Multi-modal, Pre-emptive Analgesia Decreases the Length of Hospital Stay Following Total Joint Arthroplasty

Abstract

Traditional treatment of pain following total joint arthroplasty involves postoperative oral narcotic medications and intravenous patient-controlled analgesia, both of which can result in significant postoperative morbidity. Multi-modal analgesia involving ≥2 classes of drugs acting on different receptor types may be as effective as single-narcotic/patient-controlled analgesia with fewer analgesic-related side effects. In addition, administering analgesia prior to surgery (pre-emptive) may reduce postoperative pain intensity. The current study was designed to compare the impact of multi-modal pre-emptive analgesia versus patient-controlled analgesia on postoperative nausea, rehabilitation participation, and length of stay following total joint arthroplasty. A retrospective chart review and comparison was performed for patients undergoing total joint arthroplasty who received either postoperatively patient-controlled analgesia or pre-emptive analgesia (scheduled postoperative oxycodone and a COX-2 inhibitor). Length of hospital stay for the pre-emptive group averaged 2.74 vs 3.28 days for patient-controlled analgesia patients. The patient-controlled analgesia group consumed significantly more intravenous morphine (17.7 mg vs 7.2) and experienced a three-fold increase in nausea. In addition, the patient-controlled analgesia group was twice as likely to miss therapy and nearly 2 times more likely to be discharged to an extended care facility. The use of pre-emptive oxycodone and a selective COX-2 inhibitor decreased postoperative narcotic requirements and increased participation in rehabilitation. In addition, patients receiving pre-emptive analgesics had a decreased hospital length of stay and reduced likelihood of discharge to a skilled nursing facility. These data support the continued study and use of pre-emptive multi-modal analgesia paradigms in this population.

Traditional methods of treating pain following total joint arthroplasty involve postoperative oral narcotic pain medications and intravenous patient-controlled analgesia. But such opioid use is not without side effects, including nausea, vomiting, pruritus, sedation, dizziness, bladder dysfunction, reduced gastrointestinal motility (which may lead to ileus), and sleep pattern disturbance.^1-3 Additionally, patients can develop clinically relevant tolerance to opioids within hours of their initial use.^4,5 Although opioid delivery through a patient-controlled anesthesia system has been shown to improve patient satisfaction, postoperative morbidity and length of hospital stay are not improved with patient-controlled anesthesia use.^6,7 Developing an alternative pain-control regimen that decreases the need for post-operative narcotic use and reduces post-operative morbidity and hospital length of stay has become a topic of significant interest. Multi-modal analgesia, which uses ≥2 classes of pharmacotherapy acting on different receptors, may be as efficacious at controlling postoperative pain as single-drug therapy while decreasing analgesic-related side effects.^{1, 8-11} Pre-emptive analgesia, defined as “analgesic intervention provided before surgery to prevent or reduce subsequent pain” attempts to prevent the establishment of central sensitization and therefore reduce pain intensity and decrease analgesic requirements.^12-15

The present study was designed to determine whether pre-emptive multi-modal analgesia will decrease side effects associated with opioid use, increase participation in inpatient physical therapy, and decrease length of hospital stay, as well as decrease the amount of opioid needed for pain control.

Materials and Methods

The study design was a retrospective review and comparison of patients that received either a patient-controlled anesthesia regimen postoperatively, or multi-modal pre-emptive (preoperative) and scheduled postoperative oxycodone and a COX-2 inhibitor. The pre-emptive analgesia clinical paradigm was implemented at our institution in 2004. This study was approved by the local Institutional Review Board.

All patients in the study underwent primary total joint arthroplasty performed by the same surgeon (D.G.A.) and participated pre-operatively in hospital’s “Joint Works Program.” Patients were excluded if they were undergoing revision surgery, uni-compartmental knee arthroplasty, bilateral joint arthroplasty, or received epidural anesthesia. Both groups participated in rehabilitation sessions twice daily. The anterolateral modified Hardinger approach was used for all patients in the total hip arthroplasty (THA) group, and medial para-patellar arthrotomy was the approach of choice for total knee arthroplasty (TKA). No patients received local anesthetic injections for pain.

The patient-controlled anesthesia group consisted of patients operated on from July 2003 through January 2004. They received no preoperative NSAIDs or oral opioids. Postoperatively, their pain was treated with an intravenous narcotic “patient controlled analgesia” regimen for 48 hours along with oral hydrocodone or propoxyphene. The multi-modal analgesia study group was made up of patients who underwent surgery from July 2004 through January 2005. These patients received pre-operative and scheduled oxycodone (20 mg every 12 hours) and a COX-2 inhibitor celecoxib (200 mg preop and 200 every 12 hours during hospitalization) or valdecoxib (10 mg per day preop and during hospitalization). Patients were also given “intravenous (IV) push” morphine on an “as needed” basis as well as oral hydrocodone or propoxyphene, as needed. Patients in both groups were provided the same plan of care other than the analgesia used.

Data were collected on all patients and included age, length of hospital stay (days), surgery type (TKA/THA), implant type, surgical anesthesia used, patient-controlled anesthesia regime, type and amount of oral narcotics, intravenous narcotic type and amount, and discharge disposition. Missed therapy sessions due to nausea or vomiting were also collected. Chi-square tests were used to compare categorical data and independent t tests were used to analyze continuous data. A P<.05 was considered statistically significant.

Results

Using the study entry criteria, 127 patients were identified. Of these 127 patients, 69 received a patient-controlled anesthesia regimen postoperatively and 58 received multimodal analgesia including scheduled postoperative oxycodone and a COX-2 inhibitor. Group demographics are shown in the Table. No statistically significant differences between the groups were observed for gender or age. However, the proportion of patients receiving spinal anesthesia was significantly different between the two groups (P<.05).

Both groups required the same number of hydrocodone or propoxyphene pills on an “as needed” basis (4.48 pills per patient, P>.05). The study group needed only about one-third as much IV morphine as the control group (6.4 mg vs. 17.6 mg, P=.0001). Additionally, only 7% of the study group missed rehabilitation therapy due to nausea and/or vomiting, as compared to 20% in the control group (P<.05), making the control group 3 times as likely to not participate in rehabilitation sessions. Similarly, the control group was almost twice as likely to require extended care facility placement (P<.05), with 22% of patients in the control group requiring extended care facility placement versus only 12% in the study group. Finally, length of hospital stay was significantly lower in the study group, with a length of stay of 2.74 days for the study group and 3.28 days for the controls (P=.002).

Several subgroup comparisons were made to examine the potential impact that the type of anesthesia might have on length of hospital stay and percent missing rehabilitation due to nausea. No statistically significant differences were detected when we compared spinal anesthesia patients versus patients undergoing general endotracheal anesthesia (2.69 vs 2.76 days, P=.67; 7% vs 7%, P>.05). We found that those in the control group who had spinal anesthesia had an even higher length of hospital stay and percentage missing rehabilitation (3.67 and 42%) than the control group did as a whole (3.28 and 20%). When we compared only spinal anesthesia patients in both groups and only general endotracheal anesthesia patients in each group, a statistically significant difference in length of hospital stay was still observed (3.67 vs 2.69, P=.015; 3.67 vs 2.79, P=.04).

Discussion

In our study, the use of a pre-emptive and scheduled dose of oxycodone and a selective COX-2 inhibitor was highly efficacious as compared to a postoperative patient-controlled anesthesia regimen. Multi-modal pre-emptive analgesia decreased postoperative IV narcotic requirements, increased the percentage of patients able to participate in rehabilitation therapy, decreased length of hospital stay, and decreased the percentage of patients requiring discharge to an extended care facility. It had no effect on the need for additional oral narcotics (hydrocodone or propoxyphene). Although our data was combined from 2 populations (THA and TKA patients), the observed differences in length of hospital stay and missed therapies were consistent for both when examined separately.

The goal of pre-emptive analgesia is to administer analgesics prior to noxious stimuli and therefore prevent the establishment of peripheral and central sensitization.¹⁶ Brief noxious stimuli, such as operative procedures, cause 2 major physiologic responses; an initial afferent release of pain signals, and a secondary inflammatory response.¹⁷ Both of these responses have the ability to cause prolonged changes in both the central and peripheral nervous systems that can then lead to postoperative pain that is of greater intensity and duration than would be expected.¹⁸ Central sensitization, or the hyperexcitability of spinal neurons, results from the persistent exposure of spinal neurons to the afferent input from peripheral nociceptors.¹⁹ Peripherally, the cells damaged by the noxious stimuli respond to the insult and subsequent local inflammation by releasing chemicals, such as prostaglandins and substance P.²⁰ These chemicals sensitize the peripheral nociceptors, which reduces the threshold at which the nociceptors are activated.²¹ Together, central and peripheral sensitization combine to create a hyperexcitable postoperative state called “spinal wind-up” that causes a decrease in pain threshold (allodynia) and an exaggerated, prolonged pain response (hyperalgesia).^17,22

Because of the complexity of the pathways in pain perception and transmission, multi-modal therapy is increasing in popularity.^1,20 Combined analgesic regimens that act on different sites and with different mechanisms of action may take advantage of additive or synergistic effects of the several medications. Peripherally, nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids may be used. Nonsteroidal anti-inflammatory drugs work peripherally by inhibiting the inflammatory response. They inactivate cyclooxygenase, which therefore inhibits the synthesis of prostaglandins, thus attenuating the response of both the central and peripheral nervous system to noxious stimuli.²³ Oral opioids also seem to act peripherally since all three opioids receptors (mu, delta, and kappa) have been found on peripheral nerves. However, their mechanism of peripheral analgesia has not been completely elucidated.¹⁷ Centrally, oral opioids act as endogenous opioid peptides and bind with receptors within the central nervous system, producing supraspinal anesthesia.¹⁷ There are also some indications that NSAIDs may act centrally as well by inhibiting cyclooxygenase in the spinal cord and thereby decreasing the NMDA-mediated events in the spinal cord.^{13, 24, 25} By using a combination of NSAIDs and oral opioids, one can cover both peripheral and central responses to noxious stimuli, inhibit peripheral and central sensitization, and use lower doses of both drugs.

A review by Dahl and Moiniche in 2004 in the British Medical Bulletin found equivocal evidence that pre-emptive analgesia decreases postoperative pain or need for supplemental analgesics.²⁶ The majority of studies showed no benefit to pre-emptive analgesia, but also found no deleterious effects either. However, almost all of these studies were unimodal in their use of analgesia. The authors suggest that further studies should specifically investigate multi-modal pre-emptive therapies in the quest for improved pain control postoperatively. In fact, the use of multi-modal analgesia in pre-emptive analgesia may help explain the discrepancy between the efficacy of pre-emptive analgesia in animal models and the lack thereof in most human experiments.^1,8,27 There is also evidence to suggest that the type of surgery being performed makes a difference when attempting pre-emptive analgesia. Aida et al¹² reported that pre-emptive analgesia was effective in limb surgery and mastectomy, but ineffective for gastrectomy, hysterectomy, herniorrhaphy, and appendectomy. This would suggest that careful discretion must be used when determining if a study on a particular pre-emptive analgesic technique applies to a particular surgeon’s patient population or not.

The large difference in the percentage of patients undergoing spinal anesthesia in the study group versus the control group is a confounding factor in our data. Consequently, we tried to determine if the increased use in spinal anesthesia was the reason for the better results experienced by the study group. In the study group, the difference in length of hospital stay and percent missing rehabilitation due to nausea for spinal anesthesia patients versus patients undergoing general endotracheal anesthesia was not statistically significant. Differences in length of hospital stay and percent missing rehabilitation due to nausea did not appear to be affected by the choice of anesthesia. We found that those in the control group who had spinal anesthesia had an even higher length of hospital stay and percentage missing rehabilitation. This would suggest that if the control group had contained a higher percentage of patients with spinal anesthesia and therefore more closely mirrored the study group, the control group’s length of hospital stay and percent missing rehabilitation would have been even higher than what was observed. Comparing only spinal anesthesia patients in both groups and only general endotracheal anesthesia patients in each group, we still found a statistically significant difference in length of hospital stay. So, regardless of the type of anesthesia used in the study group, patients in the control group consistently had a longer length of hospital stay than the preemptive analgesia study group.

Although the increased use of spinal anesthesia in the study group is a confounder, this factor does not appear to account for the better performance noted in the study group. Ideally, all patients would receive the same type of anesthesia or the groups would be more similar in the percentage that received general endotracheal anesthesia versus spinal anesthesia, but the evidence still strongly suggests that pre-emptive multi-modal analgesia has a positive effect on patient recovery status-post total hip and knee arthroplasty. In addition, due to the relatively small sample size and a variety of implants used in our study population, we were unable to make any determination as to the impact the device-type may have on our outcome assessments. Such confounders could be accounted for by conducting a larger, prospective randomized trial based on the current study results and the importance of this topic.

Conclusion

The use of pre-emptive oxycodone and a selective COX-2 inhibitor when compared to “on demand” (patient-controlled anesthesia) intravenous narcotics decreased postoperative IV narcotic requirements and increased rehabilitation participation by reducing nausea and vomiting. In addition, patients receiving pre-emptive analgesics had a decreased hospital length of stay and reduced likelihood of discharge to a skilled nursing facility. These data support the continued study and use of pre-emptive multi-modal analgesia paradigms in this population.

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Authors

Drs Duellman, Gaffigan, Milbrandt, and Allan are from the Division of Orthopedics and Rehabilitation, Southern Illinois University School of Medicine, Springfield, Illinois.

Drs Duellman, Gaffigan, Milbrandt, and Allan have no relevant financial relationships to disclose.

Correspondence should be addressed to: D. Gordon Allan, MD, FRCS(C), Southern Illinois University, School of Medicine, Division of Orthopedics and Rehabilitation, PO Box 19679, Springfield, IL 62794-9679.