The Effect of Postoperative Analgesia Induced by Peripheral Nerve Block on Inflammatory Biomarkers in Patients Undergoing Upper Extremity Surgery

Introduction

Anesthetic and analgesic agents, along with surgical stress, play a key role in the etiology of perioperative systemic inflammation. Regional anesthesia can help reduce surgical stress through various immunological and neurohumoral mechanisms. Epidural anesthesia administered concurrently with general anesthesia reduces cortisol and urinary adrenalin levels during abdominal aortic surgery, and performs better than general anesthesia alone1. Similarly, spinal anesthesia suppresses serum cortisol more effectively than general anesthesia2.

Pain is a key component of surgical stress, activating the hypothalamic-pituitary-adrenal axis and elevating serum cortisol levels. Inadequate analgesia increases perioperative systemic inflammation, and leads to sustained sympathetic stimulation in patients with cardiac risk factors, exposing them to postoperative myocardial injury or infarction3. Perioperative inflammation not only causes acute pain but is also associated with such adverse postoperative outcomes as chronic pain, delirium, cardiovascular events and cancer recurrence1,2. Therefore, strategies targeting the reduction of the inflammatory response may have a positive effect on recovery.

Studies have reported an association between the inflammation level and the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV)4.

In the present study, the effects of brachial plexus blocks used for postoperative analgesia on postoperative inflammatory response in patients undergoing upper extremity surgery are evaluated retrospectively based on an assessment of biomarkers.

Materials and Method

After approval for the study was granted by the ethics committee (Sancaktepe BAEK 2025/373), a retrospective review was conducted of the medical records of 67 patients who underwent unilateral upper extremity surgery in the Orthopedics and Traumatology Clinics of R.T Health Sciences University Fatih Sultan Mehmet Training and Research Hospital between November 2024 and June 2025, all of whom received general anesthesia along with a brachial plexus block for analgesia. Included in the study were patients aged 18 years or older who underwent elective forearm surgery, and whose blood count data from within the first 24 hours following surgery was available. All patients received general anesthesia either alone or in combination with ultrasound-guided infraclavicular/supraclavicular peripheral nerve block (PNB). Patients undergoing emergency surgery, those undergoing revision or bilateral surgery, those with a history of hematological, renal or hepatic disorders, those with severe respiratory or cardiac insufficiency, malignancy or coagulopathy, and those with a history of chronic analgesic use, chronic alcohol consumption or substance abuse were excluded from the study.

The patients were divided into two groups: those who received general anesthesia alone (Group G) and general anesthesia combined with brachial plexus block (Group P). Group G included 22 patients and Group P included 45 patients. General anesthesia was induced with intravenous propofol (2–2.5 mg/kg) and fentanyl (1–2 mcg/kg), and maintained with sevoflurane in an oxygen/air mixture. Additional opioids were administered as needed. Brachial plexus blocks (infraclavicular or supraclavicular) were performed under ultrasound guidance using 20 ml of 0.25% bupivacaine local anesthetic. Block success was assessed clinically by sensory loss in the corresponding dermatomes.

Demographic characteristics, American Society of Anesthesiologists (ASA) class, total leukocyte count (TLC), neutrophil count, lymphocyte count, platelet count, and mean platelet volume measured preoperatively and at 24 hours postoperatively were analyzed. Additionally, NLR, PLR, ΔTLC (preoperative TLC−postoperative TLC), ΔNLR (preoperative NLR−postoperative NLR) and ΔPLR (preoperative PLR−postoperative PLR), calculated from the above values, were also evaluated.

Results

A total of 67 patients were included in the study, with 45 in Group P and 22 in Group G. The mean age was slightly higher in Group P than in Group G (50.2 ± 20.5 vs. 41.3 ± 19.4 years, p = 0.092). Both groups had a predominance of male patients, with a comparable gender distribution (p = 0.529). The distribution of ASA scores showed no statistically significant difference between the two groups, although there was a tendency toward higher ASA classes in Group P (p = 0.057) (Table 1).

Table 1. Baseline demographic and clinical characteristics

Values are presented as mean ± standard deviation (SD) and number (percentage). Independent samples t-test was used for continuous variables, and chi-square or Fisher’s exact test for categorical variables.

An analysis of laboratory findings revealed the preoperative and postoperative total leukocyte counts (TLC), neutrophil counts, lymphocyte counts, platelet counts and mean platelet volume (MPV) to be similar between the two groups (all p > 0.05). Similarly, no significant differences were noted in the preoperative or postoperative NLR and PLR values (Table 2).

Table 2. Comparison of preoperative and postoperative hematologic and inflammatory parameters

Values are presented as mean ± standard deviation (SD). Independent samples t-test was used for normally distributed variables, while the Mann–Whitney U test was used for non-normally distributed variables. NLR and PLR values are presented as mean ± SD for consistency but were analyzed using non-parametric tests due to non-normal distribution. TLC, neutrophil, lymphocyte, and platelet counts are expressed as ×10⁹/L, and MPV is expressed in fL. NLR: neutrophil-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio; MPV: mean platelet volume.

The changes in hematologic parameters from pre- to postoperative periods (ΔTLC, ΔNLR, ΔPLR) did not differ significantly between Group P and Group G (p = 0.517, p = 0.674, and p = 0.704, respectively). Overall, none of the evaluated inflammatory markers demonstrated a statistically significant intergroup difference (Table 3).

Table 3. Changes (Δ) in hematologic and inflammatory parameters between preoperative and postoperative periods

Δ: difference between pre- and postoperative values. Values are presented as median (interquartile range). TLC: total leukocyte count; NLR: neutrophil-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio; MPV: mean platelet volume.

Discussion

In the present retrospective study, a smaller increase in inflammatory markers such as NLR, PLR and MPV was noted in patients who received PNB for postoperative pain management following forearm surgery under general anesthesia when compared to those who did not receive PNB, although the differences between the groups were not statistically significant.

Previous studies have reported the frequent use of a variety of inflammatory markers in oncology, rheumatologic disorders and surgical settings5. Biomarkers such as the NLR, PLR, TLC, and MPV can be easily derived from routine complete blood count parameters, and are readily accessible and less expensive than proinflammatory cytokines such as TNF-alpha and IL-6. In a study by Gibson et al., NLR demonstrated high sensitivity but low specificity for detecting stress and inflammatory response6. NLR and PLR reflect the dynamic relationship between adaptive and cellular response in various pathological conditions. In a study of intensive care unit patients with COVID-19 conducted by Regolo et al., NLR was reported to be associated with increased mortality7. Dynamic changes in NLR occur hours before clinical manifestations, and thereby serve as an early warning signal for imminent pathological processes8. Studies have reported that factors such as age, sex, chronic steroid use, and active hematological or malignant conditions can lead to false-positive results in NLR9. The present retrospective study examined the inflammatory biomarkers NLR, PLR, TLC and MPV, which can reflect dynamic changes in inflammatory processes, using data from the pre- and post-operative complete blood counts performed as routine in our hospital. To avoid potential false-positive results, patients with a history of hematological, renal or hepatic disorders, those with severe respiratory or cardiac insufficiency, malignancy or coagulopathy, and those with a history of chronic analgesic use, chronic alcohol consumption or substance abuse were excluded from the study.

Immune response is strongly influenced by patient-related factors, including preoperative health status and the presence of comorbid conditions10. Azab et al. demonstrated significantly higher NLR values in patients with a history of diabetes, cardiovascular disorders or smoking in comparison with patients without such conditions11. The present study identified no differences in ASA class and demographic parameters between the two groups.

The median NLR has been reported as 2.15 in studies establishing normal NLR values in healthy adult populations11. In a study by Duran et al., NLR values greater than 3.0 were associated with pathological conditions such as infections, inflammation, stress and cancer12. In a study by Zahorec et al., NLR values greater than 3.0 or less than 0.7 in adults were classified as pathological8. The median preoperative NLR values in the present study were 6.01 in Group P and 6.79 in Group G, which were well above the normal range, as all patients in the present study had fractures secondary to trauma. In the postoperative period, the median NLR values were numerically higher in the general anesthesia group compared with the PNB group.

Previous studies have established an association between postoperative pain and elevated inflammatory response13. PNB, when used as a part of multimodal analgesia, helps reduce postoperative pain. Erector spinae plane block performed for analgesia in patients undergoing posterior lumbar stabilization surgery has been found to reduce postoperative inflammatory response by decreasing NLR, PLR and opioid consumption14. Tantri et al. demonstrated that the addition of PNB to posterior lumbar decompression and stabilization procedures is associated with lower serum levels of proinflammatory cytokines such as IL-6 and IL-1015. Liu et al. reported that patients who received an ESP block for postoperative analgesia following video-assisted thoracoscopic surgery had significantly lower IL-6, IL-10 and TNF-α levels than those who received no such block16. Bagry et al. studied two groups of patients undergoing knee arthroplasty, one of which received intravenous morphine while the other received continuous PNB. C-reactive protein (CRP) and total leukocyte count were found to be lower in the group that received continuous PNB17. In their study, Köksal et al. examined two patient groups undergoing forearm surgery, one of which received infraclavicular nerve block for anesthesia, while the other received general anesthesia. The authors reported that the use of infraclavicular nerve block as an alternative to general anesthesia was associated with significant reductions in the neutrophil-to-lymphocyte ratio, total leukocyte count, and platelet-to-lymphocyte count18. Due to the retrospective design of the present study, IL-6, CRP and TNF-α level data were not available; however, lower postoperative levels of bioinflammatory markers such as NLR, PLR and MPV were observed in the patients who received PNB in addition to general anesthesia.

In clinical practice, PNBs are frequently used in patients undergoing upper extremity surgery either as the primary mode of anesthesia, or as a component of multimodal analgesia. Brachial plexus blocks used for this purpose may offer such benefits as reduced systemic inflammatory response and opioid consumption, while also helping to prevent the development of chronic pain. In a study assessing metabolic, hormonal and hemodynamic responses in patients undergoing elective surgery, regional anesthesia performed better than general anesthesia in suppressing stress response, and the former was found to be associated with a reduction in systemic cortisol levels19. In another study, regional anesthesia was shown to reduce inflammatory response through various mechanisms, including attenuating the immunosuppressive effect of surgery by inhibiting neuroendocrine stress response, decreasing postoperative opioid requirements and reducing total anesthetic consumption when used in conjunction with general anesthesia20. Due to the retrospective design of the present study and gaps in patient records, no postoperative opioid consumption data were available.

The present study is limited by the lack of an analysis examining correlations between biomarkers such as NLR, PLR, TLC and MPV, and inflammatory markers such as CRP, IL-6 and TNF-α. Another limitation is the lack of long-term data on the effect of the anesthesia technique on immune response, as the patients were not monitored beyond 24 hours following surgery. Finally, the small sample size can be regarded as another limitation. The authors believe that case series involving larger number of patients may yield results with statistically significant differences.

In conclusion, regional anesthesia involving peripheral nerve block administered as part of multimodal analgesia in patients undergoing general anesthesia, particularly when regional anesthesia is not feasible due to surgical or patient-related factors, may be beneficial in reducing postoperative systemic inflammation.