Hip replacement with a standard surgical approach

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1 This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies Hip replacement with a standard surgical approach is characterized by postoperative pain ranging from mild at rest to severely exacerbated on movement. 1 Inadequate analgesia may increase patients perioperative risks and lead to the development of chronic pain. 2 Effective postoperative pain relief aims not only to prevent these conditions but also to facilitate early O R I G I N A L A R T I C L E Pain relief after total hip replacement: oral CR oxycodone plus IV paracetamol versus epidural levobupivacaine and sufentanil. A randomized controlled trial M. 1, M. CECCONI 2, N. FASANO 1, N. LANGIANO 1, M. BUTTAZZONI 1, I. GIMIGLIANO 3, G. DELLA ROCCA 1 1Department of Anesthesia and Intensive Care Medicine, S. Maria della Misericordia University Hospital, University of Udine, Udine, Italy; 2 Department of General Intensive Care Medicine, St George s Hospital, London, UK; 3 Department of Intensive Care, University College Hospital, London, UK A B S T R A C T Background. We tested the hypothesis that pain relief after total hip replacement (THR) can be obtained with a multimodal approach using oral controlled release (CR) oxycodone plus IV paracetamol. Methods. Two hundred and sixty patients undergoing THR were randomized into two groups. A group of 130 patients (EPI) under epidural anesthesia followed by continuous infusion of levobupivacaine 0.125% and sufentanil 0.7mcg/mL at 7 ml/h was compared with a group (OXY) of 130 patients under spinal anesthesia and oral CR oxycodone 10 mg/q12h plus IV paracetamol 1g/q6h. Pain intensity at rest and dynamic by visual analogue scores (VAS), rescue dose consumption and side effects of three postoperative days (POD) were collected and analyzed with Mann-Withney test (P<0.05 was considered significant). Results. VAS values at rest were similar in both groups at POD#1, significantly lower in the OXY group either at POD#2 (P=0.018) and POD#3 (P=0.001). Dynamic VAS values were significantly lower in the EPI group at POD#1 (P=0.001), similar for both groups at POD#2 and significantly lower in the OXY group at POD#3 (P=0.026) than the comparing group. Rescue dose consumption was significantly lower in the EPI group during the POD#1 (P=0.009), similar for both groups at POD#2 and higher in the EPI at POD#3 (P=0.008). The incidence of vomiting was similar for the two groups. Nausea was more frequent in the OXY group at POD#3 and more hypotension events occurred in the OXY group at POD#2. Conclusion. Oral CR oxycodone plus IV paracetamol was as effective as epidural levobupivacaine and sufentanil for postoperative pain relief after THR. (Minerva Anestesiol 2012;78:534-41) Key words: Postoperative management - Anesthesia, epidural - Analgesics, opioid - Arthroplasty, Replacement, Hip. physiotherapy, in order to recover joints mobility. In addition, optimal analgesia is known to limit the inflammatory reaction and nociceptive transmission. 3 Epidural analgesia for postoperative pain management in orthopaedic surgery decreases postoperative mortality and morbidity; it also reduces postoperative risk of myocardial infarc- 534 MINERVA ANESTESIOLOGICA May 2012

2 tion and venous and pulmonary thromboembolism. 4, 5 However, a high level of staff intervention is required for this technique, and several complications have been described Moreover, this analgesia technique was recently limited by American Society Regional Anesthesia and Pain Medicine (ASRA) Guidelines when the newer thromboprophilaxys therapies are planned. 6 Pain management alternative choices include peripheral nerve blockade, local infiltration, intravenous or oral opioids. Single-shot or continuous lumbar plexus block reduced pain scores but only for a short duration up to 48 postoperative hours when compared with systemic analgesia. 18 Regional analgesia does, however, reduce postoperative pain and also nausea and vomiting but not appear to facilitate rehabilitation or reduce length of stay for total hip replacement (THR) in a recent meta-analisys. 15 Single wound local infiltration was clarified only as part of a multimodal pain management strategy after total hip arthroplasty (THA). The role of wound catheter administration and its placement and type are unknown. 16 Intravenous patient controlled analgesia (IV-PCA) with morphine provides adequate analgesia at rest, but not on movement, and has quite a high incidence of nausea and vomiting. 13 Oral opioids have not yet been studied as the primary analgesic modality after THA, but recently their particular formulation combined with paracetamol does appear to provide efficacy in acute postoperative pain. 14 We considered that the characteristics of oral oxycodone and IV paracetamol, started during the preoperative period, together with the ease of administration could make this multimodal approach an alternative to epidural analgesia for postoperative pain relief after hip arthroplasty. The first aim of this study was to test this hypothesis: a multimodal regimen comprised of oral oxycodone and intravenous paracetamol would provide equivalent analgesia on dynamic Visual Analogue Scale (VAS) to epidural levobupivacaine and sufentanil for the first 72 hours following THR. Secondary aim was to investigate VAS at rest, rescue dose consumption, side effects and complications. Materials and methods After University Hospital of Udine Ethics Committee approval and written informed consent, 270 patients undergoing total hip replacement (THR) were enrolled in this study (Figure 1). Inclusion criteria were ASA physical status I-III and age >18 years. Exclusion criteria were minimally invasive technique, central/ peripheral neuropathies, cognitive dysfunction, any contraindication to epidural anesthesia and/ or a known allergy to local anesthetic drugs or opioids; 260 patients were randomized into two groups: in the EPI group 130 patients received epidural levobupivacaine 0.125% plus sufentanil as a continuous infusion and in the OXY group 130 patients received oral CR oxycodone plus IV paracetamol. All patients received standardized regional technique after pre-hydratation with 500 ml Ringer s solution and premedication with IV midazolam 0.02 mg/kg. Patients in the EPI group, had a 20 gauge epidural catheter (Perifix, BBraun, Melsungen, Germany) placed at L3/4 or L4/5 interspace, using a 18 gauge Tuohy needle with the patient in sitting position. Patients were placed in supine position and after a negative test dose of 3 ml of levobupivacaine 0.5%, a total dose of 5-8 ml of the same solution was administered before the surgery. After the effects of epidural anesthesia, in the recovery room a bolus of 5-7 ml of levobupivacaine 0.125% was administered and a continuous infusion of levobupivacaine 0.125% plus sufentanil 0.7 mcg/ml was started at the rate of 7 ml/h via a portable elastomeric infusion system (LV 7 Infusor, Baxter; Deerfield, IL USA). Each day, low molecular weight heparin (LMWH), dalteparin 5000 IU/day (Fragmin; Pfizer, Rome, Italy), was given subcutaneously, as deep venous thromboprophylaxis, starting the evening before the surgery. If paresthesia in the lower limb occurred, the local anesthetic infusion was interrupted until the paresthesia resolved and then restarted at a lower rate. If paresthesia was still experienced the epidural catheter was retracted by 1 cm and the local anesthetic infusion restarted. If catheter kinking or displacement was suspected, a bolus of 3-5 ml of lidocaine 1% was administered to Vol No. 5 MINERVA ANESTESIOLOGICA 535

3 Figure 1. Flow diagram of the study. EPI: epidural; OXY: oxycodone plus paracetamol; THR: total hip replacement. ensure there was no evidence of sensory block to cold sensation (e.g. ice). In this case the local anesthetic infusion was ceased, rescue dose was administered and the catheter was removed and replaced at least h after the last dose of LMWH and at least 6-8 h before the following dose. The epidural catheter was removed at the 72 nd postoperative hour. The OXY group was given 10 mg oral CR oxycodone (Oxycontin TM ;Mundipharma Pharmaceuticals, Milano, Italy) 30 minutes before entering the operating theatre and then every 12 hrs, together with 1g IV paracetamol every 6 hrs for 72 hours. This group received intraoperative spinal anesthesia. A 25 gauge spinal Sprotte needle (Pajunk, Geisingen, Germany) was used to administer 15 mg of 0.75% plain levobupivacaine before the surgery. In this group deep venous thromboprophylaxis was achieved with mg/day fondaparinux (Arixtra; Glaxo- SmithKline; Brentford, Middlesex, UK) given subcutaneously starting 6 up to 24 hours after the end of the surgery. In both groups,vas score at rest and dynamic was assessed using a continuous 0-10 cm scale every 8 hours during the first 72 postoperative hours. When it exceeded a score of 3 cm, postoperative rescue dose for both groups consisted of 100 mg tramadol by IV infusion over 15 minutes, to a maximum of three times a day (8 hourly). Then if it exceeded a score of 5 cm a IV sufentanil c. i. of 8-10 mcg/h, with elastomeric pump, was started. All patients received a urinary catheter and were carefully instructed about their analgesic therapy and transferred from the recovery room to the ward with a VAS score less than or equal 536 MINERVA ANESTESIOLOGICA May 2012

4 to 3 cm. Both groups were assessed three times daily by an anesthesist or more frequently if pain relief was inadequate, despite a rescue dose, or if other problems occurred. VAS score values were expressed as mean of each measurement and as mean of each single day for the three daily scores. Patients characteristics (age, weight and height), rescue dose consumption, side effects (number of episodes of nausea, vomiting and hypotension, defined as a change in systolic blood pressure from lying to standing of more 20%), occurrence of transient neurological symptoms (TNS) such as paresthesia in the lower limbs, and accidental epidural catheter kinking or displacement were also recorded. Statistical analysis We calculated that to detect a difference of 30% between the two groups VAS means at rest and dynamic with a standard deviation (SD) of 1.5 at POD#1 with a power of 80.7%, 110 patients in each group would be required (accepting a two-tailed alpha error of 0.05). 15 Statistical power was calculated using GraphPadStatmate 2.0 for Windows (GraphPad Software Inc., San Diego, California, USA). Indipendent sample t- test was used to assess some demographic data (age, weight, height) and duration of operation. Categorical variables such as ASA physical status, occurrence of side effects (number of episodes of nausea, vomiting and hypotension, TNS and accidental epidural catheter kinking or displacement) and rescue dose consumption were analyzed by using either χ 2 statistics or Fischer s Exact test. A value of P<0.05 was considered significant. VAS scores at rest and on movement, were compared using the Mann-Withney test and a P<0.05 was considered significant. For TNS and the occurrence rate of catheter kinking Table I. Demographic and perioperative data (mean±sd). or displacement we considered the pure frequency. Statistical calculations were performed using SPSS (SPSS Inc, Chicago, IL, USA) for Windows. Results As shown in Figure 1, 270 consecutive patients were scheduled, 260 were enrolled in the study and none dropped out. Demographic data (age, weight and height) and duration of surgery were comparable in both groups (Table I). Dynamic VAS After an expected different value of dynamic VAS in the EPI group during the POD#1 (P=0.001), incoming from 8 th postoperative hour (P=0.022) to 32 nd postoperative hour (P=0.001),VAS score was not different during the POD#2, POD#3 and was reversed only at the 72 nd PO hour when VAS score was different in the OXY group (P=0.026) (Figure 3, Table II). VAS at rest EPI group (N.=130) OXY group (N.=130) Age (years) 65±54 63±74 Weight (kg) 75±10 73±12 Height (cm) 164± ±544 ASA (I/II/III) 21/100/9 20/103/7 Duration of surgery (min) 105±154 90±20 During the postoperative observation period, not different VAS values at rest on POD#1 were observed. Different scores in the OXY group on POD#2(P=0.005) and on POD#3 (P= 0.001) were observed. In particular these intergroups Table II. Mean dynamic VAS scores and Standard Deviation in the two groups every 8 hours for the postoperative period. 8 h 16 h 24 h 32 h 40 h 48 h 56 h 64 h 72 h EPI 2.68±1.98* 1.92±1.69* 1.65±1.49* 1.71±1.63* 1.82± ± ± ± ±1.25 OXY 3.35± ± ± ± ± ± ± ± ±0.98* *P<0.05 Vol No. 5 MINERVA ANESTESIOLOGICA 537

5 Figure 2. Resting VAS (VAS R) scores in the two groups during POD#1, POD#2 and POD#3. Median and standard deviation are represented respectively in the boxes and in the whiskers. were different from the 40 th PO hour (P=0.018) and they continue for all assessment hours (P=0.005 at the 48 th PO, P=0.001 at the 56 th PO, P=0.001 at 72 nd PO) (Figure 2, Table III). In Table IV the total amount of rescue doses (RD) are reported. In POD#1 OXY group received a higher number of administration of tramadol than EPI group (P=0.009). On the contrary in POD#3 the OXY group received a lower number of RD than EPI group (P=0.008). Analyzing the side effects (Table V), there was a similar incidence in the occurrence of nausea and vomiting during the first two postoperative days exceeded the only slightly higher incidence with statistical difference noted in POD#3 in OXY group. Also similar was the incidence of hypotension. Figure 3. Dynamic VAS (VAS D) scores in the two groups during POD#1, POD#2 and POD#3. Median and standard deviation are represented respectively in the boxes and in the whiskers. Table III. Mean VAS scores and Standard Deviation at rest in the two groups every 8 hours for the postoperative period. Table IV. The number and percentage of patients who required rescue doses in the two groups on the 1 st (0-24h), 2 nd (24-48h) and 3 rd (48-72h) postoperative day (POD). Rescue Dose 8 h 16 h 24 h 32 h 40 h 48 h 56 h 64 h 72 h EPI 1.18± ± ± ± ± ± ± ± ±1.25 OXY 1.81± ± ± ± ±1.54* 0.87±1.45* 0.69±1.26* 0.46±0.93* 0.33±0.76* *P<0.05 EPI Group n (%) OXY Group n (%) POD#1 30 (23.1) * 46 (38.3) POD#2 36 (27.7) 22 (18.3) POD#3 23 (17.7) 8 (6.7) * *P<0.05 was considered significant (t-test or Fischer s Exact test). Table V. Incidence of nausea, vomiting, hypotension and catheter displacement in the two groups (n number of episodes and % percentage of patients), respectively during the 1 st (0-24h), 2 nd (24-48h) and the 3 rd (48-72 h) postoperative days (POD). EPI Group N. -(%) OXY Group N. -(%) Nausea POD#1 33-(25.4) 31-(25.8) Nausea POD#2 16-(12.3) 24-(20.0) Nausea POD#3 2-(1.5)* 9-(7.5) Vomiting POD#1 22-(16.9) 12-(10.0) Vomiting POD#2 3-(2.3) 8- (6.7) Vomiting POD#3 0 4-(3.3) Hypotension POD#1 30-(23) 32-(24.6) Hypotension POD#2 10-(7.7) 15-(11.5) Hypotension POD#3 2-(1.5) 3-(2.5) Catheter displacement POD#1 8 (6.1) - Catheter displacement POD#2 9 (6.9) - Catheter displacement POD#3 1 (0.7) - *P<0.05 was considered significant (t-test or Fischer s Exact test). Paresthesia related to epidural catheter placement was observed in 2 cases (1.5%) during POD#1, 6 cases (4.6%) during POD#2. Epidural catheter displacement incurred in 18 patients (13.8%) and exceeding the only case occurred in POD#3 all catheters were replaced. 538 MINERVA ANESTESIOLOGICA May 2012

6 Discussion Our results show that either epidural levobupivacaine 0.125% or multimodal analgesia consisting of oral CR oxycodone plus IV paracetamol provided excellent pain relief, with both groups scoring a mean VAS lower than 3 at rest throughout the entire 72 hrs postoperative period. Primary endpoint was not reached for the entire period of observation, in fact dynamic VAS scores remained lower in multimodal regimen group only in POD#3. VAS at rest score was similar in the two groups during the two postoperative days and it becomes lower in POD#3 in OXY group. As expected we observed a greater consumption of rescue doses in the OXY group during first postoperative day due to higher dynamic VAS scores. It may appear as a failure to achieve a steady state of analgesia, even though more than 8 hours had passed from the initial administration, and a potential overlap with the effects of spinal anesthesia. During the following days, instead, oxycodone plus paracetamol provided a good analgesic effect with a low demand for rescue doses. Patients treated with epidural analgesia needed more frequent rescue doses when catheter kinking o displacement occurred. A procedure-specific systematic review on postoperative epidural analgesia showed lower pain scores with epidural techniques than IV PCA but without reaching clinical significance. 17,18 Modest reduction of pain scores needs to be discussed if is sufficient or not to support this technique as a standard of care. Epidural analgesia compared to IV PCA is equally efficient at rest but more effective on movement; however it is associated with a high incidence of catheter-related problems and side effects such a urinary retention and/or arterial hypotension. Moreover, postoperative length of stay is not reduced and rehabilitation does not appear to be facilitated by regional anesthesia or analgesia after THA. 19, 20 Many studies in several surgical setting have examined the use of oxycodone alone versus its association with paracetamol in moderate to severe acute postoperative pain (but not after THR) resulting in an increased efficacy of com- bined therapy. 14 In de Beer s study CR oxycodone plus oral acetaminophen was compared to codeine plus acetaminophen for postoperative pain relief after hip or knee arthroplasty, starting on the second postoperative day after IV morphine PCA discontinuation or epidural analgesia. This study found that the two groups experienced similar level of analgesia but there was a lower incidence of side effects and a greater satisfaction in the CR oxycodone than in codeine group. 21 In two studies, oral paracetamol and CR oxycodone intake and epidural analgesia were compared: satisfactory analgesia at rest and during mobilization was achieved with both regimes in the postoperative period after radical retropubic prostatectomy and peripheral arterial obstructive disease surgery We observed that the synergic effect of oral oxycodone plus IV paracetamol associated with the population homogeneity in our study may explain the efficacy of the single dosage in all patients without increases in the daily oxycodone dose. 14 This could be explained by oxycodone pharmacokinetics being more consistent in elderly patients or in those with mild renal or hepatic impairment: in these conditions it is not necessary to modify the dosage In the future it could be interesting to administer scheduled supplementary analgesic doses during the first postoperative day to improve the overlap with spinal anesthesia. Potentially, the use of immediate release (IR) oxycodone during the first postoperative day could be preferable to a weak opioid, such as the tramadol rescue dose used in our study. In the last few years, claims to less pain and earlier rehabilitation have been made for open joint arthroplasties done through smaller incisions and some studies have examined the effects of new pain management, anesthesia and physical therapy protocols on this mini invasive surgical procedure We have also to consider the relevance of the newer thromboprophylaxis therapies: the long half-life of drugs such as fondaparinux (approximately 17 hours), makes them a common choice for thromboprophylaxis since they are easy to administer, but it also limits a safe epidural catheter use. The need of a 48 hours window between Vol No. 5 MINERVA ANESTESIOLOGICA 539

7 two injections of fondaparinux, results in skipping one administration. 30 In fact both ASRA and ACCP discourage the use of fondaparinux in patients with an epidural catheter. 6, 12 A physician has to take into consideration the ease with which oral and intravenous drugs are administered, compared to the placement and maintenance of an epidural catheter, which is of particular importance for wards lacking an acute pain service. As a limitation of the present study, patients did not receive early hip mobilization but had an intensive physical therapy program starting on the second POD, so the dynamic pain in the first 48 hours can be ascribed to free movements and active/passive hip flexion and abduction exercises performed laying in bed. Conclusions Multimodal regimen consisting in CR oxycodone associated with intravenous paracetamol, represents an efficient, safe, easy and non invasive approach (compared with the epidural route) for postoperative pain relief after hip arthroplasty; this is relevant for all those cases of relative and absolute contraindications to neuraxial analgesia and may be a new prospective if associated to minimally invasive surgical procedure. References 1. Fischer HBJ, Simanski CJP. PROSPECT Working Group, INCONNU. A procedure-specific systematic review and consensus recommendations for analgesia after total hip replacement. Anaesthesia 2005;60: Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000;288: Karani R, Meier DE. Systemic pharmacologic postoperative pain management in the geriatric orthopaedic patient. Clin Orthop 2004;425: Rodgers A, Walker N, Schug S. 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8 of controlled-release opioids. Acta Anaesthesiol Scand 1997;41: Berry DJ, Berger RA, Callaghan JJ, Dorr LD, Duwelius PJ, Hartzband MA et al. Minimally invasive total hip arthroplasty. Development, early results, and a critical analysis. Presented at the Annual Meeting of the American Orthopaedic Association, 2003 June 14;Charleston, South Carolina, USA. J Bone Joint Surg Am 2003;85-A: Nuelle DG, Mann K. Minimal incision protocols for anesthesia, pain management and physical therapy with standard incisions in hip and knee arthroplasties: the effect on early outcomes. J Arthroplasty 2007;22: Berger RA, Sanders SA, Thill ES, Sporer SM, Della Valle C. Newer anesthesia and rehabilitation protocols enable outpatient hip replacement in selected patients. Clin Orthop Relat Res 2009;467: Rosencher N, Bonnet MP, Sessler DI. Selected new antithrombotic agents and neuraxial anaesthesia for major orthopaedic surgery: management strategies. Anaesthesia 2007;62: Received on June 21, Accepted for publication on March 16, Corresponding author: M. Divella MD, Department of Anesthesia and Intensive Care, University of Udine, Piazzale S. Maria Misericordia 15, Udine 33100, Italy. divella.michele@aoud.sanita.fvg.it This article is freely available at Vol No. 5 MINERVA ANESTESIOLOGICA 541

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