US Pharm. 2011;36(11):Epub.

Each year, hip fractures contribute to more than 225,000 hospitalizations in Medicare recipients, and this number is expected to double by the year 2040.1 Length of stay for total hip arthroplasty (THA) has declined from 1991 to 2008, but this has resulted in an increase in post–acute care admissions and rehospitalizations.2 According to the National Center for Health Statistics, the annual cost to the United States for THA exceeded $12 billion in 2009.3

The normal hip functions as a ball-and-socket joint: The femoral head (ball) moves inside the acetabulum (socket), allowing a smooth range of motion on multiple planes.4,5 Osteoarthritis (OA), the most common form of joint disease affecting the ball-and-socket joint, can lead to deterioration, deformity, pain, and loss of function.4 OA involves degeneration of cartilage, hypertrophy of bone at the articular margins, and minimal articular inflammation.6,7 Patients experience brief morning stiffness, their joint pain is relieved by rest, and they usually have no systemic symptoms.7

THA is indicated in patients who have failed conservative or previous surgical treatment for a deteriorated hip joint and have persistent, debilitating pain and a significant decline in activities of daily living.4 THA also may be indicated in patients with significant deformity and limitation of motion, but no severe pain.4 In this procedure, diseased articular surfaces of the hip are replaced with synthetic materials.4

Pharmacists in collaboration with the medical team should consider preoperative medication discontinuation to reduce the risk of excessive bleeding during the procedure and to minimize postoperative complications. Medications that should be evaluated include antiplatelets, anticoagulants, antihyperglycemics, and immunosuppressants. Pertinent drug therapies to consider in THA are preoperative antibiotics, postoperative pain control, and thromboprophylaxis.

Antibiotic Prophylaxis

The Surgical Care Improvement Project (SCIP), a collaborative effort involving organizations including the American Academy of Orthopaedic Surgeons, aims to reduce complications related to postoperative infection by optimizing the appropriate selection, administration time, and duration of antibiotics as supported by scientific evidence. SCIP recommends that patients receive cefazolin or cefuroxime as the antibiotic of choice prior to orthopedic surgery.8-10 Clindamycin and vancomycin are appropriate for patients with a confirmed beta-lactam allergy. Although the use of vancomycin is supported in patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) or in facilities with recent MRSA outbreaks, exposure to vancomycin increases the risk of vancomycin-resistant Enterococcus colonization and infection. Thus, vancomycin should be reserved for patients who are colonized with beta-lactam–resistant organisms or who have a life-threatening allergy to beta-lactam antimicrobials.11,12

Administration of prophylactic antibiotics should occur 1 hour prior to skin incision.13-17 The exception to this is vancomycin, which may be administered 2 hours prior to incision owing to its long infusion time. The dosage should be adjusted for patient weight; for instance, the cefazolin dose should be 2 g for patients weighing more than 80 kg.18 Antibiotics should continue to be administered according to their referenced dosing frequency; however, they should be discontinued within 24 hours of the end of surgery.8-10,19,20 Continuing antibiotics beyond 24 hours, even in patients with drains and catheters, has not been shown to provide additional benefit.21,22

Postoperative Pain Control

Chronic pain after THA—a significant problem in at least 12.1% (n = 1,231) of one study’s questionnaire respondents who had undergone THA within the past 12 to 18 months—is linked to genetic and psychosocial factors.23 A retrospective cohort study of patients who had THA found that, 6 months to 1 year following surgery, 93% (n = 193) of patients had a mean preoperative pain score of 7.5 on a scale of 0 to 10 and an average change in pain score of 4.8.24 Increased body mass index was associated with lower postoperative functional status and increased postoperative pain.24 The amount of pain relief the patient was able to obtain preoperatively using nonsurgical interventions was associated with a better outcome.24

Several injectable and oral pain-management options have been described.25-29 One method is to instill local anesthetics into a surgical site.25-27 A trial examining 225 patients after unilateral THA found a reduction in opioid use and related adverse events in patients receiving continuous lumbar plexus block versus patient-controlled analgesia (PCA) alone.25 Continuous spinal and epidural anesthesia with bupivacaine were found to be safe and effective for postoperative pain relief after hip replacement.26 Continuous spinal anesthesia provided a faster onset of pain relief, ensured better analgesia, and resulted in greater patient satisfaction.26 Although spinal and epidural bupivacaine provided postoperative pain relief after THA, intra-articular infusions via pain-control infusion pumps did not.12 A recent trial found no difference in the amount of narcotic use, incidence of adverse events, hospitalization days, or Western Ontario and McMaster Universities Osteoarthritis Index score between intra-articular infusions of bupivacaine and placebo.27

A multimodal regimen for THA was described in a recent study evaluating the use of gabapentin 600 mg before or after surgery.28 One to 2 hours preoperatively, patients received acetaminophen 1 g orally, celecoxib 400 mg orally, dexamethasone 8 mg intravenously, and spinal anesthesia (0.5% hypobaric bupivacaine [15 mg/3 mL] with fentanyl 10 mcg).28 On the ward, patients received acetaminophen 1,000 mg orally every 6 hours, celecoxib 200 mg orally every 12 hours, and a morphine PCA device.28 Given preoperatively or postoperatively, the single 600-mg dose of gabapentin did not reduce morphine consumption or pain scores in the hospital or at 6 months after THA within the context of the described spinal anesthesia and robust multimodal analgesia regimen.28

Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 (COX-2) inhibitors are widely used for bone fracture and orthopedic postoperative pain.29 Prostaglandins play an important role in the regulation of osteoblast and osteoclast functions, and, based on animal models, the inhibition of prostaglandin production by NSAIDs or COX-2 inhibitors retards bone formation.29 However, further investigation is needed to characterize patients at greatest risk for NSAID-induced delayed fracture healing.29

Heterotopic ossification (HO), or ectopic bone formation, is a complication following THA, particularly in high-risk patients, such as those with bilateral hypertrophic OA (males), a history of HO, or posttraumatic arthritis presenting with hypertrophic osteophytosis.30 HO is associated with pain and a reduced range of movement.30 Prophylaxis is achieved by either NSAID treatment or localized irradiation therapy given 24 hours preoperatively or within 72 hours postoperatively as single or multifraction regimens.30,31 A recent study concluded that indomethacin remains the gold standard for HO prophylaxis following THA.30 Other NSAIDs, including naproxen and diclofenac, are as effective as indomethacin and may be considered alternative first-line treatments.30 Celecoxib is also equally efficacious as indomethacin, but although it is associated with significantly fewer gastrointestinal side effects, serious concerns were raised over the safety of selective COX-2 inhibitors for the cardiovascular system; therefore, celecoxib should be used cautiously.30

Postoperative Thromboprophylaxis

Patients undergoing THA have multiple risk factors for venous thromboembolism (VTE), including major surgery, immobility, and increasing age.32 Without thromboprophylaxis, the total prevalence of deep venous thrombosis (DVT) and pulmonary embolism after THA is approximately 42% to 57% and 0.9% to 28%, respectively.32 Thromboprophylaxis following orthopedic procedures can prevent VTE, which would subsequently decrease the second most common cause of medical complication, the second most common cause of extended length of stay, and the third most common cause of excess mortality and costs in postoperative patients.32,33

The American College of Chest Physicians (ACCP) has developed evidence-based clinical practice guidelines for VTE prevention that address thromboprophylaxis specific to THA patients.32 Mechanical methods of thromboprophylaxis include graduated compression stockings, intermittent pneumatic compression devices, and venous foot pumps. These apparatuses increase venous flow outflow in addition to reducing stasis within the leg veins.32 The ACCP suggests that these devices be used in patients at high risk for bleeding since they do not inherently increase bleeding risk.32 If the high risk of bleeding is transient, then another agent should be initiated once the risk of a major bleed has been de-escalated.32 Patients using these devices should be screened regularly for correct size, proper use, and optimal adherence.32

Low-molecular-weight heparins (LMWHs), especially enoxaparin, are the most extensively studied agents for preventing VTE after THA. LMWHs have been the standard of care since clinical trials proved that they are more efficacious than low-dose unfractionated heparin (LDUH).32,34 Moreover, an ACCP review of five large clinical trials demonstrated that LMWHs had lower incidences of total DVT and an overall lower risk for major bleeds compared with vitamin K antagonists (VKAs).32 The ACCP recommends the use of enoxaparin 30 mg subcutaneously (SC) twice daily started either 12 hours before or 12 to 24 hours after hip arthroplasty for at least 10 days and up to 35 days postoperatively.32

Fondaparinux is another parenteral option available to prevent VTE. In a study comparing fondaparinux 2.5 mg SC daily to enoxaparin 30 mg SC twice daily following THA, the rates of overall DVTs between the two drugs were neither statistically nor clinically significant.35 Fondaparinux showed an increased trend toward bleeding, but this was not statistically significant.35 The ACCP advocates the use of fondaparinux 2.5 mg SC once daily started 6 to 24 hours postsurgery for at least 10 days and up to 35 days postsurgery.32

The ACCP advises that, when a VKA is used, doses should target an international normalized ratio (INR) of 2.5, with a therapeutic range of 2 to 3.32 The initial dose should be administered either the evening before or the evening after surgery and should be continued for at least 10 days and up to 35 days postsurgery.32 The patient’s INR should be regularly monitored to ensure that the INR is in the desired range.

In addition to the aforementioned treatment modalities for preventing VTE, the ACCP has determined which treatments should not be used alone. Aspirin, dextran, LDUH, graduated compression stockings, and venous foot pumps should never be the sole method of thromboprophylaxis.32

The ACCP guidelines state that the dosage of agents used for thromboprophylaxis should be reduced in patients with diminished renal function (elderly, patients with diabetes mellitus, and those at high risk for bleeding) to prevent bioaccumulation. Additionally, the drug level and anticoagulation effects of these agents should be closely monitored.32

Thromboprophylaxis against VTE has been the standard of care for more than 20 years.32 By preventing VTE, it is possible to reduce costs, length of stay, complications, and readmission following total hip replacement. Ultimately, determining which agent to use for thromboprophylaxis in preventing VTE should be assessed on an individual basis with regard to patient factors (risk factors for major bleeds or accessibility because of formulary restrictions), frequency of dosing interval, ease of administration, compliance, monitoring parameters, and cost (out-of-pocket expenses or copayments).


THA can relieve pain, restore joint function, and ultimately improve quality of life.4 More than 150,000 THAs are performed each year, but because the joint replacement can fail over time, it is preferable to delay this procedure as long as possible.4 When the decision to undergo THA is made, it is important that the pharmacist work as an integral member of the team to determine appropriate medication discontinuation, antibiotic selection and timing, pain control, and thromboprophylaxis to provide the patient with optimal care throughout his or her hospital stay.


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