Iron deficiency (ID), with or without anemia, is responsible for physical fatigue. This effect may be linked to an alteration of mitochondrial metabolism. Our aim was to assess the impact of ID on skeletal striated muscle mitochondrial metabolism. Iron-deficient non-anemic mice, obtained using a bloodletting followed by a low-iron diet for three weeks, were compared to control mice. Endurance was assessed using a one-hour submaximal exercise on a Rotarod device and activities of mitochondrial complexes I and IV were measured by spectrophotometry on two types of skeletal striated muscles, the soleus and the quadriceps. As expected, ID mice displayed hematologic markers of ID and reduced iron stores, although none of them were anemic. In ID mice, endurance was significantly reduced and activity of the respiratory chain complex I, normalized to citrate synthase activity, was significantly reduced in the soleus muscle but not in the quadriceps. Complex IV activities were not significantly different, neither in the soleus nor in the quadriceps. We conclude that ID without anemia is responsible for impaired mitochondrial complex I activity in skeletal muscles with predominant oxidative metabolism. These results bring pathophysiological support to explain the improved physical activity observed when correcting ID in human. Further studies are needed to explore the mechanisms underlying this decrease in complex I activity and to assess the role of iron therapy on muscle mitochondrial metabolism.

Editor—Interest for ‘Patient Blood Management’ is increasing because of accumulating evidence that blood transfusion may be deleterious.¹ Correction of preoperative anaemia is the first pillar of this management and is recommended before elective orthopaedic surgery.² Different strategies are used across Europe to correct anaemia,³ epoetin-α (EPO) being one of the available treatments. Indeed, EPO showed its effectiveness in reducing perioperative blood transfusion, when administered in the month preceding a major orthopaedic surgery in patients with a haemoglobin (Hb) value between 10 and 13 g dl⁻¹.⁴ Iron therapy is usually associated with EPO to cover the iron demand of increased erythropoiesis.² To date, oral iron was almost the only choice, despite its low absorption, negatively impacted by many factors (inflammation, antacids or thyroid hormones, tea …), and its gastrointestinal side-effects that may reduce patients' compliance.^5,6 A new iron compound, ferric carboxymaltose (FCM), has become available recently, allowing short i.v. infusion of doses up to 1000 mg in 15 min.^7,8 FCM has already been proposed as part of patient blood management protocols,⁹ but has not been compared with oral iron in association with EPO in orthopaedic surgery.

Cardiac surgery is known to induce acute endothelial dysfunction, which may be central to the pathophysiology of postoperative complications. Preoperative endothelial dysfunction could also be implicated in the pathophysiology of postoperative complications after cardiac surgery. However, the relationship between preoperative endothelial function and postoperative outcomes remains unknown. The primary objective was to describe the relationship between a preoperative microcirculatory dysfunction identified by iontophoresis of acetylcholine (ACh), and postoperative organ injury in patients scheduled for cardiac surgery using cardiopulmonary bypass (CPB). Sixty patients undergoing elective cardiac surgery using CPB were included in the analysis of a prospective, observational, single-center cohort study conducted from January to April 2019. Preoperative microcirculation was assessed with reactivity tests on the forearm (iontophoresis of ACh and nitroprusside). Skin blood flow was measured by laser speckle contrast imaging. Postoperative organ injury, the primary outcome, was defined as a Sequential Organ Failure Assessment score (SOFA) 48 h after surgery greater than 3. Organ injury at 48 h occurred in 29 cases (48.3%). Patients with postoperative organ injury (SOFA score > 3 at 48 h) had a longer time to reach the peak of preoperative iontophoresis of acetylcholine (133 s [104–156] vs 98 s [76–139] than patients without, P = 0.016), whereas endothelium-independent vasodilation to nitroprusside was similar in both groups. Beyond the proposed threshold of 105 s for time to reach the peak of preoperative endothelium-dependent vasodilation, three times more patients presented organ dysfunction at 48 h (76% vs 24% below or equal 105 s). In multivariable model, the time to reach the peak during iontophoresis of acetylcholine was an independent predictor of postoperative organ injury (odds ratio = 4.81, 95% confidence interval [1.16–19.94]; P = 0.030). Patients who postoperatively developed organ injury (SOFA score > 3 at 48 h) had preoperatively a longer time to reach the peak of endothelium-dependent vasodilation. Trial registration Clinical-Trials.gov, NCT03631797. Registered 15 August 2018, https://clinicaltrials.gov/ct2/show/NCT03631797

Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56;1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95%CI] 0.34 [0.13-0.86]). A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916.).