Postoperative Systemic Inflammation Research Articles

The Relationship Between Post-Operative Systemic Inflammation and Early Mortality in Patients With Ruptured Abdominal Aortic Aneurysms

The Relationship Between Post-Operative Systemic Inflammation and Early Mortality in Patients With Ruptured Abdominal Aortic Aneurysms

Mass intraoperative endothelial glycocalyx shedding affects postoperative systemic inflammation response

BacgroundOff-pump coronary artery bypass graft (OPCABG) has a high incidence of postoperative systemic inflammation response syndrome (SIRS), and perioperative endothelial glycocalyx layer (EGL) disruption can be one of the predisposing factors. We hypothesized that EGL shedding happened earlier in OPCABG which can influence on postoperative SIRS, and sevoflurane might preserve EGL better than propofol.MethodsWe randomly allocated 50 patients undergoing OPCABG to receive either sevoflurane-sufentanil or propofol-sufentanil anesthesia. Plasma syndecan-1, heparan sulfate (HS), atrial natriuretic peptide (ANP), IL-6, and cardiac troponin I (cTnI) were measured. Blood samples were collected at 6 timepoints: induction (T1), before grafting (T2), after grafting(T3), surgery done (T4), postoperative day1 (POD1,T5) and POD2 (T6). SIRS criteria and sequential organ failure assessment (SOFA) score were examined.ResultsThere were neither differences of syndecan-1, HS, IL-6 nor of SIRS criteria or SOFA score between the sevoflurane and propofol groups. All patients were pooled as a single group for further statistical analyses, plasma syndecan-1 (P < 0.001) and IL-6 (P < 0.001) increased significantly as a function of time; syndecan-1 increasing correlated significantly with the duration of coronary graft anastomosis (r = 0.329, P = 0.026). Syndecan-1(T3) correlated significantly with ANP(T3) (r = 0.0.354, P = 0.016) and IL-6 (T5) (r = 0.570, P < 0.001). The maximum value of IL-6 correlated significantly with SIRS (r = 0.378, P = 0.010), the maximum value of SOFA score (r = 0.399, P = 0.006) and ICU days (r = 0.306, P = 0.039). The maximum value of SOFA score correlated significantly with the occurrence of SIRS (r = 0.568, P < 0.001) and ICU days (r = 0.338, P = 0.022).ConclusionsOPCABG intraoperative early EGL shedding caused of grafts anastomosis greatly affected postoperative SIRS and SOFA score, sevoflurane did not clinically preserve EGL better.Trial registrationChiCTR-IOR-17012535. Registered on 01/09/2017.

Correlation between postoperative systemic inflammatory response and prognosis in patients with advanced gastric cancer.

411 Background: Several studies have shown that postoperative infectious complications correlate with poor prognosis in various malignancies, but the prognostic significance of the postoperative inflammatory response in patients with gastric cancer remains unclear. The aim of study was to examine whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with advanced gastric cancer. We evaluated C-reactive protein (CRP) and white blood cell (WBC) count as simple and versatile markers of postoperative systemic inflammation in clinical practice that may be suitable for detecting the magnitude of inflammatory reaction. Methods: This study retrospectively reviewed 444 patients who underwent radical gastrectomy for stage II/III gastric cancer. We evaluated maximum serum C-reactive protein (CRPmax) and white blood cell count (WBCmax), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers. Results: In univariate analyses, CRPmax, WBCmax and infectious complications were significantly associated with both overall survival (OS) (p&lt;0.001, p&lt;0.001 and p=0.011, respectively) and relapse-free survival (RFS) (p&lt;0.001, p=0.001 and p&lt;0.001, respectively). Multivariate analysis revealed that high CRPmax (&gt;9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.18–2.42, p=0.004) and RFS (HR 1.42, 95%CI 1.02–1.98, p=0.038), while WBCmax and infectious complications were not. Regarding the pattern of recurrence, hematogenous recurrence was significantly more frequent in the high-CRPmax group (16.7%) than in the low-CRPmax group (3.8%, p&lt;0.001). Conclusions: CRPmax, which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection.

Periodontitis and postoperative inflammation in gastric cancer patients: Propensity score analysis.

The objective of this study was to clarify the association between preoperative periodontitis and postoperative systemic inflammation in patients with gastric cancer. This retrospective cohort study analyzed data from 140 gastric cancer patients who underwent surgery at Hiroshima University Hospital between May 2019 and May 2022. Periodontal inflamed surface area (PISA) scores were determined to assess periodontitis severity using modified Nesse's methods. Propensity score matching was used to compare patients with high and low PISA scores (> or < the median PISA score of 92.4, respectively). Propensity scores were calculated using a logistic regression model, based on 17 clinical parameters: age, sex, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, cardiovascular disease, stroke, clinical stage, surgical procedure, surgical approach, neoadjuvant chemotherapy, surgery duration, blood loss during surgery, remaining teeth, and denture use. Thirty-seven patients were propensity-score-matched. Participants with high PISA scores had a higher incidence of surgical site infection (10.5%) than those with low PISA scores (5.3%). Moreover, participants with high PISA scores had significantly higher C-reactive protein levels on postoperative days 1 than those with low PISA scores. Preoperative periodontitis may determine the level of postoperative systemic inflammation in patients with gastric cancer.

Postoperative systemic inflammation after major abdominal surgery: patient-centred outcomes.

Postoperative systemic inflammation is strongly associated with surgical outcomes, but its relationship with patient-centred outcomes is largely unknown. Detection of excessive inflammation and patient and surgical factors associated with adverse patient-centred outcomes should inform preventative treatment options to be evaluated in clinical trials and current clinical care. This retrospective cohort study analysed prospectively collected data from 3000 high-risk, elective, major abdominal surgery patients in the restrictive vs. liberal fluid therapy for major abdominal surgery (RELIEF) trial from 47 centres in seven countries from May 2013 to September 2016. The co-primary endpoints were persistent disability or death up to 90 days after surgery, and quality of recovery using a 15-item quality of recovery score at days 3 and 30. Secondary endpoints included: 90-day and 1-year all-cause mortality; septic complications; acute kidney injury; unplanned admission to intensive care/high dependency unit; and total intensive care unit and hospital stays. Patients were assigned into quartiles of maximum postoperative C-reactive protein concentration up to day 3, after multiple imputations of missing values. The lowest (reference) group, quartile 1, C-reactive protein ≤ 85 mg.l-1 , was compared with three inflammation groups: quartile 2 > 85 mg.l-1 to 140 mg.l-1 ; quartile 3> 140 mg.l-1 to 200 mg.l-1 ; and quartile 4> 200 mg.l-1 to 587 mg.l-1 . Greater postoperative systemic inflammation had a higher adjusted risk ratio (95%CI) of persistent disability or death up to 90 days after surgery, quartile 4 vs. quartile 1 being 1.76 (1.31-2.36), p < 0.001. Increased inflammation was associated with increasing decline in risk-adjusted estimated medians (95%CI) for quality of recovery, the quartile 4 to quartile 1 difference being -14.4 (-17.38 to -10.71), p < 0.001 on day 3, and -5.94 (-8.92 to -2.95), p < 0.001 on day 30. Marked postoperative systemic inflammation was associated with increased risk of complications, poor quality of recovery and persistent disability or death up to 90 days after surgery.

The change of systemic inflammation response index in the treatment of patients with myasthenia gravis undergoing thymectomy: A retrospective, follow-up study

Background: This study aims to investigate the role of neutrophil-tolymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and systemic inflammation response index in patients with myasthenia gravis, thymomas and thymic hyperplasia and to identify the relationship between the inflammation response and disease activity. Methods: Between January 2010 and December 2018, a total of 97 patients (71 males, 26 females; mean age: 36.7±16.3 years; range, 15 to 76 years) who underwent extended thymectomy with the diagnosis of myasthenia gravis were retrospectively analyzed. The patients were divided into two groups as the patient group (n=42) and the control group (n=55). Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyteto-lymphocyte ratio, and systemic inflammation response index were measured one day prior to and one month after surgery. Results: The patients with thymoma were older with a higher mean pre-systemic inflammation response index value. Preoperative systemic inflammation response index, neutrophil-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio were significantly higher in patients with thymoma. A preoperative systemic inflammation response index value of less than 0.62 was accepted to indicate thymic hyperplasia and a postoperative systemic inflammation response index value higher than 2.94 was indicative of thymoma. In myasthenic patients whose steroid dose was increased and/or remained the same at the first month after surgery, postoperative monocyte-to-lymphocyte ratio and systemic inflammation response index values were found to be higher compared to preoperative values (p=0.006 and p=0.032, respectively). Patients whose pyridostigmine dose was increased and/or remained the same had significantly higher systemic inflammation response index values postoperatively (p=0.029). Conclusion: The precise cut-off values of systemic inflammation response index may be helpful for the surgeon to predict the surgical outcome and post-systemic inflammation response index may be a predictive marker for estimating postoperative treatment changes.

A randomized, double-blind pilot study of analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen following dental implant placement surgery.

Introduction: Post-surgical pain following dental implant placement surgery is typically managed with non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. However, the comparative analgesic efficacy of over-the-counter doses of non-steroidal anti-inflammatory drugs and acetaminophen in implant patients is unknown. Therefore, we compared the analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen after surgical placement of one or two dental implants. Methods: Adult patients were treated with naproxen sodium (440mg loading dose +220mg q8h, n = 15) or acetaminophen (1,000mg q6h-max daily dose 3,000mg, n = 15) for 3days after implant placement in a randomized, double-blind design. Pain was assessed on a 0-10 scale every 20min for 6h after study medication treatment. Tramadol (50mg) was available as a rescue medication. Plasma and gingival crevicular fluid (GCF) were collected prior to the surgery and 0, 1, 2, 4, 6, 24, and 72h after surgery for quantification of interleukin (IL)-6, IL-8, and IL-1β levels. Results: Pain scores were significantly lower in patients treated with naproxen sodium compared to those treated with acetaminophen. Inflammatory mediator levels in plasma and gingival crevicular fluid increased after surgery and returned to near baseline levels by 72h. Plasma IL-6 levels were significantly lower 6h after surgery in patients treated with naproxen sodium compared to acetaminophen. No differences in inflammatory mediator concentrations in gingival crevicular fluid were observed between the treatment groups. The number of implants placed and body mass index (BMI) influenced inflammatory mediator concentrations in plasma and gingival crevicular fluid, respectively. Discussion: Naproxen sodium was more effective than acetaminophen in reducing post-operative pain and systemic inflammation following surgical placement of one or two dental implants. Further studies are needed to determine whether these findings are applicable to more complex implant cases and how they affect clinical outcomes following implant placement. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04694300.

Postoperative inflammatory markers predict survival in patients after McKeown esophagectomy for esophageal cancer.

Preoperative C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) are correlated with a poor prognosis of various cancers. The significance of postoperative systemic inflammation markers for prognostic stratification of patients with esophageal cancer (EC) has not been established. Therefore, this study aimed to elucidate the impact of postoperative CAR and NLR on survival in patients with EC for prognostic stratification. A total of 235 patients who received curative esophagectomy were analyzed. A Cox proportional hazard model was performed to detect prognostic factors. Multivariate analysis revealed that postoperative CAR ≥ 0.05 (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.01-2.57) and NLR ≥ 3.0 (HR, 2.81; 95% CI, 1.79-4.40) were independent prognostic factors for overall survival. Meanwhile, postoperative CAR ≥ 0.05 (HR, 1.61; 95% CI, 1.07-2.41) and NLR ≥ 3.0 (HR, 1.92; 95% CI, 1.29-2.85) were also significant prognostic factors for relapse-free survival. In addition, the patient group with postoperative CAR ≥ 0.05 and NLR ≥ 3.0 had the worst survival. Postoperative CAR ≥ 0.05 and NLR ≥ 3.0 can predict the poor survival of patients who received curative esophagectomy for EC.

Presepsin as a promising biomarker for early detection of post-operative infection in children.

Post-operative systemic inflammation response syndrome (SIRS) is an event that results from surgical trauma, white blood cells contact activation, and intra-surgical bacterial translocation, which is difficult to distinguish from sepsis. Presepsin is a novel biomarker that is increased since the early stages of bacterial infection and can be used to confirm the diagnosis of post-operative infectious complications. This study aimed to investigate the diagnostic performance of presepsin for post-operative infectious complications compared to other well-known biomarkers. This cross-sectional study included 100 post-operative patients admitted to Cipto Mangunkusumo National Hospital and Bunda Hospital in Jakarta, Indonesia. The objective was to identify the optimal cutoff and trend of plasma presepsin concentration on the first and third day after surgery and to compare them with other biomarkers. Plasma presepsin level was higher in the infection group compared to the non-infection group (median 806.5 pg/ml vs. 717 pg/ml and 980 pg/ml vs. 516 pg/ml on the first and third day, respectively). Presepsin levels tended to increase on the third post-operative day (median + 252 pg/ml) in children with infection. The opposite trend was observed in the non-infection group from the first to the third day (median -222.5 pg/ml). Presepsin delta, a three-day difference between the first and third post-operative day, had the best diagnostic performance compared to other biomarkers (Area Under the Curve 0.825). The optimal cutoff for presepsin delta to diagnose post-operative infection was +90.5 pg/ml. Serial assessments of presepsin levels on the first and third days post-surgery and their trends are helpful diagnostic markers for clinicians to detect post-operative infectious complications in children.

Prognostic Value of the Systemic Immune Inflammation Index after Thoracic Endovascular Aortic Repair in Patients with Type B Aortic Dissection.

The study aimed at investigating the association between postoperative inflammatory scores and aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) for patients with type B aortic dissection (TBAD). This single-centre, retrospective cohort included all patients who underwent TEVAR for TBAD between November 2016 and November 2020 at a university hospital. The risk factors for AAEs were analyzed by Cox proportional hazards model regression. Prediction accuracy was assessed using the area under the receiver operating characteristic curves. This study included 186 patients with a mean age of 58.5 years and a median follow-up period of 26 months. A total of 68 patients developed AAEs. Age and postoperative systemic immune inflammation index (SII) (>2893) were associated with post-TEVAR AAEs (hazard ratio (HR) 1.03, p = 0.003; HR 1.88, p = 0.043, respectively). Increased postoperative SII and age are independent risk factors for AAE post-TEVAR in patients with TBAD.

Retroperitoneal Compared to Transperitoneal Approach for Open Abdominal Aortic Aneurysm Repair Is Associated with Reduced Systemic Inflammation and Postoperative Morbidity.

In the United Kingdom, the most common surgical approach for repair of open abdominal aortic aneurysms (AAAs) is transperitoneal (TP). However, retroperitoneal (RP) approach is favored in those with more complex vascular anatomy often requiring a cross-clamp on the aorta superior to the renal arteries. This study compared these approaches in patients matched on all major demographic, comorbid, anatomic, and physiological variables. Fifty-seven patients (TP: n = 24; RP: n = 33) unsuitable for endovascular aneurysm repair underwent preoperative cardiopulmonary exercise testing prior to open AAA repair. The surgical approach undertaken was dictated by individual surgeon preference. Postoperative mortality, complications, and length of hospital stay (LoS) were recorded. Patients were further stratified according to infrarenal (IR) or suprarenal/supraceliac (SR/SC) surgical clamping. Systemic inflammation (C-reactive protein) and renal function (serum creatinine and estimated glomerular filtration rate) were recorded. Twenty-three (96%) of TP patients only required an IR clamp compared with 12 (36%) in the RP group. Postoperative systemic inflammation was lower in RP patients (p = 0.002 vs. TP) and fewer reported pulmonary/gastrointestinal complications whereas renal impairment was more marked in those receiving SR/SC clamps (p < 0.001 vs. IR clamp). RP patients were defined by lower LoS (p = 0.001), while mid-/long-term mortality was low/comparable with TP, resulting in considerable cost savings. Despite the demands of more complicated vascular anatomy, the clinical and economic benefits highlighted by these findings justify the more routine adoption of the RP approach for complex AAA repair.

Postoperative cognitive dysfunction: time for enhanced recovery after surgery programmes.

Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent complications in elderly patients undergoing cardiac and noncardiac surgery.1 They have been associated with delayed recovery, decreased quality of life, persistent neurocognitive disorders and increased morbidity and mortality within the first year of surgery. The concern that anaesthetic and sedative agents may be implicated in the pathogenesis of POD has prompted multiple studies. Regional anaesthesia, avoiding the use of sedative–hypnotic anaesthetics, rather than general anaesthesia, has thus long been held up as one strategy to prevent postoperative cognitive dysfunction. However, two recent large, randomised studies (the REGAIN and RAGA trials) comparing regional and general anaesthesia in elderly patients undergoing hip fracture surgery reported no significant difference between groups in the percentage of patients with POCD.2,3 In their accompanying editorial, Avidan et al.4 concluded that surgery with general anaesthesia was not implicated in persistent neurocognitive disorders at a population level. Even so, there might still be individuals or patient subgroups with specific vulnerabilities to POD5 including some older surgical patients with mild cognitive impairment (MCI), characterised by subclinical or unnoticed cognitive decline often missed by most of the tests, and where POD and early POCD can reflect a cognitive trajectory towards a clinically apparent cognitive decline.5 Important risk factors for postoperative neurocognitive disorders include pre-operative general and cognitive health, and medical comorbidities.5 Prevention of POD and POCD should, therefore, focus on improvement of pre-operative fitness, optimisation of pre-operative comorbidities and mitigating physiological and biochemical disturbances secondary to surgical stress and inflammatory reactions to avert organ dysfunction and peri-operative stroke.5 Measures to reach these goals should be part of good clinical practice in all patients but they have only been scantily tested specifically to prevent POCD. Neuroinflammation secondary to surgery is also considered a major contributor to the development of POCD,6 and ageing, atherosclerosis and neurodegenerative diseases may lead to an increased systemic and cerebral inflammatory response to surgery. Also, postoperative complications, such as infection, pulmonary complications and hypoxaemia may aggravate the postoperative inflammatory reaction. Several drugs with anti-inflammatory properties (steroids, NSAIDs, intravenous lidocaine, ketamine and dexmedetomidine) have been used to mitigate postoperative systemic inflammation and subsequent neuro-inflammation but without definitive conclusions.1,6 Enhanced recovery after surgery (ERAS) programmes, as those recommended by the ERAS Society (www.erassociety.org) and GRACE (www.grace-asso.fr), form a multidisciplinary, multimodal approach designed to control surgical stress response including inflammatory reaction in order to hasten postoperative recovery and decrease postoperative complications.7,8 Their efficiency has been widely demonstrated in all surgical specialties. Interestingly, several studies using ERAS programmes for colorectal surgery 9,10 and orthopaedic surgery 11,12 reported a significant reduction in the incidence of POD and POCD. These observations are unsurprising as these programmes combine several measures recommended by the European Society of Anaesthesiology and Intensive Care to prevent POD in elderly patients13 by shortening pre-operative fasting, avoidance of premedication, multimodal opioid-sparing analgesia, avoidance of unnecessary indwelling catheters, early mobilisation, early nutrition and discharge to home environment. All these measures are likely to facilitate return to normal circadian rhythm, hasten the recovery of patients’ usual behaviour in hospital and after discharge and improve patient orientation.13 Recommending ERAS programmes to prevent POD, therefore, appears justified especially as elderly patients, at a higher risk of POD and POCD, benefit much from these programmes.14 Likewise, the POSE-study highlights the importance of a comprehensive peri-interventional and patient-centred management for older patients.15 Disappointingly, the literature abounds with examples of large RCTs with short-term interventions for POD/POCD but without information or incorporation of enhanced recovery programmes.1,2,16,17 In summary, future studies on the prevention of POD should, therefore, focus less on hypothetical short-term interventions unless fully implemented ERAS programmes have been instituted, based on the pathophysiological background 7,8 and positive preliminary observations.9–12

Right colectomy from open to robotic — a single-center experience with functional outcomes in a learning-curve setting

PurposeRight colectomy (RC) is a frequently performed procedure. Beneath standard conventional open surgery (COS), various minimally invasive techniques had been introduced. Several advantages had recently been described for robotic approaches over COS or conventional laparoscopy. Nevertheless, novel minimally invasive techniques require continuous benchmarking against standard COS to gain maximum patient safety. Bowel dysfunction is a frequent problem after RC. Together with general complication rates postoperative bowel recovery are used as surrogate parameters for postoperative patient outcome in this study.MethodsRetrospective, 10-year single-center analysis of consecutive patients who underwent sequentially either COS (n = 22), robotic-assisted (ECA: n = 39), or total robotic surgery (ICA: n = 56) for oncologic RC was performed.ResultsThe conversion from robotic to open surgery rate was low (overall: 3.2%). Slightly longer duration of surgery had been observed during the early phase after introduction of the robotic program to RC (ECA versus COS, p = 0.044), but not anymore thereafter (versus ICA). No differences were observed in oncologic parameters including rates of tumor-negative margins, lymph node-positive patients, and lymph node yield during mesocolic excision. Both robotic approaches are beneficial regarding postoperative complication rates, especially wound infections, and shorter length of in-hospital stay compared with COS. The duration until first postoperative stool is the shortest after ICA (COS: 4 [2–8] days, ECA: 3 [1–6] days, ICA: 3 [1–5] days, p = 0.0004). Regression analyses reveal neither a longer duration of surgery nor the extent of mesocolic excision, but the degree of minimally invasiveness and postoperative systemic inflammation contribute to postoperative bowel dysfunction, which prolongs postoperative in-hospital stay significantly.ConclusionThe current study reflects the institutional learning curve of oncologic RC during implementation of robotic surgery from robotic-assisted to total robotic approach without compromises in oncologic results and patient safety. However, the total robotic approach is beneficial regarding postoperative bowel recovery and general patient outcome.

Extra Loading Dose of Dexmedetomidine Enhances Intestinal Function Recovery After Colorectal Resection: A Retrospective Cohort Study

Importance: Postoperative gastrointestinal dysfunction (POGD) may be caused by postoperative vagus nerve tension inhibition and systemic inflammation. Dexmedetomidine (Dex) increases vagus nerve tone and affords an anti-inflammatory property, which may play a role in pathogenesis. Objective: To investigate whether a higher dose of Dex enhances gastrointestinal function recovery. Design: In this retrospective study, patients receiving colorectal surgery at the First Affiliated Hospital of Xi’an Jiaotong University from 2017 to 2019 were included. We evaluated the postoperative flatus time between recipients who received loading plus maintenance dose of DEX (LMD group, 237 recipients) and those who recieved maintenance dose of DEX (MD group, 302 recipients). Data were analyzed by logical regression and stratified and interaction analyses. The simulated pharmacokinetics of two DEX regimens was compared using the Tivatrainer software. Thirty paired blood samples from patients whose propensity scores matched with POGD-related factors at 24 h postoperatively were randomly selected, and their tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), d-lactate (DLA), acetylcholine (Ach), interleukin (IL)-10, lipopolysaccharide (LPS), IL-6, and inducible nitric oxide synthase (iNOS) levels were measured. Setting: Operating rooms and general surgery wards. Participants: Among the 644 patients undergoing colorectal surgery, 12 who had a colostomy, 26 without Dex infusion, 20 whose Dex administration mode cannot be classified, and 47 with a history of intestinal surgery were excluded. A total of 539 patients were included. Result: Compared with the MD group, the LMD group had a shorter recovery time to flatus; lower incidences of nausea, vomiting, abdominal distension, and abdominal pain (p < 0.05); and a slightly decreased heart rate. The LMD group was the independent factor of POGD (OR = 0.59, 95% CI = 0.41–0.87, p = 0.007) without being reversed in stratified and interaction analyses and had higher Dex plasma concentration from skin incision to 8 h postoperatively. The LMD group had a 39% and 43% increase in Ach and IL-10 levels, respectively, and a 33%–77% decrease in TNF-α, IL-6, COX-2, iNOS, LPS, and DLA levels (p < 0.05). Conclusion: Adding an extra loading dose of Dex can increase parasympathetic tone and decrease inflammation; hence, it can enhance postoperative gastrointestinal function recovery following colorectal surgery.

Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty

BackgroundDysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery.MethodsMale Sprague–Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery.ResultsHaemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1β, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68+ cells) and markers of fibrosis (α-SMA, TGF-β) were also lower in capsular tissue of ALM-treated knees at day 28.ConclusionData suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.

The effect of dexmedetomidine premedication on postoperative systemic inflammatory response in children undergoing hernia repair surgery: A randomized controlled trial.

BackgroundSurgery results in systemic inflammation, which can affect the central nervous system, leading to changes in mood, emotion, and behavior. Our previous study has shown that compared to midazolam, dexmedetomidine premedication effectively decreased children's postoperative anxiety.AimTo investigate whether dexmedetomidine infusion before hernia repair alleviates postoperative systemic inflammation in children and whether postoperative anxiety may be associated with postoperative inflammation.MethodsThis prospective double‐blind randomized controlled trial was conducted in 120 children scheduled to undergo elective hernia repair. Before anesthesia induction, all children received an intravenous infusion consisted of dexmedetomidine (n = 40; 0.5 µg/g, group D), midazolam (n = 40; 0.08 mg/kg, group M), or normal saline (n = 40; group C). One‐way ANOVA with least significant difference multiple comparison test was used for multigroup comparisons of postoperative plasma levels of inflammatory cytokines and m‐YPAS scores. Spearman rank correlation tests were used for analyzing m‐YPAS scores with postoperative plasma levels of inflammatory cytokines.ResultsPlasma levels of tumor necrosis factor‐alpha (7.0 ± 1.6 vs. 8.1 ± 1.6, mean difference [95% CI]: 1.19 [0.26–2.11], p = .008) (pg/ml) and of interleukin‐6 (1.8 ± 1.2 vs. 3.3 ± 1.6, mean difference [95% CI]: 1.49 [0.74–2.25], p < .001) (pg/ml) and neutrophils‐to‐lymphocyte ratio (1.0 ± 0.5 vs. 1.5 ± 0.7, mean difference [95% CI]: 0.48 [0.17–0.78], p < .001) were significantly lower in group D than in group C. Furthermore, compared to group M, group D showed significantly lower plasma tumor necrosis factor‐alpha levels (7.0 ± 1.6 vs. 7.9 ± 1.9, mean difference [95% CI]: 0.96 [0.04–1.88], p = .04) (pg/ml) and interleukin‐6 levels (1.8 ± 1.2 vs. 2.9 ± 1.5, mean difference [95% CI]: 1.06 [0.31–1.81], p = .004) (pg/ml), and neutrophil‐to‐lymphocyte ratio (1.0 ± 0.5 vs. 1.5 ± 0.6, mean difference [95% CI]: 0.42 [0.11–0.72], p = .004). Anxiety scores at postoperative 2 and 4 h in the three groups positively correlated with plasma levels of proinflammatory cytokines.ConclusionA single preoperative intravenous dexmedetomidine dose in children undergoing same‐day surgery reduces postoperative systemic inflammation.

ANALGESIC EFFECT OF TRAMADOL IS NOT ALTERED BY POSTOPERATIVE SYSTEMIC INFLAMMATION AFTER MAJOR ABDOMINAL SURGERY.

SUMMARYTramadol is a commonly used analgesic in intensive care units (ICUs) for acute postoperative pain. Conversion of tramadol into active metabolites may be impaired in inflammatory states. Catechol-O-methyltransferase may influence pain. The aim of the study was to examine differences in the analgesic effect of tramadol between ICU patients with and without signs of systemic inflammation. Forty-three patients were admitted to ICU after a major abdominal surgery. The patients received a dose of 100 mg of tramadol intravenously every 6 hours during the first 24 hours after surgical procedure. Pain scores were measured by the Numeric Rating Scale before and 30 minutes after tramadol administration in awake patients. Systemic inflammation was considered when at least two of the following postoperative parameters were present in the first 24 hours of ICU admission: fever or hypothermia, tachycardia, pCO2 <4.3 kPa, white blood cells >12000/mm3 or <4000/mm3, or preoperative value of C-reactive protein (CRP) >50 mg/L or/and procalcitonin (PCT) >0.5 mg/L. Catechol-O-methyltransferase was analyzed postoperatively. Fifteen (34.8%) patients met the criteria for systemic inflammation. Tramadol was proven to be an effective analgesic for the treatment of postoperative pain regardless of the presence of systemic inflammation (p<0.05). Lower perception of pain before tramadol application was observed in patients with systemic inflammation, but the difference was not significant. A negative correlation was observed between the preoperative values of CRP and PCT and the analgesic effect of tramadol assessed at the second measurement point (r=-0.358, p=0.03, and r=-0.364, p=0.02, respectively). Catechol-O-methyltransferase variants were not in correlation with pain and opioid consumption. Based on our findings, tramadol is effective in lowering pain scores after major abdominal surgery irrespective of the presence of systemic inflammation.

Who Is Afraid of CRP? Elevated Preoperative CRP Levels Might Attenuate the Increase in Inflammatory Parameters in Response to Lung Cancer Surgery.

During surgery, ATP from damaged cells induces the release of interleukin-1β, a potent pro-inflammatory cytokine that contributes to the development of postoperative systemic inflammation, sepsis and multi-organ damage. We recently demonstrated that C-reactive protein (CRP) inhibits the ATP-induced release of monocytic interleukin-1β, although high CRP levels are deemed to be a poor prognostic marker. Here, we retrospectively investigated if preoperative CRP levels correlate with postoperative CRP, leukocyte counts and fever in the context of anatomical lung resection and systematic lymph node dissection as first line lung cancer therapy. No correlation was found in the overall results. In men, however, preoperative CRP and leukocyte counts positively correlated on postoperative days one to two, and a negative correlation of CRP and fever was seen in women. These correlations were more pronounced in men taking statins and in statin-naïve women. Accordingly, the inhibitory effect of CRP on the ATP-induced interleukin-1β release was blunted in monocytes from coronary heart disease patients treated with atorvastatin compared to monocytes obtained before medication. Hence, the common notion that elevated CRP levels predict more severe postoperative inflammation should be questioned. We rather hypothesize that in women and statin-naïve patients, high CRP levels attenuate trauma-induced increases in inflammatory markers.

Differences in the prognostic impact of post-operative systemic inflammation and infection in colorectal cancer patients: Using white blood cell counts and procalcitonin levels

BackgroundSystemic inflammatory responses cause poor prognosis in cancer patients. However, post-operative systemic inflammatory response may occur owing to post-operative infection as well as cancer-related inflammation. This study aimed to identify the prognostic impact of cancer-related inflammation and infection for colorectal cancer. MethodsPatients who underwent curative surgery for colorectal cancer between January 2011 and March 2015 were enrolled. Procalcitonin (PCT) levels were measured on the fourth post-operative day; white blood cell (WBC) counts were measured daily until the fourth post-operative day. Patients were divided into groups according to the number of post-operative days required for the leukocyte count to decrease to <10,000/mm3 and PCT levels (0.5 ng/ml) as follows: group I, 0–3 days; group II, ≥4 days and high PCT; group III, ≥4 days and normal PCT. ResultsTotally, 248 patients were identified. A prolonged WBC normalization period was associated with poor disease-free survival (DFS). TNM stage III and IV and group III (hazard ratio [HR] 2.480, 95% confidence interval [CI] 1.137–5.410) were independently associated with poor DFS. In contrast, DFS was not significantly affected in group II. High PCT levels were significantly associated with post-operative infectious complications (odds ratio 10.579, 95% CI 4.182–26.764). Although infectious complication had no prognostic significance for DFS, it was an independently poor prognostic factor for overall survival (HR 3.728; 95% CI 1.291–10.766). ConclusionsThe increased post-operative systemic inflammatory response was associated with poor prognosis of colorectal cancer. Otherwise, post-operative infection affected overall mortality but was not associated with disease progression.

Postoperative C-reactive protein/albumin ratio is a biomarker of risk of recurrence and need for adjuvant chemotherapy for stage III colorectal cancer.

Adjuvant chemotherapy is generally recommended for patients with stage III colorectal cancer. Even with adjuvant chemotherapy, 20-30% of such patients develop recurrences; the risk factors for recurrence are currently unclear. The preoperative systemic inflammation index has been linked to poor prognoses in patients with colorectal cancer; however, the relationship between postoperative systemic inflammation index and recurrence is unclear. We aimed to evaluate the association between preoperative and postoperative systemic inflammation indexes and recurrence in patients with stage III colorectal cancer. The following laboratory data of 133 patients with stage III colorectal cancer were analyzed: preoperative and postoperative C-reactive protein/albumin ratios (CAR); neutrophil to lymphocyte ratios (NLR); and platelet to lymphocyte ratios (PLR) and their relationships with recurrence analyzed. The optimal cutoff values for systemic inflammation indexes were determined by examining receiver operating characteristic curves. Multivariate analyses indicated that N-stage, postoperative complications, preoperative NLR, and postoperative CAR were independent predictors of recurrence-free survival (RFS). Postoperative CAR was also an independent predictor of overall survival (OS). Patients with postoperative CAR ≥ 0.035 who did not receive adjuvant chemotherapy had shorter RFS and OS than those who did. There were no significant differences in RFS and OS between patients with postoperative CAR < 0.035 who did and did not receive adjuvant chemotherapy. Postoperative CAR is strongly associated with poor prognosis in patients with stage III colorectal cancer and is a useful biomarker for determining whether adjuvant chemotherapy should be administered.