Effect of anterior quadratus lumborum block with ropivacaine on the immune response after laparoscopic surgery in colon cancer: a substudy of a randomized clinical trial.

BACKGROUND: Surgery induces a temporal change in the immune system, which might be modified by regional anesthesia. Applying a bilateral preoperative anterior quadratus lumborum block has proven to be a safe and effective technique in pain management after abdominal and retroperitoneal surgery, but the effect on the immune response is not thoroughly investigated. METHODS: This study is a substudy of a randomized, controlled, double-blinded trial of patients undergoing laparoscopic hemicolectomy due to colon cancer. Twenty-two patients were randomized to undergo either a bilateral anterior quadratus lumborum nerve block with a total of 60 mL ropivacaine 0.375% or placebo with corresponding isotonic saline injections. The main objective of this exploratory substudy was to investigate the systemic immune response in the first postoperative day by examining changes in blood transcript levels (n=750) and stimulated secretion of cytokines (n=17) on ex vivo activation with microbial ligands and anti-CD3/CD28. RESULTS: Using unsupervised data analysis tools, we observed no effect of the bilateral anterior quadratus lumborum nerve block on gene expression in immune cells (permutational multivariate analysis of variance using distance matrices: F=0.52, p=0.96), abundances of major immune cell populations (Wilcoxon rank-sum test: p>0.05), and stimulated cytokine secretion (Wilcoxon rank-sum test: p>0.05). CONCLUSIONS: Our study provides evidence that administration of bilateral anterior quadratus lumborum nerve block as a part of a multimodal analgesic regimen in an enhanced recovery after surgery for laparoscopic hemicolectomy in this cohort does not alter the systemic immune response.Trial registration number NCT03570541.

Myocardial injury after non-cardiac surgery and per operative fibrin metabolism in patients undergoing hip-fracture surgery: an observational study.

Myocardial injury after non-cardiac surgery (MINS) is associated with a 2-3-fold increased risk of subsequent major cardiovascular events and postoperative mortality. The pathological mechanism behind MINS is not fully uncovered. We hypothesized that patients with MINS following hip fracture surgery would have an altered haemostatic balance pre- and postoperative compared with patients without MINS. This was investigated in a prospective single-centre observational study including patients consecutively. The outcomes were changes in thrombin generation, fibrinogen/fibrin turnover, tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrin structure measurements in patients developing MINS and patients who did not. Outcomes were measured preoperatively and two hours postoperatively. Seventy-two patients were included whereof 26 (36%) patients developed MINS. D-dimer delta values were significantly higher in patients developing MINS than in patients who did not (p = 0.01). After adjusting for age, sex, smoking, alcohol abuse, atrial fibrillation, anticoagulant medication preoperative CRP, preoperative creatinine and duration of surgery, the association remained significant (p = 0.04). There were no significant changes in thrombin generation, in markers of fibrinogen/fibrin turnover besides D-dimer, or in fibrin structure measurements pre- and postoperatively between patients with and without MINS. As such, a relationship between the coagulative and fibrinolytic activity and MINS cannot be ruled out in patients with MINS after hip fracture surgery. Registration: The study was an observational sub-study to a multicentre randomised clinical trial registered at ClinicalTrials.gov (NCT02344797).

Effect of Remote Ischaemic Preconditioning on Perioperative Endothelial Dysfunction in Non-Cardiac Surgery: A Randomised Clinical Trial.

Endothelial dysfunction result from inflammation and excessive production of reactive oxygen species as part of the surgical stress response. Remote ischemic preconditioning (RIPC) potentially exerts anti-oxidative and anti-inflammatory properties, which might stabilise the endothelial function after non-cardiac surgery. This was a single centre randomised clinical trial including 60 patients undergoing sub-acute laparoscopic cholecystectomy due to acute cholecystitis. Patients were randomised to RIPC or control. The RIPC procedure consisted of four cycles of five minutes of ischaemia and reperfusion of one upper extremity. Endothelial function was assessed as the reactive hyperaemia index (RHI) and circulating biomarkers of nitric oxide (NO) bioavailability (L-arginine, asymmetric dimethylarginine (ADMA), L-arginine/ADMA ratio, tetra- and dihydrobiopterin (BH4 and BH2), and total plasma biopterin) preoperative, 2-4 h after surgery and 24 h after surgery. RHI did not differ between the groups (p = 0.07). Neither did levels of circulating biomarkers of NO bioavailability change in response to RIPC. L-arginine and L-arginine/ADMA ratio was suppressed preoperatively and increased 24 h after surgery (p < 0.001). The BH4/BH2-ratio had a high preoperative level, decreased 2-4 h after surgery and remained low 24 h after surgery (p = 0.01). RIPC did not influence endothelial function or markers of NO bioavailability until 24 h after sub-acute laparoscopic cholecystectomy. In response to surgery, markers of NO bioavailability increased, and oxidative stress decreased. These findings support that a minimally invasive removal of the inflamed gallbladder countereffects reduced markers of NO bioavailability and increased oxidative stress caused by acute cholecystitis.

Effect of remote ischemic preconditioning on fibrin formation and metabolism in patients undergoing hip fracture surgery: a randomized clinical trial.

Remote ischemic preconditioning (RIPC) prior to surgery has recently been shown to reduce the risk of myocardial injury and myocardial infarction after hip fracture surgery. This study investigated whether RIPC initiated antithrombotic mechanisms in patients undergoing hip fracture surgery. This trial was a predefined sub-study of a multicentre randomized clinical trial. Adult patients with cardiovascular risk factors undergoing hip fracture surgery between September 2015 and September 2017 were randomized 1 : 1 to RIPC or control. RIPC was initiated before surgery with a tourniquet applied to the upper arm and it consisted of four cycles of 5 min of forearm ischemia followed by five minutes of reperfusion. The outcomes such as surgery-induced changes in thrombin generation, fibrinogen/fibrin turnover, tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrin structure measurements were determined preoperatively (prior to RIPC) and 2 h postoperatively. One hundred and thirty-seven patients were randomized to RIPC (n = 65) or control (n = 72). There were no significant changes in thrombin generation, fibrinogen/fibrin turnover or fibrin structure measurements determined pre and postoperatively between patients in the RIPC and control groups. Subgroup analyses on patients not on anticoagulant therapy (n = 103), patients receiving warfarin (n = 17) and patients receiving direct oral anticoagulant therapy (n = 18) showed no significant changes between the RIPC-patients and controls. RIPC did not affect changes in thrombin generation, fibrin turnover or fibrin structure in adult patients undergoing hip fracture surgery suggesting that the cardiovascular effect of RIPC in hip fracture surgery is not related to alterations in fibrinogen/fibrin metabolism.