Procedural Sedation With Dexmedetomidine in Combination With Ketamine in the Emergency Department.

BACKGROUND: Dexmedetomidine is an alternative agent for procedural sedation in the emergency department thanks to its ability to maintain hemodynamic and respiratory stability. Dexmedetomidine must, however, be combined with a powerful analgesic. OBJECTIVE: Our aim was to evaluate the quality and safety of procedural sedation using the combination of dexmedetomidine and ketamine for patients undergoing painful procedures in the emergency department. METHODS: This prospective interventional single-center study was conducted in an academic emergency department of an urban hospital in Brussels, Belgium. Patients received a bolus injection of 1 µg/kg dexmedetomidine over 10 min and then a continuous infusion of 0.6 µg/kg/h followed by a bolus of 1 mg/kg ketamine. The painful procedure was carried out 1 min later. The level of pain was evaluated with a numerical rating scale from 0 (no pain) to 10 (maximal pain). The level of patient comfort for the procedure was measured using a comfort scale. RESULTS: Thirty patients were included. Overall, 90% of patients felt little or no pain (n = 29 of 30) or discomfort (n = 28 of 30) during the procedure. One patient experienced apnea with desaturation, which was resolved by a jaw-thrust maneuver. Although 23% of patients had significant arterial hypertension, none required drug treatment. CONCLUSIONS: The combination of dexmedetomidine and ketamine provides conscious sedation, bringing comfort and pain relief to patients in optimal conditions for respiratory and hemodynamic safety. However, sedation and recovery times are longer than with conventional drug combinations. The dexmedetomidine-ketamine combination should therefore be recommended for nonurgent procedures and fragile patients.

Neutrophil:lymphocyte ratio and intraoperative use of ketorolac or diclofenac are prognostic factors in different cohorts of patients undergoing breast, lung, and kidney cancer surgery.

BACKGROUND: Inflammation is associated with a worse outcome in cancer and neutrophil:lymphocyte ratio (NLR) is a strong prognostic value. In cancer, nonsteroidal anti-inflammatory drugs (NSAIDs) could be of interest. We investigated the prognostic significance of NLR and the impact of intraoperative NSAIDs in cancer surgeries. METHODS: We performed an observational study in early breast, kidney, and lung cancers (357, 227, and 255 patients) with uni- and multivariate analyses (Cox model). RESULTS: In breast cancer (Centre 1), NLR ≥ 4 is associated with a higher risk of relapse (hazards ratio (HR) = 2.41; 95 % confidence interval (CI) 1.01-5.76; P = 0.048). In breast cancer (Centre 2), NLR ≥ 3 is associated with a higher risk of relapse (HR = 4.6; 95 % CI 1.09-19.1; P = 0.04) and higher mortality (HR = 4.0; 95 % CI 1.12-14.3; P = 0.03). In kidney cancer, NLR ≥ 5 is associated with a higher risk of relapse (HR = 1.63; 95 % CI 1.00-2.66; P = 0.05) and higher mortality (HR = 1.67; 95 % CI 1.0-2.81; P = 0.05). In lung cancer, NLR ≥ 5 is associated with higher mortality (HR = 1.45; 95 % CI 1.02-2.06; P = 0.04). The intraoperative use of NSAIDs in breast cancer patients (Centre 1) is associated with a reduced recurrence rate (HR = 0.17; 95 % CI 0.04-0.43; P = 0.0002) and a lower mortality (HR = 0.25; 95 % CI 1.08-0.75; P = 0.01). NSAIDs use at the beginning of the surgery is independently associated with a lower metastases risk after lung cancer surgery (HR = 0.16; 95 % CI 0.04-0.63; P = 0.009). Ketorolac use is independently associated with longer survival (HR = 0.55; 95 % CI 0.31-0.95; P = 0.03). CONCLUSIONS: In these cohorts, these analyses show that NLR is a strong perioperative prognosis factor for breast, lung, and kidney cancers. In this context, intraoperative NSAIDs administration could be associated with a better outcome.

The effect of clonidine, an alpha-2 adrenergic receptor agonist, on inflammatory response and postischemic endothelium function during early reperfusion in healthy volunteers.

Ischemia-reperfusion disturbs endothelial physiology and generates a proinflammatory state. Animal studies showed that clonidine administered prior hypoxia improves posthypoxic endothelial function. To investigate this effect in human, we have assessed the postischemic endothelium function and the proinflammatory state in healthy volunteers with and without clonidine. Seven volunteers were included. Each subject underwent the experimental protocol (15 minutes nondominant forearm ischemia) with and without clonidine. Endothelial function was assessed by flow-mediated dilatation (FMD) in the brachial artery before ischemia (FMDPI), immediately after ischemia (FMDIAI), and 15 minutes after ischemia (FMD15AI). Neutrophil (CD11b/CD18) and platelet (CD42b) activations were measured by flow cytometry during reperfusion in blood samples from ischemic (local) and nonischemic (systemic) forearms. Proinflammatory state was assessed by serum concentration of interleukin (IL)-1ß and -6. Clonidine does not influence baseline FMD (P = 0.118) but improves FMDIAI (P = 0.018) and FMD15AI (P = 0.018). It increases platelet activation in systemic circulation (P = 0.003) during reperfusion but not in local circulation (P = 0.086). Clonidine increases neutrophil activation in local circulation (P = 0.001) but not in systemic circulation (P = 0.642). In local circulation, clonidine decreases IL-6 (P = 0.044) but does not influence IL-1ß (P = 0.113). By contrast, it decreases both IL-6 (P = 0.026) and IL-1ß (P = 0.027) concentrations in systemic circulation. In conclusion, clonidine improves endothelial function and modulates inflammation during reperfusion.

An increase in endogenous erythropoietin concentrations has no cardioprotective effects in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: Preliminary data showed an increase in endogenous erythropoietin (EPO) concentrations after acute normovolemic hemodilution (ANH) in patients undergoing coronary artery bypass graft (CABG) surgery. Numerous studies have shown the organ protective properties of EPO. The aim of this study was to investigate the cardioprotective effects of these increased EPO concentrations that resulted from ANH during cardiac surgery. DESIGN: A prospective, randomized, blind study. SETTING: A university hospital. PARTICIPANTS: A total of 93 patients undergoing isolated CABG surgery with or without cardiopulmonary bypass (CPB). INTERVENTIONS: Subjects with CPB were randomized into the control (C) or ANH group. Those in the off-pump coronary artery bypass group underwent no treatment. In the ANH group, a precalculated amount of blood was withdrawn and replaced by colloids after the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were recorded intra- and postoperatively. Troponin concentrations were measured as a routine parameter postoperatively. Upon intensive care unit arrival, the EPO levels were higher in the ANH group than in the C group. There was no significant difference between the troponin values of the C and the ANH groups at 4 hours postoperatively. CONCLUSIONS: In patients undergoing CABG surgery on CPB, an increase in endogenous EPO concentrations in the physiologic range has no cardioprotective effects.

Chronic postsurgical pain.

PURPOSE OF REVIEW: Chronic postsurgical pain (CPSP) is the consequence of acute postoperative pain. Unfortunately, despite many attempts of improvement, the treatment of acute postoperative pain remains unsatisfactory. In the present review, the probable reasons for this will be reviewed. RECENT FINDINGS: Based on the demonstration of specific, patients-related 'pain risk', individual pain trajectories and the importance of secondary hyperalgesia in the development of CPSP, new methods have to be applied in order to determine the real efficacy of new analgesic adjuvants. The key importance of the early inflammatory reaction in the genesis of the 'postoperative syndrome' and its close interaction with the mechanisms elicited by intraoperative opioid administration must also be outlined. SUMMARY: A single treatment approach is almost unlikely to solve the problem of CPSP. Consequently, the management of postoperative pain has to become more patients' specific and etiologies sensitive.

Atraumatic splenic rupture in a patient treated with rivaroxaban: A case report and a narrative review.

Atraumatic splenic rupture (ASR) is a rare condition mostly associated with neoplastic, infectious, and inflammatory diseases. ASR associated with drug treatment is even rarer. In this case report, we highlight an unusual complication of the direct oral anticoagulant rivaroxaban. A 64-year-old male patient was admitted to the emergency department with complaints of faintness and diffuse abdominal cramps. The patient had no history of recent trauma. Clinical examination revealed hemodynamic instability with a moderate response to filling and mild abdominal discomfort on palpation. His medical history included chronic hypertension, constipation, and recent atrial flutter ablation. The patient was taking amiodarone, bisoprolol, atorvastatin, and rivaroxaban. Splenic rupture was diagnosed several hours later on contrast-enhanced abdominal computed tomography scan. Massive blood transfusions and emergency laparotomy for splenectomy were performed. Anatomopathological analysis did not reveal any neoplastic, inflammatory, or infectious causes. The patient was successfully discharged from the intensive care unit 3 days later. Clinicians must consider the possibility of ASR as a complication of rivaroxaban in patients with abdominal tenderness and hemodynamic instability. Unfortunately, clinical presentation is not always typical of a ruptured spleen. Delayed diagnosis can be life threatening or fatal. Splenectomy via laparotomy remains the best therapeutic option in cases of splenic rupture in unstable patients on direct oral anticoagulants.

Avoiding, Not Managing, Drug Withdrawal Syndrome in the Setting of COVID-19 Acute Respiratory Distress Syndrome. Comment on Ego et al. How to Manage Withdrawal of Sedation and Analgesia in Mechanically Ventilated COVID-19 Patients? J. Clin. Med. 2021, 10, 4917.

The management of sedation in the setting of COVID-19 ("COVID") by Ego et al. [...].

Effect of N-acetyl-cysteine and hyperoxia on erythropoietin production.

Previous studies in healthy subjects have shown an increase in erythropoietin (EPO) production after administration of N-acetyl-cysteine (NAC). These authors hypothesized that NAC increases intracellular reduced glutathione, decreasing reactive oxygen species and enabling EPO production. We investigated if EPO production could be stimulated with a single dose of NAC, after 90 min of pure oxygen breathing. Thirty-eight healthy volunteers were randomized into either the control (C) group or the NAC group, which received 600 mg NAC PO dissolved in a glass of orange juice, 60 min before breathing 15 L/min of 100% normobaric oxygen. Orange juice was administered to both groups. Blood samples for EPO measurement were taken at T0, before the orange juice administration, and T1, T2, T3 and T4, respectively, 8, 24, 32 and 48 h after the orange juice. The EPO concentrations of the NAC group decreased significantly at T1, followed by a significant increase compared to baseline, which was obvious until T4. The EPO concentrations of the C group did not show any significant variations. In this study, a significant increase of EPO production was observed after a short-term hyperoxic stimulus only when preceded with the administration of a single dose of NAC.

Do intraoperative analgesics influence oncological outcomes after radical prostatectomy for prostate cancer?

BACKGROUND: The potential impact of intraoperative analgesics on oncological outcome after radical prostatectomy is debated. Some investigators have suggested that use of opioids favour relapse, whereas regional analgesia and NSAIDs improve oncological outcomes. OBJECTIVE: To evaluate the impact of intraoperative analgesia (epidural and intravenous) on the incidence of biochemical recurrence-free (BRF) survival. DESIGN, SETTING AND PARTICIPANTS: This retrospective study includes 1111 consecutive retropubic radical prostatectomies (RRPs) for localised prostate cancer, performed between 1993 and 2006. Median follow-up was 38 months (interquartile range 16-69). BRF survival probabilities were compared with log-rank tests and the Cox regression model. MAIN OUTCOME MEASURES AND RESULTS: Epidural analgesia was used in 52% of patients, intravenous ketorolac in 25%, sufentanil in 97%, clonidine in 25% and ketamine in 16%. Univariate and multivariate analyses showed that intravenous sufentanil significantly reduced BRF survival rate, hazard ratio 7.78 [95% confidence interval (CI) 5.79, 9.78), for extracapsular extension stage pT 2 or less, hazard ratio 0.44 (95% CI 0.12, 0.75), Gleason score at least 7, hazard ratio 1.96 (95% CI 1.65, 2.26), positive margin, hazard ratio 1.87 (95% CI 1.58, 2.02) and lymph node involvement, hazard ratio 1.77 (95% CI 1.27, 2.27, P > 0.05). In contrast, neither epidural analgesia nor other analgesics were associated with a statistically significant effect (P > 0.05). CONCLUSION: This retrospective analysis suggests that intraoperative sufentanil administration is associated with an increased risk of cancer relapse after RRP, whereas epidural analgesia, with local anaesthetic and opioid, was not associated with a significant effect.

Is Intraoperative Opioids Avoidance A Utopia? A Matched Study in Laparoscopic Hysterectomy.

BACKGROUND: Opioid-sparing strategies are recommended, and Opioid-Free Anaesthesia (OFA) is proposed in the literature. But few data exist about the feasibility of OFA in the routine practice. From a larger series of 21,463 patients receiving OFA, this work investigates the postoperative pain and related outcomes in patients undergoing laparoscopic hysterectomy. MATERIALS AND METHODS: This matched retrospective study concerned 521 patients scheduled for a laparoscopic hysterectomy between 2010 and 2015 (118 receiving OFA and 403 receiving anaesthesia with opioids, AO). Primary outcome was pain in the Post-Anaesthetic Care Unit (PACU). RESULTS: Among the 521 included patients, 403 received sufentanil (mean±SD: 0.1±0.05 mcg/kg), the only synthetic opioid used to balance anaesthesia. Concerning the 118 patients receiving OFA, most of them received an association of clonidine (97%) and ketamine (95%). Most of the patients in both groups received non-steroidal anti-inflammatory drugs. No difference in pain scores was observed between AO and OFA (median [IQR], respectively: 4 [0-5] vs. 4.5 [0-6], P=0.74). A difference in the perioperative morphine equivalent use was observed (mean±SD: 0.18±0.06 mg/kg vs. 0.09±0.06 mg/kg, P<0.001). No difference was observed regarding the nausea/vomiting incidences, use of anti-emetics, sedation scores, or time spent at the PACU. CONCLUSION: Coming from an extensive daily practice, these data show that OFA is feasible and not associated with higher pain scores or longer PACU stay, suggesting the absence of specific immediate complications.

Goal-directed fluid management based on the pulse oximeter-derived pleth variability index reduces lactate levels and improves fluid management.

BACKGROUND: Dynamic variables predict fluid responsiveness and may improve fluid management during surgery. We investigated whether displaying the variability in the pulse oximeter plethysmogram (pleth variability index; PVI) would guide intraoperative fluid management and improve circulation as assessed by lactate levels. METHODS: Eighty-two patients scheduled for major abdominal surgery were randomized into 2 groups to compare intraoperative PVI-directed fluid management (PVI group) versus standard care (control group). After the induction of general anesthesia, the PVI group received a 500-mL crystalloid bolus and a crystalloid infusion of 2 mL · kg(-1) · h(-1). Colloids of 250 mL were administered if the PVI was >13% Vasoactive drug support was given to maintain the mean arterial blood pressure above 65 mm Hg. In the control group, an infusion of 500 mL of crystalloids was followed by fluid management on the basis of fluid challenges and their effects on mean arterial blood and central venous pressure. Perioperative lactate levels, hemodynamic data, and postoperative complications were recorded prospectively. RESULTS: Intraoperative crystalloids and total volume infused were significantly lower in the goal-directed PVI group. Lactate levels were significantly lower in the PVI group during surgery and 48 hours after surgery (P < 0.05). CONCLUSIONS: PVI-based goal-directed fluid management reduced the volume of intraoperative fluid infused and reduced intraoperative and postoperative lactate levels.

Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis.

BACKGROUND: Whether intraoperative analgesics have an impact on postoperative cancer recurrence is unknown. Some investigations suggest that the opioids could favor relapse and that regional analgesia and nonsteroidal antiinflammatory drugs could improve cancer prognosis. We retrospectively reviewed our series of breast cancer surgery patients. METHODS: This retrospective study included 327 consecutive women who underwent mastectomy with axillary dissection for breast cancer. The main objective was to compare the incidence of cancer recurrence among patients who received different analgesics during surgery. RESULTS: Perioperative characteristics, cancer prognostic factors, and the length of surgery were comparable regardless of the analgesics administered. Univariate and multivariate analyses showed a lower cancer recurrence rate when ketorolac was given before surgery (P = 0.019). Other analgesics (sufentanil, ketamine, and clonidine) were not associated with a significant reduction in cancer recurrence rates in our series. CONCLUSION: This retrospective analysis suggests that intraoperative administration of ketorolac decreases the risk of breast cancer relapse compared with other analgesícs.

Prehypoxic clonidine administration improves vasomotricity of isolated rat aorta during reoxygenation.

BACKGROUND AND OBJECTIVE: Clonidine, an alpha-2 adrenoceptor (A2A) agonist, improves posthypoxic function of several organs in humans and animal models. Mechanisms underlying these effects are not fully understood. A competent vasomotricity during reperfusion participates in the organ's recovery. This study investigates the specific effect of clonidine administration before hypoxia on posthypoxic vasomotricity in a rodent model. METHODS: Isolated aortic rings from young rats were submitted to hypoxia/reoxygenation (20/40 min). Clonidine (10(-5) mol l(-1)), alone or with various receptor antagonists such as rauwolscine (specific A2A antagonist), ARC239 (A2B/C-prefering A antagonist), BRL44408 (A2AA antagonist), nitrogen oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester) or cyclooxygenase inhibitor (indometacin), was administered in two randomized baths and washed out before hypoxia. Two other baths constituted the control group. In some experiments, clonidine was substituted by UK14.304 (A2A agonist). In all baths, posthypoxic endothelium-dependent dilatation (PED) and posthypoxic contraction were assessed. RESULTS: Clonidine improves PED (P = 0.002) and posthypoxic contraction (P = 0.001). Rauwolscine (P = 0.803) and ARC239 (P = 0.236) abolished clonidine-induced PED improvement. In the presence of BRL44408, clonidine increases posthypoxic endothelial dysfunction (P = 0.001). UK14.304 (P = 0.954) does not mimic the clonidine effect on PED. Concerning posthypoxic contraction, rauwolscine (P = 0.917), endothelial removal (P = 0.687), ARC239 (P = 0.118) or BRL44408 (P = 0.204) prevents the clonidine effect, but UK14.304 induces it (P = 0.005). Nω-Nitro-L-arginine methyl ester (P = 0.026) does not abolish it. Indometacin prevents it on PED and posthypoxic contraction (P = 0.678 and P = 0.851, respectively). CONCLUSION: Clonidine improves posthypoxic vasomotricity on isolated aortic rings. Concerning PED, two endothelial A2A subtypes are required. The clonidine effect on posthypoxic contraction requires endothelial A2A. Nitrogen oxide does not seem to be involved. Concerning the clonidine effect on PED and posthypoxic contraction, cyclooxygenase metabolites seem to be involved.

Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages.

BACKGROUND AND OBJECTIVE: Cellular immunity varies in the perioperative period. We evaluated the effects of fentanyl, clonidine and ketamine at different time points after surgery and in animals in different conditions (young vs. old). MATERIALS AND METHODS: Rats undergoing laparotomy under sevoflurane anaesthesia were assigned to receive saline, fentanyl (40 microg kg(-1)), clonidine (10 microg kg(-1)) or ketamine (10 mg kg(-1)) 1 h before surgery. Natural killer (NK) activity was quantified at different time points (immediately or after 18, 24, 48, 72 h and 8 days) in vitro by the lysis of YAC-1 cells. In-vivo assessment included counting the number of lung metastases induced by the MADB-106 cells. RESULTS: During the first 24 h after surgery, a rapid increase in NK activity was noted, followed by a significant depression returning to baseline at 8 days. Analgesics show specific effects: fentanyl depressed NK activity with or without surgery. Clonidine depressed NK activity in nonoperated animals and during the first 24 h after surgery. Ketamine depressed NK activity in nonoperated animals but, after surgery, this activity varied with the same time course as saline. Ketamine and clonidine significantly reduced the number of lung metastases in operated animals. Ketamine significantly reduced the number of metastases in old nonoperated animals. Finally, ageing has a significant negative influence. CONCLUSION: Surgery, analgesics and co-existing conditions significantly influence cellular immunity. The importance of these changes varies with time. Fentanyl had a worse influence than clonidine and ketamine, but seemed equally protective against the development of metastases.

Characterization of Preoperative, Postsurgical, Acute and Chronic Pain in High Risk Breast Cancer Patients.

BACKGROUND: Pain after breast cancer surgery remains largely unexplained and inconsistently quantified. This study aims to describe the perioperative pain patterns in patients with breast cancer, up to two years after surgery. METHODS: This is a pre-planned sub-study of the Ketorolac in Breast Cancer (KBC) trial. The KBC trial was a multicentre, prospective, double-blind, placebo-controlled, randomised trial of a single dose of 30 mg of ketorolac just before breast cancer surgery, aiming to test its effect on recurrences. This sub-study focuses only on pain outcomes. From 2013 to 2015, 203 patients were randomised to ketorolac (n = 96) or placebo (n = 107). Structured questionnaires were delivered by telephone after one and two years, exploring the presence, location, permanence, and frequency of pain. Patients' perceptions of pain were captured by an open-ended question, the responses to which were coded and classified using hierarchical clustering. RESULTS: There was no difference in pain between the ketorolac and the placebo group. The reported incidence of permanent pain was 67% and 45% at one and two years, respectively. The largest category was musculoskeletal pain. Permanent pain was mainly described in patients with musculoskeletal pain. The description of pain changed in most patients during the second postoperative year, i.e., moved from one category to another (no pain, permanent, or non-permanent pain, but also, the localisation). This phenomenon includes patients without pain at one year. CONCLUSIONS: Pain is a complex phenomenon, but also a fragile and unstable endpoint. Pain after breast cancer surgery does not necessarily mean breast pain but also musculoskeletal and other pains. The permanence of pain and the pain phenotype can change over time.

The impact of ischaemia-reperfusion on the blood vessel.

Ischaemia significantly affects the cellular homeostasis (sodium and calcium overload, intracellular acidosis, swelling, cytoskeleton injuries, mitochondrial hypercalcaemia and others). If reperfusion of an organ in ischaemia is essential for its viability and its functional recovery, the arrival of blood oxygen will cause a series of lesions; this is known as the phenomenon of ischaemia-reperfusion. Vasomotricity and the endothelial functions are significantly affected by it. Endothelium-dependent vasodilatation is more affected by ischaemia-reperfusion injuries than vasoconstriction and endothelial-independent vasodilatation. Reactive oxygen species and tumour necrosis factor-alpha seem to play a major role in this perturbation. Reperfusion also induces an important inflammatory response, characterized by a massive production of free radicals and by the activation of the complement and leucocyte neutrophils. A narrow interaction between activated endothelium and neutrophils will result in a significant concentration of neutrophils activated in the interstitium, where they release many oxygen radicals and many kinds of proteases, which destroy cells and extracellular matrix. This transfer of neutrophils from the intravascular bed to the intestitium involves several families of proteins such as selectins (P-selectin and L-selectin), integrines (intercellular adhesion molecule-1) and immunoglobulins (platelet-endothelial cell adhesion molecule-1). Last, oxidative stress, the production of cytokines and the secondary mitochondrial lesions that occur with reperfusion will induce apoptosis on the level of the parenchyma and the vascular structures. According to the stage of the vascular system considered (small arteries, capillaries or postcapillary veins), the repercussions of ischaemia-reperfusion are identical, but the clinical pictures differ. The proinflammatory state induced by reperfusion continues for several days and can affect the patient's prognosis.

Pulmonary lobectomy in two multitrauma patients under extracorporeal circulation placed preoperatively in an intensive care unit: A case report.

The clinical course of our two patients highlights the feasibility of using venovenous extracorporeal membrane oxygenation (ECMO) with heparin for multitraumatic patients needing thoracic surgery. Further research is required to determine if surgery can be performed with totally heparin-free vv-ECMO. All ICU teams should become familiar with this technique.

What Can We Learn from Sarcopenia with Curarisation in the Context of Cancer Surgery? A Review of the Literature.

INTRODUCTION: The monitoring of the curarisation is a unique opportunity to investigate the function of the neuromuscular junction (NMJ) during cancer surgery, especially in frailty-induced and age-related sarcopenia. METHOD: We conducted a comprehensive literature review in PubMed, without any limit of time related to frailty, sarcopenia, age and response to neuromuscular blockers in the context of cancer surgery. RESULTS: Several modifications appear with age: changes in cardiac output, a decrease in muscle mass and increase in body fat, the deterioration in renal and hepatic function, the plasma clearance and the volume of distribution in elderly are smaller. These changes can be exacerbated in cancer patients. We also find modifications of the NMJ: dysfunctional mitochondria, modifications in the innervation of muscle fibers and motor units, uncoupling of the excitation-contraction of muscle fibers, inflammation. Neuromuscular blocking agents (NMBAs) compete with acetylcholine and prevent it from fixing itself on its receptor. Many publications reported guidelines for using NMBAs in the elderly, based on studies comparing old people with young people. No one screened frailty before, and thus, no studies compared frail elderly and non-frail elderly undergoing cancer surgery. CONCLUSION: Despite many studies about curarisation in the specific populations, and many arguments for a potential interest for investigation, no studies investigated specifically the response to NMBAs in regard of the frailty-induced and age-related sarcopenia.

Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial.

BACKGROUND: Ketorolac has been associated with a lower risk of recurrence in retrospective studies, especially in patients with positive inflammatory markers. It is still unknown whether a single dose of pre-incisional ketorolac can prolong recurrence-free survival. METHODS: The KBC trial is a multicenter, placebo-controlled, randomized phase III trial in high-risk breast cancer patients powered for 33% reduction in recurrence rate (from 60 to 40%). Patients received one dose of ketorolac tromethamine or a placebo before surgery. Eligible patients were breast cancer patients, planned for curative surgery, and with a Neutrophil-to-Lymphocyte Ratio≥4, node-positive disease or a triple-negative phenotype. The primary endpoint was Disease-Free Survival (DFS) at two years. Secondary endpoints included safety, pain assessment and overall survival. FINDINGS: Between February 2013 and July 2015, 203 patients were assigned to ketorolac (n = 96) or placebo (n = 107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD14) years. At two years, 83.1% of the patients were alive and disease free in the ketorolac vs. 89.7% in the placebo arm (HR: 1.23; 95%CI: 0.65-2.31) and, respectively, 96.8% vs. 98.1% were alive (HR: 1.09; 95%CI: 0.34-3.51). CONCLUSIONS: A single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival difference between ketorolac tromethamine group and placebo group was not statistically significant. The study was however underpowered because of lower recurrence rates than initially anticipated. No safety concerns were observed. TRIAL REGISTRATION: ClinicalTrials.gov NCT01806259.