in their series of patients undergoing THA who received a perioperative injection. Identifying changes in patient satisfaction in the early postoperative period is a recognized problem . It is possible the VAS scale was not a sensitive enough test to detect the changes in satisfaction or a greater reduction in the VAS pain score would be required in our population to be reflected in an improved VAS satisfaction score.
We observed no difference in the operative time for our patients. Failed peripheral nerve blocks  can increase the overall theater time for a patient undergoing TKA . The technique used in our study did not affect the operative time and patients in both groups underwent the same perioperative preparation, so although not formally measured, it is reasonable to assume the overall theater time is not increased by this technique. This may represent an increased efficiency over nerve blocks.
Our injected group was not discharged in a shorter time than the noninjected group. Others investigating periarticular hip injections alone have reported more rapid discharge of their patients who received injections . A more rapid discharge also has been reported with the use of a catheter for additional instillation after perioperative injection [1, 16]. Our criteria for discharge did not differ between the groups, nor did it in these other studies. It is possible the expectations of staff were influencing the actual discharge time. A more thorough investigation of the factors involved in discharge would be required to ascertain whether this was the case.
The complication rates were similar for our two groups. Another series investigating the technique also reported no difference in complication rates . In the trial of an intraoperative injection followed by top-up via a catheter , there was an episode of deep infection in the injected group although overall no difference in complication rate. We believe one intraoperative injection is preferable to performing a top-up via catheter postoperatively. Although aseptic technique can be used to achieve this, it is a potential port for the introduction of bacteria. Continuous infusion of opioid and bupivacaine postoperatively in patients who have a TKA is associated with prolonged wound drainage .
Ropivacaine is a local anesthetic pharmacokinetically similar to bupivacaine but has a lower toxicity profile and longer duration of action [8, 18]. We measured circulating blood levels of ropivacaine in patients receiving injections. All measurements were well within the reported limits for toxicity . The addition of epinephrine helps to reduce the toxicity of the local anesthetic by keeping it localized to the area of injection .
Our data suggest periarticular intraoperative injection with multimodal drugs around THA can reduce postoperative PCA requirements with no apparent increase in risk.
We acknowledge Dr. L. Kohan and Dr. D. Kerr of Sydney, Australia, for their work in developing the multimodal drug combination used in this study. We also thank Prof C. H. Rorabeck and Dr. R. Bhandari for contributions to work with this research and the previous investigation of multimodal drug infiltration in TKAs.
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