Rationale and design of the intravenous iron for treatment of anemia before cardiac surgery trial.

Background Approximately 20% to 30% of patients awaiting cardiac surgery are anemic. Anemia increases the likelihood of requiring a red cell transfusion and is associated with increased complications, intensive care, and hospital stay following surgery. Iron deficiency is the commonest cause of anemia and preoperative intravenous (IV) iron therapy thus may improve anemia and therefore patient outcome following cardiac surgery. We have initiated the intravenous iron for treatment of anemia before cardiac surgery (ITACS) Trial to test the hypothesis that in patients with anemia awaiting elective cardiac surgery, IV iron will reduce complications, and facilitate recovery after surgery. Methods ITACS is a 1,000 patient, international randomized trial in patients with anemia undergoing elective cardiac surgery. The patients, health care providers, data collectors, and statistician are blinded to whether patients receive IV iron 1,000 mg, or placebo, at 1-26 weeks before their planned date of surgery. The primary endpoint is the number of days alive and at home up to 90 days after surgery. Results To date, ITACS has enrolled 615 patients in 30 hospitals in 9 countries. Patient mean (SD) age is 66 (12) years, 63% are male, with a mean (SD) hemoglobin at baseline of 118 (12) g/L; 40% have evidence (ferritin <100 ng/mL and/or transferrin saturation <25%) suggestive of iron deficiency. Most (59%) patients have undergone coronary artery surgery with or without valve surgery. Conclusions The ITACS Trial will be the largest study yet conducted to ascertain the benefits and risks of IV iron administration in anemic patients awaiting cardiac surgery.

Is Preoperative Endothelial Dysfunction a Potentially Modifiable Risk Factor for Renal Injury Associated With Noncardiac Surgery?

OBJECTIVES: To determine whether preoperative endothelial dysfunction provides risk stratification for perioperative renal injury in patients undergoing noncardiac surgery. The relationship between perioperative renal injury and myocardial injury after noncardiac surgery (MINS) was explored secondarily. DESIGN: An observational study. SETTING: Two academic medical centers. PARTICIPANTS: A total of 218 patients scheduled to undergo intermediate or high-risk noncardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Endothelial dysfunction was identified preoperatively by a Reactive Hyperemia-Peripheral Arterial Tonometry (RH-PAT) index. Renal injury was defined by peak delta serum creatinine (ΔSCr) or creatinine-based kidney disease: Improving global outcomes acute kidney injury (AKI) criteria within 7 days postoperatively. MINS was defined by peak troponin ≥0.04 µg/L within 3 days postoperatively. AKI occurred in 22 patients (10.1%). Median RH-PAT index within the study cohort was 1.64 (range 1.03-4.96) and did not differ between patients with or without AKI. When adjusted for covariates, there was no association between RH-PAT index and either AKI or peak ΔSCr. MINS occurred in 32 patients (14.7%) and was associated independently with the outcome of AKI (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.2-10.8; p = 0.02) and peak ΔSCr (ß-regression coefficient 23; 95% CI, 9-37; p = 0.002). Co-occurrence of AKI and MINS portended a marked increase in 30-day mortality (OR, 43; 95% CI, 6-305; p = 0.001) and delayed time to discharge (hazard ratio, 0.27; 95% CI, 0.13-0.54; p = 0.001). CONCLUSIONS: For patients undergoing noncardiac surgery, preoperative endothelial function assessed by noninvasive peripheral arterial tonometry was not associated with perioperative AKI. Perioperative renal injury was associated strongly with MINS, and this may represent a mechanism by which AKI increases adverse outcomes.

IRON NOF trial: IV iron for anaemic patients with femoral fracture.

Background: Preoperative anaemia is associated with increased use of blood transfusions, a greater risk of postoperative complications, and patient morbidity. The IRON NOF trial aimed to investigate whether the administration of i.v. iron in anaemic patients during hip fracture surgery reduced the need for blood transfusion and improved patient outcomes. Methods: This phase III double-blind, randomised, placebo-controlled trial included patients >60 yr old with preoperative anaemia undergoing surgery for femoral neck or subtrochanteric fracture across seven Australian Hospitals. Patients were randomly allocated on a 1:1 basis to receive either i.v. iron carboxymaltose 1000 mg or placebo (saline) at operation. The primary endpoint was blood transfusion use, with secondary endpoints of haemoglobin concentration at 6 weeks, length of hospital stay, rehabilitation duration to discharge, and 6-month mortality. Subgroup analysis compared outcomes in patients <80 yr old and patients >80 yr old. All analyses were performed by intention-to-treat. This trial was terminated early because of jurisdictional changes of more restrictive transfusion practices and changes in consent requirements. Results: Participants (n=143) were recruited between February 2013 and May 2017. There was no difference observed in the incidence of blood transfusion between the treatment group (18/70) (26%) compared with the placebo group (27/73) (37%) (odds ratio for transfusion if receiving placebo: 1.70; 95% confidence interval [CI] 0.83-3.47; P=0.15) and there was no overall difference in the median number of blood units transfused between groups (odds ratio 1.52; 95% CI 0.77-3.00; P=0.22). Patients receiving i.v. iron had a higher haemoglobin 6 weeks after intervention compared with the placebo group (Hb 116 g L-1vs 108 g L-1; P=0.01). No difference was observed in length of hospital stay, rehabilitation duration to discharge, or 6-month mortality. However, in younger patients without major bleeding, the use of placebo compared with i.v. iron was associated with an increased number of units of blood transfused (placebo transfusion incidence rate ratio 3.88; 95% CI 1.16-13.0; P=0.03). Conclusions: In anaemic patients undergoing surgery for hip fracture, i.v. iron did not reduce the overall proportion of patients receiving blood transfusion. The use of i.v. iron may reduce the amount of blood transfused in younger patients. The use of i.v. iron is associated with increased haemoglobin concentrations 6 weeks after the operation. Clinical trial registration: ACTRN12612000448842.

Associations between non-anaemic iron deficiency and outcomes following elective cardiac surgery (IDOCS): a prospective cohort study.

BACKGROUND: One in two adults undergoing cardiac surgery are iron deficient, best practice guidelines and consensus statements recommend routine investigation and treatment of iron deficiency before elective cardiac surgery, even in the absence of anaemia; however, it is not clear if non-anaemic iron deficiency is associated with worse outcomes in this patient population. We hypothesised that iron deficiency would be associated with worse postoperative outcomes than an iron replete state in adults without anaemia undergoing elective cardiac surgery. METHODS: We performed a prospective, cohort study at two hospitals in Australia. We recruited adults (ie, people 18 years and older) undergoing elective cardiac surgery without anaemia (defined as a haemoglobin of less than 130 g/L for men and less than 120 g/L for women), concomitant haemoglobinopathy, bone marrow pathology, haemochromatosis, or end-stage renal failure requiring dialysis. Participants were stratified as iron deficient or iron replete on the basis of preoperative testing. Iron deficiency was defined as a serum ferritin of less than 100 µg/L or 100-300 µg/L if transferrin saturation was less than 20% or C-reactive protein was more than 5 mg/L. The primary endpoint was days alive and at home at postoperative day 30. The primary analysis included all patients with data available for the primary endpoint and was adjusted for risk measured using EuroSCORE-II and body surface area. The study was prospectively registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12618000185268. FINDINGS: We conducted the study between Feb 21, 2018, and May 7, 2021. We assessed 1171 patients for eligibility and 691 were ineligible; therefore, we enrolled and followed up 480 participants. 240 (50%) were iron deficient and 240 (50%) were iron replete, 95 (20%) were women, 385 (80%) were men, and 453 (94%) were White. Complete data was available for 479 individuals (240 in the iron deficient group and 239 in the iron replete group) for the primary endpoint. The iron deficient group had a median of 22·87 days (IQR 20·65 to 24·06) alive and at home at postoperative day 30, and the iron replete group had a median of 23·18 days (IQR 20·69 to 24·70). The unadjusted difference in medians between the groups was -0·18 days (95% CI -0·73 to 0·36; p=0·51) and the adjusted difference in medians between the groups was -0·11 days (95% CI -0·66 to 0·45; p=0·70). INTERPRETATION: In non-anaemic adults undergoing elective cardiac surgery, our findings suggest that patients with iron deficiency do not have a reduction in days alive and at home at postoperative day 30 compared with patients who have a normal iron status. Routine preoperative investigation for iron deficiency in patients without anaemia undergoing elective cardiac surgery using the definitions we tested might be low-value care. FUNDING: Australian and New Zealand College of Anaesthetists Foundation.

A systematic review of ketamine as an analgesic agent in adult burn injuries.

OBJECTIVE: To assess the current literature regarding the effectiveness and side-effect profile of intravenous ketamine as a means of pain relief when compared with placebo or as an adjunct to opioid analgesia in patients exposed to burn injury. DESIGN: Electronic searches of MEDLINE, CINAHL, Embase, and The Cochrane Library databases from 1966 onward were used to identify clinical trials comparing ketamine with placebo in the adult burn population. OUTCOMES MEASURED: Effectiveness and side-effect profile of ketamine as an analgesic agent in burn injuries. RESULTS: Four experimental trials involving 67 patients were identified. Due to heterogeneity of studies, pooling of the results and meta-analysis were not possible. Intravenous ketamine showed some efficacy as an analgesic for burn injuries, with a reduction in secondary hyperalgesia when compared with opioid analgesia alone. Combination therapy of ketamine and morphine resulted in the abolishment of windup pain phenomena. The side-effect profile did not result in the withdrawal of any participants included in the studies' results. CONCLUSIONS: Further well-designed randomized controlled trials conducted in burn-specific populations are warranted, thus enabling the development of a relevant evidence base to support its clinical use.

Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function.

BACKGROUND: Endothelial function is impaired with hyperhomocysteinemia. Plasma homocysteine is increased by nitrous oxide anesthesia. The current study was designed to determine whether endothelial function is impaired after surgery and whether this is made worse by exposure to nitrous oxide. METHODS: The authors studied 59 patients with cardiovascular disease undergoing noncardiac surgery. Patients were randomly allocated to nitrous oxide-based anesthesia (n = 25) or nitrous oxide-free anesthesia (control, n = 34). Endothelial function was measured by flow-mediated dilation of the brachial artery before and 24 h after surgery. In addition, blood was drawn at both time points for the measurements of plasma homocysteine, folate, L-arginine, L-citrulline, asymmetric dimethylarginine, and nitrate concentrations. RESULTS: The median duration of general anesthesia was 4.5 h. Patients had significantly lower flow-mediated dilation after surgery (5.1 +/- 3.3 to 3.0 +/- 4.1%; P = 0.001). Duration of anesthesia affected endothelial function. In the nitrous oxide group, there was an inverse correlation with flow-mediated dilation (r = -0.60, P = 0.004), but in the control group, there was a positive correlation (r = 0.61, P < 0.001). When compared with control, nitrous oxide exposure was associated with a significant increase in postoperative homocysteine (mean difference, 4.9 microm; 95% confidence interval, 2.8-7.0 microm; P < 0.0005) and decrease in flow-mediated dilation (3.2%; 95% confidence interval, 0.1-5.3%; P = 0.001). Nitrous oxide exposure was not associated with change in nitric oxide substrates. CONCLUSIONS: Nitrous oxide-based anesthesia increased plasma homocysteine and significantly impaired endothelial function in patients undergoing noncardiac surgery. Nitrous oxide-based anesthesia could be a risk factor for postoperative cardiovascular morbidity.

Neuropathic pain and foot drop related to nerve injury after short duration surgery and caudal analgesia.

Caudal anesthesia is the most common type of regional anesthetic technique performed in children. The incidence of neurologic adverse events is extremely rare. A postoperative complication of a mild but permanent neurologic deficit after administration of a caudal anesthetic in a previously well 9-year-old boy who required emergency scrotal exploration for a testicular torsion is reported. The caudal injection provided good postoperative analgesia, which probably resulted in the patient remaining in the same position overnight. This may have contributed to the development of the neurologic deficit, probably owing to a compressive neuropathy. We suggest that, as anesthesiologists obtaining informed consent for anesthetic interventions, we now need to inform guardians/carers of pediatric patients who are to receive caudal analgesia of the extremely small material risk of neurologic damage after caudal anesthesia. Additionally, the anesthetic community may need to consider revising postoperative care instructions to prevent the future occurrence of this rare outcome, particularly if using additives that prolong analgesic block duration.