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The role of preemptive analgesia with various analgesic drugs in patients undergoing orthopedic surgeries: A systematic review 2015–2020
, Roya Najafi-Vosoughb, Hossein Mahjubc, Ahmad Moradia, Mohammad Hossein Bakhshaeia,, Arya Haddadid,
⁎Corresponding author: Mohammad Hossein Bakhshaei. bakhshaei@umsha.ac.ir
⁎⁎Corresponding author: Arya Haddadi. arya.haddadi@gmail.com
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
Effective postoperative pain management remains a major challenge, particularly in orthopedic surgeries, as poor control can increase patient stress, prolong opioid use, and delay recovery and hospital discharge. This structured review aimed to evaluate the effectiveness of various analgesic agents in preventing or reducing postoperative pain in patients undergoing orthopedic procedures.
A comprehensive systematic search was conducted in the Web of Science, PubMed, and Scopus databases from 2015 up to the end of December 2020. Additionally, the reference lists of relevant articles were screened to identify further eligible studies. Only randomized clinical trials investigating preemptive analgesia in orthopedic surgery patients were included.
Fourteen articles were initially identified, with five studies meeting the final inclusion criteria. These trials investigated the effects of different pharmacological agents on preemptive pain control. Analgesic effects were observed with intravenous ibuprofen administered prior to incision.
For dexketoprofen and tramadol, analgesic benefits were reported in postoperative administration protocols rather than true pre-incision (preemptive) use.
Preemptive administration of intravenous ibuprofen appears effective in reducing postoperative pain in adults undergoing orthopedic surgery. Evidence for dexketoprofen and tramadol relates primarily to postoperative or perioperative use rather than true preemptive administration.
Keywords
Preemptive analgesia
Orthopedic surgery
Postoperative pain
Systematic review
Randomized clinical trials
1 Introduction
Postoperative pain management has long been one of the most fundamental and complex challenges in medicine. Inadequate control of pain after surgery can lead to serious consequences, such as delayed recovery, prolonged hospitalization, reduced patient participation in rehabilitation programs, and ultimately the development of both acute and chronic complications.1,2 Despite significant advances in understanding the physiological and pharmacological mechanisms of pain, the development of standardized guidelines, and the establishment of specialized Acute Pain Services (APS), postoperative pain remains a prominent clinical problem worldwide.1,2 This issue, coupled with the increasing number of patients admitted to hospitals and intensive care units—amounting to millions annually—underscores the urgent need for innovative strategies in pain management.3
Numerous studies have demonstrated that approximately 30–70 percent of patients in intensive care units experience severe physiological stress,4 and several reports indicate that up to 70 percent of patients in medical wards and ICUs suffer from pain, with about 63 percent experiencing moderate to severe pain 5. Moreover, among patients transferred to the ICU after surgery, 77 percent report pain, and 64 percent of those able to express their pain experience moderate to severe intensity.6 These statistics clearly demonstrate that postoperative pain is not only a clinical problem but also exerts extensive, multidimensional negative effects on the physical, psychological, and social well-being of patients.
Physiologically, exposure to threats such as disease, trauma, or psychological stress triggers a series of changes in the body, including increased heart rate, enhanced metabolic activity, elevated body temperature, increased blood pressure, and accelerated heart and respiratory rates.7,8 These physiological responses can directly affect the effectiveness of pain management. Therefore, the timely and precise control of these responses is crucial to prevent the exacerbation of pain and the onset of related complications.
In this context, the proper management of analgesics—including both pain relievers and anxiolytics—is a key aspect of care in intensive care units. These medications play an important role in improving patient comfort, reducing anxiety, facilitating clinical interventions, enhancing sleep quality, aiding mechanical ventilation, and preventing complications resulting from the stress response to surgery.9,10 Moreover, an ideal analgesic should possess both sedative and analgesic properties, exhibit minimal cardiovascular side effects, offer controllable respiratory adverse events, have a rapid onset of action with high cost-effectiveness, produce inactive metabolites, and interact minimally with other drugs.10 However, it should be noted that excessive use of analgesics may lead to prolonged mechanical ventilation and ultimately result in pulmonary and neuromuscular complications due to extended stays in intensive care units.11
Given the importance of pain control, one promising strategy that has garnered attention in recent years is the concept of “preemptive analgesia.” In this approach, analgesics are administered prior to tissue injury (i.e., before the surgical incision) in order to reduce the afferent nociceptive input to the central nervous system, thereby preventing the activation of inflammatory responses and the development of chronic postoperative pain.12–15 Since postoperative pain is a common consequence of tissue injury—affecting approximately 80 percent of surgical patients, of whom 18 percent report severe pain—improving postoperative pain management strategies is clinically imperative.13,16,17
Recent meta-analyses underscore the efficacy of preemptive analgesia. For instance, Hu et al. (2018) demonstrated that a single preoperative dose of pregabalin or gabapentin reduces opioid consumption and postoperative pain in a dose-dependent manner, suggesting that optimal dosing can minimize side effects.18 Similarly, Nir et al. (2016) found that preoperative NSAIDs significantly lower postoperative analgesic requirements,19 while Robert et al. (2006) confirmed that oral gabapentin offers superior pain relief compared to placebo via mechanisms distinct from conventional opioids.20
Furthermore, concerns have been raised regarding the use of opioids as the primary agents for postoperative pain relief. Although opioids are proven to be effective, their use is associated with numerous side effects such as nausea, itching, sedation, and even addiction.14 Consequently, alternative strategies to reduce opioid consumption and improve pain control have been explored, including the use of non-opioid medications and anti-inflammatory combinations as part of multimodal or balanced anesthesia approaches. For example, gabapentin, which is used in the treatment of inflammatory and neuropathic pain, has emerged as a promising candidate for postoperative pain management due to its ability to reduce hyperalgesia and prevent neural alterations following surgical incision.21 Recent studies have shown that pregabalin, by binding to voltage-dependent calcium channels, can reduce neurotransmitter release and dampen postsynaptic excitability, thereby contributing to a decrease in postoperative pain intensity.18,22,23
Given the challenges inherent in managing postoperative pain and the need for effective and safe strategies, a detailed examination of the effects of various analgesics—such as morphine, non-steroidal anti-inflammatory drugs (NSAIDs), fentanyl, and sufentanil—in the context of preemptive analgesia in patients undergoing orthopedic surgeries is of paramount importance. This approach may not only reduce pain intensity but also decrease the consumption of postoperative analgesics, thereby mitigating the adverse effects associated with high opioid use 12,24–28.
From a clinical perspective, improved postoperative pain control not only enhances patient satisfaction but also accelerates recovery and reduces the costs associated with postoperative care and prolonged hospitalization. In this regard, the implementation of preemptive analgesia as a preventive strategy can, by reducing nociceptive input to the central nervous system, prevent the activation of inflammatory responses and the development of chronic postoperative pain 16, 19. This is especially significant in orthopedic surgeries, where pain- and inflammation-related complications are more pronounced.
Despite numerous studies in this field, the precise role of preemptive analgesia using various drugs in reducing postoperative pain has not yet been fully elucidated. Some studies have reported promising results, while others have indicated contradictory outcomes or a lack of efficacy for this approach.12,14 Therefore, a systematic review and analysis of studies from 2015 to 2020 could help identify the strengths and weaknesses of this strategy and provide practical recommendations for improving postoperative pain management in patients undergoing orthopedic surgeries.
Considering the importance of postoperative pain control and the concerns regarding the side effects of analgesics, conducting a structured review in this area can provide a comprehensive overview of the existing evidence, a detailed analysis of the variables affecting the effectiveness of preemptive analgesia, and the identification of research gaps. Accordingly, the primary aim of this study is to evaluate the effects of various analgesics—including NSAIDs, fentanyl, and sufentanil—on reducing postoperative pain in patients undergoing orthopedic surgeries. Moreover, this systematic review seeks to propose optimized strategies for improving postoperative pain control by critically analyzing previous study outcomes and to delineate directions for future research.24
Finally, given the widespread prevalence of postoperative pain and its negative impact on patient health and quality of life, the development and implementation of preemptive analgesia strategies can serve as a key approach to enhancing postoperative pain management. Therefore, the systematic review conducted in this study may pave the way for the development of novel and effective treatment protocols for reducing pain in patients undergoing orthopedic surgeries, ultimately leading to improved clinical outcomes and increased patient satisfaction.12,24,27,28
This review not only focuses on the comparative evaluation of the effects of different analgesics in the context of preemptive analgesia but also provides a comprehensive and detailed analysis of studies published between 2015 and 2020, aiming to identify the challenges and research gaps in this field. Therefore, the findings may offer useful insights to guide future research and contribute to the refinement of postoperative pain management approaches, although more recent developments beyond 2020 should also be considered in subsequent investigations.
2 Methods
In this study, conducted as a systematic review, the aim was to evaluate the effects of preemptive administration of analgesics—including morphine, fentanyl, sufentanil, and non-steroidal analgesics—in patients undergoing orthopedic surgeries between 2015 and 2020.
3 Data collection method
Relevant articles were identified through a search of three databases: Web of Science, PubMed, and Scopus. In Web of Science and PubMed, the “All Fields” option was used, while in Scopus, the “TITLE-ABS-KEY” option was applied. The search strategy employed the following combination of keywords:
(Preemptive) AND (Postoperative pain) AND (Clinical Trial) AND (NSAID OR Non-steroidal Drugs OR Morphine OR fentanyl OR sufentanil) AND (“Orthopedic surgery”)
Reference lists of selected studies were also screened to identify additional eligible papers. Grey literature (conference abstracts, theses) and non-English publications were excluded.
The full electronic search strategy for all databases is available upon request and followed PRISMA recommendations for transparency.
Eligible studies were randomized clinical trials published between 2015 and 2020 that investigated the effects of preemptive administration of analgesics in patients undergoing orthopedic surgeries. Inclusion criteria followed the PICO framework. Only studies in which the analgesic intervention was administered prior to surgical incision were considered true preemptive analgesia. Studies in which analgesics were administered at skin closure or postoperatively were discussed descriptively but interpreted with caution.
Population: patients undergoing orthopedic surgery under anesthesia; Intervention: intravenous analgesics (NSAIDs or opioids such as morphine, fentanyl, sufentanil); Comparator/Control: standard care or placebo; Outcome: postoperative pain intensity. Exclusion criteria included animal studies, reviews, and non-randomized trials, as well as studies without clear pain-related outcomes.
To facilitate data extraction and analysis, a standardized electronic form was developed. This form included the following items: first author's name, year of publication, country, gender of participants, sample size, type of analgesic used, type of surgery, intervention outcomes, and inclusion/exclusion criteria. The validity and reliability of the form were confirmed by consultation with experts in clinical research.
3.1 Data analysis
Data were analyzed descriptively. All retrieved records were imported into EndNote, where duplicates were removed. Two reviewers independently screened titles and abstracts, excluding irrelevant articles. Full texts of the remaining studies were then assessed, and disagreements were resolved by consensus or through consultation with a third reviewer.
The extracted information (as recorded in the standardized form) was then synthesized. Additionally, the quality of the included studies was assessed using the Cochrane Risk of Bias tool (see Fig. 2). A PRISMA flow diagram illustrated the study selection process, and a summary figure of the Risk of Bias assessment was generated. This review protocol was not registered in PROSPERO. However, predefined eligibility criteria, outcomes, and analysis plans were established prior to study selection to minimize selection bias.
3.2 Ethical consideration
Throughout all stages, from inception to data extraction, ethical principles and confidentiality were maintained, ensuring transparency in the selection and extraction process.
4 Results
A total of 14 studies were identified in this review, with 11 studies retrieved from the primary databases (from 2015 to December 2020) and 3 studies obtained through a search of the reference lists of selected articles. One duplicate study and 7 studies that were deemed irrelevant based on title and abstract screening were excluded. The full texts of 6 studies were then reviewed, and 1 study was further excluded based on the predefined exclusion criteria. Ultimately, 5 studies were included in the review (Fig. 1).
The included studies exhibited notable heterogeneity in terms of patient population, surgical procedures, and analgesic agents. Specifically, four trials were conducted in adults undergoing orthopedic or abdominal surgeries, whereas one trial involved pediatric patients undergoing corrective osteotomy. Furthermore, the interventions varied from non-steroidal anti-inflammatory drugs (ibuprofen, ketorolac, parecoxib, dexketoprofen) to opioids (fentanyl) and combination therapy (dexketoprofen plus tramadol). Surgical settings also differed, including hip arthroplasty, knee arthroscopy, spinal surgery, and mixed abdominal/orthopedic procedures. Due to this diversity in populations, interventions, and outcomes, the findings were narratively synthesized rather than pooled statistically, and the conclusions should be interpreted with caution.
4.1 Study 1
Gago Martinez et al. (2016) conducted a multicenter randomized clinical trial in Spain to compare the effect of intravenous ibuprofen on postoperative pain scores and morphine consumption in patients undergoing abdominal and orthopedic surgeries. A total of 206 patients were randomized to receive either 800 mg IV ibuprofen or placebo every 6 h, in addition to patient-controlled morphine. The results showed that mean morphine consumption during the first 24 h was significantly lower in the ibuprofen group (14.22 ± 3.23 mg) compared to the placebo group (29.8 ± 5.25 mg; p = 0.015). Pain scores at rest were also significantly lower in the ibuprofen group (0.86 ± 0.24) compared with placebo (4.68 ± 0.40; p = 0.020). It should be noted, however, that in this trial the intervention was administered at the time of skin closure rather than prior to the surgical incision. Therefore, the study does not strictly investigate preemptive analgesia, and its relevance to the objectives of this review should be interpreted with caution.29
4.2 Study 2
Siribumrungwong et al. (2015) conducted a prospective randomized, double-blind clinical trial in Thailand to evaluate the preemptive effects of ketorolac and parecoxib compared with placebo in patients undergoing spinal surgery. Ninety-six patients were equally divided into three groups of 32 patients each, receiving either parecoxib, ketorolac, or placebo 30 min before incision.
The results showed that both the parecoxib and ketorolac groups experienced significantly lower pain scores in the post-anesthesia care unit (PACU) compared with placebo (p = 0.050). However, these benefits were not sustained, as pain scores at later postoperative time points (including 24 h) were similar across all three groups. In terms of opioid consumption, there were no statistically significant differences among the groups at 8, 16, or 24 h, or in the overall cumulative morphine use (p > 0.05). Furthermore, no significant differences were observed regarding adverse effects or blood loss.
Taken together, this study suggests that while parecoxib and ketorolac may provide superior early pain relief in the PACU, their effects do not appear to extend beyond the immediate postoperative period, and they do not significantly reduce opioid requirements during the first 24 h after surgery.30 It should be noted that ketorolac and parecoxib were evaluated as comparative agents and were not administered in combination.
4.3 Study 3
McQuay et al. (2016) conducted a large multicenter, randomized, parallel-group clinical trial in the United Kingdom to evaluate the efficacy of dexketoprofen, tramadol, and their fixed-dose combination (25 mg/75 mg) compared with placebo in patients undergoing total hip arthroplasty. The trial was conducted in multiple phases and included several treatment arms, allowing both combination and monotherapy groups to be compared with placebo.
The results demonstrated that the combination of dexketoprofen and tramadol provided significantly greater pain relief in the first 8 h postoperatively compared to placebo (p < 0.05). Monotherapy with either dexketoprofen or tramadol also showed superiority to placebo, but the combination therapy consistently demonstrated enhanced efficacy over either agent alone, even at higher doses of tramadol. Secondary analyses confirmed these findings across different patient subgroups. Importantly, the incidence of adverse drug reactions was low and similar among all treatment groups.
It should be noted, however, that this trial focused specifically on postoperative pain management rather than preemptive administration of analgesics prior to tissue injury. Therefore, while the study provides valuable evidence regarding the efficacy of dexketoprofen–tramadol combination therapy, its direct relevance to the objectives of this systematic review is limited.31
4.4 Study 4
Song et al. (2016) conducted a randomized, blinded clinical trial in Korea to evaluate the effect of preemptive analgesia with fentanyl in children aged 3–7 years undergoing corrective osteotomy. All participants received standardized general anesthesia, including IV patient-controlled analgesia (IV-PCA) with fentanyl. In the intervention group, fentanyl was administered before the skin incision, whereas in the control group it was given 5 min after incision.
The primary outcome was pain intensity measured by the visual analog scale (VAS). Assessments were conducted during the immediate postoperative period and followed for up to several hours after surgery. The results showed no statistically significant differences between the groups in pain scores at 1 h postoperatively, nor in the need for additional rescue analgesia. Other perioperative outcomes, including IV-PCA use, were also comparable between the two groups.
This study highlights important limitations for the context of preemptive analgesia: the findings are restricted to a pediatric population, and therefore cannot be directly generalized to adult patients. Additionally, the short follow-up period limits conclusions about the longer-term effects of preemptive fentanyl administration.32 Therefore, findings from pediatric fentanyl studies should not be extrapolated to adult populations or to non-opioid analgesics such as NSAIDs.
4.5 Study 5
Uribe et al. (2018) performed a single-center, randomized clinical trial in patients undergoing knee arthroscopy to compare the effects of preemptive IV ibuprofen with IV ketorolac. A total of 51 patients completed the study, with 20 patients receiving ibuprofen (800 mg IV, administered 2 h before surgery and repeated once if necessary) and 31 patients receiving ketorolac (30 mg IV at the end of surgery).
The results demonstrated that in the post-anesthesia care unit (PACU), patients in the ibuprofen group reported significantly lower pain scores compared with those in the ketorolac group. At rest, the median VAS score was 9 (IQR: 2–25) for ibuprofen versus 33 (IQR: 12–52) for ketorolac (p = 0.006). During movement, median scores were 15 (IQR: 6–31) for ibuprofen versus 38 (IQR: 20–61) for ketorolac (p = 0.001). In other words, median pain scores were almost twice as high in the ketorolac group compared to the ibuprofen group during the early postoperative period.
These differences were most pronounced within the first 90 min after surgery, whereas from 120 min up to 24 h postoperatively, no significant differences were observed between the groups. Additional opioid use in the PACU was required in 55% of patients in the ibuprofen group compared with 83.9% in the ketorolac group, further supporting the superior early analgesic efficacy of ibuprofen.33 It should be noted that ketorolac and parecoxib were evaluated as comparative agents and were not administered in combination.
The characteristics of these studies are detailed in Tables 1–3.
| R | 1st author, Year | Journal | Participants |
| 1 | Gago Martinez, 2016 | PLOS ONE | 206Male & Female |
| 2 | Siribumrungwong, 2015 | BMC Musculoskeletal Disorders | 96Male: 33 & Female: 63 |
| 3 | McQuay, 2016 | British Journal of Anesthesia | 641Male: 295 & Female: 346 |
| 4 | Song, 2016 | Pediatric Anesthesia | 41Male: 25 & Female: 16 |
| 5 | Uribe, 2018 | Frontiers in surgery | 51Male; 35 & Female: 16 |
| R | Group | Intervention1 | Comparison | Intervention2 | Outcome |
| 1 | Ibuprofen:107Placebo:99 | Ibuprofen 800 mg every 8h IV | morphine consumptionPain (VAS) | Placebo | Mean Morphin consumption and Pain score in group I significantly lower than group P |
| 2 | ketorolac:32Parecoxib: 32 placebo: 32 | KetorolacParecoxib | Pain | Placebo | ketorolac and parecoxib showed a significantly better early postoperative pain control |
| 3 | dexketoprofentramadoldexketoprofen/tramadolPlacebo | dexketoprofentramadoldexketoprofen/tramadol | PainSPID8 | Placebo | The efficacy results confirmed the superiority of dexketoprofen/tramadol over its single components, even at higher doses (tramadol), |
| 4 | IV-PCA fentanyl administered before skin incision (preemptive)IV-PCA fentanyl administered 5 min after incision (non-preemptive) | PreemptiveIV-PCA before skin incision | pain score at postoperative 1 h | PreemptiveIV-PCA started 5 min thereafter | Preemptive analgesia using IV-PCA with fentanyl showed no significant advantages for postoperative analgesia |
| 5 | Ibuprofen:20 ketorolac:31 | IV Ibuprofen 800 mg | Pain Score (VAS) | IV ketorolac 30 mg | The use of preemptive IV ibuprofen 800 mg could be considered to reduce postoperative pain and opioid consumption |
| R | Inclusion Criteria | Exclusion Criteria | Surgery Type | Age Range |
| 1 | 1. Men or women. 2. Scheduled for elective single surgical site orthopedic surgery (hip or knee joint replacement, crossed ligaments, spine or shoulder surgery), or abdominal surgery (inguinal hernia, cholecystectomy, eventration or hiatus hernia). 3. Scheduled for general anesthesia or regional anesthesia without residual analgesia after surgery. 4. Anticipated need for postoperative narcotic analgesia administered by patient-controlled analgesia. 5. Anticipated hospital stays for at least 24 h 6. Written informed consent for participating in this study | 1. Use of NSAID within 12 h prior to the first planned dose. 2. Taking oral anticoagulants, lithium, ACE inhibitors, furosemide or aspirin. 3. Anemia (hemoglobin <60 ml/min). 15. Liver failure, ALAT or ASAT >3 times upper limit of normality or total bilirubin >2 mg/dl 16. Diagnosed of Bowel Inflammatory Disease. 17. Not able to understand the requirements of the study, or to abide by the study restrictions or to return for the required assessments | orthopedic surgery (hip or knee joint replacement, coursed ligaments, column or shoulder surgery), or abdominal surgery (inguinal hernia, cholecystectomy, eventration or hiatus hernia) | 18–60 Years |
| 2 | Eligible patients were aged 18–80 years and had an American Society of Anesthesiologist physical status (ASA) classification of I-II | History of NSAIDs or opioid or sulfonamide allergy, any coagulopathy disease or patients who current use of antiplatelet or anticoagulant drugs, severe hepatic impairment, acute peptic ulceration, congestive heart failure, pregnancy, and lactation. | Lumbar disc herniation, spondylolisthesis, spinal stenosis | 18–80 |
| 3 | men and women aged 18–80 yr, undergoing standard primary unilateral total hip arthroplasty because of osteoarthritis | Osteoarthritis secondary to systemic or metabolic diseases, trauma, or infections) Women participating in the study had to be either of non-childbearing potential or willing to use a highly effective contraceptive method. | Total hip arthroplasty | 29–80 |
| 4 | patients aged between 3 and 7 years, scheduled for corrective osteotomy and IV-PCA use | History of drug allergy or opioid side effects, developmental delays, postoperative intensive care unit admission, and sedation | Osteotomy | 3–7 |
| 5 | Candidate for arthroscopic knee surgery under general anesthesia were enrolled in this study. 18 years and older, provided a written informed consent | A history of allergy or hypersensitivity to any component of ibuprofen or other NSAIDs, aspirin (or aspirin related products), opioids or COX-2 inhibitors, or had used analgesics | Arthroscopic knee surgery. | ≤18 |
5 Discussion
In this section, the findings of this structured review are comprehensively examined. The results are interpreted, compared with existing evidence, and the strengths and limitations of the research are discussed.
Through a systematic search of databases from 2015 to 2020, this review identified five randomized clinical trials that evaluated the effects of preemptive analgesia using various analgesics in patients undergoing orthopedic surgery (and, indirectly, in some cases abdominal surgery) 29–33 (39–43). Since all the selected articles were randomized clinical trials, the findings are supported by strong empirical evidence.
In the study by Gago Martinez et al.29 conducted in Spain, intravenous ibuprofen administered preemptively in patients undergoing abdominal and orthopedic surgeries resulted in a significant reduction in pain scores and a decrease in morphine consumption during the first 24 h postoperatively. These results indicate that preemptive administration of ibuprofen effectively reduces the burden of opioid consumption and improves pain control.
Siribumrungwong et al.30 in Thailand evaluated the preemptive effects of ketorolac and parecoxib in patients undergoing spinal surgery for orthopedic indications. Their findings showed that both ketorolac and parecoxib were superior to placebo in reducing pain intensity in the post-anesthesia care unit (PACU). However, no statistically significant difference in pain scores was observed between the ketorolac and parecoxib groups. Furthermore, morphine consumption at various time points postoperatively did not differ significantly among the groups, suggesting a limited impact of these interventions on overall opioid use.
In the study conducted by McQuay et al.31 in the United Kingdom, a combination of dexketoprofen and tramadol was evaluated in patients undergoing total hip arthroscopy. The initial analysis indicated that the dexketoprofen/tramadol combination was superior to placebo. Secondary analyses further confirmed that the combination therapy was more effective than monotherapy—even when using higher doses of tramadol alone—underscoring the value of a multimodal approach to preemptive analgesia.
Song et al.32 in Korea investigated the effect of preemptive analgesia with fentanyl in children aged 3–7 years undergoing corrective osteotomy. The results showed that administering fentanyl before the skin incision did not result in a statistically significant reduction in pain scores or a decrease in the need for additional analgesia postoperatively. This outcome may be attributed to specific demographic factors or differences in drug response within the pediatric population.
Uribe et al.33 examined the effect of preemptive intravenous ibuprofen (administered as two 800 mg doses) versus a single 30 mg dose of IV ketorolac in patients undergoing knee arthroscopy. Their findings indicated that in the first 90 min after surgery, patients receiving ibuprofen experienced a significant reduction in pain scores compared to those receiving ketorolac. However, from 120 min to 24 h postoperatively, no significant differences were observed between the two groups. This suggests that the rapid onset of ibuprofen may offer advantages in early pain control, although the long-term effects appear similar.
The primary focus of this review was on orthopedic surgeries, Nevertheless, existing evidence from other studies suggests that preemptive analgesia in other surgeries such as cardiac surgery is also of interest. For example, Hanoura et al.evaluated the effects of preoperative gabapentin and pregabalin on reducing morphine consumption following coronary artery bypass surgery, and their results demonstrated that both drugs effectively decreased postoperative opioid use.34 In addition, Nasr et al. reported that continuous infusion of bupivacaine administered preoperatively led to a reduction in postoperative morphine requirements.35
Overall, the findings from the selected studies in this structured review indicate that preemptive analgesia using various analgesics positively impacts the reduction of postoperative pain intensity and opioid consumption. However, differences in efficacy among the drugs exist, which may be attributed to variations in dosage, timing of administration, type of surgery, and patient population characteristics.
In addition to reducing pain and opioid use, preemptive analgesia may also have practical benefits such as shorter recovery time, earlier mobilization, reduced hospital stay, and lower overall treatment costs. Better pain control is further linked to higher patient satisfaction and improved participation in rehabilitation. While these aspects were not directly assessed in the included studies, they highlight the broader clinical relevance of preemptive analgesia and warrant further investigation.
One of the main limitations of this review is the small number of studies. Additionally, variations in study methodologies and outcome measurements among the selected trials may affect the homogeneity of the results, thus precluding a more robust meta-analysis. Although all included studies were randomized clinical trials, variation in blinding methods, sample sizes, and outcome reporting introduces potential risk of bias, which may influence the strength and generalizability of the conclusions.
6 Conclusion
This review identified five randomized clinical trials published between 2015 and 2020 that examined the use of preemptive analgesia in orthopedic surgeries. Evidence suggests that agents such as intravenous ibuprofen, ketorolac, and dexketoprofen–tramadol combinations may reduce postoperative pain and opioid consumption, while fentanyl showed limited benefits in pediatric settings. However, these findings should be interpreted with caution, as the review was restricted to studies published within a limited time frame and no meta-analysis was conducted due to heterogeneity across populations, interventions, and outcomes. Future studies should incorporate more recent randomized trials, standardized pain outcomes (e.g., VAS/NRS and morphine equivalents), and multimodal preemptive strategies, including combinations of COX-2 inhibitors and gabapentinoids. Prospective meta-analyses may be feasible as the evidence base expands.
Guardian/patient's consent
Not applicable.
Credit author statements
Conceptualization: Soode Pashmakian, Mohammad Hossein Bakhshaei.
Methodology: Mohammad Hossein Bakhshaei, Hossein Mahjub.
Software: Roya Najafi-Vosough.
Validation: Roya Najafi-Vosough.
Formal analysis: Roya Najafi-Vosough, Soode Pashmakian.
Investigation: Soode Pashmakian, Ahmad Moradi, Hossein Mahjub.
Resources: Soode Pashmakian.
Data Curation: Soode Pashmakian, Ahmad Moradi, Hossein Mahjub.
Writing - Original Draft: Arya Haddadi, Soode Pashmakian.
Writing - Review & Editing: Soode Pashmakian, Arya Haddadi, Mohammad Hossein Bakhshaei.
Visualization: Mohammad Hossein Bakhshaei.
Supervision: Mohammad Hossein Bakhshaei.
Project administration: Mohammad Hossein Bakhshaei.
Funding acquisition: Soode Pashmakian.
All Authors confirm that this manuscript represents original work and has not been published or submitted elsewhere. All authors have reviewed and approved the final version of the manuscript, and there are no conflicts of interest to declare. Ethical standards and confidentiality were maintained throughout all stages of the review.
Ethical approval statement
Throughout all stages, from inception to data extraction, ethical principles and confidentiality were maintained, ensuring transparency in the selection and extraction process.
Data availability statement
Not applicable.
Ethical approval statement
Throughout all stages, from inception to data extraction, ethical principles and confidentiality were maintained, ensuring transparency in the selection and extraction process.
Declaration of generative AI and AI-assisted technologies in the writing process
During the preparation of this work the author(s) used [ChatGPT4/Grammarly] in order to help translate the manuscript from Persian to English and improve the language. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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