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Use of Nonopioid Analgesics and the Impact on Patient Outcomes

Sanzone, Anthony G. MD

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Journal of Orthopaedic Trauma: May 2016 - Volume 30 - Issue - p S12-S15
doi: 10.1097/BOT.0000000000000563
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Pain management in patients who have sustained a hip fracture still tends to be largely opioid-dependent, despite the emergence in recent years of other anesthetic and analgesic options. Unfortunately, this current algorithm has 2 inherent problems. First, opioids are known to cause a wide range of adverse effects or even serious life-threatening complications. Common opioid-related adverse events (ORAEs) include gastrointestinal effects (ie, nausea, vomiting, ileus, or constipation), central nervous system effects (ie, sedation, somnolence), and other problems (Fig. 1).1

Most common perioperative ORAEs.1

Opioid-related respiratory depression—the diminished effectiveness of the ventilatory function after opioid administration—is a common and serious complication during the perioperative period. Although the timing and severity of opioid-related respiratory depression are not always predictable, it can result in the severe hypoxia.2,3

Second, hip fracture occurs most frequently among the elderly—the very population that is most susceptible to the adverse effects of opioids and the risks of serious physiological complications.4,5 The effects of opioid analgesics vary widely with patient age, weight, and other factors—elderly patients typically require much lower doses—yet opioids are often prescribed according to standardized protocols, and dosages are not adjusted for elderly patients.6 Overdosing of these patients is therefore common, and the rate of ORAEs, which are dose-dependent, is much higher. Indeed, it has been documented that many elderly patients choose to suffer from inadequate postoperative pain control rather than tolerating the confusion and excessive nausea that they experience with opioids.7

Elderly patients often have other comorbidities that put them at increased risk for respiratory depression and other adverse events. For example, after 2 deaths from respiratory failure secondary to opioid toxicity in patients admitted for surgical repair of fractured neck of femur at a hospital in the United Kingdom, a retrospective analysis of records for 1511 consecutive patients requiring surgery for proximal femoral fracture was conducted.8 The analysis found that 36.1% of patients had renal dysfunction on admission (glomerular filtration rate <60 mL·min−1·1.73 m−2) and consequently had an increased risk of opioid toxicity.

In conjunction with those comorbidities, elderly patients are also more likely to be already taking other medications that have the potential to increase the risk of ORAEs, including respiratory depression.9

In orthopaedic surgery in general, there has been much interest during recent years in identifying alternative analgesic approaches that are less opioid-dependent. Unfortunately, however, very few well-designed, randomized clinical trials have evaluated alternate pain management interventions specifically in patients with hip fracture.10

The use of nerve blocks has grown in orthopaedic surgery, and evidence shows that this approach can be effective in managing the acute pain associated with hip fracture. A systematic review that included 9 hip and femoral neck fracture clinical trials explored whether regional nerve blocks reduce pain, need for parenteral opiates, and complications compared with standard pain management protocols.11 Pain scores were improved in 8 of the 9 studies, and a significant reduction in parenteral opiate use was seen in 5 of the 6 studies that included opioid use as an end point.

However, this approach is not without disadvantages. Sciatic and femoral nerve blocks seem to increase the risk of several clinically significant adverse events, including quadriceps weakness that may delay physical therapy and predisposition to falls (Table 1).12 Furthermore, limited data exist on the long-term benefit of nerve blocks after hip fracture. The systematic review described previously found that although no patients had life-threatening complications related to nerve blocks, more minor complications were under-reported compared with standard pain management.

Clinically Significant Adverse Events Associated With Sciatic and Femoral Nerve Blocks


Intravenous (IV) acetaminophen was approved in the United States in 2010 for the management of mild-to-moderate pain and the management of moderate-to-severe pain with adjunctive opioid analgesics. The effectiveness of IV acetaminophen 1 g every 6 hours was assessed in adults who underwent total hip or knee replacement.13 In this study, subjects who received opioid analgesia and IV acetaminophen reported significantly decreased pain intensity at 6 and 24 hours compared with those who received opioid analgesia and placebo. Patients who received IV acetaminophen also required 46% less morphine at 6 hours and 33% less morphine after 24 hours.

Useful insight into the benefits of IV acetaminophen in hip fracture is provided by a retrospective cohort study that examined the effectiveness of scheduled IV acetaminophen as part of the pain management protocol.14 This study reviewed the charts for 336 consecutive fractures in 332 patients.

Study Design

All patients in this study were 65 years of age or older and admitted to the orthopaedic service at a level 1 trauma center, where they received operative treatment by a fellowship-trained orthopaedic surgeon. They were divided into 2 groups (Fig. 2):

  1. Group 1—patients treated before the initiation of a standardized IV acetaminophen perioperative pain-control protocol (169 fractures);
  2. Group 2—patients treated after the IV acetaminophen protocol was initiated (167 fractures).
Retrospective cohort study of the effectiveness of IV acetaminophen in patients with hip fracture: Study design. Adapted from Bollinger et al. Geriatr Orthop Surg Rehabil. 2015.14 Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation

Data collected in this retrospective chart review included patient demographics, such as age, sex, and body mass index, as well as in-hospital variables, such as diagnosis, time to operating room, surgical treatment time, and doses of acetaminophen received. Several different outcome measures were captured; these measures included the following:

  1. Pain score;
  2. Total narcotic use;
  3. Adverse effects;
  4. Length of hospital stay;
  5. Rate of missed physical therapy sessions;
  6. Discharge disposition (home vs. secondary care facility).

Study Findings

This study revealed significant improvement in multiple parameters after the introduction of IV acetaminophen—inclusion of IV acetaminophen in the pain protocol for hip fracture was found to be associated with significant improvement in pain scores, narcotic use, length of stay, and missed physical therapy sessions (Table 2).14

Improvement in Outcomes Following the Introduction of IV Acetaminophen in Patients With Hip Fracture

Pain score—the most commonly used outcome in pain management studies—was reduced by 33%, from 4.2 to 2.8. Mean narcotic use was reduced by 31%, from 41.3 to 28.3 mg. Mean length of hospital stay was reduced by 14%, from 4.4 to 3.8 days, and the rate of missed physical therapy sessions was reduced by 52%, from 21.8% to 10.4%. In addition, patients who received IV acetaminophen were more than twice as likely to be discharged to home (19%) than patients who did not receive IV acetaminophen (7%).

This cohort study also revealed several additional interesting trends. Previous observational studies have shown that earlier surgery after hip fracture is associated with improved outcomes.15–22 That observation is further supported by this recent study,14 which found that longer time to surgery predicted higher narcotic use and longer length of stay. Surprisingly, perhaps, younger age was found to be predictive of higher pain scores and more narcotic use. Increased body mass index was associated with increased narcotic use, which is a concern, as overweight patients are at greater risk for ORAEs. Increased narcotic use in turn predicted a longer length of stay, whereas younger age, male sex, earlier surgery, and lower narcotic use all significantly increased the likelihood of patients being discharged to home rather than a secondary care facility.


Despite the limited availability of data from well-designed randomized clinical trials on pain management in patients with hip fracture, orthopaedic surgeons can take several steps that might reasonably be expected to improve patient outcomes. First, from the moment the patient arrives, emergency-room physicians should be encouraged not to heavily sedate the patient. Alternative pain medications, such as IV acetaminophen and anti-inflammatories, should be incorporated into the pain management protocol to improve pain management and reduce the amount of opioids or anesthesia required.

Nerve blocks are worthwhile, especially in conjunction with lower doses of general anesthetics. In general, the less anesthetic the patient receives, the better the functional outcome.

Limited data exist in patients with hip fracture on the effects of infiltration of the surgical site with the local anesthetic agent, bupivacaine. However, extensive use of bupivacaine in hip arthroplasty surgery suggests that it may be highly beneficial in this population.23,24 Many surgeons infiltrate short-acting bupivacaine HCl into the areas of the fracture at the beginning of the procedure and then add liposomal bupivacaine, which has a delayed onset of action but lasts as long as 48–72 hours (individual patients metabolize the drug at different rates, and the precise duration of effect can vary).25 When using liposomal bupivacaine, correct administration technique is critical.26 The medication should be expanded and injected with a small-gauge needle into as many individual locations as possible along the entire fracture site.

The surgeon should discuss with internists and anesthesiologists strategies that allow patients with hip fractures to reach the operating room in a more efficient manner; unnecessary tests should be omitted by means of predetermined protocols. It is also important to perform an effective, efficient surgery and not spend a prolonged time in the operating room because the high anesthetic load administered over the course of a longer procedure is likely to be detrimental and have a greater impact on outcome.

Postoperatively, it is essential for the surgeon to remain actively involved in the management of the patient's pain. Nurses and patients' family members should be educated that patients with hip fracture do not have to be completely sedated. Patients who are unable to communicate effectively on the morning after surgery or begin to engage in physical rehabilitation are less likely to have an optimal outcome.


There is a pressing need to reduce the dependence on opioid analgesia in patients with hip fracture—not only are these agents associated with a range of adverse events, but elderly patients are most susceptible to the undesirable effects and serious risks that accompany the use of opioids. There are alternative medications that may reduce the amount of opioid medications required and improve outcomes. Scheduled IV acetaminophen, in particular, as part of the pain management protocol for patients with hip fracture has been found to significantly improve pain scores, narcotic use, length of hospital stay, and missed physical therapy sessions. It is essential for orthopaedic surgeons to press for the use of these agents and other steps that will reduce time to surgery and facilitate earlier participation in physical therapy.


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acetaminophen; analgesia; fracture; nonopioid; pain

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