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To evaluate the efficacy of ketamine in total knee and hip arthroplasty.
Design
Evidence-based review.
Methods
Following the guidelines outlined in the PRISMA statement, a comprehensive search was conducted using Google Scholar, PubMed, CINAHL, Cochrane Collaboration, and other grey literature. Only randomized controlled studies and pre-appraised evidence such as systematic review and meta-analysis examining the effects of ketamine in total knee and hip arthroplasty were included. The quality appraisal of the literature was conducted using the proposed algorithm described in the Johns Hopkins Nursing Evidence-Based Practice Evidence Level and Quality Guide.
Findings
Three systematic reviews and meta-analyses and 2 randomized controlled trials involving 1284 patients were included in this review. The use of ketamine reduced pain scores within the 24 hours after surgery. In addition, evidence suggests that patients who were treated with ketamine consumed fewer opioids 24 and 48 hours after surgery. Furthermore, ketamine reduced the incidence of postoperative nausea and vomiting with no effects on the incidence of hallucinations and central nervous system side effects. All studies included in the review were categorized as Level I and rated Grade A implying strong confidence in the true effects of ketamine in all outcome measures in the review.
Conclusions
The current evidence demonstrates the viability of ketamine as a safe and effective alternative to opioids in the perioperative setting with major total joint arthroplasty surgery. Decreased pain scores and opioid consumption up to 48 hours into the postoperative period were observed in a number of the appraised articles.
Significant postoperative pain is a common adverse effect after major joint arthroplasty, affecting the patient's well-being and decreasing patient satisfaction scores.
Providing effective analgesic management after surgery is critical to improving patient outcomes. The traditional usage of opioid analgesics to relieve postoperative pain has been related to complications such as respiratory depression, urinary retention, nausea, vomiting, and constipation.
Avoiding opioids and their harmful side effects in the postoperative patient: exogenous opioids, endogenous endorphins, wellness, mood, and their relation to postoperative pain.
patients receiving perioperative ketamine reported a pain reduction score of 5/100 mm on the visual analog scale (VAS) 24 hours after surgery. Similarly, total opioid consumption was significantly lower by 8 mg morphine equivalents.
Pain after orthopaedic surgery: differences in patient reported outcomes in the United States vs internationally. An observational study from the PAIN OUT dataset.
Several reviews and meta-analyses have examined ketamine for use in many orthopedic cases and have found it to provide good analgesia while reducing postoperative opioid consumption.
In total knee or hip arthroplasty, the use of ketamine may provide optimal postoperative pain management and improve clinical outcomes. Therefore, this evidence-based review was conducted to critically evaluate the benefits of low-dose ketamine in total knee and hip arthroplasty.
Methods
The PICO question that guided the search was: Does ketamine improve postoperative pain management in patients undergoing knee or hip arthroplasty? The reporting of this systematic review of evidence followed the recommended process described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
Two independent researchers (MW, BW) performed a comprehensive electronic search between February and March 2021 using Google Scholar, PubMed, CINAHL, and Cochrane Collaboration databases. Other databases such as clinicaltrials.gov and professional organizations’ abstract repositories were also searched to obtain published and unpublished clinical trial results and professional poster presentations to minimize publication bias. The key search terms ketamine, orthopedic, hip arthroplasty, knee arthroplasty, postoperative pain, and joint arthroplasty were used alone or combined using appropriate Boolean operators.
The titles and abstracts were examined for inclusion by two authors separately. Any disagreements were resolved via consensus discussion between the authors.
Selection Process
Articles considered for inclusion in this review were: (1) randomized controlled trials (RCT) comparing ketamine to placebo, no ketamine or active control, (2) pre-appraised studies such as systematic review and meta-analysis papers examining ketamine and placebo, no ketamine or active control, (3) patients have undergone orthopedic surgery such as total knee and hip arthroplasty regardless of anesthetic techniques, and (4) studies published within 10 years in scholarly, peer-reviewed academic journals. The RCTs included in meta-analysis papers were not appraised individually to take advantage of the Level 1 pre-appraised evidence. Instead, we examined the meta-analysis in which the findings of the trials were evaluated. Case reports, observational studies, expert opinions, and editorials were excluded from this review.
Data Abstraction
The authors individually extracted data from included studies using a previously piloted template. The data extracted were the following: patient demographics, American Society of Anesthesiologists' Physical Status Classification, the number of participants, anesthesia techniques, the amount, route, and timing of ketamine. In addition, we abstracted the primary and secondary outcomes for the current review. Disagreements or any discrepancies in data collection were resolved through discussion until a consensus was reached.
Outcome Measures
The primary outcome was pain scores in the postoperative setting. Pain scores of each study were examined at various time points after surgery. Pain scores value reported using VAS and numeric rating scale (NRS) were converted to an 11-point scale (0 = no pain and 10 = worst pain) for consistency in data analysis. Pain scores were assessed at 6, 12, 24, and 48 hours after surgery. If pain score was not recorded in the time points specified in this review, those reported close to the time point were used for analysis.
The secondary outcomes for this evidence-based review were total opioid consumption, time to first administration of analgesic or rescue analgesia, and complications of ketamine. The total opioid consumption was evaluated at 24 and 48 hours postoperatively. This review assessed various adverse effects of ketamine, including hallucination, sedation, and the incidence of postoperative nausea and vomiting (PONV).
Quality Assessment
Two authors assessed the quality of the evidence independently. The quality appraisal of the literature was conducted using the proposed algorithm described in the Johns Hopkins Nursing Evidence-Based Practice Evidence (JHNEBP) Level and Quality Guide.
The evidence level was rated using Level I-V (see footnotes Tables 1 and 2), and quality ratings A = high quality, B = good quality, or C = low quality with major flaws were assigned. Disagreements were resolved by consensus with a third author.
Table 1The Characteristics of Systematic Review and Meta-Analysis Examining the Efficacy and Safety of Ketamine in Joint Arthroplasty
Johns Hopkins Nursing Evidence-Based Practice Model Evidence Level. Level I: RCT, systematic review of RCTs, with or without meta-analysis; Level II: Quasi-experimental study; Level III: Non-experimental study; Level IV: Opinion of respected authorities and/or nationally recognized expert committees/consensus panels based on scientific evidence; Level V: Based on experiential and non-research evidence.
All RCTs included in the meta-analyses were also pooled in 2 other meta-analyses by Wang et al19 and Xu et al.20
(n = 244)
I
A
VAS 6 hrs WMD, –0.296; 95% CI, –0.488 to –0.104; P = .003
0%
24-hr morphine consumption WMD, −17.402; 95% CI: −34.006 to −0.798; P = .040
98%
VAS 12 hrs WMD, −0.304; 95% CI: −0.491 to −0.117; P = .001
0%
48-hr morphine consumption WMD, −19.963; 95% CI: −34.056 to −5.871; P = .005
97%
VAS 24 hrs WMD, −0.252; 95% CI: −0.404 to −0.101; P = .001
71%
Length of hospital stay (days) WMD, 0.070; 95% CI: −0.314 to 0.453; P = .722
0%
VAS 48 hrs WMD, −0.007; 95% CI: −0.131 to 0.116; P = .911
80%
CI, confidence interval; I2, statistic assessing heterogeneity of the studies; IV, intravenous; MD, mean difference; VAS, visual analog score; WMD, weighted mean difference.
Johns Hopkins Nursing Evidence-Based Practice Model Evidence Level. Level I: RCT, systematic review of RCTs, with or without meta-analysis; Level II: Quasi-experimental study; Level III: Non-experimental study; Level IV: Opinion of respected authorities and/or nationally recognized expert committees/consensus panels based on scientific evidence; Level V: Based on experiential and non-research evidence.
† Johns Hopkins Nursing Evidence-Based Practice Model Quality Rating. A, high quality; B, good quality; C, low quality or major flaws.
‡ Only one RCT analyzed in this meta-analysis was not included in the meta-analysis by Wang et al.
Table 2The Characteristics of Randomized Controlled Trials not Included in the Meta-Analysis Examining the Efficacy and Safety of Ketamine in Joint Arthroplasty
Johns Hopkins Nursing Evidence-Based Practice Model Evidence Level. Level I: RCT, systematic review of RCTs, with or without meta-analysis; Level II: Quasi-experimental study; Level III: Non-experimental study; Level IV: Opinion of respected authorities and/or nationally recognized expert committees/consensus panels based on scientific evidence; Level V: Based on experiential and non-research evidence.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
VAS at rest and during movement 24, 48 and 72-hrs postoperative, opioid consumption, rescue mediation use, ketamine adverse effects
IV, intravenous; kg, kilogram; mcg, microgram; mg, milligram; TUG, timed to Up and Go; VAS, visual analog score.
Johns Hopkins Nursing Evidence-Based Practice Model Evidence Level. Level I: RCT, systematic review of RCTs, with or without meta-analysis; Level II: Quasi-experimental study; Level III: Non-experimental study; Level IV: Opinion of respected authorities and/or nationally recognized expert committees/consensus panels based on scientific evidence; Level V: Based on experiential and non-research evidence.
† Johns Hopkins Nursing Evidence-Based Practice Model Quality Rating. A, high quality; B, good quality; C, low quality or major flaws.
After the initial electronic database search, 930 articles were identified, with 643 remaining after removing duplicate results. Further screening of the identified article titles and abstracts left a remaining 22 articles. Of those, 17 did not meet the inclusion criteria. Eventually, 5 studies were included in this review: 3 systematic reviews with meta-analysis
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
A total of 1284 patients were included in this review between all studies (Table 1, Table 2, Table 3). All 3 systematic reviews and meta-analysis studies
Postoperative analgesia and early rehabilitation after total knee arthroplasty: a comparison of continuous low-dose intravenous ketamine versus nefopam.
The combination of epidural clonidine and S(+)-ketamine did not enhance analgesic efficacy beyond that for each individual drug in adult orthopedic surgery.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
not included in the meta-analysis. All patients underwent total knee or hip arthroplasty under general or regional anesthesia.
Table 3Summary of Randomized Controlled Trials Examining the Efficacy and Safety of Ketamine in Joint Arthroplasty Included in Systematic Review and Meta-Analysis
Postoperative analgesia and early rehabilitation after total knee arthroplasty: a comparison of continuous low-dose intravenous ketamine versus nefopam.
The combination of epidural clonidine and S(+)-ketamine did not enhance analgesic efficacy beyond that for each individual drug in adult orthopedic surgery.
VAS at rest and activity POD 1-3; meperidine requirements; patient satisfaction scores and adverse effects (drowsiness, PONV, pruritus and CNS responses)
CNS, central nervous system; hr, hour; hrs, hours; kg, kilogram; LOS, length of stay; mcg, microgram; mg, milligram; min, minute; mL, milliliter; NR, non-reported; OR, operating room; PCA, patient controlled analgesia; POD, postoperative day; PONV, postoperative nausea and vomiting; RCT, randomized controlled trial; THA, total hip arthroplasty; TKA, total knee arthroplasty.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
varied ranging from an initial IV bolus of 0.05 mg/kg to 1 mg/kg (Table 3). In studies with continuous infusion, the maintenance dose were between 2 mcg/kg/min to as high as 120 mcg/kg/min. Ketamine was administered through IV,
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Postoperative analgesia and early rehabilitation after total knee arthroplasty: a comparison of continuous low-dose intravenous ketamine versus nefopam.
The combination of epidural clonidine and S(+)-ketamine did not enhance analgesic efficacy beyond that for each individual drug in adult orthopedic surgery.
The combination of epidural clonidine and S(+)-ketamine did not enhance analgesic efficacy beyond that for each individual drug in adult orthopedic surgery.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Postoperative analgesia and early rehabilitation after total knee arthroplasty: a comparison of continuous low-dose intravenous ketamine versus nefopam.
The assessment methodology of postoperative pain scores differed between studies. All 3 meta-analyses converted NRS and VAS into an 11-point scale of 0 to 10, with 0 as no pain and 10 as severe pain for analysis.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
used the NRS. The time points of pain assessment contrasted among the studies included in this review. Three meta-analyses evaluated pain scores up to 48 hours after surgery.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
presented a funnel plot showing symmetrical configuration, suggesting no potential publication bias in all included RCTs in the review. In the same review, Begg's correlation test corroborated no possible risk of publication bias.
An I2 statistic of >50% was considered substantial heterogeneity. The I2 statistic differed for both primary and secondary outcomes on the reviews (Table 1). One systematic review
explored the causes of heterogeneity. However, the review authors failed to identify factors affecting the variations between the studies. The authors of the 2 RCTs
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
pooled 5 RCTs consisting of 259 patients and reported a significant reduction in the pain score of patients treated with ketamine by an average of 1.45 on a pain scale of 0 to 10 (MD, –1.45; 95% CI, –1.71 to –1.18; P < .0001). Similarly, another meta-analysis
reported a lower pain score in patients with ketamine (MD –0.296; 95% CI, –0.488 to –0.014). In the same review, patients given ketamine experienced lower pain scores within 12 hours after surgery (P = .003).
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
reported no difference in pain intensity in patients with ketamine. The other RCTs evaluated the effect of ketamine in patients undergoing bilateral knee arthroplasty.
showed a significant difference in pain score on the second knee operated with patients treated with ketamine having more pain by an average of 0.930 at rest and during movement.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
reported this outcome and suggested no difference in the number of rescue medications in patients receiving ketamine compared to placebo.
Adverse Effects
Adverse effects such as hallucinations and sedation were evaluated in the studies included in this review. The incidence of hallucinations and central nervous system (CNS) side effects were reported in two reviews. Xu and colleagues
pooled 3 RCTs consisting of 286 patients and concluded that there is no difference in the incidence of psychotic adverse effects in patients given IV ketamine compared to placebo. Similarly, 1 review
examined 2 RCTs and concluded that the use of ketamine did not cause sedation postoperatively.
Postoperative Nausea and Vomiting
There were conflicting findings regarding the effects of ketamine on the incidence of PONV. However, in a most recent review published in 2020, Wang et al
reported no significant difference in the incidence of PONV between groups. The possible explanation for the contrasting outcomes between the 2 reviews was the number of RCTs included in the analysis. In the meta-analysis conducted by Wang and colleagues,
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
not included in the systematic review and meta-analysis papers minimized study bias by using sound random sequence generation, adequate concealment of allocations before trial assignment, and blinded the participants and the study outcomes assessors. All three systematic reviews and meta-analyses adhered to universally acceptable reporting guidelines (PRISMA and Cochrane Guidelines).
The overall findings of our review suggested that patients undergoing total joint arthroplasty treated with ketamine reported lower pain scores postoperatively. In addition, a reduction in morphine equivalent consumption was observed up to 48 hours following surgery. This evidence-based review also showed the opioid-sparing effect of ketamine. Adverse side effects secondary to opioids, such as PONV, were significantly lower in patients treated with ketamine. Clinical presentations such as sedation and hallucination were not different when treated with ketamine.
A primary challenge for patients undergoing total joint arthroplasty surgery is adequate postoperative pain control. Inadequate postoperative pain management provokes stress responses causing pulmonary, immunological, and metabolic dysfunction.
Managing postoperative pain using a single modality such as opioids has been declining in recent decades because of new drugs, improved drug delivery methods, and a much greater understanding of the pain pathway.
Opioids have numerous side effects, including sedation, respiratory depression, and postoperative nausea and vomiting, leading to decreased patient safety and satisfaction.
Pain after orthopaedic surgery: differences in patient reported outcomes in the United States vs internationally. An observational study from the PAIN OUT dataset.
Greater than 80% of patients report inadequate pain control resulting in slower recovery, increased complication rates, extended length of hospital stays, and decreased patient satisfaction.
In addition, suboptimal postoperative pain control may lead to opioid tolerance and opioid dependency.
The opioid crisis in the US is becoming a national health emergency. The latest data show that the opioid problem results in the deaths of 128 people a day and an estimated economic cost of 78.5 billion dollars a year.
One of the causes of the opioid epidemic is believed to be exposure to opioids in the perioperative setting resulting in an increased number of prescriptions to treat chronic postoperative pain.
As the opioid crisis worsens, a multimodal analgesic approach is quickly becoming a priority as the need to reduce opioid consumption becomes both a legislative and practical focus of care. Decreasing the prescription rate and utilization of opioids is one approach to reducing opioid exposure.
A multimodal approach in pain management has been recommended as it provides pain relief, improves the quality of life, and decreases opioid dependency, thus aiding in fighting the opioid epidemic. Multimodal analgesia is administering 2 or more pharmacological agents or using 2 or more analgesia techniques with a different mechanism of action to reduce pain by targeting different pain pathways.
The goal of multimodal analgesia is to provide synergistic effects from 2 or more modalities to manage pain effectively. Enhanced recovery after surgery (ERAS) programs include multimodal analgesia strategies in their initiatives. In ERAS protocols specifically for orthopedic surgery, a combination of minimal opioid and optimized non-opioid techniques have improved patient outcomes, including improvement in patient pain scores, overall opioid consumption, length of stay, and patient satisfaction.
Consensus statement for perioperative care in total hip arthroplasty and total knee arthroplasty surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
The reduction in opioid consumption leads to a reduction in complications from the side effects of opioids and a better outcome in the postoperative setting.
Ketamine is a phencyclidine-derived dissociative anesthetic that works predominantly by antagonism of N-methyl-D-aspartate (NMDA) receptors.
The NMDA receptors exert nociception through the post-synaptic nerve ending on the second-order neuron in the spinal cord's dorsal horn in response to painful stimuli.
With painful stimulation, the first-order neuron releases glutamate to bind to NMDA receptors on the second-order neuron. This binding results in conformational changes to the receptors allowing the increased influx of calcium and, with prolonged stimulation, causes the development of central sensitization. Central sensitization leads to the upregulation of the nervous system into a high reactivity state, leading to chronic pain syndrome.
Ketamine works by antagonizing the NMDA receptor, thus blocking the subsequent centrally mediated pain processes reducing acute pain and preventing chronic pain. Ketamine has additional effects on pain processing. Additionally, mu receptor activation has been observed.
Dissociation of the thalamocortical region responsible for pain-sensing and perception is another property. Lastly, ketamine is noted to have antidepressant and anti-inflammatory effects, enhancing exogenous opioid use, making it a unique medication to use in pain management.
Using the Johns Hopkins EBP model, the overall quality of the evidence was considered high because of sufficient effect sizes and reasonably consistent findings. Our review showed a consistent and sound reduction in pain scores in the early postoperative period until 48 hours after surgery in patients undergoing total joint arthroplasty receiving perioperative ketamine. In addition, our findings were similar to earlier studies examining the efficacy of perioperative ketamine in other orthopedic surgeries such as shoulder, knee arthroscopy and spine cases.
We also observed that pain scores differences gradually diminish 24 to 48 hours after surgery. One possible explanation for this progressive reduction in pain scores was the duration of action of ketamine which is at least 45 minutes.
In the current review, we noted a reduction in 24-hour morphine consumption averaging 17 mg and, at 48-hours, a reduction of 20mg in patients who received perioperative ketamine. With reduced opioid consumption, opioid side effects were expected to be minimal. Evidence also showed that the incidence of sedation and other CNS effects were not significantly different in the ketamine group compared to the control or placebo.
Several limitations were identified in this review. First, the variations in the dosing regimen, timing, and routes of ketamine administration may have affected the overall pain scores. Second, different anesthetic modality choices, such as the choice between general or regional anesthesia for joint arthroplasty, could have affected the overall effect of ketamine on pain scores and opioid consumption. Third, all 3 meta-analyses acknowledged substantial heterogeneity in their estimates; however, factors affecting the effect sizes were not uncovered despite sensitivity and sub-group analyses. Last, this review did not appraise the RCTs included in the 3 SRs independently due to reliance on the previous appraisal done by the authors of the systematic reviews and meta-analyses.
Further research is needed to define the most suitable ketamine dosage for postoperative pain management. This may include dose-finding studies evaluating the effective dose in 50% and 95% of patients for total joint arthroplasty under general or regional anesthesia. Since chronic pain is becoming a common sequela after total joint arthroplasty,
further studies should examine the efficacy of ketamine on chronic pain management postoperatively. Additionally, studies are needed to investigate the appropriate dosage for obese patients with a BMI above 30, where an adjusted or ideal body weight may be utilized. Last, research on intra-articular and neuraxial ketamine administration is needed as the use of regional anesthesia in total joint arthroplasty is becoming common.
Ketamine is a common component of ERAS protocols. This literature review demonstrates the viability of ketamine as a safe and effective alternative to opioids in the perioperative setting with major total joint arthroplasty surgery. Decreased pain scores and opioid consumption up to 48 hours into the postoperative period were observed in a number of the appraised articles. Although ketamine reduced the incidence of PONV, ketamine showed no adverse effects in the postoperative period.
References
Anger M
Valovska T
Beloeil H
et al.
PROSPECT guideline for total hip arthroplasty: a systematic review and procedure-specific postoperative pain management recommendations.
Avoiding opioids and their harmful side effects in the postoperative patient: exogenous opioids, endogenous endorphins, wellness, mood, and their relation to postoperative pain.
Pain after orthopaedic surgery: differences in patient reported outcomes in the United States vs internationally. An observational study from the PAIN OUT dataset.
Inkk Trial - Intraoperative ketamine for perioperative pain management following total knee endoprosthetic arthroplasty in oncology: a double-blinded randomized trial.
Postoperative analgesia and early rehabilitation after total knee arthroplasty: a comparison of continuous low-dose intravenous ketamine versus nefopam.
The combination of epidural clonidine and S(+)-ketamine did not enhance analgesic efficacy beyond that for each individual drug in adult orthopedic surgery.
Consensus statement for perioperative care in total hip arthroplasty and total knee arthroplasty surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
Johns Hopkins Nursing Evidence-Based Practice Model Evidence Level. Level I: RCT, systematic review of RCTs, with or without meta-analysis; Level II: Quasi-experimental study; Level III: Non-experimental study; Level IV: Opinion of respected authorities and/or nationally recognized expert committees/consensus panels based on scientific evidence; Level V: Based on experiential and non-research evidence.
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